Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 216
Filtrar
1.
Nat Commun ; 15(1): 8543, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39358379

RESUMO

The immiscibility of hydrogen-helium mixture under the temperature and pressure conditions of planetary interiors is crucial for understanding the structures of gas giant planets (e.g., Jupiter and Saturn). While the experimental probe at such extreme conditions is challenging, theoretical simulation is heavily relied in an effort to unravel the mixing behavior of hydrogen and helium. Here we develop a method via a machine learning accelerated molecular dynamics simulation to quantify the physical separation of hydrogen and helium under the conditions of planetary interiors. The immiscibility line achieved with the developed method yields substantially higher demixing temperatures at pressure above 1.5 Mbar than earlier theoretical data, but matches better to the experimental estimate. Our results suggest a possibility that H-He demixing takes place in a large fraction of the interior radii of Jupiter and Saturn, i.e., 27.5% in Jupiter and 48.3% in Saturn. This indication of an H-He immiscible layer hints at the formation of helium rain and offers a potential explanation for the decrease of helium in the atmospheres of Jupiter and Saturn.

2.
ACS Nano ; 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39436831

RESUMO

Directly assembling drugs into mesoporous nanoformulations will be greatly favored due to the combination of enhanced drug delivery efficiency and mesostructure-enabled nanobio interactions. However, such an approach is hindered due to the lack of understanding of polymer nanoparticles' formation mechanism, especially the relationship between polymerization, self-assembly, and the nucleation process. Here, by investigating the levodopa and dopamine polymerization process, we identify π-cation interaction as pivotal in the self-assembly and nucleation control of dopa molecules. Thus, through manipulation of the π-cation interaction, we present the direct assembly of a commercial drug, levodopa, into mesoporous nanoformulations. The synthesized nanospheres, approximately 200 nm in diameter, exhibit uniform mesopores of around 8 nm. These nanoformulations, abundant in mesopores, enhance chiral phenylalanine interaction with α-synuclein (Syn), curbing aggregation, safeguarding neurons, and alleviating Parkinson's pathology. When combating α-synuclein, the nanoformulation achieved ∼100% inhibition of protein aggregation and sustained neuron viability up to 300%. We believe that this study may advance mesoscale self-assembly knowledge, guiding future nanopharmaceutical developments.

3.
J Am Chem Soc ; 146(39): 26983-26993, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39294849

RESUMO

While polyphenolic substances stand as excellent antibacterial agents, their antimicrobial properties rely on the auxiliary support of micro-/nanostructures. Despite offering a novel avenue for enhancing polymer performance, controllable fabrication of mesoporous polymeric nanomaterials encounters significant challenges due to intricate intermolecular forces. In this article, mesoporous catechin nanoparticles have been successfully fabricated using a balanced multivariate interaction approach. The harmonization of the water-ethanol ratio and ionic strength effectively balances the forces of hydrogen bonding and π-π stacking, facilitating the controlled assembly of mesostructures. The mesoporous catechin nanoparticles exhibit a uniform spherical structure (∼100 nm), open mesopores with a diameter of ∼15 nm, and a high surface area of ∼106 m2 g-1. While exhibiting a good biocompatibility and negative surface charge, the mesoporous catechins possess outstanding antibacterial ability and function as an antibiotic mesoformulation without the necessity of loading any drugs. This mesoformulation inhibits 50% in vitro Staphylococcus aureus growth with a low concentration of ∼10 µg mL-1 and achieves complete inhibition at ∼25 µg mL-1. In a mouse wound model, accelerated wound healing and complete closure within 6-8 days are achieved. Proteomics of bacteria reveals that the excellent antibacterial property is attributed to the synergetic effect of mesoformulation's mesostructure and the catechin molecule intervening in bacterial metabolism. Overall, this work may pave a novel way for the future exploration of polymer nanomaterials and antibiotic formulations.


Assuntos
Antibacterianos , Catequina , Nanopartículas , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Catequina/química , Catequina/farmacologia , Nanopartículas/química , Animais , Camundongos , Porosidade , Testes de Sensibilidade Microbiana , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Propriedades de Superfície , Tamanho da Partícula , Cicatrização/efeitos dos fármacos
4.
Phys Rev Lett ; 133(9): 096802, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39270186

RESUMO

The longitudinal nonreciprocal charge transport (NCT) in crystalline materials is a highly nontrivial phenomenon, motivating the design of next generation two-terminal rectification devices (e.g., semiconductor diodes beyond PN junctions). The practical application of such devices is built upon crystalline materials whose longitudinal NCT occurs at room temperature and under low magnetic field. However, materials of this type are rather rare and elusive, and theory guiding the discovery of these materials is lacking. Here, we develop such a theory within the framework of semiclassical Boltzmann transport theory. By symmetry analysis, we classify the complete 122 magnetic point groups with respect to the longitudinal NCT phenomenon. The symmetry-adapted Hamiltonian analysis further uncovers a previously overlooked mechanism for this phenomenon. Our theory guides the first-principles prediction of longitudinal NCT in multiferroic ϵ-Fe_{2}O_{3} semiconductor that possibly occurs at room temperature, without the application of external magnetic field. These findings advance our fundamental understandings of longitudinal NCT in crystalline materials, and aid the corresponding materials discoveries.

5.
Angew Chem Int Ed Engl ; : e202411849, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162073

RESUMO

Liquid water under nanoscale confinement has attracted intensive attention due to its pivotal role in understanding various phenomena across many scientific fields. MXenes serve an ideal paradigm for investigating the dynamic behaviors of nanoconfined water in a hydrophilic environment. Combining deep neural networks and an active learning scheme, here we elucidate the proton-driven dynamics of water molecules confined between V2CTx sheets using molecular dynamics simulation. Firstly, we have found that the Eigen and Zundel cations can inhibit water-induced oxidation by adjusting the orientation of water molecules, thus proposing a general antioxidant strategy. Besides, we also identified a hexagonal ice phase with abnormal bonding rules at room temperature, rather than only at ultralow temperatures as other studies reported, and further captured the proton-induced water phase transition. This highlighted the importance of protons in the maintaining stable crystal phase and phase transition of water. Furthermore, we discussed the conversions of different water structures and water diffusivity with changing proton concentrations in detail. The results provide useful guidance in practical applications of MXenes including developing antioxidant strategies, identifying novel 2D water phases and optimizing energy storage and conversion.

6.
Phys Rev Lett ; 132(25): 256801, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996260

RESUMO

Ferroelectricity in CMOS-compatible hafnia (HfO_{2}) is crucial for the fabrication of high-integration nonvolatile memory devices. However, the capture of ferroelectricity in HfO_{2} requires the stabilization of thermodynamically metastable orthorhombic or rhombohedral phases, which entails the introduction of defects (e.g., dopants and vacancies) and pays the price of crystal imperfections, causing unpleasant wake-up and fatigue effects. Here, we report a theoretical strategy on the realization of robust ferroelectricity in HfO_{2}-based ferroelectrics by designing a series of epitaxial (HfO_{2})_{1}/(CeO_{2})_{1} superlattices. The designed ferroelectric superlattices are defects free, and most importantly, on the base of the thermodynamically stable monoclinic phase of HfO_{2}. Consequently, this allows the creation of superior ferroelectric properties with an electric polarization >25 µC/cm^{2} and an ultralow polarization-switching energy barrier at ∼2.5 meV/atom. Our work may open an avenue toward the fabrication of high-performance HfO_{2}-based ferroelectric devices.

7.
Proc Natl Acad Sci U S A ; 121(26): e2401840121, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38900793

RESUMO

The recent theory-driven discovery of a class of clathrate hydrides (e.g., CaH6, YH6, YH9, and LaH10) with superconducting critical temperatures (Tc) well above 200 K has opened the prospects for "hot" superconductivity above room temperature under pressure. Recent efforts focus on the search for superconductors among ternary hydrides that accommodate more diverse material types and configurations compared to binary hydrides. Through extensive computational searches, we report the prediction of a unique class of thermodynamically stable clathrate hydrides structures consisting of two previously unreported H24 and H30 hydrogen clathrate cages at megabar pressures. Among these phases, LaSc2H24 shows potential hot superconductivity at the thermodynamically stable pressure range of 167 to 300 GPa, with calculated Tcs up to 331 K at 250 GPa and 316 K at 167 GPa when the important effects of anharmonicity are included. The very high critical temperatures are attributed to an unusually large hydrogen-derived density of states at the Fermi level arising from the newly reported peculiar H30 as well as H24 cages in the structure. Our predicted introduction of Sc in the La-H system is expected to facilitate future design and realization of hot superconductors in ternary clathrate superhydrides.

8.
Natl Sci Rev ; 11(7): nwad270, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38883291

RESUMO

Room-temperature superconductivity has been a long-held dream of mankind and a focus of considerable interest in the research field of superconductivity. Significant progress has recently been achieved in hydrogen-based superconductors found in superhydrides (hydrides with unexpectedly high hydrogen contents) that are stabilized under high-pressure conditions and are not capturable at ambient conditions. Of particular interest is the discovery of a class of best-ever-known superconductors in clathrate metal superhydrides that hold the record for high superconductivity (e.g. T c = 250-260 K for LaH10) among known superconductors and have great promise to be those that realize the long-sought room-temperature superconductivity. In these peculiar clathrate superhydrides, hydrogen forms unusual 'clathrate' cages containing encaged metal atoms, of which such a kind was first reported in a calcium hexa-superhydride (CaH6) showing a measured high T c of 215 K under a pressure of 170 GPa. In this review, we aim to offer an overview of the current status of research progress on the clathrate metal superhydride superconductors, discuss the superconducting mechanism and highlight the key features (e.g. structure motifs, bonding features, electronic structure, etc.) that govern the high-temperature superconductivity. Future research direction along this line to find room-temperature superconductors will be discussed.

9.
Front Plant Sci ; 15: 1381243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817937

RESUMO

Reducing plant height (PH) is one of the core contents of the "Green Revolution", which began in the 1960s in wheat. A number of 27 reduced-height (Rht) genes have been identified and a great number of quantitative trait loci (QTLs) for PH have been mapped on all 21 chromosomes. Nonetheless, only several genes regulated PH have been cloned. In this study, we found the interval of QTL QPh-1B included an EST-SSR marker swes1079. According to the sequence of swes1079, we cloned the TaOSCA1.4 gene. We developed a CAPS marker to analyze the variation across a natural population. The result showed that the PH was significantly different between the two haplotypes of TaOSCA1.4-1B under most of the 12 environments and the average values of irrigation and rainfed conditions. This result further demonstrated that TaOSCA1.4 was associated with PH. Then, we validated the TaOSCA1.4 via RNAi technology. The average PHs of the wild-type (WT), RNAi lines 1 (Ri-1) and 2 (Ri-2) were 94.6, 83.6 and 79.2 cm, respectively, with significant differences between the WT and Ri-1 and Ri-2. This result indicated that the TaOSCA1.4 gene controls PH. TaOSCA1.4 is a constitutively expressed gene and its protein localizes to the cell membrane. TaOSCA1.4 gene is a member of the OSCA gene family, which regulates intracellular Ca2+ concentration. We hypothesized that knock down mutants of TaOSCA1.4 gene reduced regulatory ability of Ca2+, thus reducing the PH. Furthermore, the cell lengths of the knock down mutants are not significantly different than that of WT. We speculate that TaOSCA1.4 gene is not directly associated with gibberellin (GA), which should be a novel mechanism for a wheat Rht gene.

10.
Mol Biol Rep ; 51(1): 550, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38642183

RESUMO

BACKGROUND: The therapeutic efficacy of intra-articular mesenchymal stem cells (MSCs) injection for patients with osteoarthritis (OA) currently exhibits inconsistency, and the underlying mechanism remains elusive. It has been postulated that the immunomodulatory properties and paracrine activity of MSCs might be influenced by the inflammatory micro-environment within osteoarthritic joints, potentially contributing to this observed inconsistency. METHODS: Adipose-derived MSCs (ADSCs) were isolated from SD rats and pre-treated with Toll-like receptor 3 (TLR3) agonist Poly I:C or Toll-like receptor 4 (TLR4) agonist LPS. The pre-treated ADSCs were then co-cultured with IL-1ß-induced osteoarthritic chondrocytes using a Transwell system to analyze the paracrine effect of ADSCs on reversing the osteoarthritic phenotype of chondrocytes. RESULTS: RT-PCR and Western blot analysis revealed that Poly I:C and LPS pre-treatments up-regulated the expression of IL-10 and IL-6 in ADSCs, respectively. Furthermore, only Poly I:C-preconditioned ADSCs significantly promoted proliferation while inhibiting apoptosis in IL-1ß-treated chondrocytes. Additionally, Poly I:C-preconditioned ADSCs downregulated MMP13 expression while upregulating aggrecan and collagen II expression levels in IL-1ß-treated chondrocytes. CONCLUSIONS: TLR3 activation polarizes ADSCs into an immunomodulatory phenotype distinct from TLR4 activation, exerting differential effects on reversing the osteoarthritic phenotype of chondrocytes; thus indicating that MSCs' paracrine effect regulated by TLRs signaling impacts the efficacy of intra-articular MSCs injection.


Assuntos
Condrócitos , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Condrócitos/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Células Cultivadas , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo , Ratos Sprague-Dawley , Células-Tronco Mesenquimais/metabolismo , Receptores Toll-Like/metabolismo , Fenótipo , Poli I/metabolismo , Poli I/farmacologia
11.
Small ; 20(34): e2400714, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38593314

RESUMO

Albeit microemulsion systems have emerged as efficient platforms for fabricating tunable nano/microstructures, lack of understanding on the emulsion-interfacial assembly hindered the control of fabrication. Herein, a nucleation-inhibited microemulsion interfacial assembly method is proposed, which deviates from conventional interfacial nucleation approaches, for the synthesis of polydopamine microvesicles (PDA MVs). These PDA MVs exhibit an approximate diameter of 1 µm, showcasing a pliable structure reminiscent of cellular morphology. Through modifications of antibodies on the surface of PDA MVs, their capacity as artificial antigen presentation cells is evaluated. In comparison to solid nanoparticles, PDA MVs with cell-like structures show enhanced T-cell activation, resulting in a 1.5-fold increase in CD25 expression after 1 day and a threefold surge in PD-1 positivity after 7 days. In summary, the research elucidates the influence of nucleation and interfacial assembly in microemulsion polymerization systems, providing a direct synthesis method for MVs and substantiating their effectiveness as artificial antigen-presenting cells.


Assuntos
Células Apresentadoras de Antígenos , Emulsões , Indóis , Polímeros , Indóis/química , Polímeros/química , Emulsões/química , Células Apresentadoras de Antígenos/imunologia , Humanos , Linfócitos T/imunologia
12.
Front Plant Sci ; 15: 1297812, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434433

RESUMO

Introduction: The potato (Solanum tuberosum L.), one of the most vital food crops worldwide, is sensitive to salinity. Brassinosteroids (BRs) are crucial in tolerance to various abiotic stresses. The constitutive photomorphogenesis and dwarf (CPD) gene encodes C-3 oxidase, which is a rate-limiting enzyme that controls the synthesis of BRs. Methods: In this study, we used StCPD gene overexpression (T) and un-transgenic (NT) plants obtained from our former research to illustrate adaptive resistance to salt stress at levels of phenotype; cell ultrastructure, physiology, and biochemistry; hormone; and transcription. Results: Results showed the accumulation of 2,4-epibrassionolide (EBL) in T potatoes. We found that under high salt situations, the changed Na+/K+ transporter gene expression was linked with the prevalent ionic responses in T plants, which led to lower concentrations of K+ and higher concentrations of Na+ in leaves. Furthermore, RNA-sequencing (RNA-seq) data elucidated that gene expressions in NT and T plants were significantly changed with 200-mM NaCl treatment for 24 h and 48 h, compared with the 0-h treatment. Functional enrichment analysis suggested that most of the differentially expressed genes (DEGs) were related to the regulation of BR-related gene expression, pigment metabolism process, light and action, and plant hormone signal transduction. Discussion: These findings suggested that StCPD gene overexpression can alleviate the damage caused by salt stress and enhance the salt resistance of potato plantlets. Our study provides an essential reference for further research on BR regulation of plant molecular mechanisms in potatoes with stress tolerance.

13.
Cartilage ; : 19476035241240361, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38525935

RESUMO

OBJECTIVE: Cytokines are implicated in the pathogenesis of osteoarthritis (OA), and this study aims to assess the therapeutic potential of an IL-8 neutralizing monoclonal antibody (mAb) for OA intervention. DESIGN: The study employed a rabbit model of OA induced by anterior cruciate ligament transection (ACLT) surgery to investigate the effects of an interleukin (IL)-8 neutralizing mAb, with hyaluronic acid (HA) used as a positive control. Primary outcomes assessed in the rabbits included cartilage repair, synovitis, joint effusion, changes in footprints, and lower limb loading conditions. RESULTS: Compared to HA, intra-articular injection of the IL-8 neutralizing mAb demonstrated a more pronounced attenuation of OA progression and enhancement of cartilage repair. We observed a reduction in synovitis and joint effusion, indications of bone marrow edema, as well as improvements in lower limb function. In knees treated with the neutralizing IL-8 mAb, there was a significant decrease in IL-8 levels within the synovial tissues. CONCLUSIONS: The IL-8 neutralizing mAb exhibits promising therapeutic potential in the management of OA by attenuating inflammation and facilitating cartilage repair. However, further investigations are warranted to comprehensively elucidate the underlying mechanisms, optimize treatment protocols, and ensure the long-term safety and efficacy of this innovative therapeutic approach.

14.
Front Bioeng Biotechnol ; 12: 1359212, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38410163

RESUMO

Background: Osteoarthritis (OA) is a debilitating degenerative joint disease, leading to significant pain and disability. Despite advancements, current regenerative therapies, such as mesenchymal stem cells (MSCs), face challenges in clinical efficacy and ethical considerations. This study aimed to evaluate the therapeutic potential of stromal vascular fraction gel (SVF-gel) in comparison to available treatments like hyaluronic acid (HA) and adipose-derived stem cells (ADSCs) and to assess the enhancement of this potential by incorporating tropoelastin (TE). Methods: We conducted a comparative laboratory study, establishing an indirect co-culture system using a Transwell assay to test the effects of HA, ADSCs, SVF-gel, and TE-SVF-gel on osteoarthritic articular chondrocytes (OACs). Chondrogenic and hypertrophic markers were assessed after a 72-hour co-culture. SVF-gel was harvested from rat subcutaneous abdominal adipose tissue, with its mechanical properties characterized. Cell viability was specifically analyzed for SVF-gel and TE-SVF-gel. The in vivo therapeutic effectiveness was further investigated in a rat model of OA, examining MSCs tracking, effects on cartilage matrix synthesis, osteophyte formation, and muscle weight changes. Results: Cell viability assays revealed that TE-SVF-gel maintained higher cell survival rates than SVF-gel. In comparison to the control, HA, and ADSCs groups, SVF-gel and TE-SVF-gel significantly upregulated the expression of chondrogenic markers COL 2, SOX-9, and ACAN and downregulated the hypertrophic marker COL 10 in OACs. The TE-SVF-gel showed further improved expression of chondrogenic markers and a greater decrease in COL 10 expression compared to SVF-gel alone. Notably, the TE-SVF-gel treated group in the in vivo OA model exhibited the most MSCs on the synovial surface, superior cartilage matrix synthesis, increased COL 2 expression, and better muscle weight recovery, despite the presence of fewer stem cells than other treatments. Discussion: The findings suggest that SVF-gel, particularly when combined with TE, provides a more effective regenerative treatment for OA by enhancing the therapeutic potential of MSCs. This combination could represent an innovative strategy that overcomes limitations of current therapies, offering a new avenue for patient treatment. Further research is warranted to explore the long-term benefits and potential clinical applications of this combined approach.

15.
Natl Sci Rev ; 11(1): nwae016, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38343648

RESUMO

Using first-principles calculations and crystal structure search methods, we found that many covalently bonded molecules such as H2, N2, CO2, NH3, H2O and CH4 may react with NaCl, a prototype ionic solid, and form stable compounds under pressure while retaining their molecular structure. These molecules, despite whether they are homonuclear or heteronuclear, polar or non-polar, small or large, do not show strong chemical interactions with surrounding Na and Cl ions. In contrast, the most stable molecule among all examples, N2, is found to transform into cyclo-N5- anions while reacting with NaCl under high pressures. It provides a new route to synthesize pentazolates, which are promising green energy materials with high energy density. Our work demonstrates a unique and universal hybridization propensity of covalently bonded molecules and solid compounds under pressure. This surprising miscibility suggests possible mixing regions between the molecular and rock layers in the interiors of large planets.

16.
Angew Chem Int Ed Engl ; 63(16): e202319320, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38238261

RESUMO

The chemistry of hypercoordination has been a subject of fundamental interest, especially for understanding structures that challenge conventional wisdom. The small ionic radii of Fe ions typically result in coordination numbers of 4 or 6 in stable Fe-bearing ionic compounds. While 8-coordinated Fe has been observed in highly compressed oxides, the pursuit of hypercoordinated Fe still faces significant challenges due to the complexity of synthesizing the anticipated compound with another suitable anion. Through first-principles simulation and advanced crystal structure prediction methods, we predict that an orthorhombic phase of FeF3 with exclusively 8-coordinated Fe is energetically stable above 18 GPa-a pressure more feasibly achieved compared to oxides. Inspired by this theoretical result, we conducted extensive experiments using a laser-heated diamond anvil cell technique to investigate the crystal structures of FeF3 at high-pressure conditions. We successfully synthesized the predicted orthorhombic phase of FeF3 at 46 GPa, as confirmed by in situ experimental X-ray diffraction data. This work establishes a new ionic compound featuring rare 8-coordinated Fe in a simple binary Fe-bearing system and paves the way for discovering Fe hypercoordination in similar systems.

17.
Nat Commun ; 14(1): 8127, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38065960

RESUMO

The anti-symmetric and anisotropic symmetric exchange interactions between two magnetic dipole moments - responsible for intriguing magnetic textures (e.g., magnetic skyrmions) - have been discovered since last century, while their electric analogues were either hidden for a long time or still not known. It is only recently that the anti-symmetric exchange interactions between electric dipoles was proved to exist (with materials hosting such an interaction being still rare) and the existence of anisotropic symmetric exchange interaction between electric dipoles remains ambiguous. Here, by symmetry analysis and first-principles calculations, we identify hafnia as a candidate material hosting the non-collinear dipole alignments, the analysis of which reveals the anti-symmetric and anisotropic symmetric exchange interactions between electric dipoles in this material. Our findings can hopefully deepen the current knowledge of electromagnetism in condensed matter, and imply the possibility of discovering novel states of matter (e.g., electric skyrmions) in hafnia-related materials.

18.
J Nanobiotechnology ; 21(1): 425, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37968644

RESUMO

BACKGROUND: Chemodynamic therapy (CDT) based on Fenton/Fenton-like reaction has emerged as a promising cancer treatment strategy. Yet, the strong anti-oxidation property of tumor microenvironment (TME) caused by endogenous glutathione (GSH) still severely impedes the effectiveness of CDT. Traditional CDT nanoplatforms based on core@shell structure possess inherent interference of different subunits, thus hindering the overall therapeutic efficiency. Consequently, it is urgent to construct a novel structure with isolated functional units and GSH depletion capability to achieve desirable combined CDT therapeutic efficiency. RESULTS: Herein, a surface curvature-induced oriented assembly strategy is proposed to synthesize a sushi-like novel Janus therapeutic nanoplatform which is composed of two functional units, a FeOOH nanospindle serving as CDT subunit and a mSiO2 nanorod serving as drug-loading subunit. The FeOOH CDT subunit is half covered by mSiO2 nanorod along its long axis, forming sushi-like structure. The FeOOH nanospindle is about 400 nm in length and 50 nm in diameter, and the mSiO2 nanorod is about 550 nm in length and 100 nm in diameter. The length and diameter of mSiO2 subunit can be tuned in a wide range while maintaining the sushi-like Janus structure, which is attributed to a Gibbs-free-energy-dominating surface curvature-induced oriented assembly process. In this Janus therapeutic nanoplatform, Fe3+ of FeOOH is firstly reduced to Fe2+ by endogenous GSH, the as-generated Fe2+ then effectively catalyzes overexpressed H2O2 in TME into highly lethal ·OH to achieve efficient CDT. The doxorubicin (DOX) loaded in the mSiO2 subunit can be released to achieve combined chemotherapy. Taking advantage of Fe3+-related GSH depletion, Fe2+-related enhanced ·OH generation, and DOX-induced chemotherapy, the as-synthesized nanoplatform possesses excellent therapeutic efficiency, in vitro eliminating efficiency of tumor cells is as high as ~ 87%. In vivo experiments also show the efficient inhibition of tumor, verifying the synthesized sushi-like Janus nanoparticles as a promising therapeutic nanoplatform. CONCLUSIONS: In general, our work provides a successful paradigm of constructing novel therapeutic nanoplatform to achieve efficient tumor inhibition.


Assuntos
Nanopartículas Multifuncionais , Neoplasias , Humanos , Peróxido de Hidrogênio , Protocolos de Quimioterapia Combinada Antineoplásica , Doxorrubicina/farmacologia , Glutationa , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente Tumoral
19.
Redox Biol ; 67: 102913, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37857001

RESUMO

Oxidative stress is a key factor leading to profound neurological deficits following spinal cord injury (SCI). In this study, we present the development and potential application of an iridium (iii) complex, (CpxbiPh) Ir (N^N) Cl, where CpxbiPh represents 1-biphenyl-2,3,4,5-tetramethyl cyclopentadienyl, and N^N denotes 2-(3-(4-nitrophenyl)-1H-1,2,4-triazol-5-yl) pyridine chelating agents, to address this challenge through a mechanism governed by the regulation of an antioxidant protein. This iridium complex, IrPHtz, can modulate the Oxidation Resistance 1 (OXR1) protein levels within spinal cord tissues, thus showcasing its antioxidative potential. By eliminating reactive oxygen species (ROS) and preventing apoptosis, the IrPHtz demonstrated neuroprotective and neural healing characteristics on injured neurons. Our molecular docking analysis unveiled the presence of π stacking within the IrPHtz-OXR1 complex, an interaction that enhanced OXR1 expression, subsequently diminishing oxidative stress, thwarting neuroinflammation, and averting neuronal apoptosis. Furthermore, in in vivo experimentation with SCI-afflicted mice, IrPHtz was efficacious in shielding spinal cord neurons, promoting their regrowth, restoring electrical signaling, and improving motor performance. Collectively, these findings underscore the potential of employing the iridium metal complex in a novel, protein-regulated antioxidant strategy, presenting a promising avenue for therapeutic intervention in SCI.


Assuntos
Complexos de Coordenação , Traumatismos da Medula Espinal , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Irídio/química , Irídio/farmacologia , Irídio/uso terapêutico , Antioxidantes/metabolismo , Simulação de Acoplamento Molecular , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Estresse Oxidativo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico
20.
Environ Sci Pollut Res Int ; 30(46): 102880-102893, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37670093

RESUMO

The escalating levels of surface ozone concentration pose detrimental effects on public health and the environment. Catalytic decomposition presents an optimal solution for surface ozone removal. Nevertheless, catalyst still encounters challenges such as poisoning and deactivation in the high humidity environment. The influence of support on catalytic ozone decomposition was examined at a gas hourly space velocity of 300 L·g-1·h-1 and 85% relative humidity under ambient temperature using Cu-Mn-doped oxide catalysts synthesized via a straightforward coprecipitation method. Notably, the Cu-Mn/SiO2 catalyst exhibited remarkable performance on ozone decomposition, achieving 98% ozone conversion and stability for 10 h. Further characterization analysis indicated that the catalyst's enhanced water resistance and activity could be attributed to factors such as an increased number of active sites, a large surface area, abundant active oxygen species, and a lower Mn oxidation state. The catalytic environment created by mixed oxides can offer a clearer understanding of their synergistic effects on catalytic ozone decomposition, providing significant insights into the development of water-resistant catalysts with superior performance.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA