Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 82
Filtrar
1.
J Nanobiotechnology ; 22(1): 543, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39238005

RESUMO

BACKGROUND: Human mesenchymal stem cells have attracted interest in regenerative medicine and are being tested in many clinical trials. In vitro expansion is necessary to provide clinical-grade quantities of mesenchymal stem cells; however, it has been reported to cause replicative senescence and undefined dysfunction in mesenchymal stem cells. Quality control assessments of in vitro expansion have rarely been addressed in ongoing trials. Young small extracellular vesicles from the remnant pulp of human exfoliated deciduous teeth stem cells have demonstrated therapeutic potential for diverse diseases. However, it is still unclear whether young small extracellular vesicles can reverse senescence-related declines. RESULTS: We demonstrated that mitochondrial structural disruption precedes cellular dysfunction during bone marrow-derived mesenchymal stem cell replication, indicating mitochondrial parameters as quality assessment indicators of mesenchymal stem cells. Dynamin-related protein 1-mediated mitochondrial dynamism is an upstream regulator of replicative senescence-induced dysfunction in bone marrow-derived mesenchymal stem cells. We observed that the application of young small extracellular vesicles could rescue the pluripotency dissolution, immunoregulatory capacities, and therapeutic effects of replicative senescent bone marrow-derived mesenchymal stem cells. Mechanistically, young small extracellular vesicles could promote Dynamin-related protein 1 translocation from the cytoplasm to the mitochondria and remodel mitochondrial disruption during replication history. CONCLUSIONS: Our findings show that Dynamin-related protein 1-mediated mitochondrial disruption is associated with the replication history of bone marrow-derived mesenchymal stem cells. Young small extracellular vesicles from human exfoliated deciduous teeth stem cells alleviate replicative senescence by promoting Dynamin-related protein 1 translocation onto the mitochondria, providing evidence for a potential rejuvenation strategy.


Assuntos
Senescência Celular , Dinaminas , Vesículas Extracelulares , Células-Tronco Mesenquimais , Mitocôndrias , Dinâmica Mitocondrial , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/citologia , Vesículas Extracelulares/metabolismo , Dinaminas/metabolismo , Mitocôndrias/metabolismo , Animais , Células Cultivadas , Camundongos , Masculino , Dente Decíduo/citologia , Dente Decíduo/metabolismo
2.
Nat Commun ; 15(1): 7739, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231956

RESUMO

How Cooper pairs form and condense has been the main challenge in the physics of copper-oxide high-temperature superconductors. Great efforts have been made in the 'underdoped' region of the phase diagram, through doping a Mott insulator or cooling a strange metal. However, there is still no consensus on how superconductivity emerges when electron-electron correlations dominate and the Fermi surface is missing. To address this issue, here we carry out high-resolution resonant inelastic X-ray scattering and scanning tunneling microscopy studies on prototype cuprates Bi2Sr2Ca0.6Dy0.4Cu2O8+δ near the onset of superconductivity, combining bulk and surface, momentum- and real-space information. We show that an incipient charge order exists in the antiferromagnetic regime down to 0.04 holes per CuO2 unit, entangled with a particle-hole asymmetric pseudogap. The charge order induces an intensity anomaly in the bond-buckling phonon branch, which exhibits an abrupt increase once the system enters the superconducting dome. Our results suggest that the Cooper pairs grow out of a charge-ordered insulating state, and then condense accompanied by an enhanced interplay between charge excitations and electron-phonon coupling.

3.
Int J Nanomedicine ; 19: 8751-8768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220194

RESUMO

Purpose: Periodontitis is a chronic infectious disease characterized by progressive inflammation and alveolar bone loss. Forkhead box O1 (FoxO1), an important regulator, plays a crucial role in maintaining bone homeostasis and regulating macrophage energy metabolism and osteogenic differentiation of mesenchymal stem cells (MSCs). In this study, FoxO1 was overexpressed into small extracellular vesicles (sEV) using engineering technology, and effects of FoxO1-overexpressed sEV on periodontal tissue regeneration as well as the underlying mechanisms were investigated. Methods: Human periodontal ligament stem cell (hPDLSCs)-derived sEV (hPDLSCs-sEV) were isolated using ultracentrifugation. They were then characterized using transmission electron microscopy, Nanosight, and Western blotting analyses. hPDLSCs were treated with hPDLSCs-sEV in vitro after stimulation with lipopolysaccharide, and osteogenesis was evaluated. The effect of hPDLSCs-sEV on the polarization phenotype of THP-1 macrophages was also evaluated. In addition, we measured the reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells. Experimental periodontitis was established in vivo in mice. HPDLSCs-sEV or phosphate-buffered saline (PBS) were injected into periodontal tissues for four weeks, and the maxillae were collected and assessed by micro-computed tomography, histological staining, and small animal in vivo imaging. Results: In vitro, FoxO1-overexpressed sEV promoted osteogenic differentiation of hPDLSCs in the inflammatory environment and polarized THP-1 cells from the M1 phenotype to the M2 phenotype. Furthermore, FoxO1-overexpressed sEV regulated the ROS level, ATP production, mitochondrial characteristics, and metabolism of hPDLSCs and THP-1 cells in the inflammatory environment. In the in vivo analyses, FoxO1-overexpressed sEV effectively promoted bone formation and inhibited inflammation. Conclusion: FoxO1-overexpressed sEV can regulate osteogenesis and immunomodulation. The ability of FoxO1-overexpressed sEV to regulate inflammation and osteogenesis can pave the way for the establishment of a therapeutic approach for periodontitis.


Assuntos
Vesículas Extracelulares , Proteína Forkhead Box O1 , Mitocôndrias , Osteogênese , Ligamento Periodontal , Periodontite , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Osteogênese/efeitos dos fármacos , Animais , Humanos , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Mitocôndrias/metabolismo , Periodontite/terapia , Periodontite/metabolismo , Camundongos , Ligamento Periodontal/citologia , Células THP-1 , Espécies Reativas de Oxigênio/metabolismo , Inflamação/metabolismo , Masculino , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Macrófagos/metabolismo , Regeneração , Células Cultivadas
4.
Science ; 385(6705): 161-167, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38991067

RESUMO

Black-phase formamidinium lead iodide (α-FAPbI3) perovskites are the desired phase for photovoltaic applications, but water can trigger formation of photoinactive impurity phases such as δ-FAPbI3. We show that the classic solvent system for perovskite fabrication exacerbates this reproducibility challenge. The conventional coordinative solvent dimethyl sulfoxide (DMSO) promoted δ-FAPbI3 formation under high relative humidity (RH) conditions because of its hygroscopic nature. We introduced chlorine-containing organic molecules to form a capping layer that blocked moisture penetration while preserving DMSO-based complexes to regulate crystal growth. We report power conversion efficiencies of >24.5% for perovskite solar cells fabricated across an RH range of 20 to 60%, and 23.4% at 80% RH. The unencapsulated device retained 96% of its initial performance in air (with 40 to 60% RH) after 500-hour maximum power point operation.

5.
Nat Mater ; 23(9): 1214-1221, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39009656

RESUMO

A nematic phase breaks the point-group symmetry of the crystal lattice and is known to emerge in correlated materials. Here we report the observation of an intra-unit-cell nematic order and associated Fermi surface deformation in the kagome metal ScV6Sn6. Using scanning tunnelling microscopy and scanning tunnelling spectroscopy, we reveal a stripe-like nematic order breaking the crystal rotational symmetry within the kagome lattice itself. Moreover, we identify a set of Van Hove singularities adhering to the kagome-layer electrons, which appear along one direction of the Brillouin zone and are annihilated along other high-symmetry directions, revealing rotational symmetry breaking. Via detailed spectroscopic maps, we further observe an elliptical deformation of the Fermi surface, which provides direct evidence for an electronically mediated nematic order. Our work not only bridges the gap between electronic nematicity and kagome physics but also sheds light on the potential mechanism for realizing symmetry-broken phases in correlated electron systems.

6.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38949588

RESUMO

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.


Assuntos
Cardiolipinas , Corantes Fluorescentes , Lipossomas Unilamelares , Cardiolipinas/química , Corantes Fluorescentes/química , Lipossomas Unilamelares/química , Propriedades de Superfície , Lipossomos/química , Cloreto de Sódio/química , Tensoativos/química , Estrutura Molecular
7.
ACS Appl Mater Interfaces ; 16(28): 36471-36478, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38955805

RESUMO

In the development of back electrodes for perovskite solar cells (PSCs), the major challenges are stability and cost. To address this, we present an innovative approach: Simultaneous evaporation of two independently controlled sources of metal materials was performed to achieve a uniform distribution of the alloy electrodes. In this study, Ag-Cu alloys (the molar ratio of Ag/Cu is 7/3) with a high-index crystal face (111) and a work function matching perovskite were prepared using a codeposition technique. These properties mitigate nonradiative carrier recombination at the interface and reduce the energy barrier for carrier migration. Consequently, compared to Ag based PSCs (22.77%), the implementation of Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs resulted in a power conversion efficiency of 23.72%. In a 1500 h tracking test in ambient air, the Ag-Cu alloy (Ag/Cu is 7/3)-based PSCs maintained their initial efficiency of 86%. This can be attributed to almost no migration of elements from the Ag-Cu alloy electrode to the perovskite layer. Our work presents a vital strategy for improving the stability of PSCs and reducing the costs associated with the back electrode in PSCs.

8.
Biochim Biophys Acta Mol Cell Biol Lipids ; 1869(6): 159498, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38703945

RESUMO

The biosynthetic capability of the long-chain polyunsaturated fatty acids (LC-PUFA) in teleosts are highly diversified due to evolutionary events such as gene loss and subsequent neo- and/or sub-functionalisation of enzymes encoded by existing genes. In the present study, we have comprehensively characterised genes potentially involved in LC-PUFA biosynthesis, namely one front-end desaturase (fads2) and eight fatty acid elongases (elovl1a, elovl1b, elovl4a, elovl4b, elovl5, elovl7, elovl8a and elovl8b) from an amphidromous teleost, Ayu sweetfish, Plecoglossus altivelis. Functional analysis confirmed Fads2 with Δ6, Δ5 and Δ8 desaturase activities towards multiple PUFA substrates and several Elovl enzymes exhibited elongation capacities towards C18-20 or C18-22 PUFA substrates. Consequently, P. altivelis possesses a complete enzymatic capability to synthesise physiologically important LC-PUFA including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) from their C18 precursors. Interestingly, the loss of elovl2 gene in P. altivelis was corroborated by genomic and phylogenetic analyses. However, this constraint would possibly be overcome by the function of alternative Elovl enzymes, such as Elovl1b, which has not hitherto been functionally characterised in teleosts. The present study contributes novel insights into LC-PUFA biosynthesis in the relatively understudied teleost group, Osmeriformes (Stomiati), thereby enhancing our understanding of the complement of LC-PUFA biosynthetic genes within teleosts.


Assuntos
Ácidos Graxos Dessaturases , Elongases de Ácidos Graxos , Ácidos Graxos Insaturados , Osmeriformes , Animais , Ácidos Graxos Insaturados/metabolismo , Ácidos Graxos Insaturados/biossíntese , Ácidos Graxos Insaturados/genética , Osmeriformes/metabolismo , Osmeriformes/genética , Ácidos Graxos Dessaturases/metabolismo , Ácidos Graxos Dessaturases/genética , Elongases de Ácidos Graxos/metabolismo , Elongases de Ácidos Graxos/genética , Filogenia , Proteínas de Peixes/metabolismo , Proteínas de Peixes/genética , Vias Biossintéticas/genética , Acetiltransferases/metabolismo , Acetiltransferases/genética
9.
New Phytol ; 242(6): 2570-2585, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38708492

RESUMO

In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.


Assuntos
Antocianinas , Proteínas de Arabidopsis , Epigênese Genética , Regulação da Expressão Gênica de Plantas , Histona Desmetilases com o Domínio Jumonji , Luz , Antocianinas/biossíntese , Antocianinas/genética , Arabidopsis/genética , Arabidopsis/efeitos da radiação , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cromatina/metabolismo , Metilação de DNA/genética , Histonas/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Histona Desmetilases com o Domínio Jumonji/genética , Mutação/genética , Fenótipo
10.
Proc Natl Acad Sci U S A ; 121(12): e2309054121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38466840

RESUMO

COVID-19 forced students to rely on online learning using multimedia tools, and multimedia learning continues to impact education beyond the pandemic. In this study, we combined behavioral, eye-tracking, and neuroimaging paradigms to identify multimedia learning processes and outcomes. College students viewed four video lectures including slides with either an onscreen human instructor, an animated instructor, or no onscreen instructor. Brain activity was recorded via fMRI, visual attention was recorded via eye-tracking, and learning outcome was assessed via post-tests. Onscreen presence of instructor, compared with no instructor presence, resulted in superior post-test performance, less visual attention on the slide, more synchronized eye movements during learning, and higher neural synchronization in cortical networks associated with socio-emotional processing and working memory. Individual variation in cognitive and socio-emotional abilities and intersubject neural synchronization revealed different levels of cognitive and socio-emotional processing in different learning conditions. The instructor-present condition evoked increased synchronization, likely reflecting extra processing demands in attentional control, working memory engagement, and socio-emotional processing. Although human instructors and animated instructors led to comparable learning outcomes, the effects were due to the dynamic interplay of information processing vs. attentional distraction. These findings reflect a benefit-cost trade-off where multimedia learning outcome is enhanced only when the cognitive benefits motivated by the social presence of onscreen instructor outweigh the cognitive costs brought about by concurrent attentional distraction unrelated to learning.


Assuntos
Aprendizagem , Multimídia , Humanos , Cognição/fisiologia , Memória de Curto Prazo/fisiologia , Estudantes
11.
Biomater Sci ; 12(7): 1750-1760, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38375548

RESUMO

Diabetes mellitus (DM) is characterized by prolonged hyperglycemia, impaired vascularization, and serious complications, such as blindness and chronic diabetic wounds. About 25% of patients with DM are estimated to encounter impaired healing of diabetic wounds, often leading to lower limb amputation. Multiple factors are attributed to the non-healing of diabetic wounds, including hyperglycaemia, chronic inflammation, and impaired angiogenesis. It is imperative to develop more efficient treatment strategies to tackle healing difficulties in diabetic wounds. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are promising for diabetic wound healing considering their anti-inflammatory, pro-angiogenic and pro-proliferative activities. A histone deacetylase 7 (HDAC7)-derived 7-amino-acid peptide (7A) was shown to be highly effective for angiogenesis. However, it has never been investigated whether MSC-EVs are synergistic with 7A for the healing of diabetic wounds. Herein, we propose that MSC-EVs can be combined with 7A to greatly promote diabetic wound healing. The combination of EVs and 7A significantly improved the migration and proliferation of skin fibroblasts. Moreover, EVs alone significantly suppressed LPS-induced inflammation in macrophages, and notably, the combination treatment showed an even better suppression effect. Importantly, the in vivo study revealed that the combination therapy consisting of EVs and 7A in an alginate hydrogel was more efficient for the healing of diabetic wounds in rats than monotherapy using either EV or 7A hydrogels. The underlying mechanisms include suppression of inflammation, improvement of skin cell proliferation and migration, and enhanced collagen fiber disposition and angiogenesis in wounds. In summary, the MSC-EV-7A hydrogel potentially constitutes a novel therapy for efficient healing of chronic diabetic wounds.


Assuntos
Diabetes Mellitus , Células-Tronco Mesenquimais , Humanos , Ratos , Animais , Hidrogéis/química , Angiogênese , Cicatrização , Inflamação
12.
Acta Neurol Belg ; 124(3): 879-885, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38286872

RESUMO

BACKGROUND: Identifying reliable biomarkers for early detection and prediction of cognitive impairment in Parkinson's disease (PD) is crucial for optimal patient care. This study set out to investigate the potential of YWHAG as a diagnostic biomarker for cognitive impairment in PD. METHODS: We enrolled a total of 331 PD patients and selected 241 patients that met the criteria for cognitive impairment analysis. The patients were classified into three groups: PD-NC: PD patients with normal cognition, PD-MCI: PD patients with mild cognitive impairment, and PD-D: PD patients with dementia. ELISA was employed to assess YWHAG expression, as well as the neurofilament light chain (NfL). Additionally, cognitive impairment was evaluated using MoCA scores. Correlation analysis and receiver operating curve analysis (ROC) were performed to clarify the relationship between YWHAG expression and cognitive impairment. RESULTS: Our findings revealed a significant upregulation of YWHAG expression in both the PD-MCI and PD-D groups compared to the PD-NC group. This observation aligned with the elevated expression of NfL in the PD-MCI and PD-D groups. YWHAG and NfL expression levels displayed negative correlations with MoCA scores and positive associations with age. Furthermore, ROC curve analysis demonstrated the diagnostic efficacy of YWHAG expression in distinguishing individuals with PD-NC, PD-MCI, and PD-D. CONCLUSIONS: Our findings indicate that YWHAG could serve as a promising biomarker for cognitive impairment in PD. The upregulation of YWHAG expression in PD-MCI and PD-D groups, its association with cognitive impairment, and its correlations with MoCA scores and NfL levels support its potential clinical utility.


Assuntos
Biomarcadores , Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico , Feminino , Masculino , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Idoso , Biomarcadores/sangue , Pessoa de Meia-Idade , Proteínas de Neurofilamentos/sangue , Idoso de 80 Anos ou mais , Curva ROC
13.
PLoS Pathog ; 20(1): e1011934, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206974

RESUMO

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/genética , Monócitos/metabolismo , Neoplasias Nasofaríngeas/genética , Microambiente Tumoral
14.
ACS Nano ; 18(5): 4456-4466, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38276073

RESUMO

Metal halide perovskites offer ample opportunities to develop advanced optoelectronic devices. This work showcases that the integration of metal halide perovskites into metal oxide nanoshells with controllable interior cavities can enable water-vapor-responsive dual-mode switching of fluorescence and structural color. Through a ship-in-a-bottle method to introduce a controlled amount of CsPbBr3 into MnO2 nanoshells, we have designed CsPbBr3@MnO2 yolk-shell nanostructures, which can uptake a defined amount of water to exhibit rapid (less than 1 s) and reversible (≥100 cycles) responses in both fluorescence on-off and color change when exposed to dynamic water vapor. These responses originate from the water-triggered phase transformation of CsPbBr3 to CsPb2Br5 and the structural color change of the MnO2 shell. The altered electronic and bonding structure at the oxide-halide interface, rapid water accumulation in the yolk-shell cavity, and protective effect of the oxide shell facilitate the reversible transformations. The response characteristics of the yolk-shell nanostructures have been further demonstrated in fabricating patterned films capable of multiple fluorescence/structural color responses, highlighting their potential for applications in advanced anticounterfeiting and encryption.

15.
Int Immunopharmacol ; 125(Pt A): 111077, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149575

RESUMO

Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have garnered extensive interest for their immunomodulatory properties in immune-mediated inflammatory diseases. However, the development of EVs as clinical drugs often faces challenges such as low production yield and suboptimal therapeutic efficacy. In this study, we discovered that thermally engineering was able to enhance the yield of MSC-EVs. Moreover, the PD-L1 expression of EVs released from the thermal engineering MSCs was found to be upregulated significantly, and these EVs ameliorated the symptoms and pathological damages in murine dextran sulfate sodium (DSS)-induced colitis model. The therapeutic effect on DSS-induced colitis was mediated through the regulation of the Th17/Treg cell balance, demonstrating the immunomodulatory properties of the thermally engineering MSC-EVs. Overall, our findings suggest that thermal engineering can be utilized as a promising strategy for enhancing EV production and may provide a potential therapeutic approach for clinical treatment of colitis.


Assuntos
Colite , Vesículas Extracelulares , Células-Tronco Mesenquimais , Animais , Camundongos , Linfócitos T Reguladores , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Vesículas Extracelulares/metabolismo , Células-Tronco Mesenquimais/metabolismo
16.
Proc Natl Acad Sci U S A ; 120(43): e2219491120, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37851678

RESUMO

In conventional superconductors, electron-phonon coupling plays a dominant role in generating superconductivity. In high-temperature cuprate superconductors, the existence of electron coupling with phonons and other boson modes and its role in producing high-temperature superconductivity remain unclear. The evidence of electron-boson coupling mainly comes from angle-resolved photoemission (ARPES) observations of [Formula: see text]70-meV nodal dispersion kink and [Formula: see text]40-meV antinodal kink. However, the reported results are sporadic and the nature of the involved bosons is still under debate. Here we report findings of ubiquitous two coexisting electron-mode couplings in cuprate superconductors. By taking ultrahigh-resolution laser-based ARPES measurements, we found that the electrons are coupled simultaneously with two sharp modes at [Formula: see text]70meV and [Formula: see text]40meV in different superconductors with different dopings, over the entire momentum space and at different temperatures above and below the superconducting transition temperature. These observations favor phonons as the origin of the modes coupled with electrons and the observed electron-mode couplings are unusual because the associated energy scales do not exhibit an obvious energy shift across the superconducting transition. We further find that the well-known "peak-dip-hump" structure, which has long been considered a hallmark of superconductivity, is also omnipresent and consists of "peak-double dip-double hump" finer structures that originate from electron coupling with two sharp modes. These results provide a unified picture for the [Formula: see text]70-meV and [Formula: see text]40-meV energy scales and their evolutions with momentum, doping and temperature. They provide key information to understand the origin of these energy scales and their role in generating anomalous normal state and high-temperature superconductivity.

17.
Pharmaceutics ; 15(9)2023 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-37765221

RESUMO

Mild photothermal therapy (PTT) shows great potential to treat cancers while avoiding unwanted damage to surrounding normal cells. However, the efficacy of mild PTT is normally moderate because of the low hyperthermia temperature and limited light penetration depth. Chemotherapy has unlimited penetration but often suffers from unsatisfactory efficacy in view of the occurrence of drug resistance, suboptimal drug delivery and release profile. As a result, the combinatory of chemotherapy and mild PTT would integrate their advantages and overcome the shortcomings. Herein, we synthesized an NIR-activatable and mild-temperature-sensitive nanoplatform (BDPII-gel@TSL) composed of temperature-sensitive liposomes (TSL), heat shock protein 90 (HSP90) inhibitor (geldanamycin) and photothermal agent (BDPII), for dual chemotherapy and mild PTT in cancer cells. BDPII, constructed with donor-acceptor moieties, acts as an excellent near-infrared (NIR) photothermal agent (PTA) with a high photothermal conversion efficiency (80.75%). BDPII-containing TSLs efficiently produce a mild hyperthermia effect (42 °C) under laser irradiation (808 nm, 0.5 W cm-2). Importantly, the phase transformation of TSL leads to burst release of geldanamycin from BDPII-gel@TSL, and this contributes to down-regulation of the overexpression of HSP90, ensuring efficient inhibition of cancer cell growth. This research provides a dual-sensitive synergistic therapeutic strategy for cancer cell treatment.

18.
Phys Rev Lett ; 131(11): 116002, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37774302

RESUMO

The extremely overdoped cuprates are generally considered to be Fermi liquid metals without exotic orders, whereas the underdoped cuprates harbor intertwined states. Contrary to this conventional wisdom, using Cu L_{3}-edge and O K-edge resonant x-ray scattering, we reveal a charge order (CO) correlation in overdoped La_{2-x}Sr_{x}CuO_{4} (0.35≤x≤0.6) beyond the superconducting dome. This CO has a periodicity of ∼6 lattice units with correlation lengths of ∼20 lattice units. It shows similar in-plane momentum and polarization dependence and dispersive excitations as the CO of underdoped cuprates, but its maximum intensity differs along the c direction and persists up to 300 K. This CO correlation cannot be explained by the Fermi surface instability and its origin remains to be understood. Our results suggest that CO is prevailing in the overdoped metallic regime and requires a reassessment of the picture of overdoped cuprates as weakly correlated Fermi liquids.

19.
Phys Rev Lett ; 131(2): 026701, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37505968

RESUMO

In kagome metal CsV_{3}Sb_{5}, multiple intertwined orders are accompanied by both electronic and structural instabilities. These exotic orders have attracted much recent attention, but their origins remain elusive. The newly discovered CsTi_{3}Bi_{5} is a Ti-based kagome metal to parallel CsV_{3}Sb_{5}. Here, we report angle-resolved photoemission experiments and first-principles calculations on pristine and Cs-doped CsTi_{3}Bi_{5} samples. Our results reveal that the van Hove singularity (vHS) in CsTi_{3}Bi_{5} can be tuned in a large energy range without structural instability, different from that in CsV_{3}Sb_{5}. As such, CsTi_{3}Bi_{5} provides a complementary platform to disentangle and investigate the electronic instability with a tunable vHS in kagome metals.

20.
Nano Lett ; 23(12): 5625-5633, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37310876

RESUMO

Kagome superconductors AV3Sb5 (A = K, Rb, Cs) provide a fertile playground for studying intriguing phenomena, including nontrivial band topology, superconductivity, giant anomalous Hall effect, and charge density wave (CDW). Recently, a C2 symmetric nematic phase prior to the superconducting state in AV3Sb5 drew enormous attention due to its potential inheritance of the symmetry of the unusual superconductivity. However, direct evidence of the rotation symmetry breaking of the electronic structure in the CDW state from the reciprocal space is still rare, and the underlying mechanism remains ambiguous. The observation shows unconventional unidirectionality, indicative of rotation symmetry breaking from six-fold to two-fold. The interlayer coupling between adjacent planes with π-phase offset in the 2 × 2 × 2 CDW phase leads to the preferred two-fold symmetric electronic structure. These rarely observed unidirectional back-folded bands in KV3Sb5 may provide important insights into its peculiar charge order and superconductivity.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA