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1.
Proc Natl Acad Sci U S A ; 121(6): e2318341121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289957

RESUMO

As a prototypical photocatalyst, TiO[Formula: see text] has been extensively studied. An interesting yet puzzling experimental fact was that P25-a mixture of anatase and rutile TiO[Formula: see text]-outperforms the individual phases; the origin of this mysterious fact, however, remains elusive. Employing rigorous first-principles calculations, here we uncover a metastable intermediate structure (MIS), which is formed due to confinement at the anatase/rutile interface. The MIS has a high conduction-band minimum level and thus substantially enhances the overpotential of the hydrogen evolution reaction. Also, the corresponding band alignment at the interface leads to efficient separation of electrons and holes. The interfacial confinement additionally creates a wide distribution of the band gap in the vicinity of the interface, which in turn improves optical absorption. These factors all contribute to the enhanced photocatalytic efficiency in P25. Our insights provide a rationale to the puzzling superior photocatalytic performance of P25 and enable a strategy to achieve highly efficient photocatalysis via interface engineering.

2.
Cell Mol Life Sci ; 81(1): 82, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340178

RESUMO

Interaction between programmed death-1 (PD-1) ligand 1 (PD-L1) on tumor cells and PD-1 on T cells allows tumor cells to evade T cell-mediated immune surveillance. Strategies targeting PD-1/PD-L1 have shown clinical benefits in a variety of cancers. However, limited response rates in hepatocellular carcinoma (HCC) have prompted us to investigate the molecular regulation of PD-L1. Here, we identify B cell lymphoma-2-associated transcription factor 1 (BCLAF1) as a key PD-L1 regulator in HCC. Specifically, BCLAF1 interacts with SPOP, an E3 ligase that mediates the ubiquitination and degradation of PD-L1, thereby competitively inhibiting SPOP-PD-L1 interaction and subsequent ubiquitination and degradation of PD-L1. Furthermore, we determined an SPOP-binding consensus (SBC) motif mediating the BCLAF1-SPOP interaction on BCLAF1 protein and mutation of BCLAF1-SBC motif disrupts the regulation of the SPOP-PD-L1 axis. In addition, BCLAF1 expression was positively correlated with PD-L1 expression and negatively correlated with biomarkers of T cell activation, including CD3 and CD8, as well as with the level of immune cell infiltration in HCC tissues. Besides, BCLAF1 depletion leads to a significant reduction of PD-L1 expression in vitro, and this reduction of PD-L1 promoted T cell-mediated cytotoxicity. Notably, overexpression of BCLAF1 sensitized tumor cells to checkpoint therapy in an in vitro HCC cells-Jurkat cells co-culture model, whereas BCLAF1-SBC mutant decreased tumor cell sensitivity to checkpoint therapy, suggesting that BCLAF1 and its SBC motif serve as a novel therapeutic target for enhancing anti-tumor immunity in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/metabolismo , Linhagem Celular , Neoplasias Hepáticas/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptor de Morte Celular Programada 1 , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor , Evasão da Resposta Imune/genética
3.
J Am Chem Soc ; 146(23): 16222-16228, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38778012

RESUMO

The crystal structure of a material is essentially determined by the nature of its chemical bonding. Consequently, the atomic coordination intimately correlates with the degree of ionicity or covalency of the material. Based on this principle, materials with similar chemical compositions can be successfully categorized into different coordination groups. However, counterexamples have recently emerged in complex ternary compounds. For instance, covalent IB-IIIA-VIA2 compounds, such as AgInS2, prefer a tetrahedrally coordinated structure (TCS), while ionic IA-VA-VIA2 compounds, such as NaBiS2, would favor an octahedrally coordinated structure (OCS). One naturally expects that IB-VA-VIA2 compounds with intermediate ionicity or covalency, such as AgBiS2, should then have a mix-coordinated structure (MCS) consisting of covalent AgS4 tetrahedra and ionic BiS6 octahedra. Surprisingly, only the experimental presence of the OCS was observed for AgBiS2. To resolve this puzzle, we perform first-principles studies of the phase stabilities of ternary compounds at finite temperatures. We find that AgBiS2 indeed prefers MCS at the ground state, in agreement with the typical expectation, but under experimental synthesis conditions, disordered OCS becomes energetically more favorable because of its low mixing energy and high configurational entropy. Our work elucidates the critical role of configurational disorder in stabilizing chemically unfavorable coordination, providing a rigorous rationale for the anomalous coordination preference in IB-VA-VIA2 compounds.

4.
J Am Chem Soc ; 146(18): 12864-12876, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38670931

RESUMO

Deep-ultraviolet (DUV) light sources are technologically highly important, but DUV light-emitting materials are extremely rare; AlN and its alloys are the only materials known so far, significantly limiting the chemical and structural spaces for materials design. Here, we perform a high-throughput computational search for DUV light emitters based on a set of carefully designed screening criteria relating to the sophisticated electronic structure. In this way, we successfully identify 5 promising material candidates that exhibit comparable or higher radiative recombination coefficients than AlN, including BeGeN2, Mg3NF3, KCaBr3, KHS, and RbHS. Further, we unveil the unique features in the atomic and electronic structures of DUV light emitters and elucidate the fundamental genetic reasons why DUV light emitters are extremely rare. Our study not only guides the design and synthesis of efficient DUV light emitters but also establishes the genetic nature of ultrawide-band-gap semiconductors in general.

5.
J Am Chem Soc ; 146(10): 6618-6627, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349322

RESUMO

Single-crystal semiconductor-based photocatalysts exposing unique crystallographic facets show promising applications in energy and environmental technologies; however, crystal facet engineering through solid-state synthesis for photocatalytic overall water splitting is still challenging. Herein, we develop a novel crystal facet engineering strategy through solid-state recrystallization to synthesize uniform SrTiO3 single crystals exposing tailored {111} facets. The presynthesized low-crystalline SrTiO3 precursors enable the formation of well-defined single crystals through kinetically improved crystal structure transformation during solid-state recrystallization process. By employing subtle Al3+ ions as surface morphology modulators, the crystal surface orientation can be precisely tuned to a controlled percentage of {111} facets. The photocatalytic overall water splitting activity increases with the exposure percentage of {111} facets. Owing to the outstanding crystallinity and favorable anisotropic surface structure, the SrTiO3 single crystals with 36.6% of {111} facets lead to a 3-fold enhancement of photocatalytic hydrogen evolution rates up to 1.55 mmol·h-1 in a stoichiometric ratio of 2:1 than thermodynamically stable SrTiO3 enclosed with isotropic {100} facets.

6.
Angew Chem Int Ed Engl ; : e202405880, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38870139

RESUMO

The sluggish kinetics of lithium-sulfur (Li-S) batteries severely impedes the application in extreme conditions. Bridging the electrodes, the electrolyte plays a crucial role in regulating kinetic behaviors of Li-S batteries. Herein, we report a multifunctional electrolyte additive of phenyl selenium bromide (PhSeBr) to simultaneously exert positive influences on both electrodes and the electrolyte. For the cathode, an ideal conversion routine with lower energy barrier can be attained by the redox mediator and homogenous catalyst derived from PhSeBr, thus improving the reaction kinetics and utilization of sulfur. Meanwhile, the presence of Se-Br bond helps to reconstruct a loose solvation sheath of lithium ions and a robust bilayer SEI with excellent ionic conductivity. The Li-S battery with PhSeBr displays superior long cycling stability with a reversible capacity of 1164.7 mAh g-1 after 300 cycles at 0.5 C rate. And the pouch cell exhibits a maximum capacity of 845.3 mAh and a capacity retention of 94.8 % after 50 cycles. Excellent electrochemical properties are also obtained in extreme conditions of high sulfur loadings and low temperature of -20 °C. This work demonstrates the versatility and practicability of the special additive, striking out an efficient but simple method to design advanced Li-S batteries.

7.
Hum Brain Mapp ; 44(2): 484-495, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36111884

RESUMO

The ascending arousal system plays a crucial role in individuals' consciousness. Recently, advanced functional magnetic resonance imaging (fMRI) has made it possible to investigate the ascending arousal network (AAN) in vivo. However, the role of AAN in the neuropathology of human insomnia remains unclear. Our study aimed to explore alterations in AAN and its connections with cortical networks in chronic insomnia disorder (CID). Resting-state fMRI data were acquired from 60 patients with CID and 60 good sleeper controls (GSCs). Changes in the brain's functional connectivity (FC) between the AAN and eight cortical networks were detected in patients with CID and GSCs. Multivariate pattern analysis (MVPA) was employed to differentiate CID patients from GSCs and predict clinical symptoms in patients with CID. Finally, these MVPA findings were further verified using an external data set (32 patients with CID and 33 GSCs). Compared to GSCs, patients with CID exhibited increased FC within the AAN, as well as increased FC between the AAN and default mode, cerebellar, sensorimotor, and dorsal attention networks. These AAN-related FC patterns and the MVPA classification model could be used to differentiate CID patients from GSCs with 88% accuracy in the first cohort and 77% accuracy in the validation cohort. Moreover, the MVPA prediction models could separately predict insomnia (data set 1, R2  = .34; data set 2, R2  = .15) and anxiety symptoms (data set 1, R2  = .35; data set 2, R2  = .34) in the two independent cohorts of patients. Our findings indicated that AAN contributed to the neurobiological mechanism of insomnia and highlighted that fMRI-based markers and machine learning techniques might facilitate the evaluation of insomnia and its comorbid mental symptoms.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Mapeamento Encefálico/métodos , Estado de Consciência , Cerebelo , Imageamento por Ressonância Magnética/métodos , Nível de Alerta , Encéfalo/diagnóstico por imagem
8.
Biochem Biophys Res Commun ; 640: 183-191, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36516527

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. To date, no medication has been approved to treat NAFLD. In this study, we evaluated the therapeutic effect of the natural flavone acacetin on high-fat diet (HFD)-induced NAFLD in mice and the underlying mechanisms. We found that acacetin (10, 20, 50 mg/kg/day) suppressed the increase in body weight, serum total cholesterol, triglycerides, low-density lipoprotein, aspartate aminotransferase, and alanine aminotransferase levels in mice fed with HFD with a dose-dependent manner. Hepatic lipid accumulation, iron overload, and lipid peroxidation were significantly alleviated by acacetin. Quantitative PCR and western blotting revealed that acacetin inhibited endoplasmic reticulum (ER) stress, ferroptosis, and expressions of lipid acid synthesis-related genes in the livers of HFD mice. Similar results were observed in HepG2 cells treated with oleic acid and lipopolysaccharide. The suppressive effects of acacetin on triglycerides and expression of lipid acid synthesis genes were abolished by ER stress and the ferroptosis activators, erastin or TU. Interestingly, the action of TU was more potent than that of erastin. Treatment with the ER stress inhibitor GSK and the ferroptosis inhibitor Fer-1 revealed that ER stress was the upstream signal of ferroptosis for hepatic lipid accumulation. These findings suggest the protective effect of acacetin against lipid accumulation via suppressing ER stress and ferroptosis and provide evidence that ER stress is an upstream signal of ferroptosis in lipid accumulation. Acacetin may be a promising candidate agent for NAFLD treatment.


Assuntos
Ferroptose , Flavonas , Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Flavonas/farmacologia , Flavonas/uso terapêutico , Flavonas/metabolismo , Triglicerídeos/metabolismo , Metabolismo dos Lipídeos , Estresse do Retículo Endoplasmático , Camundongos Endogâmicos C57BL
9.
Phys Chem Chem Phys ; 25(27): 17787-17792, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37394989

RESUMO

The organic molecules in hybrid perovskites can easily rotate within the inorganic lattice at room temperature, leading to a crystal-liquid duality. The liquid-like behavior of the organic molecules is commonly believed to play a critical role in the dynamical stability, but the microscopic mechanism remains unclear. Furthermore, the presence of dynamically rotating molecules raises concerns regarding the reliability of assessing the stability of hybrid perovskites based on simple yet commonly used descriptors such as the Goldschmidt tolerance factor. Here we assess the finite-temperature phonons of hybrid perovskites by mapping ab initio molecular dynamics configurations onto an equivalent dynamical pseudo-inorganic lattice and extracting the effective force constants. We find that as compared to the formamidinium or cesium cations, stronger anisotropy and wider range of the thermal motion of the methylammonium molecule are essential for enhancing the dynamical stability of hybrid perovskites. The cation radius that determines the tolerance factor is, in fact, less important. This work not only enables a pathway to further improve the stability of hybrid perovskites, but also provides a general scheme to assess the stability of hybrid materials with dynamical disorder.

10.
Small ; 18(27): e2202250, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35655327

RESUMO

Rechargeable magnesium batteries (RMBs) suffer from low capacity and poor cyclability of cathode materials, which is due to the sluggish Mg2+ diffusion kinetics and large lattice strain. Here, a layer-interweaving mechanism in lamellar cathode to simultaneously facilitate Mg2+ diffusion and release Mg2+ -insertion strain is reported. In the Cu3 V2 O7 (OH)2 ·2H2 O (CVOH) cathode, Mg2+ diffusion highways are generated by the vertical interweaving of CVOH layers and V6 O13 layers that nucleate in CVOH during discharging, which are switchable by Mg2+ insertion/extraction. These highways enhance the Mg2+ diffusion coefficient by three orders of magnitude and release 50% Mg2+ -insertion strain. This enables CVOH to exhibit a high capacity of 262 mAh g-1 at high current density of 250 mA g-1 in aqua, and extremely low capacity loss of 0.0004% per cycle in the activated carbon//CVOH cell. This work inspires designing the magnesiation phase transformation of electrodes to resolve both kinetic and strain issues for high-performance RMBs.


Assuntos
Fontes de Energia Elétrica , Magnésio , Eletrodos
11.
Nat Mater ; 20(7): 971-976, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33927392

RESUMO

Defect-induced non-radiative losses are currently limiting the performance of hybrid perovskite devices. Experimental reports have indicated the existence of point defects that act as detrimental non-radiative recombination centres under iodine-poor synthesis conditions. However, the microscopic nature of these defects is still unknown. Here we demonstrate that hydrogen vacancies can be present in high densities under iodine-poor conditions in the prototypical hybrid perovskite MAPbI3 (MA = CH3NH3). They act as very efficient non-radiative recombination centres with an exceptionally high carrier capture coefficient of 10-4 cm3 s-1. By contrast, the hydrogen vacancies in FAPbI3 [FA = CH(NH2)2] are much more difficult to form and have a capture coefficient that is three orders of magnitude lower. Our study unveils the critical but overlooked role of hydrogen vacancies in hybrid perovskites and rationalizes why FA is essential for realizing high efficiency in hybrid perovskite solar cells. Minimizing the incorporation of hydrogen vacancies is key to enabling the best performance of hybrid perovskites.

12.
Phys Rev Lett ; 128(13): 136401, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426707

RESUMO

It has been experimentally observed that light-induced lattice expansion could enhance the solar conversion efficiency in hybrid perovskites, but the origin remains elusive. By performing rigorous first-principles calculations for a prototypical hybrid-perovskite FAPbI_{3} (FA: formamidinium), we show that 1% lattice expansion could already reduce the nonradiative capture coefficient by one order of magnitude. Unexpectedly, the suppressed nonradiative capture is not caused by changes in the band gap or defect transition level due to lattice expansion, but originates from enhanced defect relaxations associated with charge-state transitions in the expanded lattice. These insights not only provide a rationale for the efficiency enhancement by lattice expansion in hybrid perovskites, but also offer a general approach to the manipulation of nonradiative capture via strain engineering in a wide spectrum of optoelectronic materials.

13.
J Clin Lab Anal ; 36(12): e24793, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36447383

RESUMO

BACKGROUND: The intake of Gynura segetum, a traditional Chinese medicine, may be induce hepatic sinusoidal obstruction syndrome (HSOS). It has a high mortality rate based on the severity of the disease and the absence of therapeutic effectiveness. Therefore, the current study was designed to investigate the effects of bicyclol on HSOS induced by Gynura segetum and the potential molecular mechanisms. METHODS: Gynura segetum (30 g/kg) was administered for 4 weeks in the model group, while the bicyclol pretreatment group received bicyclol (200 mg/kg) administration. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (CHO), triglyceride (TG), and liver histological assays were detected to assess HSOS. The gene expressions of cytochrome P450 (CYP450) isozymes were quantified by real-time PCR. Moreover, hepatocellular apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, then apoptosis and autophagy-related markers were determined using Western blot. RESULTS: As a result, bicyclol pretreatment is notably protected against Gynura segetum-induced HSOS, as observed by reducing serum ALT levels, inhibiting the reduction in CHO and TG levels, and alleviating the histopathological changes. Bicyclol pretreatment inhibited the changes in mRNA levels of CYP450 isozymes (including the increase in CYP2a5 and decrease in CYP2b10, 2c29, 2c37, 3a11, and 7b1). In addition, the upregulation of Bcl-2 and the downregulation of LC3-II/LC3-I proteins expression in HSOS were inhibited with bicyclol pretreatment. CONCLUSION: Bicyclol exerted a protective effect against HSOS induced by Gynura segetum, which could be attributed to the regulated expressions of CYP450 isozymes and alleviated the downregulation of autophagy.


Assuntos
Compostos de Bifenilo , Hepatopatia Veno-Oclusiva , Humanos , Colesterol , Hepatopatia Veno-Oclusiva/induzido quimicamente , Hepatopatia Veno-Oclusiva/tratamento farmacológico , Hepatopatia Veno-Oclusiva/metabolismo , Isoenzimas/metabolismo , Fígado/metabolismo , Compostos de Bifenilo/uso terapêutico , Família 2 do Citocromo P450/genética , Família 2 do Citocromo P450/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos
14.
Angew Chem Int Ed Engl ; 61(49): e202213160, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36228131

RESUMO

Great efforts have been made to tackle the issues of the shuttle effect and kinetics hysteresis in lithium-sulfur (Li-S) battery, but few on tuning the reaction path of sulfur cathode. Herein, we report a strategy to replace inorganic sulfur with liquid organosulfide and construct a novel liquid-liquid interface between cathode and electrolyte, which effectively inhibits the shuttle effect and simplifies the solid-liquid-solid conversion reaction to only liquid-solid process, thus greatly improving the reaction kinetics. The Li|PTS half-cell exhibits excellent cycling stability at 0.5 C, with a capacity retention of 64.9 % after 750 cycles. The Li|PTS pouch cell with a high PTS loading of 3.1 g delivers a maximum capacity of 997 mAh and maintains 82.1 % of initial capacity after 50 cycles at the current of 100 mA. This work enriches the reaction mechanism of Li-S batteries and provides new insights for the development of interphase chemistry in the design of cathodes.

15.
Angew Chem Int Ed Engl ; 61(30): e202205619, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35607762

RESUMO

A cobalt-catalyzed asymmetric sequential hydroboration/isomerization/hydroboration of 2-aryl vinylcyclopropanes was for the first time reported for the preparation of valuable chiral 1,5-bis(boronates) in good yields with excellent enantioselectivity via asymmetric sequential isomerization/hydroboration of a trisubstituted alkene intermediate. The reaction was carried out smoothly and this protocol was used for asymmetric syntheses of (-)-preclamol in gram-scale. The two primary C(sp3) -B bonds in chiral 1,5-bis(boronates) could be distinguished in iterative Suzuki-Miyaura cross-coupling reaction, delivering chiral 1,2,5-triaryl alkanes with excellent enantioselectivity. Based on experimental and computational studies, a cobalt-hydride species was proposed as the active intermediate in hydroboration, isomerization, and second hydroboration reactions.


Assuntos
Alcenos , Cobalto , Alcenos/química , Catálise , Cobalto/química , Isomerismo , Estereoisomerismo
16.
Nat Mater ; 19(8): 849-854, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32367079

RESUMO

Collective interstitial ordering is at the core of martensite formation in Fe-C-based alloys, laying the foundation for high-strength steels. Even though this ordering has been studied extensively for more than a century, some fundamental mechanisms remain elusive. Here, we show the unexpected effects of two correlated phenomena on the ordering mechanism: anharmonicity and segregation. The local anharmonicity in the strain fields induced by interstitials substantially reduces the critical concentration for interstitial ordering, up to a factor of three. Further, the competition between interstitial ordering and segregation results in an effective decrease of interstitial segregation into extended defects for high interstitial concentrations. The mechanism and corresponding impact on interstitial ordering identified here enrich the theory of phase transitions in materials and constitute a crucial step in the design of ultra-high-performance alloys.

17.
Phys Chem Chem Phys ; 23(8): 4718-4727, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33596276

RESUMO

In this work, we report a comparative study of the interfacial properties of fcc-Al/L12-Al3M (M = Sc, Ti, V, Y, Zr, Nb) from first-principles calculations. It is found that the fcc-Al(111)/L12-Al3Nb(111) interface is energetically favorable because of its negative interfacial energy (-0.225 J m-2), whereas the interfacial energies of the other five interfaces are positive. Despite their thermodynamically unfavorable characteristics, the stabilities of the formed interfaces are ranked in the order fcc-Al(111)/L12-Al3Nb(111) > fcc-Al(111)/L12-Al3Ti(111) > fcc-Al(111)/L12-Al3Zr(111) > fcc-Al(111)/L12-Al3Sc(111) > fcc-Al(111)/L12-Al3V(111) > fcc-Al(111)/L12-Al3Y(111). Moreover, the computed generalized stacking fault energy curves revealed that the (111)[11-2] slip system is preferred over the (111)[10-1] slip system under external stresses for all six interfaces. Based on the Rice ratio criterion, the interface slips also energetically favor the generation of stacking faults instead of cleavage for these interface systems; this finding implied that these interfaces did not greatly influence the plastic deformation behavior of aluminum. Furthermore, the derived bulk elastic properties indicate that fcc-Al, L12-Al3Nb, and L12-Al3V tend to present ductile behavior, while L12-Al3Zr, L12-Al3Ti, L12-Al3Y, and L12-Al3Sc are found to be brittle compounds. Nevertheless, all of these intermetallics can strengthen the aluminum matrix without losing much plasticity to provide a higher elastic modulus than aluminum along with the ductile interface nature of fcc-Al(111)/L12-A13M(111).

18.
Lasers Med Sci ; 36(2): 339-347, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32623604

RESUMO

This study aims to evaluate the photodynamic efficacy of purpurin 18 (pu-18) on triple negative breast cancer both in vitro and in vivo. Two states of 4T1 cells, 2D culture and 3D spheroids, were used to evaluate the photodynamic action of pu-18 in vitro. The in vitro study results indicated that for the 4T1 2D cell culture, the photodynamic therapy (PDT) treatment showed significant photocytotoxicity at low pu-18 concentrations following light irradiation. Pu-18 was found to distribute on the lysosomes, mitochondria, Golgi apparatus, and endoplasmic reticulum. After irradiation, pu-18 can generate ROS to destroy the mitochondrial membrane potential (MMP) and eventually induce apoptosis in the 2D 4T1 cells. Light-activated pu-18 could also induce the destruction of the 3D 4T1 cell spheroids. The in vivo study was conducted by using a subcutaneous 4T1 breast cancer animal model. The results demonstrated that pu-18 could remain in the tumor for more than 4 days by direct intra-tumoral injection. The PDT treatment was performed every 2 days for a total of 3 times. The results showed that PDT treatment could significantly inhibit tumor growth in vivo, indicating a good photodynamic efficacy of pu-18 in the mouse breast cancer model, without influencing weight and major organ function. The survival pattern results showed that PDT treatment could largely extend the survival time of mice with breast cancer. The preliminary conclusion is that photodynamic treatment using pu-18 is effective at preventing the growth of triple negative breast cancer cells both in vitro and in vivo. A combination of light irradiation and pu-18 could therefore be a worthwhile approach for the treatment of triple negative breast cancer.


Assuntos
Apoptose , Fotoquimioterapia , Porfirinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Peso Corporal/efeitos dos fármacos , Peso Corporal/efeitos da radiação , Linhagem Celular Tumoral , Feminino , Humanos , Luz , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/farmacologia , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/patologia , Esferoides Celulares/efeitos da radiação , Frações Subcelulares/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/efeitos da radiação
19.
Molecules ; 26(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064330

RESUMO

Several genetic studies have identified a rare variant of triggering receptor expressed on myeloid cells 2 (TREM2) as a risk factor for Alzheimer's disease (AD). However, findings on the effects of TREM2 on Aß deposition are quite inconsistent in animal studies, requiring further investigation. In this study, we investigated whether elevation of TREM2 mitigates Aß pathology in TgCRND8 mice. We found that peripheral nerve injury resulted in a robust elevation of TREM2 exclusively in reactive microglia in the ipsilateral spinal cord of aged TgCRND8 mice at the age of 20 months. TREM2 expression appeared on day 1 post-injury and the upregulation was maintained for at least 28 days. Compared to the contralateral side, neither amyloid beta plaque load nor soluble Aß40 and Aß42 levels were attenuated upon TREM2 induction. We further showed direct evidence that TREM2 elevation in reactive microglia did not affect amyloid-ß pathology in plaque-bearing TgCRND8 mice by applying anti-TREM2 neutralizing antibody to selectively block TREM2. Our results question the ability of TREM2 to ameliorate established Aß pathology, discouraging future development of disease-modifying pharmacological treatments targeting TREM2 in the late stage of AD.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Glicoproteínas de Membrana/metabolismo , Microglia/metabolismo , Microglia/patologia , Receptores Imunológicos/metabolismo , Envelhecimento/patologia , Animais , Plexo Braquial , Proteínas de Ligação ao Cálcio/metabolismo , Modelos Animais de Doenças , Masculino , Camundongos Transgênicos , Proteínas dos Microfilamentos/metabolismo , Nervos Periféricos/patologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Corno Dorsal da Medula Espinal/patologia
20.
Phys Rev Lett ; 125(3): 037401, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32745394

RESUMO

Using first-principles approaches we find that the Auger recombination in PbSe is anomalous in three distinct ways. First, the direct Auger coefficient is 4 orders of magnitude lower than that of other semiconductors with similar band gaps, a result that can be attributed to the lack of involvement of a heavy-hole band. Second, phonon-assisted indirect Auger recombination prevails, contrary to the common belief that direct Auger is dominant in narrow-gap semiconductors. Third, an unexpectedly weak temperature dependence of the Auger coefficient is observed, which we can now attribute to the indirect nature of the Auger process. The widely accepted explanation of this behavior in terms of an unusual temperature dependence of the band gap is only a secondary effect. Our results elucidate the mechanisms underlying the anomalous Auger recombination in IV-VI semiconductors in general, which is critical for understanding and engineering carrier transport.

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