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1.
Adv Mater ; : e2409319, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302002

RESUMEN

Blue perovskite light-emitting diodes (PeLEDs) have attracted enormous attention; however, their unsatisfactory device efficiency and spectral stability still remain great challenges. Unfavorable low-dimensional phase distribution and defects with deeper energy levels usually cause energy disorder, substantially limiting the device's performance. Here, an additive-interface optimization strategy is reported to tackle these issues, thus realizing efficient and spectrally stable blue PeLEDs. A new type of additive-formamidinium tetrafluorosuccinate (FATFSA) is introduced into the quasi-2D mixed halide perovskite accompanied by interface engineering, which effectively impedes the formation of undesired low-dimensional phases with various bandgaps throughout the entire film, thereby boosting energy transfer process for accelerating radiative recombination; this strategy also diminishes the halide vacancies especially chloride-related defects with deep energy level, thus reducing nonradiative energy loss for efficient radiative recombination. Benefitting from homogenized energy landscape throughout the entire perovskite emitting layer, PeLEDs with spectrally-stable blue emission (478 nm) and champion external quantum efficiency (EQE) of 21.9% are realized, which represents a record value among this type of PeLEDs in the pure blue region.

2.
Int J Biol Macromol ; 278(Pt 2): 134628, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39128736

RESUMEN

An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1-6-linked ß-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1ß, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.


Asunto(s)
Peso Molecular , Polisacáridos , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Ratones , Animales , Células RAW 264.7 , Hidrólisis , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Monosacáridos/análisis , Citocinas/metabolismo
3.
J Sci Food Agric ; 2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39118479

RESUMEN

BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.

4.
ACS Appl Mater Interfaces ; 16(30): 39664-39672, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39025786

RESUMEN

Reducing the crystal size of perovskites to the strong quantum confinement regime is an effective way to realize blue luminescence for light-emitting applications. However, challenges remain in directly constraining the crystal growth during film preparation to achieve three-dimensional quantum confinement, and the widely used long-chain ligands may bring difficulties for charge transport and unfavorably affect the device performance. Herein, we report a novel strategy for fabricating strongly confined blue-emitting perovskite nanocrystalline films via synergistic steric effect modulation by precursors and antisolvents. We synthesize cesium pentafluoropropanoate (CsPFPA) as a new type of precursor agent, where the steric effect of the PFPA group can help constrain the growth of perovskite crystals and passivate the defects. Furthermore, different types of antisolvents with varied molecular sizes and steric hindrance are used to regulate the size of perovskite crystals and improve film quality. Consequently, highly emissive blue perovskite films are realized with the emission wavelength effectively tuned in the blue region by varying the concentration of CsPFPA as well as the type of antisolvents. Based on the strongly confined perovskite films, blue light-emitting diodes (LEDs) are constructed, showing good spectral tunability and stability in the electroluminescence. This work demonstrates a novel pathway for developing bright perovskite blue emitters for LEDs, which may potentially advance their future applications in display and lighting.

5.
Carbohydr Polym ; 342: 122203, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39048182

RESUMEN

Red fluorescent hydrogels possessing injectable and self-healing properties have widespread potential in biomedical field. It is still a challenge to achieve a biomacromolecules based dynamic hydrogels simultaneously combining with excellent red fluorescence, good mechanical properties, and biocompatibility. Here we first explore hydrophilic inclusion complex of (R-CDs@α-CD) derived from hydrophobic red fluorescent carbon dots (R-CDs) and α-cyclodextrin (α-CD), and then achieved a red fluorescent and dynamic polysaccharide R-CDs@α-CD/CEC-l-OSA hydrogel. The nanocomposite hydrogel can be fabricated through controlled doping of red fluorescent R-CDs@α-CD into dynamic polymer networks, taking reversibly crosslinked N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) as an example. The versatile red fluorescent hydrogel simultaneously combines the features of injection, biocompatibility, and augmented mechanical properties and self-healing behavior, especially in rapid self-recovery even after integration. The R-CDs@α-CD uniformly dispersed into dynamic hydrogel played the role of killing two birds with one stone, that is, endowing red emission of a hydrophilic fluorescent substance, and improving mechanical and self-healing properties as a dynamic nano-crosslinker, via forming hydrogen bonds as reversible crosslinkings. The novel red fluorescent and dynamic hydrogel based on polysaccharides is promising for using as biomaterials in biomedical field.


Asunto(s)
Alginatos , Carbono , Quitosano , Hidrogeles , Nanocompuestos , Puntos Cuánticos , Alginatos/química , Quitosano/química , Carbono/química , Nanocompuestos/química , Hidrogeles/química , Puntos Cuánticos/química , Puntos Cuánticos/toxicidad , Colorantes Fluorescentes/química , alfa-Ciclodextrinas/química , Materiales Biocompatibles/química , Animales , Interacciones Hidrofóbicas e Hidrofílicas
6.
Chem Sci ; 15(29): 11374-11381, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39055034

RESUMEN

Chiral hybrid metal halides (CHMHs) have received a considerable amount of attention in chiroptoelectronics, spintronics, and ferroelectrics due to their superior optoelectrical properties and structural flexibility. Owing to limitations in synthesis, the theoretical prediction of room-temperature stable chiral three-dimensional (3D) CHFClNH3PbI3 has not been successfully prepared, and the optoelectronic properties of such structures cannot be studied. Herein, we have successfully constructed two pairs of chiral 3D lead iodide hybrids (R/S/Rac-3AEP)Pb2I6 (3R/S/Rac, 3AEP = 3-(1-aminoethyl)pyridin-1-ium) and (R/S/Rac-2AEP)Pb2I6 (2R/S/Rac, 2AEP = 2-(1-aminoethyl)pyridin-1-ium) through chiral introduction and ortho substitution strategies, and obtained bulk single crystals of 3R/S/Rac. The 3R/S exhibits optical activity and bulk photovoltaic effect induced by chirality. The 3R crystal device exhibits stable circularly polarized light performance at 565 nm with a maximum anisotropy factor of 0.07, responsivity of 0.25 A W-1, and detectivity of 3.4 × 1012 jones. This study provides new insights into the synthesis of chiral 3D lead halide hybrids and the development of chiral electronic devices.

7.
Injury ; 55(9): 111724, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39054232

RESUMEN

Severe burns related to fires and explosions of lithium-ion batteries of electric motorcycles have not been reported to date. We retrospectively studied 419 patients admitted to our burn intensive care unit from January 2016 to December 2021. Of these 419 patients, 26 (22 male, 4 female; median age, 42 years) had burns related to lithium-ion battery fires and explosions, and all of their injury characteristics were similar to those of traditional flame burns. Lithium-ion battery-related burns were the eighth most common cause of burn injuries among all hospitalized patients. The 26 patients comprised 10 unemployed and 16 employed individuals. Twenty-three patients were injured at home during the battery charging process, and three were injured outdoors (one by a fire while the electric motorcycle was stationary and the others two by a fire while riding the motorcycle). The burn sites were distributed over the whole body; the burn area ranged from 10 % to 100 % of the total body surface area, and the burn depth ranged from superficial second-degree burns to third-degree burns. Twenty-three patients had inhalation injuries, and ten underwent prophylactic tracheostomy and intubation. Multiple operations were required for wound repair. Although convenient, lithium-ion electric motorcycles can also cause severe burns. To prevent these injuries, we must increase public safety awareness and education, develop new battery energy storage systems and battery management systems, and ensure the safety of batteries. Consumers should be aware of the potential dangers of lithium-ion batteries and comply with related security measures.


Asunto(s)
Quemaduras , Suministros de Energía Eléctrica , Explosiones , Incendios , Litio , Motocicletas , Humanos , Masculino , Femenino , Adulto , Estudios Retrospectivos , Quemaduras/etiología , Litio/efectos adversos , Persona de Mediana Edad , Suministros de Energía Eléctrica/efectos adversos , Adulto Joven , Unidades de Quemados , Unidades de Cuidados Intensivos
8.
Small ; : e2402028, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970557

RESUMEN

2D-3D tin-based perovskites are considered as promising candidates for achieving efficient lead-free perovskite solar cells (PSCs). However, the existence of multiple low-dimensional phases formed during the film preparation hinders the efficient transport of charge carriers. In addition, the non-homogeneous distribution of low-dimensional phases leads to lattice distortion and increases the defect density, which are undesirable for the stability of tin-based PSCs. Here, mixed spacer cations [diethylamine (DEA+) and phenethylamine (PEA+)] are introduced into tin perovskite films to modulate the distribution of the 2D phases. It is found that compared to the film with only PEA+, the combination of DEA+ and PEA+ favors the formation of homogeneous low-dimensional perovskite phases with three octahedral monolayers (n = 3), especially near the bottom interface between perovskite and hole transport layer. The homogenization of 2D phases help improve the film quality with reduced lattice distortion and released strain. With these merits, the tin PSC shows significantly improved stability with 94% of its initial efficiency retained after storing in a nitrogen atmosphere for over 4600 h, and over 80% efficiency maintained after continuous illumination for 400 h.

9.
Sci Rep ; 14(1): 17676, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39085267

RESUMEN

This paper proposes a transformer fault diagnosis method based on ACGAN and CGWO-LSSVM to address the problem of misjudgment and low diagnostic accuracy caused by the small number and uneven distribution of some fault samples in transformer fault diagnosis. Firstly, generate adversarial networks through auxiliary classification conditions, The ACGAN method expands a small and imbalanced number of samples to obtain balanced and expanded data; Secondly, the non coding ratio method is used to construct the characteristics of dissolved gases in oil, and kernel principal component analysis is used, KPCA method for feature fusion; Finally, using the improved cubic gray wolf optimization algorithm, CGWO for least square support vector machines, optimize the parameters of the LSSVM model and construct a transformer fault diagnosis model. The results show that the proposed method has a low false alarm rate and a diagnostic accuracy of 97.66%, compared to IGOA-LSSVM the IChOA-LSSVM and PSO-LSSVM methods improved accuracy by 0.12, 1.76, and 2.58%, respectively. This method has been proven to solve the problems of misjudgment and low diagnostic accuracy caused by small sample sizes and uneven distribution. It is suitable for multi classification fault diagnosis of transformer imbalanced datasets and is superior to other methods.

10.
Bioorg Med Chem Lett ; 111: 129880, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38996941

RESUMEN

Viral infectivity factor (Vif) has been recognized as a new therapeutic target for human immunodeficiency virus-1 (HIV-1) infected patients. In our previous work, we have synthesized a novel class of Vif inhibitors with 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold, which show obvious activity in HIV-1 infected cells and are also effective against drug-resistant strains. Proteolytic targeting chimera (PROTAC) utilizes the ubiquitin-proteasome system to degrade target proteins, which is well established in the field of cancer, but the antiviral PROTAC molecules are rarely reported. In order to explore the effectiveness of PROTAC in the antiviral area, we designed and synthesized a series of degrader of HIV-1 Vif based on 2-amino-N-(5-hydroxy-2-methoxyphenyl)-6-((4-nitrophenyl)thio)benzamide scaffold. Among them, L15 can degrade Vif protein obviously in a dose-dependent manner and shows certain antivirus activity. Meanwhile, molecular dynamics simulation indicated that the ternary complex formed by L15, Vif, and E3 ligase adopted a reasonable binding mode and maintained a stable interaction. This provided a molecular basis and prerequisite for the selective degradation of the Vif protein by L15. This study reports the HIV-1 Vif PROTAC for the first time and represents the proof-of-concept of PROTACs-based antiviral drug discovery in the field of HIV/ acquired immune deficiency syndrome (AIDS).


Asunto(s)
Fármacos Anti-VIH , VIH-1 , Productos del Gen vif del Virus de la Inmunodeficiencia Humana , VIH-1/efectos de los fármacos , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/antagonistas & inhibidores , Productos del Gen vif del Virus de la Inmunodeficiencia Humana/metabolismo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Humanos , Relación Estructura-Actividad , Estructura Molecular , Benzamidas/farmacología , Benzamidas/química , Benzamidas/síntesis química , Descubrimiento de Drogas , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad Microbiana , Proteolisis/efectos de los fármacos , Simulación de Dinámica Molecular
11.
Zool Res ; 45(4): 833-844, 2024 07 18.
Artículo en Inglés | MEDLINE | ID: mdl-39004861

RESUMEN

Porcine reproductive and respiratory syndrome (PRRS) is a globally prevalent contagious disease caused by the positive-strand RNA PRRS virus (PRRSV), resulting in substantial economic losses in the swine industry. Modifying the CD163 SRCR5 domain, either through deletion or substitution, can eff1ectively confer resistance to PRRSV infection in pigs. However, large fragment modifications in pigs inevitably raise concerns about potential adverse effects on growth performance. Reducing the impact of genetic modifications on normal physiological functions is a promising direction for developing PRRSV-resistant pigs. In the current study, we identified a specific functional amino acid in CD163 that influences PRRSV proliferation. Viral infection experiments conducted on Marc145 and PK-15 CD163 cells illustrated that the mE535G or corresponding pE529G mutations markedly inhibited highly pathogenic PRRSV (HP-PRRSV) proliferation by preventing viral binding and entry. Furthermore, individual viral challenge tests revealed that pigs with the E529G mutation had viral loads two orders of magnitude lower than wild-type (WT) pigs, confirming effective resistance to HP-PRRSV. Examination of the physiological indicators and scavenger function of CD163 verified no significant differences between the WT and E529G pigs. These findings suggest that E529G pigs can be used for breeding PRRSV-resistant pigs, providing novel insights into controlling future PRRSV outbreaks.


Asunto(s)
Antígenos CD , Antígenos de Diferenciación Mielomonocítica , Mutación Puntual , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Receptores de Superficie Celular , Animales , Porcinos , Síndrome Respiratorio y de la Reproducción Porcina/genética , Síndrome Respiratorio y de la Reproducción Porcina/virología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Animales Modificados Genéticamente/genética , Línea Celular
12.
Food Chem ; 458: 140111, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38968716

RESUMEN

Anthocyanins, natural pigments known for their vibrant hues and beneficial properties, undergo intricate genetic control. However, red vegetables grown in plant factories frequently exhibit reduced anthocyanin synthesis compared to those in open fields due to factors like inadequate light, temperature, humidity, and nutrient availability. Comprehending these factors is essential for optimizing plant factory environments to enhance anthocyanin synthesis. This review insights the impact of physiological and genetic factors on the production of anthocyanins in red lettuce grown under controlled conditions. Further, we aim to gain a better understanding of the mechanisms involved in both synthesis and degradation of anthocyanins. Moreover, this review summarizes the identified regulators of anthocyanin synthesis in lettuce, addressing the gap in knowledge on controlling anthocyanin production in plant factories, with potential implications for various crops beyond red lettuce.


Asunto(s)
Antocianinas , Lactuca , Humanos , Lactuca/química , Lactuca/genética , Lactuca/metabolismo , Instalaciones Industriales y de Fabricación , Antocianinas/biosíntesis , Antocianinas/química , Plantas Modificadas Genéticamente , Luz , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Concentración de Iones de Hidrógeno , Color
13.
Angew Chem Int Ed Engl ; 63(36): e202407508, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-38877782

RESUMEN

All-inorganic cesium lead triiodide perovskites (CsPbI3) have attracted increasing attention due to their good thermal stability, remarkable optoelectronic properties, and adaptability in tandem solar cells. However, N2-filled glovebox is generally required to strictly control the humidity during film fabrication due to the moisture-induced black-to-yellow phase transition, which remains a great hinderance for further commercialization. Herein, we report an effective approach via incorporating multifunctional ethacridine lactate (EAL) to mitigate moisture invasion and enable the fabrication of efficient inverted (p-i-n) CsPbI3 perovskite solar cells (PSCs) under ambient condition. It is revealed that the lactate anions accelerate the crystallization of CsPbI3, shortening the exposure time to moisture during film fabrication. Meanwhile, the conjugated backbone and multiple functional groups in the ethacridine cations can interact with I- and Pb2+ to reduce the undesired defects, stabilize the perovskite structure and facilitate the charge transport in the film. Moreover, EAL incorporation also leads to better energy alignment, thus favoring charge extraction at both upper and bottom interfaces. Consequently, the device efficiency and stability are enormously enhanced, with the champion efficiency reaching 21.08 %. This even surpasses the highest value reported for the devices fabricated in glovebox, representing a record efficiency of inverted all-inorganic PSCs.

14.
Front Bioeng Biotechnol ; 12: 1393154, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38938983

RESUMEN

Purpose: Conventional cephalomedullary nails (CMNs) are commonly employed for internal fixation in the treatment of reverse obliquity intertrochanteric (ROI) fractures. However, the limited effectiveness of conventional CMNs in addressing ROI fractures results in significant implant-related complications. To address challenges associated with internal fixation, a novel Proximal Femoral Bionic Nail (PFBN) has been developed. Methods: In this study, a finite element model was constructed using a normal femoral specimen, and biomechanical verification was conducted using the GOM non-contact optical strain measurement system. Four intramedullary fixation approaches-PFBN, Proximal Femoral Nail Antirotation InterTan nail (ITN), and Gamma nail (Gamma nail)-were employed to address three variations of ROI fractures (AO/OTA 31-A3). The biomechanical stability of the implant models was evaluated through the calculation of the von Mises stress contact pressure and displacement. Results: Compared to conventional CMNs, the PFBN group demonstrated a 9.36%-59.32% reduction in the maximum VMS at the implant. The A3.3 ROI fracture (75% bone density) was the most unstable type of fracture. In comparison to conventional CMNs, PFBN demonstrated more stable data, including VMS values (implant: 506.33 MPa, proximal fracture fragment: 34.41 MPa), contact pressure (13.28 MPa), and displacement (17.59 mm). Conclusion: Compared to the PFNA, ITN, and GN, the PFBN exhibits improvements in stress concentration, stress conduction, and overall model stability in ROI fractures. The double triangle structure aligns better with the tissue structure and biomechanical properties of the proximal femur. Consequently, the PFBN has significant potential as a new fixation strategy for the clinical treatment of ROI fractures.

15.
J Immunother Cancer ; 12(6)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38908854

RESUMEN

BACKGROUND AND AIMS: The immunosuppressive tumor microenvironment (TME) plays an essential role in cancer progression and immunotherapy response. Despite the considerable advancements in cancer immunotherapy, the limited response to immune checkpoint blockade (ICB) therapies in patients with hepatocellular carcinoma (HCC) remains a major challenge for its clinical implications. Here, we investigated the molecular basis of the protein O-fucosyltransferase 1 (POFUT1) that drives HCC immune evasion and explored a potential therapeutic strategy for enhancing ICB efficacy. METHODS: De novo MYC/Trp53-/- liver tumor and the xenograft tumor models were used to evaluate the function of POFUT1 in immune evasion. Biochemical assays were performed to elucidate the underlying mechanism of POFUT1-mediated immune evasion. RESULTS: We identified POFUT1 as a crucial promoter of immune evasion in liver cancer. Notably, POFUT1 promoted HCC progression and inhibited T-cell infiltration in the xenograft tumor and de novo MYC/Trp53-/- mouse liver tumor models. Mechanistically, we demonstrated that POFUT1 stabilized programmed death ligand 1 (PD-L1) protein by preventing tripartite motif containing 21-mediated PD-L1 ubiquitination and degradation independently of its protein-O-fucosyltransferase activity. In addition, we further demonstrated that PD-L1 was required for the tumor-promoting and immune evasion effects of POFUT1 in HCC. Importantly, inhibition of POFUT1 could synergize with anti-programmed death receptor 1 therapy by remodeling TME in the xenograft tumor mouse model. Clinically, POFUT1 high expression displayed a lower response rate and worse clinical outcome to ICB therapies. CONCLUSIONS: Our findings demonstrate that POFUT1 functions as a novel regulator of tumor immune evasion and inhibition of POFUT1 may be a potential therapeutic strategy to enhance the efficacy of immune therapy in HCC.


Asunto(s)
Antígeno B7-H1 , Fucosiltransferasas , Inmunoterapia , Neoplasias Hepáticas , Fucosiltransferasas/metabolismo , Fucosiltransferasas/genética , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Ratones , Animales , Antígeno B7-H1/metabolismo , Inmunoterapia/métodos , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Escape del Tumor , Microambiente Tumoral , Evasión Inmune , Línea Celular Tumoral
16.
Cancer Lett ; 595: 217006, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-38823763

RESUMEN

Driver genomic mutations in tumors define specific molecular subtypes that display distinct malignancy competence, therapeutic resistance and clinical outcome. Although TP53 mutation has been identified as the most common mutation in hepatocellular carcinoma (HCC), current understanding on the biological traits and therapeutic strategies of this subtype has been largely unknown. Here, we reveal that fatty acid ß oxidation (FAO) is remarkable repressed in TP53 mutant HCC and which links to poor prognosis in HCC patients. We further demonstrate that carnitine palmitoyltransferase 1 (CPT1A), the rate-limiting enzyme of FAO, is universally downregulated in liver tumor tissues, and which correlates with poor prognosis in HCC and promotes HCC progression in the de novo liver tumor and xenograft tumor models. Mechanically, hepatic Cpt1a loss disrupts lipid metabolism and acetyl-CoA production. Such reduction in acetyl-CoA reduced histone acetylation and epigenetically reprograms branched-chain amino acids (BCAA) catabolism, and leads to the accumulation of cellular BCAAs and hyperactivation of mTOR signaling. Importantly, we reveal that genetic ablation of CPT1A renders TP53 mutant liver cancer mTOR-addicted and sensitivity to mTOR inhibitor AZD-8055 treatment. Consistently, Cpt1a loss in HCC directs tumor cell therapeutic response to AZD-8055. CONCLUSION: Our results show genetic evidence for CPT1A as a metabolic tumor suppressor in HCC and provide a therapeutic approach for TP53 mutant HCC patients.


Asunto(s)
Carcinoma Hepatocelular , Carnitina O-Palmitoiltransferasa , Neoplasias Hepáticas , Mutación , Proteína p53 Supresora de Tumor , Humanos , Carnitina O-Palmitoiltransferasa/genética , Carnitina O-Palmitoiltransferasa/metabolismo , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Animales , Ratones , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Aminoácidos de Cadena Ramificada/metabolismo , Línea Celular Tumoral , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Metabolismo de los Lípidos/genética , Transducción de Señal , Acetilcoenzima A/metabolismo , Regulación Neoplásica de la Expresión Génica , Masculino
17.
J Agric Food Chem ; 72(23): 13382-13392, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38814005

RESUMEN

Cadmium (Cd) is a transition metal ion that is extremely harmful to human and animal biological systems. Cd is a toxic substance that can accumulate in the food chain and cause various health issues. Sulforaphane (SFN) is a natural bioactive compound with potent antioxidant properties. In our study, 80 1 day-old chicks were fed with Cd (140 mg/kg BW/day) and/or SFN (50 mg/kg BW/day) for 90 days. The blood-thymus barrier (BTB) is a selective barrier separating T-lymphocytes from blood and cortical capillaries in the thymus cortex. Our research revealed that Cd could destroy the BTB by downregulating Wnt/ß-catenin signaling and induce immunodeficiency, leading to irreversible injury to the immune system. The study emphasizes the health benefits of SFN in the thymus. SFN could ameliorate Cd-triggered BTB dysfunction and pyroptosis in the thymus tissues. SFN modulated the PI3K/AKT/FOXO1 axis, improving the level of claudin-5 (CLDN5) in the thymus to alleviate BTB breakdown. Our findings indicated the toxic impact of Cd on thymus, and BTB could be the specific target of Cd toxicity. The finding also provides evidence for the role of SFN in maintaining thymic homeostasis for Cd-related health issues.


Asunto(s)
Cadmio , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Sulfóxidos , Timo , Animales , Humanos , Masculino , Cadmio/toxicidad , Pollos , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Isotiocianatos/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Transducción de Señal/efectos de los fármacos , Timo/efectos de los fármacos , Timo/metabolismo
18.
Small ; : e2401429, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38808805

RESUMEN

Plastics serve as an essential foundation in contemporary society. Nevertheless, meeting the rigorous performance demands in advanced applications and addressing their end-of-life disposal are two critical challenges that persist. Here, an innovative and facile method is introduced for the design and scalable production of polycarbonate, a key engineering plastic, simultaneously achieving high performance and closed-loop chemical recyclability. The bisphenol framework of polycarbonate is strategically adjusted from the low-bond-dissociation-energy bisphenol A to high-bond-dissociation-energy 4,4'-dihydroxydiphenyl, in combination with the incorporation of polysiloxane segments. As expected, the enhanced bond dissociation energy endows the polycarbonate with an extremely high glow-wire flammability index surpassing 1025 °C, a 0.8 mm UL-94 V-0 rating, a high LOI value of 39.2%, and more than 50% reduction of heat and smoke release. Furthermore, the π-π stacking interactions within biphenyl structures resulted in a significant enhancement of mechanical strength by as more as 37.7%, and also played a positive role in achieving a lower dielectric constant. Significantly, the copolymer exhibited outstanding closed-loop chemical recyclability, allowing for facile depolymerization into bisphenol monomers and the repolymerized copolymer retains its high heat and fire resistance. This work provides a novel insight in the design of high-performance and closed-loop chemical recyclable polymeric materials.

19.
Biochem Biophys Res Commun ; 717: 150061, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38718570

RESUMEN

Epithelial mesenchymal transition (EMT) is a critical process implicated in the pathogenesis of retinal fibrosis and the exacerbation of diabetic retinopathy (DR) within retinal pigment epithelium (RPE) cells. Apigenin (AP), a potential dietary supplement for managing diabetes and its associated complications, has demonstrated inhibitory effects on EMT in various diseases. However, the specific impact and underlying mechanisms of AP on EMT in RPE cells remain poorly understood. In this study, we have successfully validated the inhibitory effects of AP on high glucose-induced EMT in ARPE-19 cells and diabetic db/db mice. Notably, our findings have identified CBP/p300 as a potential therapeutic target for EMT in RPE cells and have further substantiated that AP effectively downregulates the expression of EMT-related genes by attenuating the activity of CBP/p300, consequently reducing histone acetylation alterations within the promoter region of these genes. Taken together, our results provide novel evidence supporting the inhibitory effect of AP on EMT in RPE cells, and highlight the potential of specifically targeting CBP/p300 as a strategy for inhibiting retinal fibrosis in the context of DR.


Asunto(s)
Apigenina , Transición Epitelial-Mesenquimal , Glucosa , Histonas , Epitelio Pigmentado de la Retina , Transición Epitelial-Mesenquimal/efectos de los fármacos , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Animales , Apigenina/farmacología , Acetilación/efectos de los fármacos , Humanos , Glucosa/metabolismo , Glucosa/toxicidad , Histonas/metabolismo , Línea Celular , Ratones , Factores de Transcripción p300-CBP/metabolismo , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Ratones Endogámicos C57BL , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Retinopatía Diabética/tratamiento farmacológico , Proteína p300 Asociada a E1A/metabolismo , Masculino , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Proteína de Unión a CREB/metabolismo , Proteína de Unión a CREB/genética
20.
ACS Appl Mater Interfaces ; 16(22): 28771-28779, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38795117

RESUMEN

Blue perovskite light-emitting diodes (LEDs) have emerged as promising candidates for full-color display and lighting applications. However, the fabrication of blue-emitting perovskite films typically requires an inert environment, leading to increased complexity and cost in the manufacturing process, which is undesirable for applications of perovskite LEDs. Herein, we report a strategy to fabricate bright blue-emitting perovskite films in ambient air by incorporating phosphonic chlorides in a perovskite precursor solution. We used two different phosphonic chlorides, diphenylphosphonic chloride (DPPC) and phenylphosphonic dichloride (PPDC), and comparatively studied their effects on the properties of perovskite films and the blue LEDs. It is found that PPDC possesses a stronger chlorination ability due to higher hydrolysis reactivity; meanwhile, it has a stronger interaction with the perovskite compared to DPPC, resulting in an improved film quality and enhanced blue emission with a photoluminescence quantum yield of 45%, which represents the record value for the air-processed blue perovskite films. Blue perovskite LEDs are fabricated, and the emission wavelengths are effectively tuned by controlling the concentration of phosphonic chlorides. Benefiting from the optimized perovskite films with reduced nonradiative recombination and promoted charge injection and transport, the PPDC-derived blue perovskite LEDs exhibit improved performance with an external quantum efficiency of 3.3% and 1.2% for the 490 and 480 nm emission wavelength, respectively.

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