Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 393
Filtrar
1.
Genes Dev ; 33(17-18): 1252-1264, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31395740

RESUMO

Although MAX is regarded as an obligate dimerization partner for MYC, its function in normal development and neoplasia is poorly defined. We show that B-cell-specific deletion of Max has a modest effect on B-cell development but completely abrogates Eµ-Myc-driven lymphomagenesis. While Max loss affects only a few hundred genes in normal B cells, it leads to the global down-regulation of Myc-activated genes in premalignant Eµ-Myc cells. We show that the balance between MYC-MAX and MNT-MAX interactions in B cells shifts in premalignant B cells toward a MYC-driven transcriptional program. Moreover, we found that MAX loss leads to a significant reduction in MYC protein levels and down-regulation of direct transcriptional targets, including regulators of MYC stability. This phenomenon is also observed in multiple cell lines treated with MYC-MAX dimerization inhibitors. Our work uncovers a layer of Myc autoregulation critical for lymphomagenesis yet partly dispensable for normal development.


Assuntos
Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Carcinogênese/genética , Regulação Neoplásica da Expressão Gênica , Linfoma/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Deleção de Genes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/farmacologia , Cinurenina/genética , Cinurenina/metabolismo , Linfoma/fisiopatologia , Camundongos , Organoides/crescimento & desenvolvimento , Organoides/fisiopatologia , Oximas/farmacologia , Sulfonamidas/farmacologia
2.
Biochem Biophys Res Commun ; 692: 149360, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38081108

RESUMO

BACKGROUND: Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor ß1 (TGF-ß1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-ß1 in MFBs activation for fibrous reparation in mice with MI. METHODS: Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-ß1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. RESULT: Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-ß1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-ß1 and nuclear translocation of Smad2/3. CONCLUSION: This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-ß1, especially in immature scar area, which ultimately promotes fibrous scar maturation.


Assuntos
Infarto do Miocárdio , Miofibroblastos , Animais , Camundongos , Actinas/metabolismo , Cicatriz/metabolismo , Colágeno/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibrose , Integrina alfaV/metabolismo , Infarto do Miocárdio/patologia , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
3.
Cell Commun Signal ; 22(1): 245, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671456

RESUMO

BACKGROUND: The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. RESULTS: In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-ß1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. CONCLUSIONS: Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.


Assuntos
Bleomicina , Senescência Celular , Ritmo Circadiano , Fibrose Pulmonar , Animais , Humanos , Masculino , Camundongos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Ritmo Circadiano/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
4.
PLoS Biol ; 19(10): e3001085, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34669700

RESUMO

Male germ cell (GC) production is a metabolically driven and apoptosis-prone process. Here, we show that the glucose-sensing transcription factor (TF) MAX-Like protein X (MLX) and its binding partner MondoA are both required for male fertility in the mouse, as well as survival of human tumor cells derived from the male germ line. Loss of Mlx results in altered metabolism as well as activation of multiple stress pathways and GC apoptosis in the testes. This is concomitant with dysregulation of the expression of male-specific GC transcripts and proteins. Our genomic and functional analyses identify loci directly bound by MLX involved in these processes, including metabolic targets, obligate components of male-specific GC development, and apoptotic effectors. These in vivo and in vitro studies implicate MLX and other members of the proximal MYC network, such as MNT, in regulation of metabolism and differentiation, as well as in suppression of intrinsic and extrinsic death signaling pathways in both spermatogenesis and male germ cell tumors (MGCTs).


Assuntos
Apoptose , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Glucose/metabolismo , Espermatogênese , Estresse Fisiológico , Animais , Sequência de Bases , Sobrevivência Celular , Éxons/genética , Fertilidade , Deleção de Genes , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Marcação de Genes , Metabolismo dos Lipídeos , Masculino , Camundongos Knockout , Modelos Biológicos , Neoplasias Embrionárias de Células Germinativas/patologia , Análise de Componente Principal , RNA/genética , RNA/metabolismo , Proteínas Repressoras/metabolismo , Reprodução , Células de Sertoli/metabolismo , Espermatogênese/genética , Espermatozoides/metabolismo , Neoplasias Testiculares/patologia , Testículo/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Gênica
5.
Langmuir ; 40(4): 2369-2376, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38230676

RESUMO

Urinary tract infections (UTIs) have greatly affected human health in recent years. Accurate and rapid diagnosis of UTIs can enable a more effective treatment. Herein, we developed a multichannel sensor array for efficient identification of bacteria based on three antimicrobial agents (vancomycin, lysozyme, and bacitracin) functional gold nanoclusters (AuNCs). In this sensor, the fluorescence intensity of the three AuNCs was quenched to varying degrees by the bacterial species, providing a unique fingerprint for different bacteria. With this sensing platform, seven pathogenic bacteria, different concentrations of the same bacteria, and even bacterial mixtures were successfully differentiated. Furthermore, UTIs can be accurately identified with our sensors in ∼30 min with 100% classification accuracy. The proposed sensing systems offer a rapid, high-throughput, and reliable sensing platform for the diagnosis of UTIs.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Humanos , Ouro , Vancomicina , Bactérias , Espectrometria de Fluorescência
6.
Pharmacol Res ; 206: 107268, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908614

RESUMO

Heart failure (HF) has emerged as the most pressing health concerns globally, and extant clinical therapies are accompanied by side effects and patients have a high burden of financial. The protein products of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes have a variety of cardioprotective effects, including antioxidant, metabolic functions and anti-inflammatory. By evaluating established preclinical and clinical research in HF to date, we explored the potential of Nrf2 to exert unique cardioprotective functions as a novel therapeutic receptor for HF. In this review, we generalize the progression, structure, and function of Nrf2 research in the cardiovascular system. The mechanism of action of Nrf2 involved in HF as well as agonists of Nrf2 in natural compounds are summarized. Additionally, we discuss the challenges and implications for future clinical translation and application of pharmacology targeting Nrf2. It's critical to developing new drugs for HF.

7.
J Med Ethics ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527787

RESUMO

Respect for patient autonomy is paramount in resolving ethical tensions in end-of-life care. The concept of relational autonomy has contributed to this debate; however, scholars often use this concept in a fragmented manner. This leads to partial answers on ascertaining patients' true wishes, meaningfully engaging patients' significant others, balancing interests among patients and significant others, and determining clinicians' obligations to change patients' unconventional convictions to enhance patient autonomy. A satisfactory solution based on relational autonomy must incorporate patients' competence (apart from decisional capacity), authenticity (their true desires or beliefs) and the involvement level of their significant others. To that end, we argue that John Christman's procedural approach to relational autonomy provides critical insights, such as the diachronic or socio-historical personhood, sustained critical reflection and his recent explication of the nature of asymmetrical relationships and helpful interlocutors. This study reviews Christman's account, proposes minor modifications and advocates for an integrated three-dimensional model for medical decision-making. Clarifying the relationship among the three elements promotes an ethical framework with a coherent understanding of relational autonomy. This model not only provides a descriptive and normative framework for end-of-life care practice but also reconsiders the nature of the clinician-patient relationship and its normative implications. We further present a case study to illustrate the merits of our proposed model. Altogether, our proposal will help navigate complex medical decision-making, foster trust and negotiate shared values between patients and their significant others, particularly in end-of-life care.

8.
J Formos Med Assoc ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38570237

RESUMO

In the wake of the COVID-19 pandemic, the fluctuating nurse resignation rates highlighted an understudied area in healthcare: post-pandemic challenges in clinical settings. This study, conducted from May to November 2023, employed a qualitative inquiry using focus groups to delve into these challenges. Six focus group sessions, involving 33 nurse participants recruited through snowball sampling from various hospital settings were conducted to explore their clinical experiences during and after the pandemic. Thematic analysis revealed two primary themes: the 'Invisibility of Nurses' within the healthcare system and the 'Moral Duty of Nursing Practice'. These findings illuminate a tension between the overlooked role of nurses and their ethical obligations, underscoring a critical need for policy reassessment. The study advocates for systemic changes, particularly in the undervaluation of the nursing profession and the National Health Insurance system, to address the poor working environment and mitigate long-term nursing shortages. This research deepens understanding of post-pandemic nursing workforce challenges in Taiwan, highlighting the need for policy evolution to enhance recognition and support for the nursing industry. It is suggested to provide tangible compensation to acknowledge nurses' daily care and health education for patients. A healthier working environment can be enhanced by collaborative efforts between healthcare institutions and nurses.

9.
Chem Soc Rev ; 52(13): 4132-4148, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37314457

RESUMO

As an economical solar energy conversion technology, organic photovoltaics (OPVs) are regarded as a promising solution to environmental problems and energy challenges. With the highest efficiency of OPVs exceeding 20%, the research focus will shift from efficiency-oriented aspects to commercialization-oriented aspects in the near future. Semi-transparent OPVs (STOPVs) are one of the most possible commercialized forms of OPVs, and have achieved power conversion efficiency over 14% with average visible light transmittance over 20% so far. In this tutorial review, we first systematically summarize the device structures, operating principles and evaluation parameters of STOPVs, and compare them with those of opaque OPVs. Then, strategies to construct high-performance STOPVs by cooperatively optimizing materials and devices are proposed. Methods to realize the scale-up of STOPVs in terms of minimization of electrode and interconnect resistance are summarized. The potential applications of STOPVs in multifunctional windows, agrivoltaics and floating photovoltaics are also discussed. Finally, this review highlights major challenges and research directions that need to be addressed prior to the future commercialization of STOPVs.

10.
Genes Dev ; 30(23): 2637-2648, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28007786

RESUMO

Myc plays critical roles in the self-renewal division of various stem cell types. In spermatogonial stem cells (SSCs), Myc controls SSC fate decisions because Myc overexpression induces enhanced self-renewal division, while depletion of Max, a Myc-binding partner, leads to meiotic induction. However, the mechanism by which Myc acts on SSC fate is unclear. Here we demonstrate a critical link between Myc/Mycn gene activity and glycolysis in SSC self-renewal. In SSCs, Myc/Mycn are regulated by Foxo1, whose deficiency impairs SSC self-renewal. Myc/Mycn-deficient SSCs not only undergo limited self-renewal division but also display diminished glycolytic activity. While inhibition of glycolysis decreased SSC activity, chemical stimulation of glycolysis or transfection of active Akt1 or Pdpk1 (phosphoinositide-dependent protein kinase 1 ) augmented self-renewal division, and long-term SSC cultures were derived from a nonpermissive strain that showed limited self-renewal division. These results suggested that Myc-mediated glycolysis is an important factor that increases the frequency of SSC self-renewal division.


Assuntos
Autorrenovação Celular/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Glicólise/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Espermatogônias/citologia , Células-Tronco/metabolismo , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Animais , Divisão Celular/genética , Proliferação de Células/genética , Técnicas de Inativação de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Proto-Oncogênica N-Myc/genética , Proteínas Proto-Oncogênicas c-myc/genética , Fatores de Processamento de RNA/metabolismo , Células-Tronco/enzimologia
11.
Genes Dev ; 30(11): 1289-99, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27298335

RESUMO

Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma. MYCL (L-Myc) is frequently amplified in human SCLC, but its roles in SCLC progression are poorly understood. We isolated preneoplastic neuroendocrine cells from a mouse model of SCLC and found that ectopic expression of L-Myc, c-Myc, or N-Myc conferred tumor-forming capacity. We focused on L-Myc, which promoted pre-rRNA synthesis and transcriptional programs associated with ribosomal biogenesis. Deletion of Mycl in two genetically engineered models of SCLC resulted in strong suppression of SCLC. The high degree of suppression suggested that L-Myc may constitute a therapeutic target for a broad subset of SCLC. We then used an RNA polymerase I inhibitor to target rRNA synthesis in an autochthonous Rb/p53-deleted mouse SCLC model and found significant tumor inhibition. These data reveal that activation of RNA polymerase I by L-Myc and other MYC family proteins provides an axis of vulnerability for this recalcitrant cancer.


Assuntos
Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Polimerase I/metabolismo , Carcinoma de Pequenas Células do Pulmão/enzimologia , Carcinoma de Pequenas Células do Pulmão/genética , Animais , Animais Geneticamente Modificados , Benzotiazóis/farmacologia , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inativação Gênica , Neoplasias Pulmonares/fisiopatologia , Camundongos , Naftiridinas/farmacologia , Proteínas Proto-Oncogênicas c-myc/genética , RNA Polimerase I/antagonistas & inibidores , Ribossomos/metabolismo , Carcinoma de Pequenas Células do Pulmão/fisiopatologia , Carga Tumoral/efeitos dos fármacos , Células Tumorais Cultivadas
12.
Molecules ; 29(6)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38542969

RESUMO

Although much promising synthetic progress in conjugated polymer-based organic solar cells (OSCs) has resulted in significant improvement in power conversion efficiencies (PCEs) of from over 15 to >19.0% in the last five years, the sophisticated and complex reactions from at least two families' monomers with remarkably different electron push-pull effects could still pose an unavoidable material burden for the commercialization of OSCs in the coming future. Therefore, the method of preparing a homopolymer from a sole monomer would significantly reduce the synthetic steps and costs in order to pave the way for the large-scale production of OSC materials. Therefore, alkylthio-thiophenyl-substituted benzo[1,2-b;4,5-b']dithiophene (BDTTS) as the sole and key structural moiety with dihalogen and distannyl functional groups was designed and synthesized, respectively, in this study, for facile monomer syntheses and polymerizations to achieve three wide-bandgap homopolymer donors of BDTTS-alt-BDTT-Cl (P13), BDTTS-alt-BDTT (P15), and BDTTS (P14), respectively. The structural symmetry dependency on their physical, electrochemical, and optical properties, thin-film morphologies, and photovoltaic (PV) performance was investigated in detail. As a result, OSCs based on the asymmetric polymer P15, paired with BTP-eC9 as the electron acceptor, presented the best PV performance, with a PCE of 11.5%, a fill factor (FF) of 65.87%, and a short-circuit current (JSC) of 22.04 mA·cm-2, respectively. This PCE value is among the highest ones reported for BDT-type homopolymer donor-based OPVs, providing us with knowledge for obtaining promising PV performance from devices made of P15-like materials.

13.
Hu Li Za Zhi ; 71(2): 26-33, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38532672

RESUMO

As populations age, average life expectancy increases and the complexity of diseases rises, leading to nursing care and healthcare systems facing severe challenges related to inadequate resources. Artificial intelligence (AI), including elements such as investigation, integration, learning, prediction, and decision-making, holds significant potential for application in clinical care not only to enhance care quality but also to help guide the future direction of healthcare. AI applications are already being increasingly utilized to improve the quality of clinical care and to streamline workflows. However, because nursing education has lagged behind in terms of adopting AI, greater attention must be given to training up nursing students with AI-related knowledge and application skills. AI technologies should be integrated into nursing curricula and clinical internships to adapt to the rapidly changing high-tech healthcare environment, enabling the more-effective use of AI technology in providing high-quality and safe nursing care.


Assuntos
Inteligência Artificial , Educação em Enfermagem , Humanos , Aprendizagem , Currículo , Conhecimento
14.
J Am Chem Soc ; 145(34): 18931-18938, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37590883

RESUMO

Interfacial charge transfer on the surface of heterogeneous photocatalysts dictates the efficiency of reactive oxygen species (ROS) generation and therefore the efficiency of aerobic oxidation reactions. Reticular chemistry in metal-organic frameworks (MOFs) allows for the rational design of donor-acceptor pairs to optimize interfacial charge-transfer kinetics. Herein, we report a series of isostructural fcu-topology Ni8-MOFs (termed JNU-212, JNU-213, JNU-214, and JNU-215) with linearly bridged bipyrazoles as organic linkers. These crystalline Ni8-MOFs can maintain their structural integrity in 7 M NaOH at 100 °C for 24 h. Experimental studies reveal that linker engineering by tuning the electron-accepting capacity of the pyrazole-bridging units renders these Ni8-MOFs with significantly improved charge separation and transfer efficiency under visible-light irradiation. Among them, the one containing a benzoselenadiazole unit (JNU-214) exhibits the best photocatalytic performance in the aerobic oxidation of benzylamines with a conversion rate of 99% in 24 h. Recycling experiments were carried out to confirm the stability and reusability of JNU-214 as a robust heterogeneous catalyst. Significantly, the systematic modulation of the electron-accepting capacity of the bridging units in donor-acceptor-donor MOFs provides a new pathway to develop viable noble-metal-free heterogeneous photocatalysts for aerobic oxidation reactions.

15.
J Am Chem Soc ; 145(40): 22176-22183, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37779382

RESUMO

Single crystals with chiral shapes aroused the interest of chemists due to their fascinating polarization rotation properties. Although the formation of large-scale spiral structures is considered to be a potential factor in chiral crystals, the precise mechanism behind their formation remains elusive. Herein, we present a rare phenomenon involving the multitransfer and expression of chirality at micro-, meso-, and macroscopic levels, starting from chiral carbon atoms and extending to the double-helical secondary structure, ultimately resulting in the chiral geometry of crystals. The assembly of the chiral double helices is facilitated by the dual characteristics of amide groups derived from amino acids, which serve as both hydrogen bond donors and receptors, similar to the assembly pattern observed in DNA. Crystal face analysis and theoretical morphology reveal two critical factors for the mechanism of the chiral crystal: inherent intrinsically symmetrical distribution of crystal faces and their acquired growth. Importantly, the magnetic circular dichroism (MCD) study reveals the strong magneto-optical response of the hypersensitive f-f transition in the UV-vis-NIR region, which is much stronger than previously observed signals. Remarkably, an external magnetic field can reverse the CD signal. This research highlights the potential of lanthanide-based chiral helical structures as promising magneto-optical materials.

16.
Small ; 19(12): e2206461, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36587969

RESUMO

Structurally-colored photonic hydrogels which are fabricated by introducing hydrogels into thin films or photonic crystal structures are promising candidates for biosensing. Generally, the design of photonic hydrogel biosensors is based on the sensor-analyte interactions induced charge variation within the hydrogel matrix, or chemically grafting binding sites onto the polymer chains, to achieve significant volume change and color variation of the photonic hydrogel. However, relatively low anti-interference capability or complicated synthesis hinder the facile and low-cost fabrication of high-performance photonic hydrogel biosensors. Here, a facilely prepared supramolecular photonic hydrogel biosensor is developed for high-sensitivity detection of alkaline phosphatase (ALP), which is an extensively considered clinical biomarker for a variety of diseases. Responding to ALP results in the broken supramolecular crosslinking and thus increased lattice distancing of the photonic hydrogel driven by synergistic repulsive force between nanoparticles embedded in photonic crystal structure and osmotic swelling pressure. The biosensor shows sensitivity of 7.3 nm spectral shift per mU mL-1 ALP, with detection limit of 0.52 mU mL-1 . High-accuracy colorimetric detection can be realized via a smartphone, promoting point-of-care sensing and timely diagnosis of related pathological conditions.


Assuntos
Técnicas Biossensoriais , Hidrogéis , Hidrogéis/química , Fosfatase Alcalina , Polímeros/química , Pressão Osmótica , Técnicas Biossensoriais/métodos
17.
J Biomed Sci ; 30(1): 96, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110940

RESUMO

BACKGROUND: Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections. METHODS: In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant. RESULTS: The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them. CONCLUSIONS: These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections.


Assuntos
Enterovirus Humano A , Enterovirus Humano D , Infecções por Enterovirus , Enterovirus , Reishi , Criança , Animais , Humanos , Camundongos , Enterovirus Humano D/genética , Enterovirus Humano A/genética , Vacinas Combinadas , Antígenos Virais , Imunoglobulina A , Imunoglobulina G
18.
Cell Commun Signal ; 21(1): 39, 2023 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-36803515

RESUMO

BACKGROUND: Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. RESULTS: In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. CONCLUSIONS: Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Video Abstract.


Assuntos
Fatores de Transcrição ARNTL , Asma , Animais , Camundongos , Remodelação das Vias Aéreas , Fatores de Transcrição ARNTL/metabolismo , Asma/metabolismo , Autofagia , Células Epiteliais/metabolismo , Material Particulado/toxicidade , Material Particulado/metabolismo , Proteína Supressora de Tumor p53/metabolismo
19.
Inorg Chem ; 62(49): 20202-20208, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37993990

RESUMO

Single-emission luminescence sensors are less than satisfactory for complex systems due to their susceptibility to environmental disturbances. Lanthanum-based metal-organic frameworks (Ln-MOFs) with highly stable ratiometric dual-emission are regarded as promising luminescence probes owing to their fascinating ligand-to-metal energy transfer behaviors (also known as the antenna effect). Herein, we report the synthesis of a pair of isostructural europium-based MOFs (termed JNU-219 and JNU-220) by utilizing two X-shaped tetracarboxylate linkers, 4,4',4″,4‴-benzene-2,3,5,6-tetrayl-tetrabenzoate (BTEB) and 4,4',4″,4‴-pyrazine-2,3,5,6-tetrayl-tetrabenzoate (BTTB). Both JNU-219 and JNU-220 present the characteristic red luminescence of Eu3+, yet the pyrazine functionalization of the BTTB linker renders JNU-220 with significantly increased luminescence emission, almost 30 times that of JNU-219. As a result, the detection limit of JNU-220 for the ratiometric luminescence sensing of PO43- was determined to be as low as 0.22 µM, which is far superior to those of other reported MOF materials. Additionally, we demonstrate the excellent stability and reusability of JNU-220, further verifying its potential as a robust ratiometric luminescence probe.

20.
Phys Chem Chem Phys ; 25(4): 2916-2925, 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36637076

RESUMO

Being fluorine-free and a high performance material as a small organic acceptor molecule, BTP-eC9 has been well mixed with BDT-based PM6 donor polymers for providing satisfactory photovoltaic properties, especially towards future large scale/large area solar cell production. However, as one of the key electrical outputs from such binary active layer materials, the open circuit voltage (VOC) was limited to ca. 0.84 V, which needs to be further improved for BTP-eC9 to have a bright future. This paper focuses on the molecular design of alkylthio- and alkoxy-phenyl flanked benzo[1,2-b:4,5-b']dithiophene-based conjugated polymers (PBDT-PS-ttTPD or P10 for short and PBDT-PO-ttTPD or P11), which were successfully synthesized and applied as donor materials for pairing with BTP-eC9 in organic photovoltaic (OPV) devices. By fine-tuning the side chains of the benzodithiophene (BDT) moiety, such non-fullerene OPV devices with normal configuration demonstrate an attractively high open circuit voltage (VOC) of 0.89 and 0.87 V in P10/BTP-eC9 and P11/BTP-eC9 based binary single bulk heterojunction OPV devices, while still maintaining an excellent JSC of 22.7 and 20.0 mA cm-2 with a final power conversion efficiency (PCE) of 12.93% and 9.37%, respectively. The alkylthio-phenyl chain substituted BDT polymer exhibits better photovoltaic performance in all aspects than the alternative with alkoxy chains due to the synergistic effect of the alkylthio-phenyl flanked BDT, TPD, and π-bridge (thieno[3,2-b]thiophene).

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA