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1.
Cell ; 184(22): 5559-5576.e19, 2021 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-34678143

RESUMEN

Glucose consumption is generally increased in tumor cells to support tumor growth. Interestingly, we report that glycogen accumulation is a key initiating oncogenic event during liver malignant transformation. We found that glucose-6-phosphatase (G6PC) catalyzing the last step of glycogenolysis is frequently downregulated to augment glucose storage in pre-malignant cells. Accumulated glycogen undergoes liquid-liquid phase separation, which results in the assembly of the Laforin-Mst1/2 complex and consequently sequesters Hippo kinases Mst1/2 in glycogen liquid droplets to relieve their inhibition on Yap. Moreover, G6PC or another glycogenolysis enzyme-liver glycogen phosphorylase (PYGL) deficiency in both human and mice results in glycogen storage disease along with liver enlargement and tumorigenesis in a Yap-dependent manner. Consistently, elimination of glycogen accumulation abrogates liver growth and cancer incidence, whereas increasing glycogen storage accelerates tumorigenesis. Thus, we concluded that cancer-initiating cells adapt a glycogen storing mode, which blocks Hippo signaling through glycogen phase separation to augment tumor incidence.


Asunto(s)
Carcinogénesis/metabolismo , Carcinogénesis/patología , Glucógeno/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Línea Celular , Modelos Animales de Enfermedad , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Glucosa-6-Fosfatasa/metabolismo , Glucógeno Fosforilasa/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Vía de Señalización Hippo , Humanos , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/genética , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Estadificación de Neoplasias , Transición de Fase , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Proteínas Tirosina Fosfatasas no Receptoras/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Serina-Treonina Quinasa 3/metabolismo , Proteínas Señalizadoras YAP/metabolismo
2.
Cell ; 166(1): 102-14, 2016 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-27293192

RESUMEN

Co-option of RAG1 and RAG2 for antigen receptor gene assembly by V(D)J recombination was a crucial event in the evolution of jawed vertebrate adaptive immunity. RAG1/2 are proposed to have arisen from a transposable element, but definitive evidence for this is lacking. Here, we report the discovery of ProtoRAG, a DNA transposon family from lancelets, the most basal extant chordates. A typical ProtoRAG is flanked by 5-bp target site duplications and a pair of terminal inverted repeats (TIRs) resembling V(D)J recombination signal sequences. Between the TIRs reside tail-to-tail-oriented, intron-containing RAG1-like and RAG2-like genes. We demonstrate that ProtoRAG was recently active in the lancelet germline and that the lancelet RAG1/2-like proteins can mediate TIR-dependent transposon excision, host DNA recombination, transposition, and low-efficiency TIR rejoining using reaction mechanisms similar to those used by vertebrate RAGs. We propose that ProtoRAG represents a molecular "living fossil" of the long-sought RAG transposon.


Asunto(s)
Elementos Transponibles de ADN , Evolución Molecular , Anfioxos/genética , Recombinación V(D)J , Animales , Proteínas de Unión al ADN , Proteínas de Homeodominio , Secuencias Repetidas Terminales
3.
Nature ; 618(7967): 921-927, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37380691

RESUMEN

Spin-triplet topological superconductors should exhibit many unprecedented electronic properties, including fractionalized electronic states relevant to quantum information processing. Although UTe2 may embody such bulk topological superconductivity1-11, its superconductive order parameter Δ(k) remains unknown12. Many diverse forms for Δ(k) are physically possible12 in such heavy fermion materials13. Moreover, intertwined14,15 density waves of spin (SDW), charge (CDW) and pair (PDW) may interpose, with the latter exhibiting spatially modulating14,15 superconductive order parameter Δ(r), electron-pair density16-19 and pairing energy gap17,20-23. Hence, the newly discovered CDW state24 in UTe2 motivates the prospect that a PDW state may exist in this material24,25. To search for it, we visualize the pairing energy gap with µeV-scale energy resolution using superconductive scanning tunnelling microscopy (STM) tips26-31. We detect three PDWs, each with peak-to-peak gap modulations of around 10 µeV and at incommensurate wavevectors Pi=1,2,3 that are indistinguishable from the wavevectors Qi=1,2,3 of the prevenient24 CDW. Concurrent visualization of the UTe2 superconductive PDWs and the non-superconductive CDWs shows that every Pi:Qi pair exhibits a relative spatial phase δϕ ≈ π. From these observations, and given UTe2 as a spin-triplet superconductor12, this PDW state should be a spin-triplet PDW24,25. Although such states do exist32 in superfluid 3He, for superconductors, they are unprecedented.

4.
Immunity ; 49(2): 264-274.e4, 2018 08 21.
Artículo en Inglés | MEDLINE | ID: mdl-30076099

RESUMEN

Follicular T helper (Tfh) cells highly express the programmed cell death-1 (PD-1) molecule. Whereas inhibition of T cell receptor (TCR) signaling and CD28 co-stimulation is thought to be the primary mode of PD-1 functions, whether and how PD-1 regulates Tfh cell development and function is unclear. Here we showed that, when engaged by the ensemble of bystander B cells constitutively expressing PD-1 ligand 1 (PD-L1), PD-1 inhibited T cell recruitment into the follicle. This inhibition involved suppression of PI3K activities downstream of the follicle-guidance receptor CXCR5, was independent of co-signaling with the TCR, and necessitated ICOS signaling to overcome. PD-1 further restricted CXCR3 upregulation on Tfh cells, serving to concentrate these cells toward the germinal center territory, where PD-L1-PD-1 interactions between individual Tfh and B cells optimized B cell competition and affinity maturation. Therefore, operating in both costimulation-independent and -dependent manners, PD-1 controls tissue positioning and function of Tfh cells.


Asunto(s)
Antígeno B7-H1/metabolismo , Centro Germinal/citología , Fosfatidilinositol 3-Quinasas/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Linfocitos T Colaboradores-Inductores/citología , Animales , Linfocitos B/inmunología , Diferenciación Celular/inmunología , Línea Celular , Movimiento Celular/inmunología , Femenino , Centro Germinal/inmunología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores CXCR3/genética , Receptores CXCR5/genética , Linfocitos T Colaboradores-Inductores/inmunología
5.
Nature ; 567(7749): 525-529, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30814730

RESUMEN

T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular mechanisms that underlie this dysfunction remain unclear. Here, using an in vitro T cell tolerance induction system in mice, we characterize genome-wide epigenetic and gene expression features in tolerant T cells, and show that they are distinct from effector and regulatory T cells. Notably, the transcription factor NR4A1 is stably expressed at high levels in tolerant T cells. Overexpression of NR4A1 inhibits effector T cell differentiation, whereas deletion of NR4A1 overcomes T cell tolerance and exaggerates effector function, as well as enhancing immunity against tumour and chronic virus. Mechanistically, NR4A1 is preferentially recruited to binding sites of the transcription factor AP-1, where it represses effector-gene expression by inhibiting AP-1 function. NR4A1 binding also promotes acetylation of histone 3 at lysine 27 (H3K27ac), leading to activation of tolerance-related genes. This study thus identifies NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumour immunotherapy.


Asunto(s)
Regulación de la Expresión Génica/genética , Genoma , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Linfocitos T/metabolismo , Linfocitos T/patología , Acetilación , Animales , Infecciones por Arenaviridae/inmunología , Infecciones por Arenaviridae/virología , Línea Celular Tumoral , Colitis/inmunología , Colitis/patología , Colitis/terapia , Epigénesis Genética , Femenino , Histonas/química , Histonas/metabolismo , Tolerancia Inmunológica/genética , Inmunoterapia , Virus de la Coriomeningitis Linfocítica/inmunología , Ratones , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/terapia , Linfocitos T/inmunología , Factor de Transcripción AP-1/metabolismo , Transcripción Genética
6.
Proc Natl Acad Sci U S A ; 119(37): e2207449119, 2022 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-36067325

RESUMEN

The elementary CuO2 plane sustaining cuprate high-temperature superconductivity occurs typically at the base of a periodic array of edge-sharing CuO5 pyramids. Virtual transitions of electrons between adjacent planar Cu and O atoms, occurring at a rate t/ℏ and across the charge-transfer energy gap [Formula: see text], generate "superexchange" spin-spin interactions of energy [Formula: see text] in an antiferromagnetic correlated-insulator state. However, hole doping this CuO2 plane converts this into a very-high-temperature superconducting state whose electron pairing is exceptional. A leading proposal for the mechanism of this intense electron pairing is that, while hole doping destroys magnetic order, it preserves pair-forming superexchange interactions governed by the charge-transfer energy scale [Formula: see text]. To explore this hypothesis directly at atomic scale, we combine single-electron and electron-pair (Josephson) scanning tunneling microscopy to visualize the interplay of [Formula: see text] and the electron-pair density nP in Bi2Sr2CaCu2O8+x. The responses of both [Formula: see text] and nP to alterations in the distance δ between planar Cu and apical O atoms are then determined. These data reveal the empirical crux of strongly correlated superconductivity in CuO2, the response of the electron-pair condensate to varying the charge-transfer energy. Concurrence of predictions from strong-correlation theory for hole-doped charge-transfer insulators with these observations indicates that charge-transfer superexchange is the electron-pairing mechanism of superconductive Bi2Sr2CaCu2O8+x.

7.
PLoS Genet ; 18(5): e1010222, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35604931

RESUMEN

Insertion of new material into the Escherichia coli peptidoglycan (PG) sacculus between the cytoplasmic membrane and the outer membrane requires a well-organized balance between synthetic and hydrolytic activities to maintain cell shape and avoid lysis. Since most bacteria carry multiple enzymes carrying the same type of PG hydrolytic activity, we know little about the specific function of given enzymes. Here we show that the DD-carboxy/endopeptidase PBP4 localizes in a PBP1A/LpoA and FtsEX dependent fashion at midcell during septal PG synthesis. Midcell localization of PBP4 requires its non-catalytic domain 3 of unknown function, but not the activity of PBP4 or FtsE. Microscale thermophoresis with isolated proteins shows that PBP4 interacts with NlpI and the FtsEX-interacting protein EnvC, an activator of amidases AmiA and AmiB, which are needed to generate denuded glycan strands to recruit the initiator of septal PG synthesis, FtsN. The domain 3 of PBP4 is needed for the interaction with NlpI and EnvC, but not PBP1A or LpoA. In vivo crosslinking experiments confirm the interaction of PBP4 with PBP1A and LpoA. We propose that the interaction of PBP4 with EnvC, whilst not absolutely necessary for mid-cell recruitment of either protein, coordinates the activities of PBP4 and the amidases, which affects the formation of denuded glycan strands that attract FtsN. Consistent with this model, we found that the divisome assembly at midcell was premature in cells lacking PBP4, illustrating how the complexity of interactions affect the timing of cell division initiation.


Asunto(s)
Proteínas de Escherichia coli , Escherichia coli , Transportadoras de Casetes de Unión a ATP/metabolismo , Amidohidrolasas/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Endopeptidasas , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Lipoproteínas/metabolismo , N-Acetil Muramoil-L-Alanina Amidasa/metabolismo , Peptidoglicano/metabolismo
8.
Nano Lett ; 24(22): 6658-6664, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38770882

RESUMEN

Synthetic quantum systems provide a pathway for exploring the physics of complex quantum matter in a programmable fashion. This approach becomes particularly advantageous when it comes to systems that are thermodynamically unfavorable. By sculpting the potential landscape of Cu(111) surfaces with carbon monoxide quantum corrals in a cryogenic scanning tunneling microscope, we created analogue simulators of planar organic molecules, including antiaromatic and non-Kekulé species that are generally reactive or unstable. Spectroscopic imaging of such synthetic molecules reveals close replications of molecular orbitals obtained from ab initio calculations of the organic molecules. We further illustrate the quantitative nature of such analogue simulators by faithful extraction of bond orders and global aromaticity indices, which are otherwise technically daunting using real molecules. Our approach therefore sets the stage for new research frontiers pertaining to the quantum physics and chemistry of designer nanostructures.

9.
J Proteome Res ; 23(3): 1062-1074, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38373391

RESUMEN

Hepatocellular carcinoma (HCC) is susceptible to early recurrence, but it lacks effective predictive biomarkers. In this study, we retrospectively selected 179 individuals as a discovery cohort (126 HCC patients and 53 liver cirrhosis (LC) patients) for screening candidate serum biomarkers of early recurrence based on data independent acquisition-mass spectrometry strategy. And then, the candidate biomarkers were validated in an additional independent cohort with 192 individuals (142 HCC patients and 50 LC patients) using parallel reaction monitoring targeted quantitative techniques (PXD047852). Eventually, we validated that gelsolin (GSN) concentrations were significantly lower in HCC than in LC (p < 0.0001), patients with low GSN concentrations had a poor prognosis (p < 0.0001), and GSN concentrations were significantly lower in early recurrence HCC than in late recurrence HCC (p < 0.0001). These trends were also observed in alpha-fetoprotein (AFP)-negative HCC patients. The area under the curve of machine-learning-based predictive model (GSN and microvascular invasion) for predicting early recurrence risk reached 0.803 (95% confidence interval (CI): 0.786-0.820) and maintained the same efficacy in AFP-negative patients. In conclusion, GSN is a novel serum biomarker for early recurrence of HCC. The model could provide timely warning to HCC patients at high risk of recurrence.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Gelsolina , Carcinoma Hepatocelular/diagnóstico , alfa-Fetoproteínas , Proteómica , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico , Biomarcadores , Cirrosis Hepática/diagnóstico
10.
J Am Chem Soc ; 146(14): 9851-9859, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38530323

RESUMEN

The formation of oil-in-water Pickering emulsions stabilized by lamellar zeolite MWW (International Zeolite Association, three-letters code) emulsifier without surface grafting is investigated. The crucial emulsification factors are the oligolayer morphology and amphiphilicity developed upon acidic treatment (NH4+ exchange/calcination, HNO3 treatment). In contrast with the readily available/abundant hydrophilic ≡Si-OH group in layer MWW, the lipophilicity generated by strong acid sites is another key to the success of emulsification. Hydrocarbon-strong acid site interaction is long known in petrochemistry and superacid research. However, to the best of our knowledge, this interaction was first introduced to gain lipophilicity in emulsion formation. Finally, the Pd-loaded acidic form of the MWW zeolite successfully stabilized the toluene/H2O emulsion system. The biphasic interfacial nitroarene hydrogenation demonstrated excellent catalytic performance. Overall, this work provided not only a new kind of intrinsic solid to emulsify the organic-aqueous biphase system but also a new mechanism to generate lipophilicity. Both are important for the applications and designs of Pickering emulsion materials.

11.
J Am Chem Soc ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990700

RESUMEN

Dynamically populating triplet excitons under external stimuli is desired to develop smart optoelectronic materials, but it remains a formidable challenge. Herein, we report a resonance-induced excited state regulation strategy to dynamically modulate the triplet exciton population by introducing a self-adaptive N-C═O structure to phosphors. The developed phosphors activated under high-power ultraviolet irradiation exhibited enhanced photoactivated organic ultralong room temperature phosphorescence (PA-OURTP) with lifetimes of up to ∼500 ms. The enhanced PA-OURTP was ascribed to activated N-C═O resonance variation-induced intersystem crossing to generate excess triplet excitons. The excellent PA-OURTP performance and ultralong deactivation time under ambient conditions of the developed materials could function as a reusable recorded medium for time-sensitive information encryption through optical printing. This study provides an effective approach to dynamically regulating triplet excitons and offers valuable guidance to develop high-performance PA-OURTP materials for security printing applications.

12.
J Am Chem Soc ; 146(23): 16039-16051, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38832517

RESUMEN

Efficient methane photooxidation to formic acid (HCOOH) has emerged as a sustainable approach to simultaneously generate value-added chemicals and harness renewable energy. However, the persistent challenge lies in achieving a high yield and selectivity for HCOOH formation, primarily due to the complexities associated with modulating intermediate conversion and desorption after methane activation. In this study, we employ first-principles calculations as a comprehensive guiding tool and discover that by precisely controlling the O2 activation process on noble metal cocatalysts and the adsorption strength of carbon-containing intermediates on metal oxide supports, one can finely tune the selectivity of methane photooxidation products. Specifically, a bifunctional catalyst comprising Pd nanoparticles and monoclinic WO3 (Pd/WO3) would possess optimal O2 activation kinetics and an intermediate oxidation/desorption barrier, thereby promoting HCOOH formation. As evidenced by experiments, the Pd/WO3 catalyst achieves an exceptional HCOOH yield of 4.67 mmol gcat-1 h-1 with a high selectivity of 62% under full-spectrum light irradiation at room temperature using molecular O2. Notably, these results significantly outperform the state-of-the-art photocatalytic systems operated under identical condition.

13.
Rep Prog Phys ; 87(4)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38373354

RESUMEN

Use and performance criteria of photonic devices increase in various application areas such as information and communication, lighting, and photovoltaics. In many current and future photonic devices, surfaces of a semiconductor crystal are a weak part causing significant photo-electric losses and malfunctions in applications. These surface challenges, many of which arise from material defects at semiconductor surfaces, include signal attenuation in waveguides, light absorption in light emitting diodes, non-radiative recombination of carriers in solar cells, leakage (dark) current of photodiodes, and light reflection at solar cell interfaces for instance. To reduce harmful surface effects, the optical and electrical passivation of devices has been developed for several decades, especially with the methods of semiconductor technology. Because atomic scale control and knowledge of surface-related phenomena have become relevant to increase the performance of different devices, it might be useful to enhance the bridging of surface physics to photonics. Toward that target, we review some evolving research subjects with open questions and possible solutions, which hopefully provide example connecting points between photonic device passivation and surface physics. One question is related to the properties of the wet chemically cleaned semiconductor surfaces which are typically utilized in device manufacturing processes, but which appear to be different from crystalline surfaces studied in ultrahigh vacuum by physicists. In devices, a defective semiconductor surface often lies at an embedded interface formed by a thin metal or insulator film grown on the semiconductor crystal, which makes the measurements of its atomic and electronic structures difficult. To understand these interface properties, it is essential to combine quantum mechanical simulation methods. This review also covers metal-semiconductor interfaces which are included in most photonic devices to transmit electric carriers to the semiconductor structure. Low-resistive and passivated contacts with an ultrathin tunneling barrier are an emergent solution to control electrical losses in photonic devices.

14.
Anal Chem ; 96(21): 8740-8746, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38722256

RESUMEN

Pressure and temperature, as common physical parameters, are important for monitoring human health. In contrast, single-mode monitoring is prone to causing experimental errors. Herein, we innovatively designed a dual-mode flexible sensing platform based on a platinum/zinc-meso-tetrakis(4-carboxyphenyl)porphyrin (Pt/Zn-TCPP) nanozyme for the quantitative monitoring of carcinoembryonic antigen (CEA) in biological fluids with pressure and temperature readouts. The Pt/Zn-TCPP nanozyme with catalytic and photothermal efficiencies was synthesized by means of integrating photosensitizers into porous materials. The flexible sensing system after the antigen-antibody reaction recognized the pressure using a flexible skin-like pressure sensor with a digital multimeter readout, whereas the temperature was acquired via the photoheat conversion system of the Pt/Zn-TCPP nanozyme under 808 nm near-infrared (NIR) irradiation using a portable NIR imaging camera on a smartphone. Meanwhile, the dual-mode flexible sensing system was carried out on a homemade three-dimensional (3D)-printed device. Results revealed that the developed dual-mode immunosensing platform could exhibit good pressure and temperature responses within the dynamic range of 0.5-100 ng mL-1 CEA with the detection limits of 0.24 and 0.13 ng mL-1, respectively. In addition, the pressure and temperature were sensed simultaneously without crosstalk interference. Importantly, the dual-mode flexible immunosensing system can effectively avoid false alarms during the measurement, thus providing great potential for simple and low-cost development for point-of-care testing.


Asunto(s)
Antígeno Carcinoembrionario , Platino (Metal) , Presión , Temperatura , Zinc , Platino (Metal)/química , Inmunoensayo/métodos , Zinc/química , Antígeno Carcinoembrionario/análisis , Humanos , Porfirinas/química , Nanoestructuras/química , Límite de Detección
15.
Anal Chem ; 96(28): 11463-11471, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-38962829

RESUMEN

In this work, we reported a cholesterol oxidase (Chox)-loaded platinum (Pt) nanozyme with the collaborative cascade nanoreactor for the construction of nanozyme-enzyme-linked immunosorbent assay (N-ELSA) models to realize high-throughput rapid evaluation of cancer markers. Considering the high specific surface area and manipulable surface sites, ZIF-8 was used as a substrate for natural enzyme and nanozyme loading. The constructed ZIF-8-Pt nanozyme platform exhibited efficient enzyme-like catalytic efficiency with a standard corrected activity of 60.59 U mg-1, which was 12 times higher than that of the ZIF-8 precursor, and highly efficient photothermal conversion efficiency (∼35.49%). In N-ELISA testing, developed multienzyme photothermal probes were immobilized in microplates based on antigen-antibody-specific reactions. Cholesterol was reacted in a cascade to reactive oxygen radicals, which attacked 3,3',5,5'-tetramethylbenzidine, causing it to oxidize and color change, thus exhibiting highly enhanced efficient photothermal properties. Systematic temperature evaluations were performed by a hand-held microelectromechanical system thermal imager under the excitation of an 808 nm surface light source to determine the cancer antigen 15-3 (CA15-3) profiles in the samples. Encouragingly, the temperature signal from the microwells increased with increasing CA15-3, with a linear range of 2 mU mL-1 to 100 U mL-1, considering it to be the sensor with the widest working range for visualization and portability available. This work provides new horizons for the development of efficient multienzyme portable colorimetric-photothermal platforms to help advance the community-based process of early cancer detection.


Asunto(s)
Colesterol Oxidasa , Platino (Metal) , Humanos , Platino (Metal)/química , Colesterol Oxidasa/química , Colesterol Oxidasa/metabolismo , Ensayo de Inmunoadsorción Enzimática , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Bencidinas/química , Colesterol/química , Colesterol/metabolismo , Colesterol/análisis , Ensayos Analíticos de Alto Rendimiento , Zeolitas/química
16.
Cancer Immunol Immunother ; 73(2): 26, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38280084

RESUMEN

Clinically, a considerable number of non-small cell lung cancer (NSCLC) patients are unable to receive or resist chemotherapy, and the efficacy of non-chemotherapy treatment strategies based on anti-angiogenic agents combined with immune checkpoint blockade is still unsatisfactory. Neoantigen vaccine, based on personalized tumor DNA mutations, could elicit tumor specific T cell infiltration into the tumor site, exerting potent anti-tumor efficacy. Here, we evaluated the feasibility and safety of a new antitumor strategy by adding neoantigen vaccine to the regimen of bevacizumab and anti-PD-1 antibody. Firstly, 7 novel immunogenic neoantigen peptides were identified and developed for neoantigen vaccine (LLCvac), which can elicit strong antitumor immune response in vivo. Then, in orthotopic lung cancer model, LLCvac further combining with bevacizumab and anti-PD-1 antibody exerted a stronger antitumor effect, exhibiting significant decrease of tumor volume without obvious toxicity. Furthermore, tumor immune microenvironment assessment also showed that the proportion of neoantigen-specific T cells in blood could be induced dramatically by the combined therapy. And a large amount of neoantigen-specific Ki67-positive CD8+ T cells were found in tumor tissues, which infiltrated tumor tissues effectively to kill tumor cells expressing identified neoantigens. Overall, these results suggested that this combined therapy could safely induce robust antitumor efficacy, serving as an effective chemotherapy-free strategy for NSCLC treatment.


Asunto(s)
Vacunas contra el Cáncer , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Antígenos de Neoplasias , Bevacizumab/uso terapéutico , Vacunas contra el Cáncer/farmacología , Vacunas contra el Cáncer/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Linfocitos T CD8-positivos , Neoplasias Pulmonares/tratamiento farmacológico , Microambiente Tumoral
17.
Small ; : e2310957, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38698608

RESUMEN

The efficacy of traditional radiotherapy (RT) has been severely limited by its significant side effects, as well as tumor hypoxia. Here, the nanoscale cerium (Ce)-based metaloxo clusters (Ce(IV)6)-porphyrin (meso-tetra (4-carboxyphenyl) porphyrin, TCPP) framework loaded with L-arginine (LA) (denoted as LA@Ce(IV)6-TCPP) is developed to serve as a multifarious radio enhancer to heighten X-ray absorption and energy transfer accompanied by O2/NO generation for hypoxia-improved RT-radiodynamic therapy (RDT) and gas therapy. Within tumor cells, LA@Ce(IV)6-TCPP will first react with endogenous H2O2 and inducible NO synthase (iNOS) to produce O2 and NO to respectively increase the oxygen supply and reduce oxygen consumption, thus alleviating tumor hypoxia. Then upon X-ray irradiation, LA@Ce(IV)6-TCPP can significantly enhance hydroxyl radical (•OH) generation from Ce(IV)6 metaloxo clusters for RT and synchronously facilitate singlet oxygen (1O2) generation from adjacently-coordinated TCPP for RDT. Moreover, both the •OH and 1O2 can further react with NO to generate more toxic peroxynitrite anions (ONOO-) to inhibit tumor growth for gas therapy. Benefitting from the alleviation of tumor hypoxia and intensified RT-RDT synergized with gas therapy, LA@Ce(IV)6-TCPP elicited superior anticancer outcomes. This work provides an effective RT strategy by using low doses of X-rays to intensify tumor suppression yet reduce systemic toxicity.

18.
Small ; 20(16): e2309264, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38010948

RESUMEN

In this work, sub-nanometer Co clusters anchored on porous nitrogen-doped carbon (C─N─Co NCs) are successfully prepared by high-temperature annealing and pre-fabricated template strategies for non-invasive sensing of clozapine (CLZ) as an efficient substrate adsorption and electrocatalyst. The introduction of Co sub-nanoclusters (Co NCs) provides enhanced electrochemical performance and better substrate adsorption potential compared to porous and nitrogen-doped carbon structures. Combined with ab initio calculations, it is found that the favorable CLZ catalytic performance with C─N─Co NCs is mainly attributed to possessing a more stable CLZ adsorption structure and lower conversion barriers of CLZ to oxidized state CLZ. An electrochemical sensor for CLZ detection is conceptualized with a wide operating range and high sensitivity, with monitoring capabilities validated in a variety of body fluid environments. Based on the developed CLZ sensing system, the CLZ correlation between blood and saliva and the accuracy of the sensor are investigated by the gold standard method and the rat model of drug administration, paving the way for non-invasive drug monitoring. This work provides new insights into the development of efficient electrocatalysts to enable drug therapy and administration monitoring in personalized healthcare systems.


Asunto(s)
Antipsicóticos , Clozapina , Ratas , Animales , Antipsicóticos/uso terapéutico , Carbono/química , Monitoreo de Drogas , Nitrógeno , Clozapina/química , Clozapina/uso terapéutico
19.
Opt Express ; 32(6): 10527-10534, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38571261

RESUMEN

In the traditional dry etching process for photonic device fabrication, the etching effect is influenced in many ways, usually resulting in relatively large sidewall roughness and high transmission loss. In this study, an effective method, namely the secondary coating method, is proposed to reduce the transmission loss of a Ge-Sb-Se chalcogenide waveguide and increase the quality factor (Q-factor) of a Ge-Sb-Se chalcogenide micro-ring resonator. The Ge-Sb-Se waveguide and micro-ring resonator are fabricated by ultraviolet exposure/electron beam lithography and inductively coupled plasma etching technology. Afterward, a 10 nm-thick Ge-Sb-Se thin film is deposited by thermal evaporation. The measurements show that after secondary coating, the sidewall roughness of the waveguide is reduced from 11.96 nm to 6.52 nm, with the transmission loss reduced from 2.63± 0.19 dB/cm to 1.86± 0.11 dB/cm at 1.55 µm wavelength. Keeping an equal coupling condition with equal radius and coupling distance, the Q-factor of the micro-ring resonator is improved by 47.5% after secondary coating. All results indicate that the secondary coating method is a feasible way to generate low-loss and high Q-factor integrated chalcogenide photonic devices.

20.
Opt Express ; 32(8): 13384-13395, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38859310

RESUMEN

We introduce a unique dual-function detector with an asymmetric light illumination based on the black silicon co-hyperdoped with sulfur and nitrogen for light and gas detection, and the properties in NO2 gas sensing and photoelectric detection are studied under various light and gas environments, respectively. Enhanced performance of the device under certain light and gas conditions is observed. When illuminated at the optimal wavelength, the gas sensors' responsivity to NO2 can be enhanced by approximately 5 to 200 times over 730 nm illumination, respectively. The photodetectors' photoresponsivity increases 15 to 200 times in a 300 ppm NO2 gas environment compared to air. Such mutual enhancement achieved through the clever combination of light and gas implies a novel approach to improve the performance of the black silicon detectors in both gas sensing and photoelectric detection.

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