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1.
Sci Rep ; 14(1): 13292, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858578

RESUMEN

In the process of feeding the distilling bucket after vapor detection, the existing methods can only realize the lag detection after the steam overflow, and can not accurately detect the location of the steam, etc. At the same time, in order to effectively reduce the occupancy of the computational resources and improve the deployment performance, this study established infrared image dataset of fermented grains surface, and fused the YOLO v5n and the knowledge distillation and the model pruning algorithms, and an lightweight method YOLO v5ns-DP was proposed as as a model for detecting temperature changes in the surface layer of fermented grains during the process of feeding the distilling. The experimental results indicated that the improvement makes YOLOv5n improve its performance in all aspects. The number of parameters, GLOPs and model size of YOLO v5ns-DP have been reduced by 28.6%, 16.5%, and 26.4%, respectively, and the mAP has been improved by 0.6. Therefore, the algorithm is able to predict in advance and accurately detect the location of the liquor vapor, which effectively improves the precision and speed of the detection of the temperature of the surface fermented grains , and well completes the real-time detecting task.

2.
ACS Appl Mater Interfaces ; 16(26): 33169-33181, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38915234

RESUMEN

Inducing immunogenic cell death (ICD) is a promising strategy for cancer immunotherapy. Shikonin (SHK), a naphthoquinone compound from Lithospermum erythrorhizon, can stimulate antitumor immunity by inducing ICD. Nevertheless, the immunogenicity of tumor cells killed by SHK is weak. Endoplasmic reticulum (ER) stress is an important intracellular pathway of the ICD effect. Curcumin (CUR) can directly induce ER stress by disrupting Ca2+ homeostasis, which might enhance SHK-induced ICD effect. A self-delivery ICD effect nanobooster (CS-PEG NPs) was developed by the self-assembly of SHK (ICD inducer) and CUR (ICD enhancer) with the assistance of DSPE-PEG2K for cancer chemoimmunotherapy. CS-PEG NPs possessed effective CT26 tumor cell cellular uptake and tumor accumulation ability. Moreover, enhanced cytotoxicity against tumor cells and apoptosis promotion were achieved due to the synergistic effect of CUR and SHK. Notably, CS-PEG NPs induced obvious Ca2+ homeostasis disruption, ER stress, and ICD effect. Subsequently, the neoantigens produced by the robust ICD effect in vivo promoted dendritic cell maturation, which further recruited and activated cytotoxic T lymphocytes. Superior antitumor efficacy and systemic antitumor immunity were observed in the CT26-bearing BALB/c mouse model without side effects in major organs. This study offers a promising self-delivery nanobooster to induce strong ICD effect and antitumor immunity for cancer chemoimmunotherapy.


Asunto(s)
Curcumina , Estrés del Retículo Endoplásmico , Muerte Celular Inmunogénica , Inmunoterapia , Ratones Endogámicos BALB C , Naftoquinonas , Animales , Naftoquinonas/química , Naftoquinonas/farmacología , Muerte Celular Inmunogénica/efectos de los fármacos , Ratones , Curcumina/química , Curcumina/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Línea Celular Tumoral , Nanopartículas/química , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/patología , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Femenino
3.
Nat Commun ; 15(1): 4932, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858365

RESUMEN

This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs' 5' splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.


Asunto(s)
Herpesvirus Humano 3 , ARN Circular , ARN Viral , Replicación Viral , ARN Circular/genética , ARN Circular/metabolismo , Herpesvirus Humano 3/genética , Humanos , ARN Viral/genética , ARN Viral/metabolismo , Replicación Viral/genética , Línea Celular Tumoral , Latencia del Virus/genética , Infección por el Virus de la Varicela-Zóster/virología , Aciclovir/farmacología , Aciclovir/uso terapéutico , Exones/genética
4.
Phytother Res ; 38(7): 3660-3694, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38748620

RESUMEN

Diosmetin, a natural occurring flavonoid, is primarily found in citrus fruits, beans, and other plants. Diosmetin demonstrates a variety of pharmacological activities, including anticancer, antioxidant, anti-inflammatory, antibacterial, metabolic regulation, cardiovascular function improvement, estrogenic effects, and others. The process of literature search was done using PubMed, Web of Science and ClinicalTrials databases with search terms containing Diosmetin, content, anticancer, anti-inflammatory, antioxidant, pharmacological activity, pharmacokinetics, in vivo, and in vitro. The aim of this review is to summarize the in vivo, in vitro and clinical studies of Diosmetin over the last decade, focusing on studies related to its anticancer, anti-inflammatory, and antioxidant activities. It is found that DIO has significant therapeutic effects on skin and cardiovascular system diseases, and its research in pharmacokinetics and toxicology is summarized. It provides the latest information for researchers and points out the limitations of current research and areas that should be strengthened in future research, so as to facilitate the relevant scientific research and clinical application of DIO.


Asunto(s)
Antioxidantes , Flavonoides , Humanos , Flavonoides/farmacología , Flavonoides/farmacocinética , Antioxidantes/farmacología , Antioxidantes/farmacocinética , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/farmacocinética , Enfermedades Cardiovasculares/tratamiento farmacológico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/farmacocinética
5.
Nat Commun ; 15(1): 2238, 2024 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472213

RESUMEN

Soft magnetic materials with stable permeability up to hundreds of megahertz (MHz) are urgently needed for integrated transformers and inductors, which are crucial in the more-than-Moore era. However, traditional frequency-stable soft magnetic ferrites suffer from low saturation magnetization and temperature instability, making them unsuitable for integrated circuits. Herein, we fabricate a frequency-stable soft magnetic composite featuring a magnetic vortex structure via cold-sintering, where ultrafine FeSiAl particles are magnetically isolated and covalently bonded by Al2SiO5/SiO2/Fe2(MoO4)3 multilayered heterostructure. This construction results in an ultrastable permeability of 13 up to 1 gigahertz (GHz), relatively large saturation magnetization of 105 Am2/kg and low coercivity of 48 A/m, which we ascribe to the elimination of domain walls associated with almost uniform single-vortex structures, as observed by Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the ultimate compressive strength has been simultaneously increased up to 337.1 MPa attributed to the epitaxially grown interfaces between particles. This study deepens our understanding on the characteristics of magnetic vortices and provides alternative concept for designing integrated magnetic devices.

6.
Pigment Cell Melanoma Res ; 37(3): 411-425, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38411373

RESUMEN

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Although primary UM can be effectively controlled, a significant proportion of cases (40% or more) eventually develop distant metastases, commonly in the liver. Metastatic UM remains a lethal disease with limited treatment options. The initiation of UM is typically attributed to activating mutations in GNAQ or GNA11. The elucidation of the downstream pathways such as PKC/MAPK, PI3K/AKT/mTOR, and Hippo-YAP have provided potential therapeutic targets. Concurrent mutations in BRCA1 associated protein 1 (BAP1) or splicing factor 3b subunit 1 (SF3B1) are considered crucial for the acquisition of malignant potential. Furthermore, in preclinical studies, actionable targets associated with BAP1 loss or oncogenic mutant SF3B1 have been identified, offering promising avenues for UM treatment. This review aims to summarize the emerging targeted and epigenetic therapeutic strategies for metastatic UM carrying specific driver mutations and the potential of combining these approaches with immunotherapy, with particular focus on those in upcoming or ongoing clinical trials.


Asunto(s)
Melanoma , Mutación , Neoplasias de la Úvea , Neoplasias de la Úvea/genética , Neoplasias de la Úvea/patología , Neoplasias de la Úvea/terapia , Humanos , Melanoma/genética , Melanoma/patología , Melanoma/terapia , Mutación/genética , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Animales , Inmunoterapia
7.
Nat Commun ; 15(1): 1497, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374257

RESUMEN

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

8.
Mater Horiz ; 11(4): 995-1007, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38047955

RESUMEN

Transcutaneous energy-harvesting technology based on ultrasound-driven piezoelectric nanogenerators is the most promising technology in medical and industrial applications. Based on ultrasonic coupling effects at the interfaces, the interfacial architecture is a critical parameter to attain desirable electromechanical properties of nanocomposites. Herein, we successfully synthesized core-conductive shell-structured BaTiO3@Carbon [BT@Carbon] nanoparticles [NPs] as nanofillers to design implantable poly(vinylidenefluoride-co-chlorotrifluoroethylene)/BT@Carbon [P(VDF-CTFE)/BT@Carbon] piezoelectric nanogenerators (PENGs) and actuators for harvesting ultrasound (US) underneath the skin. For US-driven PENGs, the electrons and holes are generated not only from the interfaces between the BT@Carbon NPs and the matrix, but also from the dipoles vibrating in the smaller lamellae of ferroelectric ß-phase crystals in poled nanocomposites. Remarkably, P(VDF-CTFE)/BT@Carbon piezoelectric nanogenerators could attain an extraordinary output power of 521 µW cm-2 under ultrasound stimulation, which is far greater than that of force-induced PVDF-based nanogenerators and other ultrasound-driven triboelectric generators. Furthermore, the US-PENG actuator system, which is composed of an amplifier and a microcontroller, could efficiently convert ultrasonic energy into electricity or instructions to switch on/off small electronics in the tissues and organs of mice. Finally, the nanocomposite-based US-driven PENGs have a good biocompatibility, with no cytotoxicity or immune response in vivo, indicating their potential for developing wireless power generators and actuators for medical implant devices.

9.
Nanoscale ; 15(48): 19586-19597, 2023 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-38015611

RESUMEN

Spinel ferrites have drawn intensive attention because of their adjustable magnetic properties by ion doping, among which calcium (Ca) is an essential dopant that is widely employed in massive production. However, its exact lattice occupation and relationship with intrinsic magnetic properties remain unclear. Here, we successfully prepared Ca-doped cobalt ferrite (CoFe2O4) nanoparticles by electrospinning. Ca2+ is observed to occupy both the tetrahedral Fe site and the octahedral Co site using spherical aberration correction transmission electron microscopy (TEM) and prefers to occupy the octahedral site at a high doping level. Such dual occupation behavior affects the tetrahedral and octahedral sublattices differently, resulting in nonmonotonic saturation magnetization variation, reduced magnetocrystalline anisotropy and negative magnetization in the zero field cooling (ZFC) process. By controlling the Ca doping amount, increased saturation magnetization and reduced coercivity can be obtained simultaneously. Our findings establish the relationship between the atomic-scale structural change and the macroscopic magnetic properties of spinel ferrites, promoting the development of new ferrite materials.

10.
Nanotechnology ; 35(9)2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37995378

RESUMEN

Gallium oxide (Ga2O3) possesses a band gap of approximately 4.9 eV, aligning its detection wavelength within the solar-blind region, making it an ideal semiconductor material for solar-blind photodetectors. This study aims to enhance the performance of Ga2O3ultraviolet (UV) detectors by pre-depositing a Ga2O3seed layer on ac-plane sapphire substrate. The x-ray diffraction and x-ray photoelectron spectroscopy analyses validated that the deposited films, following high-temperature annealing, comprisedß-Ga2O3. Comparing samples with and without a 20 nm seed layer, it was found that the former exhibited fewer oxygen defects and substantially improved crystal quality. The incorporation of the seed layer led to the realization of detectors with remarkably low dark current (≤15.3 fA). Moreover, the photo-to-dark current ratio was enhanced by 30% (surpassing 1.3 × 104) and the response/recovery time reduced to 0.9 s/0.01 s, indicating faster performance. Furthermore, these detectors demonstrated higher responsivity (4.8 mA W-1), improved detectivity (2.49 × 1016Jones), and excellent solar-blind characteristics. This study serves as a foundational stepping toward achieving high-qualityß-Ga2O3thin film and UV detector arrays.

11.
Front Med (Lausanne) ; 10: 1267512, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38034530

RESUMEN

Introduction: Early stable deep molecular response (DMR) to nilotinib is associated with goal of treatment-free remission (TFR) in patients with chronic-phase chronic myeloid leukemia (CML-CP). It is important to early distinguish between patients who can achieve a DMR and those who are fit for TFR. Methods: We performed a multicenter study to explore the early cumulative MR4.5 rate at 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. Of the 29 institutes, 106 patients with ND-CML-CP received nilotinib (300 mg BID). Results and discussion: The cumulative MR4.5 rate of nilotinib treatment at 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates for nilotinib at 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with an ultra-early molecular response (u-EMR) at 6 weeks were not significantly different in obtaining DMR or MMR by 24 months compared with those without u-EMR (p = 0.7584 and p = 0.9543, respectively). Our study demonstrated that nilotinib treatment in patients with ND-CML-CP contributed to obtain high early MR4.5.

12.
Water Sci Technol ; 88(8): 1982-2001, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37906454

RESUMEN

For the low efficiency and large loss of cascade pumping stations, aiming to maximize system efficiency, an optimized scheduling model of cascade pumping stations is established with consideration of multiple constraints, and the optimal scheduling method based on the improved sparrow search algorithm (BSSA) is proposed. The BSSA is initialized by the Bernoulli chaotic map to solve the insufficient initial diversity of the sparrow search algorithm (SSA). The random boundary strategy is introduced to avoid local optimum when dealing with the scheduling problem of pumping stations. The performance and improvement strategy of BSSA are verified by eight benchmark functions. Results show that BSSA has better convergence accuracy and faster speed. BSSA is applied to a three-stage pumping station considering three flow conditions, and compared with the current scheme, particle swarm optimization and genetic algorithm optimization schemes, the operation efficiency of SSA can be increased by 0.72-0.96%, and operation cost can be reduced by ¥263,000/a-¥363,300/a. On this basis, the improvement of 0.04-0.30% and ¥14,800/a-¥109,900/a can be further achieved by the BSSA, which confirms the feasibility and effectiveness of BSSA to solve the pumping station optimal scheduling problem. The findings present useful reference for the optimized scheduling of pumping station system.


Asunto(s)
Algoritmos , Benchmarking , Agua Subterránea
13.
Viruses ; 15(8)2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37632045

RESUMEN

Human cytomegalovirus (HCMV) is a widespread pathogen that poses significant risks to immunocompromised individuals. Its genome spans over 230 kbp and potentially encodes over 200 open-reading frames. The HCMV transcriptome consists of various types of RNAs, including messenger RNAs (mRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), with emerging insights into their biological functions. HCMV mRNAs are involved in crucial viral processes, such as viral replication, transcription, and translation regulation, as well as immune modulation and other effects on host cells. Additionally, four lncRNAs (RNA1.2, RNA2.7, RNA4.9, and RNA5.0) have been identified in HCMV, which play important roles in lytic replication like bypassing acute antiviral responses, promoting cell movement and viral spread, and maintaining HCMV latency. CircRNAs have gained attention for their important and diverse biological functions, including association with different diseases, acting as microRNA sponges, regulating parental gene expression, and serving as translation templates. Remarkably, HCMV encodes miRNAs which play critical roles in silencing human genes and other functions. This review gives an overview of human cytomegalovirus and current research on the HCMV transcriptome during lytic and latent infection.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Humanos , Citomegalovirus/genética , ARN Circular/genética , Transcriptoma , MicroARNs/genética , ARN Mensajero
14.
Materials (Basel) ; 16(12)2023 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-37374561

RESUMEN

Transmission electron microscopy (TEM) is indispensable to reveal the cellular nanostructure of the 2:17-type Sm-Co based magnets which act as the first choice for high-temperature magnet-associated devices. However, structural deficiencies could be introduced into the TEM specimen during the ion milling process, which would provide misleading information to understand the microstructure-property relationship of such magnets. In this work, we performed a comparative investigation of the microstructure and microchemistry between two TEM specimens prepared under different ion milling conditions in a model commercial magnet Sm13Gd12Co50Cu8.5Fe13Zr3.5 (wt.%). It is found that additional low-energy ion milling will preferably damage the 1:5H cell boundaries, while having no influence on the 2:17R cell phase. The structure of cell boundary transforms from hexagonal into face-centered-cubic. In addition, the elemental distribution within the damaged cell boundaries becomes discontinuous, segregating into Sm/Gd-rich and Fe/Co/Cu-rich portions. Our study suggested that in order to reveal the true microstructure of the Sm-Co based magnets, the TEM specimen should be carefully prepared to avoid structural damage and artificial deficiencies.

15.
PLoS One ; 18(6): e0285699, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37267400

RESUMEN

The aim of this article is to explore the impact of housing investment on household entrepreneurship. Using survey data from China and employing a Probit model, we examine three aspects of housing status and innovatively subdivide household entrepreneurship into agricultural entrepreneurship and business entrepreneurship. The results show that households with higher housing investment are less likely to become agricultural entrepreneurs, but more likely to start a new business. Households with full-owned housing enjoy a higher likelihood to become business entrepreneurs. However, other ownerships have no relation with the choice of entrepreneurship. More housing loans discourage entrepreneurial activities. One exception is that bank loan raises the chance of being agricultural entrepreneurs. Households who build their own houses have a higher agricultural entrepreneurship. Buying market price houses encourages households to be business entrepreneurs. Low-price house and inherited house prevent households from being business entrepreneurs.


Asunto(s)
Emprendimiento , Vivienda , Comercio , Empleo , China
16.
ACS Appl Mater Interfaces ; 15(2): 3307-3316, 2023 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-36596237

RESUMEN

Van der Waals semiconductors have been really confirmed in two-dimensional (2D) layered systems beyond the traditional limits of lattice-matching requirements. The extension of this concept to the 1D atomic level may generate intriguing physical functionalities due to its non-covalent bonding surface. However, whether the curvature of the lattice in such rolled-up structures affects their optoelectronic features or the performance of devices established on them remains an open question. Here, MoS2-based nanoscrolls were obtained by virtue of an alkaline solution-assisted method and the 0D/1D (BaTiO3/MoS2) strategy to tune their optoelectronic properties and improve the light sensing performance was explored. The capillary force generated by a drop of NaHCO3 solution could drive the delamination of nanosheets from the underlying substrate and a spontaneous rolling-up process. The package of BaTiO3 particles in MoS2 nanoscrolls has been evident by TEM image, and the optical characterizations were mirrored via micro-Raman spectroscopy and photoluminescence. These bare MoS2 nanoscrolls reveal a reduced photoresponse compared to the plane structures due to the curvature of the lattice. However, such BaTiO3/MoS2 nanoscrolls exhibit a significantly improved photodetection (Rhybrid = 73.9 A/W vs Ronly = 1.1 A/W and R2D = 1.5 A/W at 470 nm, 0.58 mW·cm-2), potentially due to the carrier extraction/injection occurring between BaTiO3 and MoS2. This study thereby provides an insight into 1D van der Waals material community and demonstrates a general approach to fabricate high-performance 1D van der Waals optoelectronic devices.

17.
Biomater Res ; 26(1): 64, 2022 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-36435809

RESUMEN

BACKGROUND: It is highly desirable to develop new therapeutic strategies for gastric cancer given the low survival rate despite improvement in the past decades. Cadherin 17 (CDH17) is a membrane protein highly expressed in cancers of digestive system. Nanobody represents a novel antibody format for cancer targeted imaging and drug delivery. Nanobody targeting CHD17 as an imaging probe and a delivery vehicle of toxin remains to be explored for its theragnostic potential in gastric cancer. METHODS: Naïve nanobody phage library was screened against CDH17 Domain 1-3 and identified nanobodies were extensively characterized with various assays. Nanobodies labeled with imaging probe were tested in vitro and in vivo for gastric cancer detection. A CDH17 Nanobody fused with toxin PE38 was evaluated for gastric cancer inhibition in vitro and in vivo. RESULTS: Two nanobodies (A1 and E8) against human CDH17 with high affinity and high specificity were successfully obtained. These nanobodies could specifically bind to CDH17 protein and CDH17-positive gastric cancer cells. E8 nanobody as a lead was extensively determined for tumor imaging and drug delivery. It could efficiently co-localize with CDH17-positive gastric cancer cells in zebrafish embryos and rapidly visualize the tumor mass in mice within 3 h when conjugated with imaging dyes. E8 nanobody fused with toxin PE38 showed excellent anti-tumor effect and remarkably improved the mice survival in cell-derived (CDX) and patient-derived xenograft (PDX) models. The immunotoxin also enhanced the anti-tumor effect of clinical drug 5-Fluorouracil. CONCLUSIONS: The study presents a novel imaging and drug delivery strategy by targeting CDH17. CDH17 nanobody-based immunotoxin is potentially a promising therapeutic modality for clinical translation against gastric cancer.

18.
Nanomaterials (Basel) ; 12(20)2022 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-36296869

RESUMEN

The acetone-sensing performance of BiFeO3 is related to structural phase transformation, morphology and band gap energy which can be modulated by rare-earth ions doping. In this work, Bi1-xErxFeO3 nanoparticles with different amounts of Er doping were synthesized via the sol-gel method. The mechanism of Er doping on acetone-sensing performance of Bi1-xErxFeO3 (x = 0, 0.05, 0.1 and 0.2) sensors was the focus of the research. The optimal working temperature of Bi0.9Er0.1FeO3 (300 °C) was decreased by 60 °C compared to BiFeO3 (360 °C). The Bi0.9Er0.1FeO3 sample demonstrated the optimal response to 100 ppm acetone (43.2), which was 4.8 times that of pure BFO at 300 °C. The primary reason, which enhances the acetone-sensing performance, could be the phase transformation induced by Er doping. The lattice distortions induced by phase transformation are favorable to increasing the carrier concentration and mobility, which will bring more changes to the hole-accumulation layer. Thus, the acetone-sensing performance of Bi0.9Er0.1FeO3 was improved.

19.
Pharmacol Res ; 184: 106464, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36162600

RESUMEN

Uveal melanoma (UM) is the most common intraocular cancer in adults. UMs are usually initiated by a mutation in GNAQ or GNA11 (encoding Gq or G11, respectively), unlike cutaneous melanomas (CMs), which usually carry a BRAF or NRAS mutation. Currently, there are no clinically effective targeted therapies for UM carrying Gq/11 mutations. Here, we identified a causal link between Gq activating mutations and hypersensitivity to bromodomain and extra-terminal (BET) inhibitors. BET inhibitors transcriptionally repress YAP via BRD4 regardless of Gq mutation status, independently of Hippo core components LATS1/2. In contrast, YAP/TAZ downregulation reduces BRD4 transcription exclusively in Gq-mutant cells and LATS1/2 double knockout cells, both of which are featured by constitutively active YAP/TAZ. The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.


Asunto(s)
Melanoma , Proteínas Nucleares , Animales , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Melanoma/tratamiento farmacológico , Melanoma/genética , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinasas , Proteínas Proto-Oncogénicas B-raf/genética , Transducción de Señal , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neoplasias de la Úvea
20.
PLoS Pathog ; 18(9): e1010794, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-36070294

RESUMEN

Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-ß promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-ß promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-ß1 and IL6 promoters. The specific regulation of SPHK2 on IFN-ß promoter through TET3 can in turn recruit HDAC1 to the IFN-ß promoter, enhancing the deacetylation of IFN-ß promoter, therefore leading to the inhibition of IFN-ß transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.


Asunto(s)
Gripe Humana , Interferón beta , Fosfotransferasas (Aceptor de Grupo Alcohol) , Humanos , Virus de la Influenza A , Gripe Humana/enzimología , Interferón beta/genética , Interferón beta/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Replicación Viral
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