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1.
Am J Transl Res ; 16(7): 2756-2764, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39114701

RESUMEN

OBJECTIVE: To evaluate the efficacy of Sulodexide in treating idiopathic membranous nephropathy (IMN) in the Chinese population. METHODS: We systematically reviewed all eligible randomized clinical trials (RCTs) conducted in China that investigated the effects of Sulodexide on IMN. Three RCTs published between 2013 and 2022 were included, encompassing a total of 146 patients. The primary outcomes evaluated were changes in urine total protein (UTP), serum albumin (ALB), cholesterol (CHOL), and fibrinogen (FIB) levels. RESULTS: Statistically significant differences were observed in the Sulodexide treatment group compared to the control group for the following parameters: reduction in UTP and CHOL, increase in ALB, and reduction in FIB levels. CONCLUSION: Sulodexide, when combined with conventional therapy, effectively reduces UTP and CHOL levels, decreases FIB levels, and increases ALB in Chinese patients with IMN.

2.
BMC Microbiol ; 24(1): 291, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097685

RESUMEN

BACKGROUND: Taxol, derived from Taxus trees, is a valuable natural resource for the development of anticancer drugs. Endophytic fungi from Taxus trees are a promising alternative source of Taxol. However, the impact of plant-endophytic microbial interaction on the host's Taxol biosynthesis is largely unknown. RESULTS: In the current study, the diversity of endophytic fungi in three different Taxus species was analyzed using Internal Transcribed Spacer sequencing. A total of 271 Operational Taxonomic Units (OTUs) were identified, grouping into 2 phyla, 8 classes, 16 orders, 19 families, and 19 genera. Alpha and beta diversity analysis indicated significant differences in endophytic fungal communities among the various Taxus trees. At the genus level, Alternaria and Davidiella were predominantly found in T. mairei and T. media, respectively. By utilizing a previously published dataset, a Pearson correlation analysis was conducted to predict the taxol biosynthesis-related fungal genera. Following screening, two isolates of Alternaria (L7 and M14) were obtained. Effect of inoculation with Alternaria isolates on the gene expression and metabolite accumulation of T. mairei was determined by transcriptomic and untargeted metabolomic studies. The co-inoculation assay suggests that the two Alternaria isolates may have a negative regulatory effect on taxol biosynthesis by influencing hormone signaling pathways. CONCLUSION: Our findings will serve as a foundation for advancing the production and utilization of Taxus and will also aid in screening endophytic fungi related to taxol production.


Asunto(s)
Alternaria , Endófitos , Paclitaxel , Taxus , Taxus/microbiología , Paclitaxel/biosíntesis , Endófitos/genética , Endófitos/metabolismo , Endófitos/aislamiento & purificación , Endófitos/clasificación , Alternaria/genética , Alternaria/metabolismo , Alternaria/clasificación , Alternaria/aislamiento & purificación , Filogenia , Hongos/genética , Hongos/metabolismo , Hongos/clasificación , Hongos/aislamiento & purificación , ADN de Hongos/genética , ADN Espaciador Ribosómico/genética
3.
Nat Commun ; 15(1): 6904, 2024 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134537

RESUMEN

Rechargeable sodium-chlorine (Na-Cl2) batteries show high theoretical specific energy density and excellent adaptability for extreme environmental applications. However, the reported cycle life is mostly less than 500 cycles, and the understanding of battery failure mechanisms is quite limited. In this work, we demonstrate that the substantially increased voltage polarization plays a critical role in the battery failure. Typically, the passivation on the porous cathode caused by the deposition of insulated sodium chloride (NaCl) is a crucial factor, significantly influencing the three-phase chlorine (NaCl/Na+, Cl-/Cl2) conversion kinetics. Here, a self-depassivation strategy enabled by iodine anion (I-)-tuned NaCl deposition was implemented to enhance the chlorine reversibility. The nucleation and growth of NaCl crystals are well balanced through strong coordination of the NaI deposition-dissolution process, achieving depassivation on the cathode and improving the reoxidation efficiency of solid NaCl. Consequently, the resultant Na-Cl2 battery delivers a super-long cycle life up to 2000 cycles.

4.
ACS Nano ; 18(34): 23702-23710, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39147598

RESUMEN

The most reported two-dimensional (2D) reconfigurable multivalued logic (RMVL) devices primarily involve a planar configuration and carrier transport, which limits the high-density circuit integration and high-speed logic operation. In this work, the vertical transistors with reconfigurable MoTe2 homojunction are developed for low-power, high-speed, multivalued logic circuits. Through top/bottom dual-gate modulation, the transistors can be configured into four modes: P-i-N, N-i-P, P-i-P, and N-i-N. The reconfigurable rectifying and photovoltaic behaviors are observed in P-i-N and N-i-P configurations, exhibiting ideal diode characteristics with a current rectification ratio over 105 and sign-reversible photovoltaic response with a photoswitching ratio up to 7.44 × 105. Taking advantage of the seamless homogeneous integration and short vertical channel architecture, the transistor can operate as an electrical switch with an ultrafast speed of 680 ns, surpassing the conventional p-n diode. The MoTe2 half-wave rectifier is then applied in high-frequency integrated circuits using both square wave and sinusoidal waveforms. By applying an electrical pulse with a 1/4 phase difference between two input signals, the RMVL circuit has been achieved. This work proposes a universal and reconfigurable vertical transistor, enabled by dual-gate electrostatic doping on top/bottom sides of MoTe2 homojunction, suggesting a high integration device scheme for high-speed RMVL circuits and systems.

5.
Ecotoxicol Environ Saf ; 283: 116784, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39088896

RESUMEN

2-ethylhexyl diphenyl phosphate (EHDPHP) is a widely used organophosphorus flame retardant and plasticizer, which is commonly found in the environment. EHDPHP not only potentially harms the environment but also causes different degrees of damage to the organism. In this study, the duodenum of chicks was selected as the potential toxic target organ to explore the mechanism of duodenal injury induced by EHDPHP exposure. Ninety one-day-old healthy male chicks were selected and randomly divided into C1(control group), C2(solvent control group), L(800 mg/kg), M(1600 mg/kg), H(3200 mg/kg) according to different doses of EHDPHP after one week of environmental adaptation. The chicks were given continuous gavage for 14 d, 28 d, and 42 d. It was found that constant exposure to EHDPHP caused an increase in duodenal MDA content, a decrease in P-gp, SOD, GSH-Px activities, and a decrease in duodenal mucosal immune factor (sIgA, GSH-Px). The expression of sIgM and mucosal link proteins (CLDN, OCLN, ZO-1, JAM) decreased, and the expression of the inflammatory protein (NF-κB, COX2) in duodenal tissues was up-regulated. The results showed that continuous exposure to EHDPHP could cause duodenal oxidative stress, inflammation, and mucosal barrier damage in chicks, which provided a basis for studying the mechanism of toxic damage caused by EHDPHP in poultry.

6.
Adv Sci (Weinh) ; : e2401915, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958519

RESUMEN

Resistive switching memories have garnered significant attention due to their high-density integration and rapid in-memory computing beyond von Neumann's architecture. However, significant challenges are posed in practical applications with respect to their manufacturing process complexity, a leakage current of high resistance state (HRS), and the sneak-path current problem that limits their scalability. Here, a mild-temperature thermal oxidation technique for the fabrication of low-power and ultra-steep memristor based on Ag/TiOx/SnOx/SnSe2/Au architecture is developed. Benefiting from a self-assembled oxidation layer and the formation/rupture of oxygen vacancy conductive filaments, the device exhibits an exceptional threshold switching behavior with high switch ratio exceeding 106, low threshold voltage of ≈1 V, long-term retention of >104 s, an ultra-small subthreshold swing of 2.5 mV decade-1 and high air-stability surpassing 4 months. By decreasing temperature, the device undergoes a transition from unipolar volatile to bipolar nonvolatile characteristics, elucidating the role of oxygen vacancies migration on the resistive switching process. Further, the 1T1R structure is established between a memristor and a 2H-MoTe2 transistor by the van der Waals (vdW) stacking approach, achieving the functionality of selector and multi-value memory with lower power consumption. This work provides a mild-thermal oxidation technology for the low-cost production of high-performance memristors toward future in-memory computing applications.

7.
Biol Trace Elem Res ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958867

RESUMEN

Cadmium(Cd) is a toxic heavy metal widely present in the environment, capable of accumulating in the liver and causing liver damage. In this study, the mechanism of cadmium-induced liver fibrosis in chickens was investigated from the perspective of hepatocyte epithelial-mesenchymal transition (EMT) based on the establishment of a model of chicken cadmium toxicity and a model of cadmium-stained cells in a chicken hepatocellular carcinoma cell line (LMH). The 7-day-old chickens were randomly divided into the regular group (C group) and cadmium poisoning group (Cd group), and the entire test cycle was 60 days. Three sampling time points of 20 days, 40 days, and 60 days were established. By testing the liver coefficient, histopathological and ultrastructural changes in chicken livers were observed. The enzyme activities of liver function and the expression changes of fibrosis markers (COL1A1, Fibronectin), epithelial-mesenchymal transition markers (E-cadherin, Vimentin, and α-SMA), and the critical factors of the TGF-ß/SMAD signaling pathway (TGF-ß1, SMAD 2, and SMAD 3) were detected in the liver expression changes. The results showed that at the same sampling time point, the chicken liver coefficient in group Cd was significantly higher than that in control group (P < 0.01); the activities of the liver function enzymes ALT and AST in chickens in the Cd group were significantly higher than those in the C group (P < 0.01); liver hepatocytes degenerated and necrotic, the number of erythrocytes in the blood vessels was increased, and inflammatory cells infiltrated in the sinusoidal gap; the perisinusoidal gap of the liver was enlarged, and there was an apparent aggregation of collagen fibers in the intervening period as seen by transmission electron microscopy. The results of Masson staining showed that the percentage of fiber area was significantly higher in the chickens' livers of the Cd group. The fiber area percentage was significantly higher. The results of real-time fluorescence quantitative PCR and Western Blot showed that the expression of E-cadherin in the livers of chickens in the Cd group was significantly lower than that in the C group (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß1, SMAD 2, and SMAD 3 was significantly higher than that in the C group (P < 0.01). The results of in vitro assays showed that in the LMH cell model established by adding trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, and oxidized picric acid, an inhibitor of the TGF-ß/SMAD signaling pathway, the expression of E-cadherin was significantly reduced in cadmium-stained LMH cells (P < 0.01). The expression of α-SMA, Vimentin, COL1A1, Fibronectin, TGF-ß, SMAD 2, and SMAD 3 was significantly elevated (P < 0.01). Cadmium and Trimethylamine N-oxide, an activator of the TGF-ß/SMAD signaling pathway, promoted the expression of these factors. In contrast, the inhibitor of the TGF-ß/SMAD signaling pathway, Oxymatrine, a TGF-ß/SMAD signaling pathway inhibitor, significantly slowed down these changes. These results suggest that cadmium induces hepatic epithelial-mesenchymal transition by activating the TGF-ß/SMAD signaling pathway in chicken hepatocytes, promoting hepatic fibrosis.

8.
Nat Commun ; 15(1): 6261, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048552

RESUMEN

Visual adaptive devices have potential to simplify circuits and algorithms in machine vision systems to adapt and perceive images with varying brightness levels, which is however limited by sluggish adaptation process. Here, the avalanche tuning as feedforward inhibition in bionic two-dimensional (2D) transistor is proposed for fast and high-frequency visual adaptation behavior with microsecond-level accurate perception, the adaptation speed is over 104 times faster than that of human retina and reported bionic sensors. As light intensity changes, the bionic transistor spontaneously switches between avalanche and photoconductive effect, varying responsivity in both magnitude and sign (from 7.6 × 104 to -1 × 103 A/W), thereby achieving ultra-fast scotopic and photopic adaptation process of 108 and 268 µs, respectively. By further combining convolutional neural networks with avalanche-tuned bionic transistor, an adaptative machine vision is achieved with remarkable microsecond-level rapid adaptation capabilities and robust image recognition with over 98% precision in both dim and bright conditions.


Asunto(s)
Redes Neurales de la Computación , Retina , Humanos , Retina/fisiología , Percepción Visual/fisiología , Algoritmos , Biónica/instrumentación , Transistores Electrónicos , Adaptación Ocular/fisiología
9.
ACS Appl Mater Interfaces ; 16(27): 35323-35332, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38946487

RESUMEN

The micro- and nanostructures of III-nitride semiconductors captivate strong interest owing to their distinctive properties and myriad potential applications. Nevertheless, challenges endure in managing the damage inflicted on crystals through top-down processes or achieving extensive control over the large-area growth of these microstructures via bottom-up methods, thereby impacting their optical and electronic properties. Here, we present novel epitaxially grown 3D GaN truncated pyramid arrays (TPAs) on patterned Si substrates, devoid of any catalyst. These GaN TPAs feature highly ordered, large-scale structures, attributed to the utilization of 3D Si substrates and thin AlN interlayers to alleviate epitaxial strains and limit dislocation formation. Comprehensive characterization via scanning electron microscopy, transmission electron microscopy, Raman spectroscopy, and cathodoluminescence attests to the superior structural and optical attributes of these crystals. Furthermore, photoluminescence and ultraviolet (UV)-visible diffuse reflectance spectroscopy reveal sharp band-edge emission and significant light trapping in the UV bands. Employing these GaN TPAs, we constructed metal-semiconductor-metal visible-blind UV photodetectors (PDs) incorporating Ti3C2 MXene as Schottky electrodes. These PDs display exceptional responsivity, achieving 5.32 × 103 mA/W at 255 nm and an ultrahigh UV/visible rejection ratio (R255nm/R450nm) approaching 106, which are 1-2 orders of magnitude higher than most recently reported works. This exploration showcases novel GaN-based microstructures characterized by uniformity, ordered geometry, and exemplary crystalline integrity, paving the way for developing optoelectronic applications.

10.
Sci Total Environ ; 946: 174229, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38917895

RESUMEN

Ozone pollution is an important environmental issue in many countries. Accurate forecasting of ozone concentration enables relevant authorities to enact timely policies to mitigate adverse impacts. This study develops a novel hybrid deep learning model, named wind direction-based dynamic spatio-temporal graph network (WDDSTG-Net), for hourly ozone concentration prediction. The model uses a dynamic directed graph structure based on hourly changing wind direction data to capture evolving spatial relationships between air quality monitoring stations. It applied the graph attention mechanism to compute dynamic weights between connected stations, thereby aggregating neighborhood information adaptively. For temporal modeling, it utilized a sequence-to-sequence model with attention mechanism to extract long-range temporal dependencies. Additionally, it integrated meteorological predictions to guide the ozone forecasting. The model achieves a mean absolute error of 6.69 µg/m3 and 18.63 µg/m3 for 1-h prediction and 24-h prediction, outperforming several classic models. The model's IAQI accuracy predictions at all stations are above 75 %, with a maximum of 81.74 %. It also exhibits strong capabilities in predicting severe ozone pollution events, with a 24-h true positive rate of 0.77. Compared to traditional static graph models, WDDSTG-Net demonstrates the importance of incorporating short-term wind fluctuations and transport dynamics for data-driven air quality modeling. In principle, it may serve as an effective data-driven approach for the concentration prediction of other airborne pollutants.

11.
Opt Lett ; 49(12): 3472-3475, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38875648

RESUMEN

We propose and experimentally demonstrate a dual-wavelength distributed feedback (DFB) laser array utilizing a four-phase-shifted sampled Bragg grating. By using this grating, the coupling coefficient is enhanced by approximately 2.83 times compared to conventional sampled Bragg gratings. The devices exhibit a stable dual-mode lasing achieved by introducing further π-phase shifts at 1/3 and 2/3 positions along the cavity. These devices require only one stage of lithography to define both the ridge waveguide and the gratings, mitigating issues related to misalignment between them. A dual-wavelength laser array has been fabricated with frequency spacings of 320 GHz, 500 GHz, 640 GHz, 800 GHz, and 1 THz. When integrated with semiconductor optical amplifiers, the output power of the device can reach 23.6 mW. Furthermore, the dual-wavelength lasing is maintained across a wide range of injection currents, with a power difference of <3 dB between the two primary modes. A terahertz (THz) signal has been generated through photomixing in a photoconductive antenna, with the measured power reaching 12.8 µW.

12.
Environ Sci Technol ; 58(24): 10817-10827, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38832598

RESUMEN

Direct photoreduction of FeIII is a widely recognized route for accelerating FeIII/FeII cycle in photo-Fenton chemistry. However, most of the wavelengths covering the full spectral range are insufficient to supply enough photon energy for the direct reduction process. Herein, the hitherto neglected mechanism of FeIII reduction that the FeIII indirect reduction pathway initiated by light energy-dependent reactivity variation and reactive excited state (ES) was explored. Evolution of excited-state FeIII species (*FeIII) resulting from metal-centered charge excitation (MCCE) of FeIII is experimentally verified using pulsed laser femtosecond transient absorption spectroscopy with UV-vis detection and theoretically verified by quantum chemical calculation. Intense photoinduced intravalence charge transition was observed at λ = 380 and 466 nm, revealing quartet 4MCCE and doublet 2MCCE and their exponential processes. Light energy-dependent variation of *FeIII reactivity was kinetically certified by fitting the apparent rate constant of the radical-chain sequence of photo-Fenton reactions. Covalency is found to compensate for the intravalence charge separation following photoexcitation of the metal center in the MCCE state of Fenton photosensitizer. The *FeIII is established as a model, demonstrating the intravalence hole delocalization in the ES can be leveraged for photo-Fenton reaction or other photocatalytic schemes based on electron transfer chemistry.


Asunto(s)
Hierro , Hierro/química , Oxidación-Reducción , Peróxido de Hidrógeno/química , Cinética
13.
Sci Data ; 11(1): 627, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871784

RESUMEN

Infectious keratitis is among the major causes of global blindness. Anterior segment optical coherence tomography (AS-OCT) images allow the characterizing of cross-sectional structures in the cornea with keratitis thus revealing the severity of inflammation, and can also provide 360-degree information on anterior chambers. The development of image analysis methods for such cases, particularly deep learning methods, requires a large number of annotated images, but to date, there is no such open-access AS-OCT image repository. For this reason, this work provides a dataset containing a total of 1168 AS-OCT images of patients with keratitis, including 768 full-frame images (6 patients). Each image has associated segmentation labels for lesions and cornea, and also labels of iris for full-frame images. This study provides a great opportunity to advance the field of image analysis on AS-OCT images in both two-dimensional (2D) and three-dimensional (3D) and would aid in the development of artificial intelligence-based keratitis management.


Asunto(s)
Aprendizaje Profundo , Queratitis , Tomografía de Coherencia Óptica , Humanos , Queratitis/diagnóstico por imagen , Imagenología Tridimensional , Córnea/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador
14.
Eur J Pharmacol ; 976: 176693, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38834095

RESUMEN

ß-arrestin2 is a versatile protein for signaling transduction in brain physiology and pathology. Herein, we investigated the involvement of ß-arrestin2 in pharmacological effects of fluoxetine for depression. A chronic mild stress (CMS) model was established using wild-type (WT) and ß-arrestin2-/- mice. Behavioral results demonstrated that CMS mice showed increased immobility time in the tail suspension test and forced swimming test, elevated concentrations of pro-inflammatory factors in peripheral blood, increased expression of pyroptosis-related proteins, and increased co-labeling of glial fibrillary acidic protein and Caspase1 p10 in the hippocampus compared to the CON group. Treatment with fluoxetine (FLX) ameliorated these conditions. However, compared with the ß-arrestin2-/- CMS group, these results of the ß-arrestin2-/- CMS + FLX group showed no significant changes. These results suggested that the above effects of FLX could be eliminated by knocking out ß-arrestin2. Mass spectrometry implying that FLX promoted the binding of ß-arrestin2 to the NLRP2 inflammasome of depressed mice. Subsequently, the results of the cellular experiments suggested that the 5HT2B receptor antagonist may attenuate L-kynurenine + ATP-induced cell pyroptosis by attenuating NLRP2 binding to ß-arrestin2. We further found that the lack of ß-arrestin2 eliminated the anti-pyroptosis effect of fluoxetine. In conclusion, ß-arrestin2 is an essential protein for fluoxetine to alleviate pyroptosis in the hippocampal astrocytes of CMS mice. Mechanistically, we found that the 5-HT2BR-ß-arrestin2-NLRP2 axis is vital for maintaining the antidepressant effects of fluoxetine.


Asunto(s)
Antidepresivos , Astrocitos , Depresión , Modelos Animales de Enfermedad , Fluoxetina , Piroptosis , Estrés Psicológico , Arrestina beta 2 , Animales , Fluoxetina/farmacología , Fluoxetina/uso terapéutico , Piroptosis/efectos de los fármacos , Arrestina beta 2/metabolismo , Ratones , Depresión/tratamiento farmacológico , Depresión/metabolismo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Masculino , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ratones Endogámicos C57BL , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Ratones Noqueados , Conducta Animal/efectos de los fármacos , Inflamasomas/metabolismo , Enfermedad Crónica
15.
Comput Biol Med ; 177: 108602, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38805809

RESUMEN

High-quality 3D corneal reconstruction from AS-OCT images has demonstrated significant potential in computer-aided diagnosis, enabling comprehensive observation of corneal thickness, precise assessment of morphological characteristics, as well as location and quantification of keratitis-affected regions. However, it faces two main challenges: (1) prevalent medical image segmentation networks often struggle to accurately process low-contrast corneal regions, which is a vital pre-processing step for 3D corneal reconstruction, and (2) there are no reconstruction methods that can be directly applied to AS-OCT sequences with 180-degree scanning. To combat these, we propose CSCM-CCA-Net, a simple yet efficient network for accurate corneal segmentation. This network incorporates two key techniques: cascade spatial and channel-wise multifusion (CSCM), which captures intricate contextual interdependencies and effectively extracts low-contrast and obscure corneal features; and criss cross augmentation (CCA), which enhances shape-preserved feature representation to improve segmentation accuracy. Based on the obtained corneal segmentation results, we reconstruct the 3D volume data and generate a topographic map of corneal thickness through corneal image alignment. Additionally, we design a transfer function based on the analysis of intensity histogram and gradient histogram to explore more internal cues for better visualization results. Experimental results on CORNEA benchmark demonstrate the impressive performance of our proposed method in terms of both corneal segmentation and 3D reconstruction. Furthermore, we compare CSCM-CCA-Net with state-of-the-art medical image segmentation approaches using three challenging medical fundus segmentation datasets (DRIVE, CHASEDB1, FIVES), highlighting its superiority in terms of segmentation accuracy. The code and models will be made available at https://github.com/qianguiping/CSCM-CCA-Net.


Asunto(s)
Córnea , Humanos , Córnea/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Imagenología Tridimensional/métodos , Algoritmos , Procesamiento de Imagen Asistido por Computador/métodos
16.
Int Immunopharmacol ; 133: 112145, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38691920

RESUMEN

Treatment strategies for paediatric neuroblastoma as well as many other cancers are limited by the unfavourable tumour microenvironment (TME). In this study, the TMEs of neuroblastoma were grouped by their genetic signatures into four distinct subtypes: immune enriched, immune desert, non-proliferative and fibrotic. An Immune Score and a Proliferation Score were constructed based on the molecular features of the subtypes to quantify the immune microenvironment or malignancy degree of cancer cells in neuroblastoma, respectively. The Immune Score correlated with a patient's response to immunotherapy; the Proliferation Score was an independent prognostic biomarker for neuroblastoma and proved to be more accurate than the existing clinical predictors. This double scoring system was further validated and the conserved molecular pattern associated with immune landscape and malignancy degree was confirmed. Axitinib and BI-2536 were confirmed as candidate drugs for neuroblastoma by the double scoring system. Both in vivo and in vitro experiments demonstrated that axitinib-induced pyroptosis of neuroblastoma cells activated anti-tumour immunity and inhibited tumour growth; BI-2536 induced cell cycle arrest at the S phase in neuroblastoma cells. The comprehensive double scoring system of neuroblastoma may predict prognosis and screen for therapeutic strategies which could provide personalized treatments.


Asunto(s)
Axitinib , Inmunoterapia , Neuroblastoma , Microambiente Tumoral , Neuroblastoma/inmunología , Neuroblastoma/terapia , Neuroblastoma/patología , Neuroblastoma/tratamiento farmacológico , Humanos , Microambiente Tumoral/inmunología , Pronóstico , Animales , Inmunoterapia/métodos , Línea Celular Tumoral , Axitinib/uso terapéutico , Niño , Masculino , Femenino , Preescolar , Ratones , Lactante , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular/efectos de los fármacos
17.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 617-626, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38708493

RESUMEN

OBJECTIVE: To investigate immunogenic and toxic effects of graphene oxide (GO) nanoparticles in mouse skeletal muscles and in human blood in vitro. METHODS: GO nanoparticles prepared using a probe sonicator were supended in deionized H2O or PBS, and particle size and surface charge of the nanoparticles were measured with dynamic light scattering (DLS). Different concentrations (0.5, 1.0 and 2.0 mg/mL) of GO suspension or PBS were injected at multiple sites in the gastrocnemius muscle (GN) of C57BL/6 mice, and inflammatory response and immune cell infiltrations were detected with HE and immunofluorescence staining. We also examined the effects of GO nanoparticles on human red blood cell (RBC) morphology, hemolysis and blood coagulation using scanning electron microscope (SEM), spectrophotometry, and thromboelastography (TEG). RESULTS: GO nanoparticles suspended in PBS exhibited better colloidal dispersity, stability and surface charge effects than those in deionized H2O. In mouse GNs, injection of GO suspensions dose- and time-dependently resulted in sustained muscular inflammation and myofiber degeneration at the injection sites, which lasted till 8 weeks after the injection; immunofluorescence staining revealed obvious infiltration of monocytes, macrophages, dendritic cells and CD4+ T cells around the injection sites in mouse GNs. In human RBCs, incubation with GO suspensions at 0.2, 2.0 and 20 mg/mL, but not at 0.002 or 0.02 mg/mL, caused significant alterations of cell morphology and hemolysis. TEG analysis showed significant abnormalities of blood coagulation parameters following treatment with high concentrations of GO. CONCLUSION: GO nanoparticles can induce sustained inflammatory and immunological responses in mouse GNs and cause RBC hemolysis and blood coagulation impairment, suggesting its muscular toxicity and hematotoxicity at high concentrations.


Asunto(s)
Eritrocitos , Grafito , Hemólisis , Ratones Endogámicos C57BL , Músculo Esquelético , Nanopartículas , Animales , Grafito/toxicidad , Grafito/química , Ratones , Eritrocitos/efectos de los fármacos , Humanos , Músculo Esquelético/efectos de los fármacos , Hemólisis/efectos de los fármacos , Tamaño de la Partícula , Coagulación Sanguínea/efectos de los fármacos
18.
Adv Mater ; 36(28): e2313721, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38669677

RESUMEN

Germanium-based monochalcogenides (i.e., GeS and GeSe) with desirable properties are promising candidates for the development of next-generation optoelectronic devices. However, they are still stuck with challenges, such as relatively fixed electronic band structure, unconfigurable optoelectronic characteristics, and difficulty in achieving free-standing growth. Herein, it is demonstrated that two-dimensional (2D) free-standing GeS1-xSex (0 ≤ x ≤ 1) nanoplates can be grown by low-pressure rapid physical vapor deposition (LPRPVD), fulfilling a continuously composition-tunable optical bandgap and electronic band structure. By leveraging the synergistic effect of composition-dependent modulation and free-standing growth, GeS1-xSex-based optoelectronic devices exhibit significantly configurable hole mobility from 6.22 × 10-4 to 1.24 cm2V-1s⁻1 and tunable responsivity from 8.6 to 311 A W-1 (635 nm), as x varies from 0 to 1. Furthermore, the polarimetric sensitivity can be tailored from 4.3 (GeS0.29Se0.71) to 1.8 (GeSe) benefiting from alloy engineering. Finally, the tailored imaging capability is also demonstrated to show the application potential of GeS1-xSex alloy nanoplates. This work broadens the functionality of conventional binary materials and motivates the development of tailored polarimetric optoelectronic devices.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38684053

RESUMEN

Metal-oxide-semiconductor field-effect transistors as basic electronic devices of integrated circuits have been greatly developed and widely used in the past decades. However, as the thickness of the conducting channel decreases, the interface electronic scattering between the gate oxide layer and the channel significantly impacts the performance of the transistor. To address this issue, van der Waals heterojunction field-effect transistors (vdWJFETs) have been proposed using two-dimensional semiconductors, which utilize the built-in electric field at the sharp van der Waals interface to regulate the channel conductance without the need of a complex gate oxide layer. In this study, a novel dual-junction vdWJFET composed of a MoS2 channel and a Te nanosheet gate has been developed. This device achieves an ultralow subthreshold swing (SS) and an extremely low current hysteresis, greatly surpassing the single-junction vdWJFET. In the transistor, the SS decreases from 475.04 to 68.3 mV dec-1, nearly approaching the theoretical limit of 60 mV dec-1 at room temperature. The pinch-off voltage (Vp) decreases from -4.5 to -0.75 V, with a current hysteresis of ∼10 mV and a considerable field-effect mobility (µ) of 36.43 cm2 V-1 s-1. The novel dual-junction vdWJFET provides a new approach to realize a transistor with a theoretical ideal SS and a negligible current hysteresis toward low-power electronic applications.

20.
Ecotoxicol Environ Saf ; 275: 116235, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38520809

RESUMEN

Many gastrointestinal simulation methods have been used to predict bioavailability, but the suitability of different methods for the same metal(loid)s varies widely, which inevitably affects the accuracy of human health risk assessment. Arsenic is a common and important contaminant in many contaminated land situations. It can be readily absorbed and has teratogenic and mutagenic toxicity. Therefore, in this study, four the most commonly used in vitro simulation methods (the Physiologically Based Extraction Test (PBET), In Vitro Gastrointestinal Method (IVG), Soluble Bioavailability Research Consortium (SBRC), the Unified BARGE Method (UBM)) were tested against an in vivo animal live model, to evaluate their effectiveness for the prediction of soil As bioavailability in 10 industrially contaminated soils. The soil As relative bioavailability (RBA) varied between 15% and 68% in the different soils. As bioaccessibility differed between the 4 gastro-intestinal simulation methods. Gastric phase of UBM (UBMG) predicted As relative bioavailability the best of the 4 assays (R2 = 0.81). This study provides theoretical and technical support to refine human health risk assessment of As in soils from urban industrial legacy contaminated sites.


Asunto(s)
Arsénico , Contaminantes del Suelo , Animales , Humanos , Arsénico/análisis , Suelo , Disponibilidad Biológica , Contaminantes del Suelo/análisis , Contaminación Ambiental
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