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The efficacy of Adoptive Cell Therapy (ACT) for solid tumor is still mediocre. This is mainly because tumor cells can hijack ACT T cells' immune checkpoint pathways to exert immunosuppression in the tumor microenvironment. Immune Checkpoint Inhibitors such as anti-PD-1 (aPD1) can counter the immunosuppression, but the synergizing effects of aPD1 to ACT was still not satisfactory. Here we demonstrate an approach to safely anchor aPD1-formed nanogels onto T cell surface via bio-orthogonal click chemistry before adoptive transfer. The spatial-temporal co-existence of aPD1 with ACT T cells and the responsive drug release significantly improved the treatment outcome of ACT in murine solid tumor model. The average tumor weight of the group treated by cell-surface anchored aPD1 was only 18 % of the group treated by equivalent dose of free aPD1 and T cells. The technology can be broadly applicable in ACTs employing natural or Chimeric Antigen Receptor (CAR) T cells.
Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Animais , Terapia Baseada em Transplante de Células e Tecidos , Inibidores de Checkpoint Imunológico , Imunoterapia Adotiva , Camundongos , Nanogéis , Neoplasias/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Microambiente TumoralRESUMO
Precise and timely leaf area index (LAI) estimation for winter wheat is crucial for precision agriculture. The emergence of high-resolution unmanned aerial vehicle (UAV) data and machine learning techniques offers a revolutionary approach for fine-scale estimation of wheat LAI at the low cost. While machine learning has proven valuable for LAI estimation, there are still model limitations and variations that impede accurate and efficient LAI inversion. This study explores the potential of classical machine learning models and deep learning model for estimating winter wheat LAI using multispectral images acquired by drones. Initially, the texture features and vegetation indices served as inputs for the partial least squares regression (PLSR) model and random forest (RF) model. Then, the ground-measured LAI data were combined to invert winter wheat LAI. In contrast, this study also employed a convolutional neural network (CNN) model that solely utilizes the cropped original image for LAI estimation. The results show that vegetation indices outperform the texture features in terms of correlation analysis with LAI and estimation accuracy. However, the highest accuracy is achieved by combining both vegetation indices and texture features to invert LAI in both conventional machine learning methods. Among the three models, the CNN approach yielded the highest LAI estimation accuracy (R 2 = 0.83), followed by the RF model (R 2 = 0.82), with the PLSR model exhibited the lowest accuracy (R 2 = 0.78). The spatial distribution and values of the estimated results for the RF and CNN models are similar, whereas the PLSR model differs significantly from the first two models. This study achieves rapid and accurate winter wheat LAI estimation using classical machine learning and deep learning methods. The findings can serve as a reference for real-time wheat growth monitoring and field management practices.
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Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.
Assuntos
Lesões Encefálicas , Gasderminas , Hemorragia Subaracnóidea , Humanos , Lesões Encefálicas/metabolismo , Inflamassomos/metabolismo , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Piroptose , Hemorragia Subaracnóidea/metabolismo , Gasderminas/antagonistas & inibidoresRESUMO
Shear thickening fluid (STF) is investigated to strength soft armor; however, its impact resistance still does not meet practical needs. In this work, a small amount of hydroxylated fullerene (C60) was mixed with STF to improve the thickening ratio. First, furfuryl alcohol (FA) was grafted onto C60 through a Diels-Alder (D-A) reaction to improve the dispersity of C60 in the STF. Sheath-core composite fibers (polyketone (PK) as the sheath and STF as the core) were then fabricated by coaxial electrospinning. Finally, composite fibers containing STF and C60 were wrapped on the surface of aramid yarns to fabricate a core-spun yarn. Under impact, these core-spun yarns manifested the characteristics of aramid fibers and the thickening advantages of the STF, solving problems of the hygroscopicity, migration, and leakage of STF. In addition, the content of STF was also greatly increased. The spike punching resistance of the core-spun yarn fabric is about 2.8 times that of the aramid fabric (AF) under the same area density. Impact-resistant core-spun yarn fabrics could provide a new direction for the development of soft armor.
RESUMO
BACKGROUND: Diffuse axonal injury (DAI) accounts for 30-40% of total neurotrauma,majority among them manifest with consciousness disturbance.At present, the understanding of the treatment of coma and awakening in patients with DAIs is still limited.This study is characterized by the use of electroacupuncture along with conventional Western medicine to promote consciousness more effectively in comatose patients with DAIs, shorten their time spent in a coma, and gain time for more favorable treatments during follow-up rehabilitation in order to improve the cure rate, reduce the morbidity rate, and achieve better therapeutic effects. METHODS: In this randomized controlled study, 145 comatose patients with DAIs (type III) were divided into the treatment group (n = 71) and control group (n = 74). The patients in the control group were treated with conventional Western medicine, while those in the treatment group were treated with both electroacupuncture and conventional treatment. The Glasgow Coma Scale (GCS) scores and consciousness-promotion rates of both groups were observed before treatment as well as 10, 20, and 30 days after treatment. Meanwhile, serum acetylcholinesterase E (AchE) concentrations in both groups were measured with ELISA, while AchE activity was determined with the rate method. Correlations between GCS score, AchE concentration, and AchE activity in the treatment group were analyzed by using the stepwise multiple regression method. RESULTS: The GCS scores in the treatment group showed significant increases after the first, second, and third courses of treatment when compared to the pre-treatment scores (P <0.05). After 1 course of treatment, the GCS scores in the control group were not statistically significantly different compared to the pre-treatment scores(P >0.05), whereas after 2 and 3 courses of treatment, the differences were of greater statistical significance (P <0.05). Statistically significant differences between the 2 groups were found in GCS scores in the same course of treatment (P <0.05). The consciousness-promotion rates between the 2 groups after the same treatment course were statistically significantly different (P <0.05). Both the standardized regression coefficients and partial correlation coefficients showed that AchE concentration had a certain influence on GCS score (|Beta| = 0.3601; r Y2.1 = 0.726). CONCLUSIONS: Conventional Western medicine combined with electroacupuncture treatment may promote the consciousness of patients with DAIs and shorten the amount of time they spend comatose. Furthermore, the neurotransmitter AchE may play a role in the pathophysiological mechanism of consciousness promotion.
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Both topography and the occurrence of wildfire can strongly affect soil properties in forest successions. Although numerous studies have examined the effects of fire and topography, few have explored their shifting relative importance with time since fire. We measured physical, chemical, and biological soil properties in two topographic positions (north-facing and south-facing) in a Chinese boreal forest along a gradient of fire history. In the control site, topography strongly influenced soil properties, with north-facing slopes having higher soil moisture (SM), depth of organic matter layer (OML), total carbon and inorganic N concentrations, and lower pH, dissolved organic carbon (DOC) and nitrogen (DON). In the 1-year-post-fire site, wildfire erased topographic effects on soil variables, and greater changes in soil properties occurred on the north-facing slopes. The wildfire significantly increased soil pH, DON, ammonium and nitrate, and decreased SM, OML, DOC and microbial biomass, while no significant differences in soil properties appeared between high- and low-severity plots. In the 11-year-post-fire site, most soil properties were similar to the control except for microbial biomass, OML and DOC; topography again became a significant factor in explaining variations in soil properties. Fire severity was highly correlated only with soil pH in the 1-year-post-fire site, whereas topographic factors were always correlated with some soil properties in the three sites. In the 1-year-post-fire site, wildfire explained almost five times more variance than topography for most soil properties, whereas in the 11-year-post-fire site, the proportion of variance explained by topography increased and even surpassed that by wildfire. These results demonstrate that the resilience of Larix gmelinii forest soils might be controlled by wildfires in the short term but by topography in the long term.