The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for ...the Kras
Tp53
(KP) and the Kras
Lkb1
(KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8
and CD4
T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.
Inorganic–organic hybrid molecular multiferroic and magnetoelectric materials, similar to multiferroic oxide compounds, have recently attracted increasing attention because they exhibit diverse ...architectures, a flexible framework, fascinating physics, and potential magnetoelectric functionalities in novel multifunctional devices such as energy transformation devices, sensors, and information storage systems. Herein, the classification of multiferroicity and magnetoelectricity is briefly outlined and then the recent advances in the multiferroicity and magnetoelectricity of inorganic–organic hybrid molecular materials, particularly magnetoelectricity and the relevant magnetoelectric mechanisms and their categories are summarized. In addition, a personal perspective and an outlook are provided.
Magnetoelectricity plays a huge role in the development of next‐generation devices. Since the discovery of multiferroic properties in inorganic–organic hybrid molecular materials, the related magnetoelectric behaviors have been gradually discovered and advanced at a vigorous pace. This brief development of multiferroicity/magnetoelectricity in inorganic–organic hybrid molecular materials shows their prospect for future development.
Quantum teleportation provides a 'disembodied' way to transfer quantum states from one object to another at a distant location, assisted by previously shared entangled states and a classical ...communication channel. As well as being of fundamental interest, teleportation has been recognized as an important element in long-distance quantum communication, distributed quantum networks and measurement-based quantum computation. There have been numerous demonstrations of teleportation in different physical systems such as photons, atoms, ions, electrons and superconducting circuits. All the previous experiments were limited to the teleportation of one degree of freedom only. However, a single quantum particle can naturally possess various degrees of freedom--internal and external--and with coherent coupling among them. A fundamental open challenge is to teleport multiple degrees of freedom simultaneously, which is necessary to describe a quantum particle fully and, therefore, to teleport it intact. Here we demonstrate quantum teleportation of the composite quantum states of a single photon encoded in both spin and orbital angular momentum. We use photon pairs entangled in both degrees of freedom (that is, hyper-entangled) as the quantum channel for teleportation, and develop a method to project and discriminate hyper-entangled Bell states by exploiting probabilistic quantum non-demolition measurement, which can be extended to more degrees of freedom. We verify the teleportation for both spin-orbit product states and hybrid entangled states, and achieve a teleportation fidelity ranging from 0.57 to 0.68, above the classical limit. Our work is a step towards the teleportation of more complex quantum systems, and demonstrates an increase in our technical control of scalable quantum technologies.
•The multi-objective optimization method is developed for thermal-fluid problems.•Pareto-optimal solutions based on the multi-objective function are provided.•A novel model for heat transfer ...enhancement and pressure drop reduction.•The influence of non-Newtonian fluid on the microchannel heat transfer system is considered.
This paper presents a multi-objective topology optimization method for convective heat transfer problems based on Navier-Stokes and heat transport equations. In this research, the pressure drop (or energy dissipation) function and the recoverable thermal power function are combined and optimized as a multi-objective function. A Pareto algorithm is constructed, based on a weighted-sum method using different weight coefficients. The Pareto solutions composed of a set of optimal solutions are obtained to reveal the trade-off relationship between the objective functions. The effects of non-Newtonian fluid on the flow-channel arrangement and heat transfer performance are numerically studied. In the numerical method, the interpolation term in the density-based topology optimization method is modified, while the filtering method is used to solve the problems of grayscale and the flow channel discontinuity. The results show that the differences between the optimal structures for non-Newtonian fluid and Newtonian fluid are more obvious at Re = 0.01 in the dual-terminal devices. Under the same situation, blood (non-Newtonian fluid) has greater energy dissipation and better heat transfer performance than water (Newtonian fluid).
There is an increasingly urgent need of lightweight components in aerospace industry, among which aluminum (Al) alloys have been the optimal materials of choice for aircraft structural parts since ...being used in the Junkers F.13 aircraft in the 1920s. Compared to other metal materials, Al alloys have a lower density, and the use of Al alloys reduces the total weight of the aircraft and improves fuel efficiency and load capacity. Meanwhile, the strength and hardness of Al alloys with alloying and heat treatment can be significantly enhanced for uses in high loads and vibration environments. Furthermore, in the harsh aerospace environment, aircraft may receive various climatic conditions and chemical corrosion. Due to good corrosion and fatigue resistance, Al alloys demonstrate excellent performance under these conditions, ensuring the long–term service life of aircraft. In addition, Al alloys have good recyclability, and they can be recycled to reduce resource consumption and environmental load, in line with the principle of sustainable development. In recent years, although composites have been widely used in aerospace, high–strength Al alloys are still in an indispensable position. Therefore, this article reviews the progress and applications of Al alloys commonly used in aerospace. The common strengthening methods and advanced manufacturing and processing technologies of Al alloy are also discussed, which can provide references for the development of advanced high–performance aviation Al alloys in the future.
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Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence ...is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA) as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: −0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
It is desirable to obtain high levels of viable Lacticaseibacillus paracasei, a widely used food probiotic whose antibacterial activity and potential application in milk remain largely ...uninvestigated. Here, we isolated and purified the L. paracasei strain XLK 401 from food-grade blueberry ferments and found that it exhibited strong antibacterial activity against both gram-positive and gram-negative foodborne pathogens, including Staphylococcus aureus, Salmonella paratyphi B, Escherichia coli O157, and Shigella flexneri. Then, we applied alternating tangential flow (ATF) technology to produce viable L. paracasei XLK 401 cells and its cell-free supernatant (CFS). Compared with the conventional fed-batch method, 22 h of ATF-based processing markedly increased the number of viable cells of L. paracasei XLK 401 to 12.14 ± 0.13 log cfu/mL. Additionally, the CFS exhibited good thermal stability and pH tolerance, inhibiting biofilm formation in the abovementioned foodborne pathogens. According to liquid chromatography-mass spectrometry analysis, organic acids were the main antibacterial components of XLK 401 CFS, accounting for its inhibition activity. Moreover, the CFS of L. paracasei XLK 401 effectively inhibited the growth of multidrug-resistant gram-positive Staph. aureus and gram-negative E. coli O157 pathogens in milk, and caused a reduction in the pathogenic cell counts by 6 to 7 log cfu/mL compared with untreated control, thus considerably maintaining the safety of milk samples. For the first time to our knowledge, ATF-based technology was employed to obtain viable L. paracasei on a large scale, and its CFS could serve as a broad-spectrum biopreservative for potential application against foodborne pathogens in milk products.
Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this ...study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.
Objective
Osteosarcoma is a primary malignancy originating from mesenchymal tissue characterized by rapid growth, early metastasis and poor prognosis. Ginsenoside Rg5 (G‐Rg5) is a minor ginsenoside ...extracted from Panax ginseng C.A. Meyer which has been discovered to possess anti‐tumor properties. The objective of current study was to explore the mechanism of G‐Rg5 in the treatment of osteosarcoma by network pharmacology and molecular docking technology.
Methods
Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases were used to obtain the pharmacological targets of G‐Rg5. Related genes of osteosarcoma were searched for in the GeneCards, OMIM and DrugBank databases. The targets of G‐Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G‐Rg5 in the treatment of osteosarccoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein–protein interaction (PPI) network, and the Database for Annotation, Visualization and Integrated Discovery (DAVID) platform was used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. AutoDock vina software was used to perform molecular docking between G‐Rg5 and hub targets. The hub genes were imported into the Kaplan–Meier Plotter online database for survival analysis.
Results
A total of 61 overlapping targets were obtained. The related signaling pathways mainly included PI3K‐Akt signaling pathway, Proteoglycans in cancer, Lipid and atherosclerosis and Kaposi sarcoma‐associated herpesvirus infection. Six hub targets including PIK3CA, SRC, TP53, MAPK1, EGFR, and VEGFA were obtained through PPI network and targets‐pathways network analyses. The results of molecular docking showed that the binding energies were all less than –7 kcal/mol. And the results of survival analysis showed TP53 and VEGFA affect the prognosis of sarcoma patients.
Conclusion
This study explored the possible mechanism of G‐Rg5 in the treatment of osteosarcoma using network pharmacology method, suggesting that G‐Rg5 has the characteristics of multi‐targets and multi‐pathways in the treatment of osteosarcoma, which lays a foundation for the follow‐up experimental and clinical researches on the therapeutic effects of G‐Rg5 on osteosarcoma.
The pharmacological targets of Rg5 were selected from the Pharmmapper, SwissTargetPrediction and similarity ensemble approach databases. The osteosarcoma genes were found from the GeneCards, OMIM, and drugbank databases.The targets of G‐Rg5 and the related genes of osteosarcoma were intersected to obtain the potential target genes of G‐Rg5 against osteosarcoma. The STRING database and Cytoscape 3.8.2 software were used to construct the protein–protein interaction (PPI) network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were identified by the DAVID database. Hub genes were obtained through PPI network and targets‐pathways network analyses. AutoDock vina software was used to perform molecular docking between G‐Rg5 and hub targets. The hub genes were then imported into the Kaplan–Meier Plotter online database for survival analysis.
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