The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the ...inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8
T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8
T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.
Development of efficient therapeutic strategy to incorporate ultrasound (US)-triggered sonodynamic therapy (SDT) and ferroptosis is highly promising in cancer therapy. However, the SDT efficacy is ...severely limited by the hypoxia and high glutathione (GSH) in the tumor microenvironment, and ferroptosis is highly associated with reactive oxygen species (ROS) and GSH depletion.
A manganese porphyrin-based metal-organic framework (Mn-MOF) was constructed as a nanosensitizer to self-supply oxygen (O
) and decrease GSH for enhanced SDT and ferroptosis.
and
analysis, including characterization, O
generation, GSH depletion, ROS generation, lipid peroxidation, antitumor efficacy and tumor immune microenvironment were systematically evaluated.
Mn-MOF exhibited catalase-like and GSH decreasing activity
. After efficient internalization into cancer cells, Mn-MOF persistently catalyzed tumor-overexpressed H
O
to
produce O
to relieve tumor hypoxia and decrease GSH and GPX4, which facilitated the formation of ROS and ferroptosis to kill cancer cells upon US irradiation in hypoxic tumors. Thus, strong anticancer and anti-metastatic activity was found in H22 and 4T1 tumor-bearing mice after a single administration of Mn-MOF upon a single US irradiation. In addition, Mn-MOF showed strong antitumor immunity and improved immunosuppressive microenvironment upon US irradiation by increasing the numbers of activated CD8
T cells and matured dendritic cells and decreaing the numbers of myeloid-derived suppressor cells in tumor tissues.
Mn-MOF holds great potential for hypoxic cancer therapy.
•Kinetic study of inactivation efficacy and content of reactive species.•Better bactericidal efficacy achieved by producing reactive species controllably.•Assessment of biological effects of ...gas-liquid phase plasma bacteria inactivation.•Development of a practical way for disinfection with gas-liquid phase discharge.
Disinfection of bacteria-contaminated water is crucial to public health. In this work, a gas-liquid phase air and oxygen plasma is designed to selectively and controllably generate reactive species and efficiently inactivate Staphylococcus aureus (S. aureus) in the liquid. Optical emission spectroscopy (OES) and fluorescent probes are used to analyze the formation of reactive species induced by the plasma in the gas-liquid and liquid phases. OH radicals are observed to be the predominant species in the liquid induced by the oxygen plasma. In the air plasma, owing to the presence of active nitrogen, nitrogen-containing reactive species including NO, HNO2, HNO3, and ONOOH are generated in the liquid. The bactericidal and biological effects associated with the formation of liquid products are investigated. The different bactericidal effects of the air and oxygen plasma (direct and indirect) treatment show that the inactivation efficacy is related to the species and content of the reactive oxygen and nitrogen species produced by the air and oxygen plasma in the liquid. The better inactivation effect of direct oxygen plasma treatment stems from the larger concentration of OH radicals. The presence of active nitrogen, formation of nitrogen-based reactive species, and acidification are responsible for the better bactericidal activity in the air plasma indirect treatment. Cell membrane damage and accumulation of intracellular reactive oxygen species result in inactivation of S. aureus. Selective and more efficient formation of reactive species is attractive to industrial processes such as waste water treatment.
The multi-electrode arc plasma has attracted wide attention in various scientific studies. A multi-cathode arc plasma generator with a 20 mm-diameter anode channel is studied in this work. ...Experiments were carried out to obtain arc plasma images and the arc voltage spectrum at different currents. At a current of 30A, the arc produced by the cathode is independent, and at a current of 50A, the arc produced by the cathode is coupled together in the center of the arc chamber. The results show that both the voltage and spatial distribution of each arc of multiple arcs are more stable when the current is 50A. Additionally, we constructed a 3D stable non-local thermal equilibrium model to calculate the temperature, current density, and Lorentz force fields of the multi-cathode torch. The voltages obtained in numerical and experimental results show good agreement. The numerical results show that the Lorentz force distributions and current intensity increase as current increases. The greater the current, the stronger the interaction between the arc plasmas. In addition, the speed of the multi-cathode plasma is lower than that in a traditional arc torch. The combined results are then used to analyze the forming mechanism of arc plasma in the multi-cathode torch. Lorentz forces play a critical role in the characteristics of the plasma in the multi-cathode arc generator.
Abstract
Due to improper selection of gradient update direction or learning rate, SGD optimization algorithms for deep learning suffer from oscillation and slow convergence. Although Adam algorithm ...can adaptively adjust the update direction and learning rate at the same time, it still has the overshoot phenomenon, and hence suffers from wasting computing resources and slow convergence. In this work, the PID controller from the feedback control area is borrowed to re‐express the adaptive optimization algorithm (the Adam optimization algorithm is derived into the integral I component form) of deep learning. In order to alleviate the overshoot phenomenon and hence speed up the convergence of Adam, a complete adaptive PID optimizer (adaptive‐PID) is proposed by incorporating the proportional P and derivative D component. Extensive experiments on standard data sets verify that the proposed adaptive‐PID algorithm significantly outperforms Adam algorithm in terms of convergence rate and accuracy.
A series of new compounds were synthesised by adding azo functional groups and chlorine substituent to the central bent-cores to form a 4-chloro-1,3-dizaophenylene bent-core. The structure, mesogenic ...properties, and photosensitivity of these compounds were characterised. The results show these synthesised compounds exhibit a broad temperature window up to 63.8°C for nematic phase and the rapid rate of trans - cis photoisomerisation. For instance, at 95°C, compound 4c in nematic phase became an isotropic liquid under UV-irradiation in 3 s and could be restored to nematic under natural visible light in 5 s. Quantum mechanics calculation confirms that using azos instead of esters as the central linkages can effectively reduce the molecular dipole moment, which appears to promote favourable mesogenic and photonic characteristics. Moreover, varying the carbon number in the terminal alkyl chains can alter molecular dipole moment and polarisability anisotropy, which are strongly correlated with the phase transition temperature and temperature range of the nematic phase. These findings suggest that 1) changing azo group position can effectively alter the intermolecular interactions by varying molecular polarity and polarisability; 2) reducing long-range electrostatic interactions can promote favourable mesogenic and possibly photonic properties of azobenzene bent-core liquid crystal.
Ceramic waste forms are designed to immobilize radionuclides for permanent disposal in geological repositories. One of the principal criteria for the effective incorporation of waste elements is ...their compatibility with the host material. In terms of performance under environmental conditions, the resistance of the waste forms to degradation over long periods of time is a critical concern when they are exposed to natural environments. Due to their unique crystallographic features and behavior in nature environment as exemplified by their natural analogues, ceramic waste forms are capable of incorporating problematic nuclear waste elements while showing promising chemical durability in aqueous environments. Recent studies of apatite- and hollandite-structured waste forms demonstrated an approach that can predict the compositions of ceramic waste forms and their long-term dissolution rate by a combination of computational techniques including machine learning, first-principles thermodynamics calculations, and modeling using kinetic rate equations based on critical laboratory experiments. By integrating the predictions of elemental incorporation and degradation kinetics in a holistic framework, the approach could be promising for the design of advanced ceramic waste forms with optimized incorporation capacity and environmental degradation performance. Such an approach could provide a path for accelerated ceramic waste form development and performance prediction for problematic nuclear waste elements.
In this study, a multiple cathodes arc plasma generator was employed for the preparation of spherical tungsten powder. The annular and axisymmetric cathode configuration of the generator allowed for ...axial powder feeding. The investigation focused on the effect of the powder feed rate, power and plasma composition on the powder spheroidization rate using experimental and numerical modelling approach. The experimental results showed that the spheroidization rate increased significantly, when the powder feed rate decreased from 30 to 5 g/min, and the spheroidization rate was more than 95% at 5 g/min. The spherical tungsten powders prepared in this torch had good flowability, high apparent density, and uniform particle diameter distribution. A three-dimensional local thermal equilibrium model was used to analyze the temperature and the velocity field in the arc plasma generator. The results of numerical simulation showed that the arc plasma in the multi-cathode generator had high temperature and low velocity, and the powders had good trajectory in the axial direction. In summary, multi-cathode arc generators have great potential in tungsten powder spheroidization.
With the continuous construction of transportation infrastructure, intersection nodes have been increasing rapidly, bringing growing numbers of tunnel- and exit-adjacent sections (TEAS) in mountain ...expressways in China. With the complex variation in the surrounding environment, drivers always face congestion and confusion on tunnel and the exit connecting sections (TECS) without adequate length, meanwhile excessively long TECS create detours. To better provide a sustainable design strategy for TEAS, based on a certain section of expressway in Shaanxi, China, this paper establishes a theoretical calculation model through analysis. The characteristics of traffic flow and drivers' light adaptation at tunnel exit are obtained through data collection and driving tests, and the length requirements of the tunnel and exit connecting sections (TECS) are discussed. A VISSIM microscopic simulation model is also built under various design schemes and entropy-based multi-attribute decision making (EBMADM) is used to objectively calculate the weights of the four selected evaluation indexes. Then, the design schemes of the TECS with different lengths have been comprehensively evaluated. The results show the match between the evaluation results of EBMADM with theoretical calculations under existing traffic conditions, which proves the rationality of EBMADM in such problems. For more cases, the results of the EBMADM evaluation show a positive correlation between the length of TECS for the best performing design scheme with traffic volume and diverging ratio.
Plant metabolites play vital roles in regulating the behavior of herbivore insects. Virus infection can universally alter plant metabolites to manipulate the orientation and feeding behaviors of ...insect vector, to favor the transmission of virus. Thus, determining the differentially accumulated metabolites of plant upon virus infection could provide insights into understanding how the triple interactions among plant, virus and insect vector happens. Our previous studies have found that vector whitefly Bemisia tabaci (Gennadius, Hemiptera: Aleyrodidae) showed different orientation behavior and performance on CCYV-infected and healthy cucumber plants. Cucurbit chlorotic yellows virus (CCYV) is exclusively transmitted by B. tabaci in a semi-persistent mode. In this study, we take the CCYV, B. tabaci and cucumber as a research system to explore the functions of phyto-metabolites in the triple interactions.
A total of 612 metabolites changed upon CCYV infection were monitored. Metabolites mainly enriched in flavonoids, lipids, nucleotides and their derivatives. At 7 days post CCYV inoculation (dpi), the contents of lipids, terpenoids and flavonoids remarkably decreased, while amino acids, nucleotides and their derivatives notably up-accumulated. At 15 dpi, the accumulation of flavonoids were still significantly reduced upon CCYV infection, while lipids, amino acids, nucleotides and derivatives were remarkably enhanced. Most of significantly increased metabolites were lipids (lysophosphatidylethanolamine, LPE; lysophosphatidylcholine, LPC and their isomers). Also, the number of significantly changed metabolites increased with the infection period. However, only a few organic acids and phenolic acids showed difference between CCYV-infected and healthy cucumber plants.
CCYV infection repressed the defensive flavonoids, terpeneoids metabolism but triggered the lipids, amino acids and nucleotides metabolism with the inoculation period. This result suggests that CCYV-infection makes cucumber plants more susceptible for whiteflies attack and CCYV infection. The reduction of defensive comounds and the increase of amino acids may be partially responsible for enhancing feeding preference of whiteflies to CCYV-infected hosts. CCYV may hijacked lipid metabolism for virus replication and assembly.
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