Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block ...the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.
A low-carbon energy transition is permeating many industrialized countries due to the overuse of fossil fuels and the climate change. Some countries stress the hydrogen energy in optimizing their ...energy structures. This article examines both the markets and the policies of the hydrogen industry in the World's Top 4 largest economies. To make the comparative analysis more logical, a novel conceptual model for energy transition -- the institution-economics-technology-behavior framework -- has been adopted to make a multi-dimensional discussion. The results show that: (1) From the perspective of strategic intention, developing hydrogen energy is conductive to the energy transition. (2) From the horizontal comparison, each country has its own advantages, however, the main driving factors are different. (3) From the vertical comparison, the hydrogen energy development in each country is still in the stage of quantitative change, and the inflection point of qualitative change has not been reached yet.
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•A novel conceptual model -- IETB framework -- is adopted.•Hydrogen energy serves three functions in the energy transition.•The World's Top 4 largest economies are used for comparative analysis.•Each country has different advantages of developing its own hydrogen energy.•Qualitative inflection point of hydrogen energy development has not yet reached.
Immunotherapies that harness the immune system to kill cancer cells have showed significant therapeutic efficacy in many human malignancies. A growing number of studies have highlighted the relevance ...of neoantigens in recognizing cancer cells by intrinsic T cells. Cancer neoantigens are a direct consequence of somatic mutations presenting on the surface of individual cancer cells. Neoantigens are fully cancer-specific and exempt from central tolerance. In addition, neoantigens are important targets for checkpoint blockade therapy. Recently, technological innovations have made neoantigen discovery possible in a variety of malignancies, thus providing an impetus to develop novel immunotherapies that selectively enhance T cell reactivity for the destruction of cancer cells while leaving normal tissues unharmed. In this review, we aim to introduce the methods of the identification of neoantigens, the mutational patterns of human cancers, related clinical trials, neoantigen burden and sensitivity to immune checkpoint blockade. Moreover, we focus on relevant challenges of targeting neoantigens for cancer treatment.
To dynamically adjust the edge preservation and smoothness of low-light images, this paper proposed a fractional order gradient descent with momentum radial basis function neural network (FOGDMRBF) ...to optimizing Retinex.Its convergence is proved. In order to speed up the convergence process, an adaptive learning rate is used to adjust the training process reasonably. The results verify the theoretical results of the proposed algorithm such as its monotonicity and convergence. The descending curve of error values by FOGDM is more smoother than gradient descent and gradient descent with momentum method. The influence of regularization parameter is analyzed and compared. Compared with Dark Channel Prior, Histogram Equalization, Homomorphic Filtering and Multiple Exposure Fusion, the halo and noise generated are significantly reduced with higher Peak Signal-to-Noise Ratio and Structural Similarity Index.
Ethylenediamine tetraacetate-intercalated Fe-Mn layered double hydroxides (MnFe-EDTA-LDHs) were prepared by coprecipitation. The influence of different factors on Cl− adsorption by MnFe-EDTA-LDHs was ...investigated. Additionally, MnFe-EDTA-LDHs were incorporated into the concrete to study the Cl− erosion properties. The result showed that the Cl− adsorption on MnFe-EDTA-LDHs was affected by the initial pH, dosage, and coexisting anions. The Cl− adsorption process by MnFe-EDTA-LDHs accorded with the pseudo-second-order model and the Redlich–Peterson model. The maximum adsorption capacity of Cl− on MnFe-EDTA-LDHs reached 129.50 mg/g. The adsorption mechanism involved the complexation of O-containing groups, ion exchange, and electrostatic interaction. Moderate additions of MnFe-EDTA-LDHs improved the resistance of the concrete to Cl− erosion, while excessive additions reduced the Cl− erosion resistance. This work indicated that MnFe-EDTA-LDHs effectively retarded the Cl− erosion on concrete.
This paper proposes a data-driven risk assessment model for ship overtaking based on the particle swarm optimization (PSO) improved kernel density estimation (KDE). By minimizing the mean square ...error between the real probability distribution of the ship overtaking point and the kernel density estimation probability distribution calculated by the current kernel density bandwidth, the longitude and latitude of the ship overtaking point are displayed by the color corresponding to the probability as the cost objective function of the search bandwidth of the algorithm. This can better show the distribution of the overtaking points of channel propagation traffic flow. A probability-based ship-overtaking risk evaluation model is developed through the bandwidth and density analysis optimized by an intelligent algorithm. In order to speed up searching the optimal variable width of the kernel density estimator for ship encountering positions, an improved adaptive variable-width kernel density estimator is proposed. The latter reduces the risk of too smooth probability density estimation phenomenon. Its convergence is proved. Finally, the model can efficiently evaluate the risk status of ship overtaking and provide navigational auxiliary decision support for pilots.
Tumor complexity makes the development of highly sensitive tumor imaging probes an arduous task. Here, we construct a peptide‐based near‐infrared probe that is responsive to fibroblast activation ...protein‐α (FAP‐α), and specifically forms nanofibers on the surface of cancer‐associated fibroblasts (CAFs) in situ. The assembly/aggregation‐induced retention (AIR) effect results in enhanced accumulation and retention of the probe around the tumor, resulting in a 5.5‐fold signal enhancement in the tumor 48 h after administration compared to that of a control molecule that does not aggregate. The probe provides a prolonged detectable window of 48 h for tumor diagnosis. The selective assembly of the probe results in a signal intensity over four‐ and fivefold higher in tumor than in the liver and kidney, respectively. With enhanced tumor imaging capability, this probe can visualize small tumors around 2 mm in diameter.
Image of health: A peptide probe labeled with a near‐infrared dye has been developed that can be specifically tailored with a fibroblast activation protein‐α and then self‐assembled in situ into nanofibers on the surface of cancer‐associated fibroblasts. The selective assembly of the probe has resulted in tumor imaging with high sensitivity and specificity, with tumors as small as 2 mm in diameter visualized.
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