Immunotherapy has gained increasing focus in treating pancreatic ductal adenocarcinoma (PDAC), since conventional therapies like chemotherapy could not provide satisfactory improvement in overall ...survival outcome of PDAC patients. However, it is still not the game changing solution due to the unique tumor microenvironment and low cancer immunogenicity of PDAC. Thus, inducing more intratumoral effector immune cells as well as reversing immunosuppression is the core of PDAC treatment. Herein, we demonstrate an exosome-based dual delivery biosystem for enhancing PDAC immunotherapy as well as reversing tumor immunosuppression of M2-like tumor associated macrophages (M2-TAMs) upon disruption of galectin-9/dectin 1 axis. The deliver system is constructed from bone marrow mesenchymal stem cell (BM-MSC) exosomes, electroporation-loaded galectin-9 siRNA, and surficially modified with oxaliplatin (OXA) prodrug as an immunogenic cell death (ICD)-trigger. The use of biomaterials, BM-MSC exosomes, can significantly improve tumor targeting efficacy, thus increasing drug accumulation in the tumor site. The combined therapy (iEXO-OXA) elicits anti-tumor immunity through tumor-suppressive macrophage polarization, cytotoxic T lymphocytes recruitment and Tregs downregulation, and achieves significant therapeutic efficacy in cancer treatment.
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We demonstrate that the thermoelectric properties of p-type chalcogenides can be effectively improved by band convergence and hierarchical structure based on a high-entropy-stabilized matrix. The ...band convergence is due to the decreased light and heavy band energy offsets by alloying Cd for an enhanced Seebeck coefficient and electric transport property. Moreover, the hierarchical structure manipulated by entropy engineering introduces all-scale scattering sources for heat-carrying phonons resulting in a very low lattice thermal conductivity. Consequently, a peak zT of 2.0 at 900 K for p-type chalcogenides and a high experimental conversion efficiency of 12% at ΔT = 506 K for the fabricated segmented modules are achieved. This work provides an entropy strategy to form all-scale hierarchical structures employing high-entropy-stabilized matrix. This work will promote real applications of low-cost thermoelectric materials.
Fruits are the defining feature of angiosperms, likely have contributed to angiosperm successes by protecting and dispersing seeds, and provide foods to humans and other animals, with many ...morphological types and important ecological and agricultural implications. Rosaceae is a family with ∼3000 species and an extraordinary spectrum of distinct fruits, including fleshy peach, apple, and strawberry prized by their consumers, as well as dry achenetum and follicetum with features facilitating seed dispersal, excellent for studying fruit evolution. To address Rosaceae fruit evolution and other questions, we generated 125 new transcriptomic and genomic datasets and identified hundreds of nuclear genes to reconstruct a well-resolved Rosaceae phylogeny with highly supported monophyly of all subfamilies and tribes. Molecular clock analysis revealed an estimated age of ∼101.6 Ma for crown Rosaceae and divergence times of tribes and genera, providing a geological and climate context for fruit evolution. Phylogenomic analysis yielded strong evidence for numerous whole genome duplications (WGDs), supporting the hypothesis that the apple tribe had a WGD and revealing another one shared by fleshy fruit-bearing members of this tribe, with moderate support for WGDs in the peach tribe and other groups. Ancestral character reconstruction for fruit types supports independent origins of fleshy fruits from dry-fruit ancestors, including the evolution of drupes (e.g., peach) and pomes (e.g., apple) from follicetum, and drupetum (raspberry and blackberry) from achenetum. We propose that WGDs and environmental factors, including animals, contributed to the evolution of the many fruits in Rosaceae, which provide a foundation for understanding fruit evolution.
High‐throughput explorations of novel thermoelectric materials based on the Materials Genome Initiative paradigm only focus on digging into the structure‐property space using nonglobal indicators to ...design materials with tunable electrical and thermal transport properties. As the genomic units, following the biogene tradition, such indicators include localized crystal structural blocks in real space or band degeneracy at certain points in reciprocal space. However, this nonglobal approach does not consider how real materials differentiate from others. Here, this study successfully develops a strategy of using entropy as the global gene‐like performance indicator that shows how multicomponent thermoelectric materials with high entropy can be designed via a high‐throughput screening method. Optimizing entropy works as an effective guide to greatly improve the thermoelectric performance through either a significantly depressed lattice thermal conductivity down to its theoretical minimum value and/or via enhancing the crystal structure symmetry to yield large Seebeck coefficients. The entropy engineering using multicomponent crystal structures or other possible techniques provides a new avenue for an improvement of the thermoelectric performance beyond the current methods and approaches.
Entropy as a global gene‐like performance indicator is validated by screening multicomponent thermoelectric materials with high entropy, and can be designed via a high‐throughput approach. Optimizing entropy can lead to greatly improved thermoelectric performance through either a significantly depressed lattice thermal conductivity down to its theoretical minimum value and/or via enhancing the structure symmetry to yield large Seebeck coefficients.
The book is an in-depth study of the origins and the trajectories of the law governing social policies in Brazil, China, India, and South Africa, four middle-income countries in the global South with ...a history in social policy making that starts in the 1920s. The policies of these countries affect almost half of the world’s population. The book takes the legal framework of the policies as a starting point, but the main interest lies behind the letter of the law: What were the objectives and goals of social policy over the course of the last 100 years? What were the ideas, ideologies, and values pursued by relevant actors? The book comprises four country studies and a comparative study. The country studies concentrate on the political and social context of social policy making in Brazil, China, India, and South Africa as well as on the ideas, ideologies, and values underpinning the constitution, statutory laws, and case law that frame and shape social policy at the national level. The country studies are complemented by a comparative study exploring and describing the commonalities and differences in the ideational approaches to social policies across the four countries, nationally and – in the formative decades – internationally. The comparative study also identifies the characteristics that make Brazilian, Chinese, Indian, and South African social policies distinct from European social policies. With its emphasis on law and drawing on legal scholarship, the book adds a new dimension to the existing accounts on welfare state building, which, so far, are dominated by European narratives and by scholars with a background in sociology, political science, and development studies. This book is relevant to specialists and peers and will be invaluable to those individuals interested in the fields of comparative and international social security law, human rights law, comparative constitutional law, constitutional history, law and development studies, comparative social policies, global social policies, social work, and welfare state theory. The Open Access version of this book, available at www.taylorfrancis.com, has been made available under a Creative Commons Attribution-Non Commercial-No Derivatives 4.0 license.
Thermal conductivity is a very basic property that determines how fast a material conducts heat, which plays an important and sometimes a dominant role in many fields. However, because materials with ...phase transitions have been widely used recently, understanding and measuring temperature‐dependent thermal conductivity during phase transitions are important and sometimes even questionable. Here, the thermal transport equation is corrected by including heat absorption due to phase transitions to reveal how a phase transition affects the measured thermal conductivity. In addition to the enhanced heat capacity that is well known, it is found that thermal diffusivity can be abnormally lowered from the true value, which is also dependent on the speed of phase transitions. The extraction of the true thermal conductivity requires removing the contributions from both altered heat capacity and thermal diffusivity during phase transitions, which is well demonstrated in four selected kinds of phase transition materials (Cu2Se, Cu2S, Ag2S, and Ag2Se) in experiment. This study also explains the lowered abnormal thermal diffusivity during phase transitions in other materials and thus provides a novel strategy to engineer thermal conductivity for various applications.
The thermal transport equation is corrected to reveal how phase transitions affect the measured thermal conductivity. Thermal diffusivity can be abnormally lowered from the true value, which is also dependent on the speed of phase transitions. The extraction of the true thermal conductivity requires removing the contributions from both altered heat capacity and thermal diffusivity during phase transitions.
Many superionic mixed ionic-electronic conductors with a liquid-like sublattice have been identified as high efficiency thermoelectric materials, but their applications are limited due to the ...possibility of decomposition when subjected to high electronic currents and large temperature gradients. Here, through systematically investigating electromigration in copper sulfide/selenide thermoelectric materials, we reveal the mechanism for atom migration and deposition based on a critical chemical potential difference. Then, a strategy for stable use is proposed: constructing a series of electronically conducting, but ion-blocking barriers to reset the chemical potential of such conductors to keep it below the threshold for decomposition, even if it is used with high electric currents and/or large temperature differences. This strategy not only opens the possibility of using such conductors in thermoelectric applications, but may also provide approaches to engineer perovskite photovoltaic materials and the experimental methods may be applicable to understanding dendrite growth in lithium ion batteries.
Summary
Rice (Oryza sativa) is a short‐day (SD) plant originally having strong photoperiod sensitivity (PS), with SDs promoting and long days (LDs) suppressing flowering. Although the evolution of PS ...in rice has been extensively studied, there are few studies that combine the genetic effects and underlying mechanism of different PS gene combinations with variations in PS.
We created a set of isogenic lines among the core PS‐flowering genes Hd1, Ghd7 and DTH8 using CRISPR mutagenesis, to systematically dissect their genetic relationships under different day‐lengths. We investigated their monogenic, digenic, and trigenic effects on target gene regulation and PS variation.
We found that Hd1 and Ghd7 have the primary functions for promoting and repressing flowering, respectively, regardless of day‐length. However, under LD conditions, Hd1 promotes Ghd7 expression and is recruited by Ghd7 and/or DTH8 to form repressive complexes that collaboratively suppress the Ehd1‐Hd3a/RFT1 pathway to block heading, but under SD conditions Hd1 competes with the complexes to promote Hd3a/RFT1 expression, playing a tradeoff relationship with PS flowering. Natural allelic variations of Hd1, Ghd7 and DTH8 in rice populations have resulted in various PS performances.
Our findings reveal that rice PS flowering is controlled by crosstalk of two modules – Hd1–Hd3a/RFT1 in SD conditions and (Hd1/Ghd7/DTH8)–Ehd1–Hd3a/RFT1 in LD conditions – and the divergences of these genes provide the basis for rice adaptation to broad regions.