ABSTRACT
Materials are more easily damaged during accidents that involve rapid deformation. Here, a design strategy is described for electronic materials comprised of conducting polymers that defies this orthodox property, making their extensibility and toughness dynamically adaptive to deformation rates. This counterintuitive property is achieved through a morphology of interconnected nanoscopic core-shell micelles, where the chemical interactions are stronger within the shells than the cores. As a result, the interlinked shells retain material integrity under strain, while the rate of dissociation of the cores controls the extent of micelle elongation, which is a process that adapts to deformation rates. A prototype based on polyaniline shows a 7.5-fold increase in ultimate elongation and a 163-fold increase in toughness when deformed at increasing rates from 2.5 to 10 000% min-1 . This concept can be generalized to other conducting polymers and highly conductive composites to create "self-protective" soft electronic materials with enhanced durability under dynamic movement or deformation.
ABSTRACT
bHLH transcription factors are involved in multiple aspects of plant biology, such as the response to abiotic stress. Erigeron breviscapus is a composite plant, and its rich flavonoids have strong preventive and therapeutic effects on cardio cerebral vascular disease. EbbHLH80, a gene from E. breviscapus that positively regulates flavonoid synthesis, was previously characterized. However, it is unclear whether EbbHLH80 increases flavonoid accumulation, which affects salt tolerance. The function of EbbHLH80 in transgenic tobacco seeds was identified by phylogenetic analysis and metabolome-transcriptome analysis. We investigated the role of EbbHLH80 in salt stress response. Our results showed that the expression of EbbHLH80 increased following salt treatment. Integrating the metabolome and transcriptome analysis of EbbHLH80-OE and Yunyan 87 (WT) seeds, we identified several genes and metabolites related to flavonoid biosynthesis and salt stress. Moreover, EbbHLH80-OE plants displayed higher salt tolerance than wild-type plants during seed germination and seedling growth. After salt treatment, transgenic tobacco had significantly lower levels of reactive oxygen species (ROS) than WT, with enhanced levels of antioxidant enzyme expression. Altogether, our results demonstrated that EbbHLH80 might be a positive regulator, promoting salt tolerance by modulating ROS scavenging and increasing stress-responsive genes.
Subject(s)
Flavonoids , Plant Proteins , Reactive Oxygen Species/metabolism , Flavonoids/pharmacology , Flavonoids/metabolism , Plant Proteins/genetics , Phylogeny , Stress, Physiological/genetics , Gene Expression Regulation, Plant , Plants, Genetically Modified/metabolismABSTRACT
Foaming effect strongly impacts the physical and mechanical properties of foam glass materials, but an understanding of its mechanism especially at the molecular level is still limited. In this study, the foaming effects of dextrin, a mixture of dextrin and carbon, and different carbon allotropes are investigated with respect to surface morphology as well as physical and mechanical properties, in which 1 wt.% carbon black is identified as an optimal choice for a well-balanced material property. More importantly, the different foaming effects are elucidated by all-atomistic molecular dynamics simulations with molecular-level insights into the structure-property relationships. The results show that smaller pores and more uniform pore structure benefit the mechanical properties of the foam glass samples. The foam glass samples show excellent chemical and thermal stability with 1 wt.% carbon as the foaming agent. Furthermore, the foaming effects of CaSO4 and Na2HPO4 are investigated, which both create more uniform pore structures. This work may inspire more systematic approaches to control foaming effect for customized engineering needs by establishing molecular-level structure-property-process relationships, thereby, leading to efficient production of foam glass materials with desired foaming effects.
ABSTRACT
The increasing demand for safe and effective treatments of chronic pain has promoted the investigation of novel analgesic drugs. Some herbals have been known to be able to relieve pain, while the chemical basis and target involved in this process remained to be clarified. The current study aimed to find anti-nociceptive candidates targeting transient receptor potential ankyrin 1 (TRPA1), a receptor that implicates in hyperalgesia and neurogenic inflammation. In the current study, 156 chemicals were tested for blocking HEK293/TRPA1 ion channel by calcium-influx assay. Docking study was conducted to predict the binding modes of hit compound with TRPA1 using Discovery Studio. Cytotoxicity in HEK293 was conducted by Cell Titer-Glo assay. Additionally, cardiotoxicity was assessed via xCELLigence RTCA system. We uncovered that cardamonin selectively blocked TRPA1 activation while did not interact with TRPV1 nor TRPV4 channel. A concentration-dependent inhibitory effect was observed with IC50 of 454 nM. Docking analysis of cardamonin demonstrated a compatible interaction with A-967079-binding site of TRPA1. Meanwhile, cardamonin did not significantly reduce HEK293 cell viability, nor did it impair cardiomyocyte constriction. Our data suggest that cardamonin is a selective TRPA1 antagonist, providing novel insight into the target of its anti-nociceptive activity.
Subject(s)
Chalcones/chemistry , Chalcones/pharmacology , Chronic Pain/drug therapy , Molecular Docking Simulation , Nerve Tissue Proteins/antagonists & inhibitors , TRPC Cation Channels/antagonists & inhibitors , Transient Receptor Potential Channels/antagonists & inhibitors , Animals , Calcium Channels/genetics , Calcium Channels/metabolism , Chronic Pain/metabolism , Chronic Pain/pathology , HEK293 Cells , Humans , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Rats , Rats, Sprague-Dawley , TRPA1 Cation Channel , TRPC Cation Channels/genetics , TRPC Cation Channels/metabolism , Transient Receptor Potential Channels/genetics , Transient Receptor Potential Channels/metabolismABSTRACT
Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali, was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC50 value of 13.0 µM. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 µM. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC50 value was determined as 21.9 µM. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.
Subject(s)
Adipocytes/metabolism , Calcium/metabolism , Cytoplasm/metabolism , Drugs, Chinese Herbal/chemistry , Lipid Metabolism/physiology , Sapogenins/pharmacology , 3T3 Cells , Adipocytes/drug effects , Animals , Astragalus Plant/chemistry , Astragalus propinquus , Cytoplasm/drug effects , Drugs, Chinese Herbal/pharmacology , Lipid Metabolism/drug effects , MiceABSTRACT
The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy.
Subject(s)
Abietanes , Analgesics , Anti-Inflammatory Agents , Nerve Tissue Proteins/antagonists & inhibitors , Transient Receptor Potential Channels/antagonists & inhibitors , Abietanes/chemistry , Abietanes/pharmacology , Analgesics/chemistry , Analgesics/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Calcium Channels/genetics , HEK293 Cells , Humans , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/genetics , Oximes/pharmacology , Pain Management , TRPA1 Cation Channel , Transient Receptor Potential Channels/agonists , Transient Receptor Potential Channels/geneticsABSTRACT
Panax notoginseng (PN) is one of the commonly used clinical medicines for cardiovascular diseases and possesses a variety of pharmacological effects. P. notoginseng saponins (PNS) are the most important bioactive components in PN. The purpose of this study was to explain the mechanism of PNS on molecular network level. 18 targets of the main medicinal ingredients of PNS were gained by virtual screening based on pharmacophores and data mining. A protein interaction network of PNS was constructed with 189 nodes and 721 interactions. By a graph theoretic clustering algorithm Molecular Complex Detection (MCODE), 14 modules were detected. Gene ontology (GO) enrichment analysis of the modules demonstrated that the roles of PNS played in cardiovascular disease related to multiple biological processes, which could represent the characteristics of traditional Chinese medicine (TCM) as a whole to regulate the disease. The results showed that the blood circulation and hemostasis efficacy of PN related with the biological processes such as positive regulation of cAMP metabolic and biosynthetic process, platelet activation and regulation of blood vessel size, regulation of T cell proliferation and differentiation and so on. Therefore, the module-based network analysis will be an effective method for better understanding TCM.
Subject(s)
Drugs, Chinese Herbal/chemistry , Panax notoginseng/chemistry , Protein Interaction Maps/drug effects , Proteins/chemistry , Saponins/chemistry , HumansABSTRACT
The dearth of knowledge on the diverse structures and functions in bacterial collagen-like proteins is in stark contrast to the deep grasp of structures and functions in mammalian collagen, the ubiquitous triple-helical scleroprotein that plays a central role in tissue architecture, extracellular matrix organization, and signal transduction. To fill and highlight existing gaps due to the general paucity of data on bacterial CLPs, we comprehensively reviewed the latest insight into their functional and structural diversity from multiple perspectives of biology, computational simulations, and materials engineering. The origins and discovery of bacterial CLPs were explored. Their genetic distribution and molecular architecture were analyzed, and their structural and functional diversity in various bacterial genera was examined. The principal roles of computational techniques in understanding bacterial CLPs' structural stability, mechanical properties, and biological functions were also considered. This review serves to drive further interest and development of bacterial CLPs, not only for addressing fundamental biological problems in collagen but also for engineering novel biomaterials. Hence, both biology and materials communities will greatly benefit from intensified research into the diverse structures and functions in bacterial collagen-like proteins.
Subject(s)
Bacterial Proteins , Collagen , Animals , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Collagen/metabolism , Biocompatible Materials , Mammals/metabolismABSTRACT
The ability to fabricate anisotropic collagenous materials rapidly and reproducibly has remained elusive despite decades of research. Balancing the natural propensity of monomeric collagen (COL) to spontaneously polymerize in vitro with the mild processing conditions needed to maintain its native substructure upon polymerization introduces challenges that are not easily amenable with off-the-shelf instrumentation. To overcome these challenges, we have designed a platform that simultaneously aligns type I COL fibrils under mild shear flow and builds up the material through layer-by-layer assembly. We explored the mechanisms propagating fibril alignment, targeting experimental variables such as shear rate, viscosity, and time. Coarse-grained molecular dynamics simulations were also employed to help understand how initial reaction conditions including chain length, indicative of initial polymerization, and chain density, indicative of concentration, in the reaction environment impact fibril growth and alignment. When taken together, the mechanistic insights gleaned from these studies inspired the design, iteration, fabrication, and then customization of the fibrous collagenous materials, illustrating a platform material that can be readily adapted to future tissue engineering applications.
Subject(s)
Collagen , Fibrillar Collagens , Tissue Engineering , Collagen Type IABSTRACT
Hemsleya chinensis is a Chinese traditional medicinal plant, containing cucurbitacin IIa (CuIIa) and cucurbitacin IIb (CuIIb), both of which have a wide range of pharmacological effects, including antiallergic, anti-inflammatory, and anticancer properties. However, few studies have been explored on the key enzymes that are involved in cucurbitacins biosynthesis in H. chinensis. Oxidosqualene cyclase (OSC) is a vital enzyme for cyclizing 2,3-oxidosqualene and its analogues. Here, a gene encoding the oxidosqualene cyclase of H. chinensis (HcOSC6), catalyzing to produce cucurbitadienol, was used as a template of mutagenesis. With the assistance of AlphaFold2 and molecular docking, we have proposed for the first time to our knowledge the 3D structure of HcOSC6 and its binding features to 2,3-oxidosqualene. Mutagenesis experiments on HcOSC6 generated seventeen different single-point mutants, showing that single-residue changes could affect its activity. Three key amino acid residues of HcOSC6, E246, M261 and D490, were identified as a prominent role in controlling cyclization ability. Our findings not only comprehensively characterize three key residues that are potentially useful for producing cucurbitacins, but also provide insights into the significant role they could play in metabolic engineering.
ABSTRACT
Silk-elastin-like protein (SELP) is an excellent biocompatible and biodegradable material for hydrogels with tunable properties that can respond to multiple external stimuli. By integrating fully atomistic, replica exchange molecular dynamics simulations with detailed experiments, we predict and measure structural responses to changes in temperature and ion concentration of a novel SELP sequence, as well as a diazonium-coupled version. A single SELP molecule shrinks at high temperatures, whereas diazonium coupling decreases this thermo-responsiveness. Diazonium coupling weakens electrostatic interactions, leading to an insignificant ionic response in the single chain, while also decreasing gelation rates by reducing the number of exposed dityrosine crosslink sites and their solvent-accessible surface areas. With further data from our coarse-grained crosslinked SELP model and our experiments, we find that three effects are critical for SELP cluster's physical response to external stimuli: (1) the structural transition of SELPs at high temperature, (2) the geometry restraints in hydrogel networks, and (3) the electrostatic interactions between molecules. This molecular understanding of the thermal and ion response in single molecules of SELPs and their crosslinked networks may further improve and help innovate SELP's stimuli-responsive properties, creating significant opportunities for applications in biomedical devices and other engineering applications.
Subject(s)
Elastin , Silk , Amino Acid Sequence , Elastin/chemistry , Hydrogels/chemistry , Silk/chemistryABSTRACT
Metacognition refers to the ability to be aware of one's own cognition. Ample evidence indicates that metacognition in the human primate is highly dissociable from cognition, specialized across domains, and subserved by distinct neural substrates. However, these aspects remain relatively understudied in macaque monkeys. In the present study, we investigated the functionality of macaque metacognition by combining a confidence proxy, hierarchical Bayesian meta-d' computational modelling, and a single-pulse transcranial magnetic stimulation technique. We found that Brodmann area 46d (BA46d) played a critical role in supporting metacognition independent of task performance; we also found that the critical role of this region in meta-calculation was time-sensitive. Additionally, we report that macaque metacognition is highly domain-specific with respect to memory and perception decisions. These findings carry implications for our understanding of metacognitive introspection within the primate lineage.
Subject(s)
Metacognition , Animals , Bayes Theorem , Cognition/physiology , Haplorhini , Humans , Metacognition/physiology , Task Performance and AnalysisABSTRACT
Efficiently manipulating and reproducing collagen (COL) alignment in vitro remains challenging because many of the fundamental mechanisms underlying and guiding the alignment process are not known. We reconcile experiments and coarse-grained molecular dynamics simulations to investigate the mechanical behaviors of a growing COL scaffold and assay how changes in fiber alignment and various cross-linking densities impact their alignment dynamics under shear flow. We find higher cross-link densities and alignment levels significantly enhance the apparent tensile/shear moduli and strength of a bulk COL system, suggesting potential measures to facilitate the design of stronger COL based materials. Since fibril alignment plays a key factor in scaffold mechanics, we next investigate the molecular mechanism behind fibril alignment with Couette flow by computationally investigating the effects of COL's structural properties such as chain lengths, number of chains, tethering conditions, and initial COL conformations on the COL's final alignment level. Our computations suggest that longer chain lengths, more chains, greater amounts of tethering, and initial anisotropic COL conformations benefit the final alignment, but the effect of chain lengths may be more dominant over other factors. These results provide important parameters for consideration in manufacturing COL-based scaffolds where alignment and cross-linking are necessary for regulating performance.
Subject(s)
Collagen , Tissue Scaffolds , Anisotropy , Collagen/chemistry , Tissue Scaffolds/chemistryABSTRACT
Although chemical crosslinking has been extensively explored to enhance the mechanical properties of network-type materials for structural and energy (electrochemical, thermal, etc.) applications, loading-induced energy dissipations usually occur through a single channel that either leads to network brittleness or low strength/stiffness. In this work, we apply coarse-grained molecular dynamics simulations to explore the potential of hybridly double-crosslinked carbon nanotube (CNT) networks as a light weight functional material with combined strength and toughness. While increasing the crosslinking density or strong crosslink composition may, in general, enhance the strength and toughness, further increasing the two parameters would surprisingly lead to deteriorated strength and toughness. We find that double-crosslinked networks can nicely achieve cooperative energy dissipation with minimal structural damage. In particular, the weak crosslinks serve as "sacrificial bonds" to dissipate elastic energies from external loading, while the strong crosslinks act as "structure holders" and break at a much later stage during the tensile test. Therefore, the combination of more than one type of crosslinking with hybrid potential energy landscapes and breaking time scales can prevent premature simultaneous breaking of multiple strong crosslinks. By deploying intermediate amounts of weak and strong crosslinks, we observe an outstanding density-normalized strength of 227-2130 kPa m3 kg-1 as compared to many structural materials and advanced nanocomposites. The crosslinking strategies developed here would pave new avenues for the rational design of functional network materials beyond CNTs, such as hydrogels, nanofibers, and nanocomposites.
ABSTRACT
Erigeron breviscapus, a traditional Chinese medicinal plant, is enriched in flavonoids that are beneficial to human health. While we know that R2R3-MYB transcription factors (TFs) are crucial to flavonoid pathway, the transcriptional regulation of flavonoid biosynthesis in E. breviscapus has not been fully elucidated. Here, EbMYBP1, a R2R3-MYB transcription factor, was uncovered as a regulator involved in the regulation of flavonoid accumulation. Transcriptome and metabolome analysis revealed that a large group of genes related to flavonoid biosynthesis were significantly changed, accompanied by significantly increased concentrations of the flavonoid in EbMYBP1-OE transgenic tobacco compared with the wild-type (WT). In vitro and in vivo investigations showed that EbMYBP1 participated in flavonoid biosynthesis, acting as a nucleus-localized transcriptional activator and activating the transcription of flavonoid-associated genes like FLS, F3H, CHS, and CHI by directly binding to their promoters. Collectively, these new findings are advancing our understanding of the transcriptional regulation that modulates the flavonoid biosynthesis.
ABSTRACT
Erigeron breviscapus is a Compositae plant, and its rich flavonoids have shown strong preventative and curative effects in the treatment of cardio- and cerebrovascular diseases. bHLH genes play a crucial role in plant growth and development. There are 116 EbbHLH genes in E. breviscapus, and each gene has been named based on its chromosome location. Our phylogenetic analysis divided these genes into 18 subfamilies. To further investigate its function, EbbHLH80 was isolated from E. breviscapus leaves. Next, transcriptomic and metabolomic analyses of tobacco leaves were performed. Among 421 differentially accumulated compounds, 98 flavonoids were identified. In addition, differentially expressed genes were identified using RNA-seq, and further analysis suggested that EbbHLH80-OE could not only regulate the expression of some structural genes in the flavonoid biosynthesis pathway to achieve flavonoid accumulation but also be involved in the regulation of a series of downstream pathways, such as stress response, ABA and ethylene signal transduction, to affect plant growth and development. The results of our analysis provide new insights into the function of EbbHLH80 and lay the foundation for future functional studies on E. breviscapus.
ABSTRACT
The stiffnesses, ß-structures, hydrogen bonds, and vibrational modes of wild-type collagen triple helices are compared with osteogenesis imperfecta-related mutants using integrative structural and dynamic analysis via molecular dynamics simulations and Markov state models. Differences in these characteristics are strongly related to the unwound structural states in the mutated regions that are specific to each mutation.
Subject(s)
Collagen Type I/analysis , Glycine/analysis , Markov Chains , Molecular Dynamics Simulation , Osteogenesis Imperfecta/diagnosis , Collagen Type I/genetics , Glycine/genetics , Humans , Molecular Conformation , Mutation , Osteogenesis Imperfecta/geneticsABSTRACT
Carbon fibers (CFs) show great potential for high-performance supercapacitors in miniature electronics fields, where high energy density and long cycling life are required. However, superior combination of these two attributes in CF-based supercapacitors still presents a long-standing challenge. Herein, straight carbon nanotubes (CNTs) with radial orientation and high chemical/physical stability are served as nanoscale conductive skeletons on CFs for supporting the polyaniline (PANI)/SnS2. The SnS2 with nanoflower-like features significantly increases the specific capacitance and specific surface area (SSA); furthermore, the PANI nanolayers covered on SnS2 petals enable secondary specific capacitance enhancement and inhibition of volume expansion of SnS2 during charging/discharging processes. Benefiting from these structural merits, the resultant PANI/SnS2@CNTs/CFs hybrids exhibit high SSA (2732.5 m2 g-1), high specific capacitance (891 F g-1 at 20 mV s-1) and excellent cycling stability (83.8% after 6000 cycles at 2 A g-1). Moreover, the hybrids deliver a superior energy density of 38.7 W h kg-1 at a power density of 1 kW kg-1 and outstanding performance stability, which should prove to be vastly advantageous as compared to the reported CF-based supercapacitors. Our work puts forward a new thinking of rational construction of high-performance CF-based supercapacitors that can be used in practical energy storage devices.
ABSTRACT
Materials chemistry is at the forefront of the global "Fourth Industrial Revolution", in part by establishing a "Materials 4.0" paradigm. A key aspect of this paradigm is developing methods to effectively integrate hardware, software, and biological systems. Towards this end, we must have intimate knowledge of the virtual space in materials design: materials omics (materiomics), materials informatics, computational modelling and simulations, artificial intelligence (AI), and big data. We focus on the discovery and design of next-generation bio-inspired materials because the design space is so huge as to be almost intractable. With nature providing researchers with specific guiding principles, this material design space may be probed most efficiently through digital, high-throughput methods. Therefore, to enhance awareness and adoption of digital approaches in soft polymeric bio-inspired materials discovery and design, we detail multiscale simulation techniques in soft matter from the molecular level to the macroscale. We also highlight the unique role that artificial intelligence and materials databases will play in molecular simulations as well as soft materials discovery. Finally, we showcase several case studies that concretely apply computational modelling and simulations for integrative soft bio-inspired materials design with experiments.
Subject(s)
Artificial Intelligence , Biomimetic Materials/chemistry , Drug Design , Polymers/chemistryABSTRACT
We present a combination of first-principles calculations and the Boltzmann transport theory to understand the carrier transport and thermoelectric performance of mixed halide perovskite alloys CsPb(I1-xBrx)3 with different Br compositions. Our computational results correlate the conduction band splitting in CsPb(I1-xBrx)3 to the significant anisotropy in their carrier transport properties, such as effective masses and deformation potential constants. Such band splitting originates from the symmetry-broken crystal structures of CsPb(I1-xBrx)3 polymorphs: with residue stresses/strains in asymmetric CsPb(I1-xBrx)3, nondegenerate orbitals reconstruct the conduction band and reduce the Pb-halide antibonding character along certain directions. While the Seebeck coefficient (S) and the relaxation time-normalized electrical conductivity (σ/τ) show weak directional anisotropy, the carrier relaxation time (τ) is highly direction-dependent. The reconstruction of the conduction band finally leads to significantly anisotropic and enhanced thermoelectric power factors (PF = S2σ) in CsPb(I1-xBrx)3 compared to those in pure CsPbI3 and CsPbBr3, showing anomalous nonlinear alloy behavior. A delicate balance between S2σ and combined measurement of the carrier effective mass and deformation potential constant, m*EDP, is confirmed. The lattice thermal conductivities of CsPb(I1-xBrx)3 are significantly suppressed compared to those of their pure counterparts due to strong mass disordering and strain fields upon halogen substitution. As a result, symmetry breaking in CsPb(I1-xBrx)3 leads to anisotropy in carrier transport, high PF, and scattered phonon transport (ultralow thermal conductivity), concurrently contributing to their promising thermoelectric figures of merit (ZT) up to 1.7 at room temperature. The principles behind the asymmetry-induced factors would serve as new design concepts to tailor the thermoelectric properties of alloys, mixtures, superlattices, and low-dimensional materials.