High-throughput Study Research Articles

ReDD-COFFEE: a ready-to-use database of covalent organic framework structures and accurate force fields to enable high-throughput screenings

A diverse database of 268 687 covalent organic framework geometries and accompanyingab initioderived system-specific force fields is developed. This database is ready-to-use, as shown by our high-throughput study for vehicular methane storage.

A combined miRNA–piRNA signature in the serum and urine of rabbits infected with Toxoplasma gondii oocysts

BackgroundIncreasing evidence has shown that non-coding RNA (ncRNA) molecules play fundamental roles in cells, and many are stable in body fluids as circulating RNAs. Study on these ncRNAs will provide insights into toxoplasmosis pathophysiology and/or help reveal diagnostic biomarkers.MethodsWe performed a high-throughput RNA-Seq study to comprehensively profile the microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) in rabbit serum and urine after infection with Toxoplasma gondii oocysts during the whole infection process.ResultsTotal RNA extracted from serum and urine samples of acutely infected [8 days post-infection (DPI)], chronically infected (70 DPI) and uninfected rabbits were subjected to genome-wide small RNA sequencing. We identified 2089 miRNAs and 2224 novel piRNAs from the rabbit sera associated with T. gondii infection. Meanwhile, a total of 518 miRNAs and 4182 novel piRNAs were identified in the rabbit urine associated with T. gondii infection. Of these identified small ncRNAs, 1178 and 1317 serum miRNAs and 311 and 294 urine miRNAs were identified as differentially expressed (DE) miRNAs in the acute and chronic stages of infections, respectively. A total of 1748 and 1814 serum piRNAs and 597 and 708 urine piRNAs were found in the acute and chronic infection stages, respectively. Of these dysregulated ncRNAs, a total of 88 common DE miRNAs and 120 DE novel piRNAs were found in both serum and urine samples of infected rabbits.ConclusionsThese findings provide valuable data for revealing the physiology of herbivore toxoplasmosis caused by oocyst infection. Circulating ncRNAs identified in this study are potential novel diagnostic biomarkers for the detection/diagnosis of toxoplasmosis in herbivorous animals.Graphical

Trophectoderm non-coding RNAs reflect the higher metabolic and more invasive properties of young maternal age blastocysts

Increasing female age is accompanied by a corresponding fall in her fertility. This decline is influenced by a variety of factors over an individual’s life course including background genetics, local environment and diet. Studying both coding and non-coding RNAs of the embryo could aid our understanding of the causes and/or effects of the physiological processes accompanying the decline including the differential expression of sub-cellular biomarkers indicative of various diseases. The current study is a post-hoc analysis of the expression of trophectoderm RNA data derived from a previous high throughput study. Its main aim is to determine the characteristics and potential functionalities that characterize long non-coding RNAs. As reported previously, a maternal age-related component is potentially implicated in implantation success. Trophectoderm samples representing the full range of maternal reproductive ages were considered in relation to embryonic implantation potential, trophectoderm transcriptome dynamics and reproductive maternal age. The long non-coding RNA (lncRNA) biomarkers identified here are consistent with the activities of embryo-endometrial crosstalk, developmental competency and implantation and share common characteristics with markers of neoplasia/cancer invasion. Corresponding genes for expressed lncRNAs were more active in the blastocysts of younger women are associated with metabolic pathways including cholesterol biosynthesis and steroidogenesis.

SARS-CoV-2 quasi-species analysis from patients with persistent nasopharyngeal shedding

At the time of a new and unprecedented viral pandemic, many questions are being asked about the genomic evolution of SARS-CoV-2 and the emergence of different variants, leading to therapeutic and immune evasion and survival of this genetically highly labile RNA virus. The nasopharyngeal persistence of infectious virus beyond 17 days proves its constant interaction with the human immune system and increases the intra-individual mutational possibilities. We performed a prospective high-throughput sequencing study (ARTIC Nanopore) of SARS-CoV-2 from so-called "persistent" patients, comparing them with a non-persistent population, and analyzing the quasi-species present in a single sample at time t. Global intra-individual variability in persistent patients was found to be higher than in controls (mean 5.3%, Standard deviation 0.9 versus 4.6% SD 0.3, respectively, p < 0.001). In the detailed analysis, we found a greater difference between persistent and non-persistent patients with non-severe COVID 19, and between the two groups infected with clade 20A. Furthermore, we found minority N501Y and P681H mutation clouds in all patients, with no significant differences found both groups. The question of the SARS-CoV-2 viral variants’ genesis remains to be further investigated, with the need to prevent new viral propagations and their consequences, and quasi-species analysis could be an important key to watch out.

Distinctive Brain Malformations in Zhu-Tokita-Takenouchi-Kim Syndrome.

Zhu-Tokita-Takenouchi-Kim syndrome is a severe multisystem malformation disorder characterized by developmental delay and a diverse array of congenital abnormalities. However, these currently identified phenotypic components provide limited guidance in diagnostic situations, due to both the nonspecificity and variability of these features. Here we report a case series of 7 individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome, 5 ascertained by their presentation with the neuronal migration disorder, periventricular nodular heterotopia. Individuals with a molecular diagnosis of Zhu-Tokita-Takenouchi-Kim syndrome were recruited from 2 sources, a high-throughput sequencing study of individuals with periventricular nodular heterotopia or from clinical diagnostic sequencing studies. We analyzed available brain MR images of recruited individuals to characterize periventricular nodular heterotopia distribution and to identify the presence of any additional brain abnormalities. Pathogenic variants in SON, causative of Zhu-Tokita-Takenouchi-Kim syndrome, were identified in 7 individuals. Brain MR images from these individuals were re-analyzed. A characteristic set of imaging anomalies in addition to periventricular nodular heterotopia was identified, including the elongation of the pituitary stalk, cerebellar enlargement with an abnormally shaped posterior fossa, rounding of the caudate nuclei, hippocampal malformations, and cortical anomalies including polymicrogyria or dysgyria. The recurrent neuroradiologic changes identified here represent an opportunity to guide diagnostic formulation of Zhu-Tokita-Takenouchi-Kim syndrome on the basis of brain MR imaging evaluation.

CircSUCO promotes proliferation and differentiation of chicken skeletal muscle satellite cells via sponging miR-15

ABSTRACT 1. In a previous high-throughput sequencing study, a novel circular RNA (circRNA) generated from a SUN domain containing ossification factor (SUCO) gene transcript (circSUCO) was differentially expressed during the embryonic muscle development. This study aimed to further explore the effect of circSUCO on chicken skeletal muscle development. 2. The experiment analysed the expression patterns of circSUCO in Tianfu broilers and clarified its function in the chicken skeletal muscle satellite cells (SMSC) after circSUCO knockdown. The qPCR results showed circSUCO was highly expressed in skeletal muscle and has different expression levels during various development periods. 3. Mechanistically, a series of in vitro experiments showed that circSUCO interference suppressed proliferation and differentiation of SMSC. In addition, it was observed that circSUCO competitively binds with microRNAs such as miR-15a, miR-15b-5p, and miR-15c-5p according to the dual-luciferase assay and qPCR. 4. Correlation was positive between the circSUCO expression level and the ratio of the breast muscle. The results revealed that circSUCO could play a positive role in proliferation and differentiation of SMSC via sponging miR-15a, miR-15b-5p, and miR-15c-5p, hence, may contribute to skeletal muscle development in chicken.

Elucidating the Chemical Order and Disorder in High-Entropy MXenes: A High-Throughput Survey of the Atomic Configurations in TiVNbMoC3 and TiVCrMoC3

Expanding the MXene design space from ordered and random double-transition-metal (DTM) MXenes to include high-entropy (HE) MXenes with four or more principal elements enables a powerful approach for enhancing MXene properties. While many DTM MXenes possess unique structures that strongly influence material properties, HE MXenes are largely unknown because they are only recently synthesized. Since certain combinations of transition metals (TMs), e.g., Mo-Ti and Cr-Ti, lead to ordered DTM MXene phases, where Mo/Cr atoms occupy the outer TM layers and Ti atoms occupy the inner layers, it is critical to investigate any possibilities of TM segregation in the atomic layers of HE MXenes. Therefore, we present a high-throughput first-principles study of the atomic configurations of two recently synthesized HE M4C3 MXenes: TiVNbMoC3 and TiVCrMoC3. Combining density functional theory, cluster expansion, and Monte Carlo simulations, we predict a unique preferential occupancy of the TM atoms in the four layers within the single-phase HE MXenes, even at temperatures as high as 2900 K. Across a wide compositional range, the outer (inner) layers are predominantly occupied by two of the four TM elements, with Cr most preferentially occupying the outer layers, followed by Mo, V, Nb, and Ti. The strong compositional dependence of the interlayer segregation highlights the HE MXenes’ tunability. Within each TM layer, the atoms largely form a solid solution, with a tendency for Nb-V separation at lower temperatures. Our results elucidate the chemical order and disorder in HE MXenes, guiding experiments in designing MXenes with enhanced properties within the huge compositional space.

High-throughput experimental study on the microstructural and compositional variations of mechanical properties for AlCoCrFeNi high entropy alloys

To efficiently establish the relationship among microstructure, composition and mechanical properties of the AlCoCrFeNi high entropy alloys, a high-throughput experimental method has been developed combining diffusion couple with the nanoindentation technique. In this paper, B2(A2) denotes that A2 (disordered bcc) particles are coherently dispersed in the B2 (ordered bcc) matrix, and vice versa for A2(B2). A B2(A2)-A2(B2)-fcc sandwich microstructure was produced by annealing an Al1.1CoCrFeNi/CoCrFeNi diffusion couple. The following nanoindentation measurements found that the hardness of the A2(B2) structure is slightly lower than that of B2(A2), but the elastic modulus and ductility behave differently. The fcc region, on the other hand, has a larger ductility than both B2(A2) and A2(B2). In addition, the elastic modulus of fcc decreases with the increasing Al content, whereas the hardness does not significantly change with composition.

Discovering design principles of collagen molecular stability using a genetic algorithm, deep learning, and experimental validation

Collagen is the most abundant structural protein in humans, providing crucial mechanical properties, including high strength and toughness, in tissues. Collagen-based biomaterials are, therefore, used for tissue repair and regeneration. Utilizing collagen effectively during materials processing ex vivo and subsequent function invivo requires stability over wide temperature ranges to avoid denaturation and loss of structure, measured as melting temperature (Tm). Although significant research has been conducted on understanding how collagen primary amino acid sequences correspond to Tm values, a robust framework to facilitate the design of collagen sequences with specific Tm remains a challenge. Here, we develop a general model using a genetic algorithm within a deep learning framework to design collagen sequences with specific Tm values. We report 1,000 de novo collagen sequences, and we show that we can efficiently use this model to generate collagen sequences and verify their Tm values using both experimental and computational methods. We find that the model accurately predicts Tm values within a few degrees centigrade. Further, using this model, we conduct a high-throughput study to identify the most frequently occurring collagen triplets that can be directly incorporated into collagen. We further discovered that the number of hydrogen bonds within collagen calculated with molecular dynamics (MD) is directly correlated to the experimental measurement of triple-helical quality. Ultimately, we see this work as a critical step to helping researchers develop collagen sequences with specific Tm values for intended materials manufacturing methods and biomedical applications, realizing a mechanistic materials by design paradigm.

Multiomics approach reveals the ubiquitination-specific processes hijacked by SARS-CoV-2

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn’t code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets.

A high-throughput ab-initio study of diverse glasses: Accuracy of the atomic structure and refractive index

A high-throughput method to predict the spectral refractive index of glasses from a purely ab-initio approach is presented. Atomic structures for 34 different and diverse glass chemistries are generated using high-throughput simulation framework that can quickly generate data. Predicted mechanical properties ensure the generated structures are the representative atomistic model, and we suggest a scaling factor to match the experimental refractive index (RI) using high-throughput values. Calculated RI in this work aligns with experimentally measured values, with an average error of < 0.9%. On the other hand, the predicted absorption coefficient is limited to comparing qualitative trends across different glass chemistries.

Massively parallel genomic perturbations with multi-target CRISPR interrogates Cas9 activity and DNA repair at endogenous sites

Here we present an approach that combines a clustered regularly interspaced short palindromic repeats (CRISPR) system that simultaneously targets hundreds of epigenetically diverse endogenous genomic sites with high-throughput sequencing to measure Cas9 dynamics and cellular responses at scale. This massive multiplexing of CRISPR is enabled by means of multi-target guide RNAs (mgRNAs), degenerate guide RNAs that direct Cas9 to a pre-determined number of well-mapped sites. mgRNAs uncovered generalizable insights into Cas9 binding and cleavage, revealing rapid post-cleavage Cas9 departure and repair factor loading at protospacer adjacent motif-proximal genomic DNA. Moreover, by bypassing confounding effects from guide RNA sequence, mgRNAs unveiled that Cas9 binding is enhanced at chromatin-accessible regions, and cleavage by bound Cas9 is more efficient near transcribed regions. Combined with light-mediated activation and deactivation of Cas9 activity, mgRNAs further enabled high-throughput study of the cellular response to double-strand breaks with high temporal resolution, revealing the presence, extent (under 2 kb) and kinetics (~1 h) of reversible DNA damage-induced chromatin decompaction. Altogether, this work establishes mgRNAs as a generalizable platform for multiplexing CRISPR and advances our understanding of intracellular Cas9 activity and the DNA damage response at endogenous loci.

PBC, an easy and efficient strategy for high-throughput protein C-terminome profiling.

High-throughput profiling of protein C-termini is still a challenging task. Proteomics provides a powerful technology for systematic and high-throughput study of protein C-termini. Various C-terminal peptide enrichment strategies based on chemical derivatization and chromatography separation have been reported. However, they are still costly and time-consuming, with low enrichment efficiency for C-terminal peptides. In this study, by taking advantage of the high reaction selectivity of 2-pyridinecarboxaldehyde (2-PCA) with an α-amino group on peptide N-terminus and high affinity between biotin and streptavidin, we developed a 2-PCA- and biotin labeling–based C-terminomic (PBC) strategy for a high-efficiency and high-throughput analysis of protein C-terminome. Triplicates of PBC experiments identified a total of 1,975 C-terminal peptides corresponding to 1,190 proteins from 293 T cell line, which is 180% higher than the highest reported number of C-terminal peptides identified from mammalian cells by chemical derivatization–based C-terminomics study. The enrichment efficiency (68%) is the highest among the C-terminomics methods currently reported. In addition, we not only uncovered 50 proteins with truncated C-termini which were significantly enriched in extracellular exosome, vesicle, and ribosome by a bioinformatic analysis but also systematically characterized the whole PTMs on C-terminal in 293 T cells, suggesting PBC as a powerful tool for protein C-terminal degradomics and PTMs investigation. In conclusion, the PBC strategy would benefit high-efficiency and high-throughput profiling of protein C-terminome.

Design of Organic-Inorganic Hybrid Heterostructured Semiconductors via High-Throughput Materials Screening for Optoelectronic Applications.

Organic-inorganic hybrid semiconductors, of which organometal halide perovskites are representative examples, have drawn significant research interest as promising candidates for next-generation optoelectronic applications. This interest is mainly ascribed to the emergent optoelectronic properties of the hybrid semiconductors that are distinct from those of their purely inorganic and organic counterparts as well as different material fabrication strategies and the other material (e.g., mechanical) properties that combine the advantages of both. Herein, we present a high-throughput first-principles material screening study of the hybrid heterostructured semiconductors (HHSs) that differ entirely from organometal halide perovskite hybrid ion-substituting semiconductors. HHSs crystallize as superlattice structures composed of inorganic tetrahedrally coordinated semiconductor sublayers and organic sublayers made of bidentate chain-like molecules. By changing the composition (e.g., IV, III-V, II-VI, I-III-VI2 semiconductor) and polymorph (e.g., wurtzite and zinc-blende) of the inorganic components, the type of organic molecules (e.g., ethylenediamine, ethylene glycol, and ethanedithiol), and the thickness of the composing layers across 234 candidate HHSs, we investigated their thermodynamic, electronic structure, and optoelectronic properties. Thermodynamic stability analysis indicates the existence of 96 stable HHSs beyond the ZnTe/ZnSe-based ones synthesized experimentally. The electronic structure and optoelectronic properties of HHSs can be modulated over a wide range by manipulating their structural variants. A machine learning approach was further applied to the high-throughput calculated data to identify the critical descriptors determining thermodynamic stability and electronic band gap. Our results indicate promising prospects and provide valuable guidance for the rational design of organic-inorganic hybrid heterostructured semiconductors for potential optoelectronic applications.

Charting the Atomic C Interaction with Transition Metal Surfaces.

Carbon interaction with transition metal (TM) surfaces is a relevant topic in heterogeneous catalysis, either for its poisoning capability, for the recently attributed promoter role when incorporated in the subsurface, or for the formation of early TM carbides, which are increasingly used in catalysis. Herein, we present a high-throughput systematic study, adjoining thermodynamic plus kinetic evidence obtained by extensive density functional calculations on surface models (324 diffusion barriers located on 81 TM surfaces in total), which provides a navigation map of these interactions in a holistic fashion. Correlation between previously proposed electronic descriptors and ad/absorption energies has been tested, with the d-band center being found the most suitable one, although machine learning protocols also underscore the importance of the surface energy and the site coordination number. Descriptors have also been tested for diffusion barriers, with ad/absorption energies and the difference in energy between minima being the most appropriate ones. Furthermore, multivariable, polynomial, and random forest regressions show that both thermodynamic and kinetic data are better described when using a combination of different descriptors. Therefore, looking for a single perfect descriptor may not be the best quest, while combining different ones may be a better path to follow.

A Fluorescence-based Assay of Membrane Potential for High-throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines.

Fluorescence-based studies are suitable for high-throughput plate reader assays of cells in culture. They have been commonly employed for drug discovery campaigns targeting recombinant ion channel proteins overexpressed in cells such as HEK-293 cells. However, there is increasing emphasis on the use of tissue-relevant cell lines for studying the effects of small molecule interventions. The following protocol describes the adaptation of a fluorescence-based membrane potential assay for the study of ion channels endogenously expressed in epithelial cell lines. The membrane potential assay details a high-throughput assay for chloride channel activity of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in two commonly studied epithelial cell lines, Caco-2 and Calu-3. In addition, this paper describes a novel application of this system to measure the activity of the Epithelial Sodium Channel (ENaC) in a high-throughput format in the same epithelial cell lines. Together, these fluorescence-based assays provide a robust and flexible platform for studying small molecule modulators, targeting two epithelial channels in a relevant cellular context.

How adsorbed H, O, OH, and Cl affect plain adsorption of imidazole on copper

In real environments, metal surfaces are never clean. Even during active dissolution in corrosion, they are likely covered with adsorbed species such as O, OH, H, and Cl. For this reason, we addressed how such species (hereinafter labeled as X(ads)) affect the adsorption bonding of imidazole—used as an archetypal model of azole corrosion inhibitors—on Cu(111). To this end, we performed a systematic high-throughput DFT study by considering over 400 different adsorption configurations, where the effects of coverage, the type of X(ads) species, and the distance between imidazole and X(ads) were scrutinized. Our calculations indicate that O and Cl enhance the adsorption bonding of imidazole, H has almost no effect, whereas OH either diminishes or has a negligible impact on the adsorption of imidazole. The effect of the X(ads) species on the imidazole adsorption usually diminishes with the increasing distance between X(ads) and imidazole and with decreasing X(ads) coverage. Three coadsorption effects of X(ads) on non-dissociative adsorption of imidazole were identified. The first stabilizing effect, operative for O and OH, is due to the hydrogen bond formation with the nearby adsorbed imidazole. The second stabilizing effect, relevant for O and Cl, is due to the X(ads) induced enhancement of the N–Cu bond between the nearby adsorbed imidazole and the surface; this effect enhances with increasing coverage of X(ads). The last effect is related to the X(ads) induced work function change and can be stabilizing (for O and Cl), negligible (for H), or destabilizing (in the case of OH) for adsorption of imidazole and explains why the impact of X(ads) on adsorption bonding of imidazole diminishes with the X(ads) coverage. Finally, if the coverage of X(ads) is too high, then the chemisorption of imidazole is prevented either sterically or due to the unavailability of free surface sites.

Characteristics of Wild Bird Resistomes and Dissemination of Antibiotic Resistance Genes in Interconnected Bird-Habitat Systems Revealed by Similarity of blaTEM Polymorphic Sequences.

Wild birds are known to harbor and discharge antibiotic-resistant bacteria (ARB) and their associated antibiotic resistance genes (ARGs). However, assessments of their contribution to the dissemination of antibiotic resistance in the environment are limited to culture-dependent bacterial snapshots. Here, we present a high-throughput sequencing study that corroborates extensive ARG exchange between wild bird feces and their habitats and implies the need to scrutinize high-mobility birds as potential vectors for global propagation of ARGs. We characterized the resistome (281 ARGs) and microbiome of seven wild bird species and their terrestrial and aquatic habitats. The resistomes of bird feces were influenced by the microbial community structure, mobile genetic elements (MGEs), and residual antibiotics. We designated 33 ARGs found in more than 90% of the bird fecal samples as core ARGs of wild bird feces, among which 16 ARGs were shared as core ARGs in both wild bird feces and their habitats; these genes represent a large proportion of both the bird feces (35.0 ± 15.9%) and the environmental resistome (29.9 ± 21.4%). One of the most detected β-lactam resistance genes (blaTEM, commonly harbored by multidrug resistant "superbugs") was used as molecular marker to demonstrate the high interconnectivity of ARGs between the microbiomes of wild birds and their habitats. Overall, this work provides a comprehensive analysis of the wild bird resistome and underscores the importance to consider genetic exchange between animals and the environment in the One Health approach.

A high-throughput DNA sequencing study of fecal bacteria of seven Mexican horse breeds.

Horses are non-ruminant, herbivorous mammals, been used through history for various purposes, with a gut microbiota from cecum to the colon, possessing remarkable fermentative capacity. We studied the fecal microbiota of Azteca, Criollo, Frisian, Iberian, Pinto, Quarter and Spanish horse breeds living in Mexico by next-generation DNA sequencing of 16S rRNA gene libraries. Dominant phyla Firmicutes, Bacteroidetes, Proteobacteria, Spirochaetes, Fibrobacteres, Actinobacteria and Verrucomicrobia have different relative abundances among breeds, with contrasted alpha and beta diversities as well. Heatmap analysis revealed that Ruminococcaceae, Lachnospiraceae, Mogibacteriaceae families, and order Clostridiales are more abundant in Spanish, Azteca, Quarter and Criollo breeds. The LEfSe analysis displayed higher abundance of order Bacteroidales, family BS11, and genera Faecalibacterium, Comamonas, Collinsella, Acetobacter, and Treponema in Criollo, Azteca, Iberian, Spanish, Frisian, Pinto, and Quarter horse breeds. The conclusion is that dominant bacterial taxa, found in fecal samples of horse breeds living in Mexico, have different relative abundances.

High-throughput first-principles study of physical properties of L12-Al3M particles

The mechanical, thermal and electrical properties of L12-Al3M (M=RE (Sc, Y, La-Lu), Li, Na, Ca, Fe and Cu) in Al based alloys at various temperatures and pressures have been investigated by combining first-principles calculations with quasi-harmonic approximation. The results show that the lattice constant, lattice mismatch, and formation enthalpy of L12-Al3M compounds are closely related to the radius of M atoms and electrons transferred from M to Al. Al3La presents the largest strengthening effect, while Al3Sc shows the most stability. The elastic parameters of Al3M compounds increased linearly with the increase of pressure, but slightly decreased with temperature, while Poissson’s ratio ν and Pugh’s ratio B/G maintain the characteristic of brittleness. The calculated electrical conductivity of L12-Al3M is nearly unchanged, whereas the thermal conductivity is increased with the increase of temperature. The lower values of Seebeck coefficient and merit ZT clearly indicate that these L12-Al3M compounds show metallic bond feature and are not suitable for thermoelectric devices. Finally, the thermal conductivities (TCs) of Al alloys containing L12-Al3M as functional of compound concentration and temperature are obtained based on the Maxwell model. These results are helpful for designing high performance heat-resistance Al alloys.