How the AI-assisted discovery and synthesis of a ternary oxide highlights capability gaps in materials science.

Exploratory synthesis has been the main generator of new inorganic materials for decades. However, our Edisonian and bias-prone processes of synthetic exploration alone are no longer sufficient in an age that demands rapid advances in materials development. In this work, we demonstrate an end-to-end attempt towards systematic, computer-aided discovery and laboratory synthesis of inorganic crystalline compounds as a modern alternative to purely exploratory synthesis. Our approach initializes materials discovery campaigns by autonomously mapping the synthetic feasibility of a chemical system using density functional theory with AI feedback. Following expert-driven down-selection of newly generated phases, we use solid-state synthesis and in situ characterization via hot-stage X-ray diffraction in order to realize new ternary oxide phases experimentally. We applied this strategy in six ternary transition-metal oxide chemistries previously considered well-explored, one of which culminated in the discovery of two novel phases of calcium ruthenates. Detailed characterization using room temperature X-ray powder diffraction, 4D-STEM and SQUID measurements identifies the structure and composition and confirms distinct properties, including distinct defect concentrations, of one of the new phases formed in our experimental campaigns. While the discovery of a new material guided by AI and DFT theory represents a milestone, our procedure and results also highlight a number of critical gaps in the process that can inform future efforts towards the improvement of AI-coupled methodologies.

Molecular mechanism of miRNA-23a in sepsis-induced lung injury.

OBJECTIVE: MicroRNA-23a-3p (miR-23a) is a novel gene regulator involved in inflammation. This study aimed to explore the molecular mechanism of miR-23a in sepsis-induced lung injury both in vitro and in vivo. METHODS: Lipopolysaccharide (LPS)- and ATP-stimulated human myeloid leukemia mononuclear cells (THP-1) and Human Bronchial Epithelial Cells (BEAS-2B) cell lines were used, while cecal ligation and puncture (CLP)-induced sepsis BABL/c mice were constructed. The mRNA expression levels of interleukin (IL)-18, IL-1ß, and miR-23a were determined, and Western blotting was used to measure CXCR4/PTEN/PI3K/AKT signaling. The concentrations of cytokines and Nod-like receptor family pyrin domain-containing 3 (NLRP3) were determined using an enzyme-linked immunosorbent assay. Lung tissue of mice was subjected to hematoxylin-eosin staining for examining myocardial injury. RESULTS: MiR-23a inhibited NLRP3 inflammasome activation in LPS- and ATP-stimulated THP-1 and BEAS-2B cells (P<0.05). Overexpression of miR-23a decreased the lactate dehydrogenase release rate in the cells (P<0.05). Meanwhile, miR-23a overexpression decreased the concentration and gene expression of IL-1ß and IL-18 in CXCR4 positive cells (P<0.05). Conversely, miR-23a knockdown increased the concentration and gene expression of IL-1ß and IL-18 (P<0.05). Additionally, PTEN and p53 proteins were up-regulated in miR-23a mimic group and down-regulated in miR-23a inhibitor group (P<0.05). Furthermore, miR-23a expression was decreased in sepsis-induced lung injury mice (P<0.05). MiR-23a overexpression reduced the sepsis-induced lung injury probably by inhibiting acetylcholinesterase activity and expression levels of IL-1ß, IL-18, capase-1, and NLRP3 (P<0.05). CONCLUSION: miR-23a can significantly alleviate sepsis-induced lung injury in CLP-induced septic mice and LPS-stimulated cell lines by suppressing NLRP3 inflammasome activation and inflammatory response, while promoting the CXCR4/PTEN/PI3K/AKT pathway.

A framework for materials informatics education through workshops.

Abstract: The burgeoning field of materials informatics necessitates a focus on educating the next generation of materials scientists in the concepts of data science, artificial intelligence (AI), and machine learning (ML). In addition to incorporating these topics in undergraduate and graduate curricula, regular hands-on workshops present the most effective medium to initiate researchers to informatics and have them start applying the best AI/ML tools to their own research. With the help of the Materials Research Society (MRS), members of the MRS AI Staging Committee, and a dedicated team of instructors, we successfully conducted workshops covering the essential concepts of AI/ML as applied to materials data, at both the Spring and Fall Meetings in 2022, with plans to make this a regular feature in future meetings. In this article, we discuss the importance of materials informatics education via the lens of these workshops, including details such as learning and implementing specific algorithms, the crucial nuts and bolts of ML, and using competitions to increase interest and participation.

Mechanism of miR-338-3p in sepsis-induced acute lung injury via indirectly modulating ATF4.

Sepsis is recognized as an inflammation-related syndrome in response to invading pathogens. Many patients suffer from sepsis including transplant recipients. Lipopolysaccharide (LPS) is known to trigger sepsis-related organ dysfunction. This study expounded on the possible effect of microRNA (miR)-338-3p in sepsis-induced acute lung injury (ALI). Firstly, human bronchial epithelial cell line 16HBE received LPS treatment to establish the cell models of sepsis-induced ALI. The expression patterns of miR-338-3p, long non-coding RNA OPA-interacting protein 5 antisense transcript 1 (lncRNA OIP5-AS1), and activating transcription factor 4 (ATF4) in 16HBE cells were examined. Afterwards, 16HBE cell viability, the apoptosis rate, and the levels of inflammation and lactate dehydrogenase (LDH) were determined to assess the degree of cell injury. We disclosed that LPS treatment triggered 16HBE cell injury, downregulated miR-338-3p, and upregulated OIP5-AS1 and ATF4. miR-338-3p overexpression repressed LPS-induced 16HBE cell injury. miR-338-3p diminished OIP5-AS1 stability via binding to OIP5-AS1 and downregulated OIP5-AS1 expression and OIP5-AS1 can enhance ATF4 mRNA stability and upregulate ATF4 mRNA level. The rescue experiments showed that ATF4 overexpression aggravated LPS-induced 16HBE cell injury. Overall, miR-338-3p overexpression decreased OIP5-AS1 expression and stability and further downregulated ATF4 mRNA level, thereby mitigating LPS-induced 16HBE cell injury.

Machine Learning Guided Dopant Selection for Metal Oxide-Based Photoelectrochemical Water Splitting: The Case Study of Fe2 O3 and CuO.

Doping is an effective strategy for tuning metal oxide-based semiconductors for solar-driven photoelectrochemical (PEC) water splitting. Despite decades of extensive research effort, the dopant selection is still largely dependent on a trial-and-error approach. Machine learning (ML) is promising in providing predictable insights on the dopant selection for high-performing PEC systems because it can uncover correlations from the seemingly ambiguous linkages between vast features of dopants and the PEC performance of doped photoelectrodes. Herein, the authors successfully build ML model to predict the doping effect of 17 metal dopants into hematite (Fe2 O3 ), a prototype photoelectrode material. Their findings disclose the critical parameters from the 10 intrinsic features of each dopant. The model is further experimentally validated by the coherent prediction on Y and La dopants' behaviors. Further interpretation of the ML model suggests that the chemical state is the most significant selection criteria, meanwhile, dopants with higher metal-oxygen bond formation enthalpy and larger ionic radius are favored in improving the charge separation and transfer (CST) in the Fe2 O3 photoanodes. The generic feature of this ML guided selection criteria has been further extended to CuO-based photoelectrodes showing improved CST by alkaline metal ions doping.

Variable Temperature Behaviour of the Hybrid Double Perovskite MA2KBiCl6.

Perovskite-related materials show very promising properties in many fields. Pb-free perovskites are particularly interesting, because of the toxicity of Pb. In this study, hybrid double perovskite MA2KBiCl6 (MA = methylammonium cation) was found to have interesting variable temperature behaviours. Both variable temperature single crystal X-ray diffraction, synchrotron powder diffraction, and Raman spectroscopy were conducted to reveal a rhombohedral to cubic phase transition at around 330 K and an order to disorder transition for inorganic cage below 210 K.

Predicting Antimicrobial Activity of Conjugated Oligoelectrolyte Molecules via Machine Learning.

New antibiotics are needed to battle growing antibiotic resistance, but the development process from hit, to lead, and ultimately to a useful drug takes decades. Although progress in molecular property prediction using machine-learning methods has opened up new pathways for aiding the antibiotics development process, many existing solutions rely on large data sets and finding structural similarities to existing antibiotics. Challenges remain in modeling unconventional antibiotic classes that are drawing increasing research attention. In response, we developed an antimicrobial activity prediction model for conjugated oligoelectrolyte molecules, a new class of antibiotics that lacks extensive prior structure-activity relationship studies. Our approach enables us to predict the minimum inhibitory concentration for E. coli K12, with 21 molecular descriptors selected by recursive elimination from a set of 5305 descriptors. This predictive model achieves an R2 of 0.65 with no prior knowledge of the underlying mechanism. We find the molecular representation optimum for the domain is the key to good predictions of antimicrobial activity. In the case of conjugated oligoelectrolytes, a representation reflecting the three-dimensional shape of the molecules is most critical. Although it is demonstrated with a specific example of conjugated oligoelectrolytes, our proposed approach for creating the predictive model can be readily adapted to other novel antibiotic candidate domains.

circ­Grm1 promotes pulmonary artery smooth muscle cell proliferation and migration via suppression of GRM1 expression by FUS.

Pulmonary arterial hypertension is a progressive and fatal disease. Recent studies suggest that circular RNA (circRNAs/circs) can regulate various biological processes, including cell proliferation. Therefore, it is possible that circRNA may have important roles in pulmonary artery smooth muscle cell proliferation in hypoxic pulmonary hypertension (HPH). The aim of the present study was to determine the role and mechanism of circRNA­glutamate metabotropic receptor 1 (circ­Grm1; mmu_circ_0001907) in pulmonary artery smooth muscle cell (PASMC) proliferation and migration in HPH. High­throughput transcriptome sequencing was used to screen circRNAs and targeted genes involved in HPH. Cell Counting Kit­8 (CCK­8), 5­ethynyl­2­deoxyuridine and wound healing assays were employed to assess cell viability and migration. Reverse transcription­quantitative PCR and western blotting were used to detect target gene expression in different groups. Bioinformatical approaches were used to predict the interaction probabilities of circ­Grm1 and Grm1 with FUS RNA binding protein (FUS). The interactions of circ­Grm1, Grm1 and FUS were evaluated using RNA silencing and RNA immunoprecipitation assays. The results demonstrated that circ­Grm1 was upregulated in hypoxic PASMCs. Further experiments revealed that the knockdown of circ­Grm1 could suppress the proliferation and migration of hypoxic PASMCs. Transcriptome sequencing revealed that Grm1 could be the target gene of circ­Grm1. It was found that circ­Grm1 could competitively bind to FUS and consequently downregulate Grm1. Moreover, Grm1 could inhibit the function of circ­Grm1 by promoting the proliferative and migratory abilities of hypoxic PASMCs. The results also demonstrated that circ­Grm1 influenced the biological functions of PASMCs via the Rap1/ERK pathway by regulating Grm1. Overall, the current results suggested that circ­Grm1 was associated with HPH and promoted the proliferation and migration of PASMCs via suppression of Grm1 expression through FUS.

Discovery of temperature-induced stability reversal in perovskites using high-throughput robotic learning.

Stability of perovskite-based photovoltaics remains a topic requiring further attention. Cation engineering influences perovskite stability, with the present-day understanding of the impact of cations based on accelerated ageing tests at higher-than-operating temperatures (e.g. 140°C). By coupling high-throughput experimentation with machine learning, we discover a weak correlation between high/low-temperature stability with a stability-reversal behavior. At high ageing temperatures, increasing organic cation (e.g. methylammonium) or decreasing inorganic cation (e.g. cesium) in multi-cation perovskites has detrimental impact on photo/thermal-stability; but below 100°C, the impact is reversed. The underlying mechanism is revealed by calculating the kinetic activation energy in perovskite decomposition. We further identify that incorporating at least 10 mol.% MA and up to 5 mol.% Cs/Rb to maximize the device stability at device-operating temperature (<100°C). We close by demonstrating the methylammonium-containing perovskite solar cells showing negligible efficiency loss compared to its initial efficiency after 1800 hours of working under illumination at 30°C.

Safety and Transcriptome Analysis of Live Attenuated Brucella Vaccine Strain S2 on Non-pregnant Cynomolgus Monkeys Without Abortive Effect on Pregnant Cynomolgus Monkeys.

Brucellosis, caused by Brucella spp., is an important zoonotic disease leading to enormous economic losses in livestock, posing a great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2, a safe and effective vaccine, is widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly humans. In this study, we used cynomolgus monkey as an animal model to evaluate the safety of the S2 vaccine strain on primates. In addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe for cynomolgus monkeys. The transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly upregulated and 315 were remarkably downregulated. The Gene Ontology (GO) classification and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that these DEGs were involved in various biological processes (BPs), including the chemokine signaling pathway, actin cytoskeleton regulation, the defense response, immune system processing, and the type-I interferon signaling pathway. The molecular functions of the DEGs were mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding, and actin-binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex, and blood microparticle. Our findings alleviate the concerns over the safety of the S2 vaccine on primates and provide a genetic basis for the response from a mammalian host following vaccination with the S2 vaccine.

Author Correction: How machine learning can help select capping layers to suppress perovskite degradation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

How machine learning can help select capping layers to suppress perovskite degradation.

Environmental stability of perovskite solar cells (PSCs) has been improved by trial-and-error exploration of thin low-dimensional (LD) perovskite deposited on top of the perovskite absorber, called the capping layer. In this study, a machine-learning framework is presented to optimize this layer. We featurize 21 organic halide salts, apply them as capping layers onto methylammonium lead iodide (MAPbI3) films, age them under accelerated conditions, and determine features governing stability using supervised machine learning and Shapley values. We find that organic molecules' low number of hydrogen-bonding donors and small topological polar surface area correlate with increased MAPbI3 film stability. The top performing organic halide, phenyltriethylammonium iodide (PTEAI), successfully extends the MAPbI3 stability lifetime by 4 ± 2 times over bare MAPbI3 and 1.3 ± 0.3 times over state-of-the-art octylammonium bromide (OABr). Through characterization, we find that this capping layer stabilizes the photoactive layer by changing the surface chemistry and suppressing methylammonium loss.

Complete Genome Sequence of Mycoplasma bovis Strain XBY01, Isolated from Henan Province, China.

We report the complete genome sequence of Mycoplasma bovis strain XBY01, which was isolated from a severely diseased young calf in Henan Province, China, in 2019. The genome of XBY01 contains a single circular chromosome of 986,067 bp, with a GC content of 29.30%.

Mutations in PB2 and HA enhanced pathogenicity of H4N6 avian influenza virus in mice.

The H4 subtype avian influenza virus (AIV) continues to circulate in both wild birds and poultry, and occasionally infects mammals (e.g. pigs). H4-specific antibodies have also been detected in poultry farm workers, which suggests that H4 AIV poses a potential threat to public health. However, the molecular mechanism by which H4 AIVs could gain adaptation to mammals and whether this has occurred remain largely unknown. To better understand this mechanism, an avirulent H4N6 strain (A/mallard/Beijing/21/2011, BJ21) was serially passaged in mice and mutations were characterized after passaging. A virulent mouse-adapted strain was generated after 12 passages, which was tentatively designated BJ21-MA. The BJ21-MA strain replicated more efficiently than the parental BJ21, both in vivo and in vitro. Molecular analysis of BJ21-MA identified four mutations, located in proteins PB2 (E158K and E627K) and HA (L331I and G453R, H3 numbering). Further studies showed that the introduction of E158K and/or E627K substitutions into PB2 significantly increased polymerase activity, which led to the enhanced replication and virulence of BJ21-MA. Although individual L331I or G453R substitutions in HA did not change the pathogenicity of BJ21 in mice, both mutations significantly enhanced virulence. In conclusion, our data presented in this study demonstrate that avian H4 virus can adapt to mammals by point mutations in PB2 or HA, which consequently poses a potential threat to public health.

Deletion of the LuxR-type regulator VjbR in Brucella canis affects expression of type IV secretion system and bacterial virulence, and the mutant strain confers protection against Brucella canis challenge in mice.

Brucella spp. are facultative intracellular pathogens and zoonotic agents which pose a huge threat to human health and animal husbandry. The B. melitensis, B. abortus, and B. suis cause undulant fever and influenza-like symptoms in humans. However, the effects of B. canis have not been extensively studied. The quorum sensing-dependent transcriptional regulator VjbR influences the Brucella virulence in smooth type Brucella strains, such as B. melitensis, B. abortus and rough type Brucella ovis. However, the function of VjbR in the rough-type B. canis is unknown. In the present study, we discovered that deletion of this regulator significantly affected Brucella virulence in macrophage and mice infection models. The expression levels of virB operon and the ftcR gene were significantly altered in the vjbR mutant strain. We further investigated the protective effect of different doses of the vjbR mutant in mice and the results indicated that VjbR conferred protection against the virulent B. canis strain. This study presents the first evidence that the transcriptional regulator VjbR has important function in B. canis. In addition, according to its reduced virulence and the protective immunity it induces in mice, it can be a potential live attenuated vaccine against B. canis.

Investigation and Characterization of Synthesis Conditions on Sucrose-ammonium Dihydrogen Phosphate (SADP) Adhesive: Bond Performance and Chemical Transformation.

Sucrose is one of the most abundantly available renewable chemicals in the world, and it is expected to be utilized as a raw material for wood-based material products. Herein, a novel adhesion system that was based on sucrose and ammonium dihydrogen phosphate (ADP) was synthesized into an adhesive with 80% solid content, and this eco-friendly was utilized on the fabrication of plywood. The effects of the synthesis conditions on the plywood bond performance and synthesis mechanism were investigated. The optimal synthesis conditions were as follows: the mass proportion between sucrose and ADP was 90/10, the synthesis temperature was 90 °C, and the synthesis time was 3 h. The bonding performance of the plywood that was bonded by optimal SADP adhesive satisfied the GB/T 9846-2015 standard. The chemical analysis was performance tested by using High-Performance Liquid Chromatography (HPLC), Attenuated Total Reflection-Fourier Transform Infrared Spectra (ATR-FTIR), and Pyrolysis Gas Chromatography and Mass Spectrometry (Py-GC/MS) to understand the chemical transformation during the synthesis process. The chemical analysis results confirmed that the hydrolysis and conversation reaction of sucrose occurred in the synthesized SADP adhesive, and ADP promoted the pyrolysis efficiency of sucrose.

Further Exploration of Sucrose-Citric Acid Adhesive: Investigation of Optimal Hot-Pressing Conditions for Plywood and Curing Behavior.

In previous research, sucrose and citric acid were used to synthesize an eco-friendly plywood adhesive. Herein, further research was performed to determine the optimal hot-pressing conditions and curing behavior of a sucrose-citric acid (SC) adhesive. The results of dry and wet shear strength measurements showed that the optimal hot-pressing temperature, hot-pressing time, and spread rate of plywood samples bonded by the SC adhesive were 190 °C, 7 min, and 140 g/m2, respectively. When plywood was bonded at the optimal hot-pressing conditions, the wet shear strength met the requirements of the China National Standard GB/T 9846-2015. Thermal analysis showed that the thermal degradation and endothermic reaction temperatures of the SC 25/75 adhesive were lower than either sucrose or citric acid individually. In addition, the insoluble mass proportion increased with the heating temperature and time. The Pyrolysis Gas Chromatography and Mass Spectrometr (Py-GC/MS) analysis confirmed that the SC adhesive was cured by the reaction between furan compounds, saccharide, and citric acid, and the resulting polymer appeared to be joined by ether linkages.

Further Exploration of Sucrose-Citric Acid Adhesive: Synthesis and Application on Plywood.

The development of eco-friendly adhesives is a major research direction in the wood-based material industry. Previous research has already demonstrated the mixture of sucrose and citric acid could be utilized as an adhesive for the manufacture of particleboard. Herein, based on the chemical characteristics of sucrose, a synthesized sucrose-citric acid (SC) adhesive was prepared, featuring suitable viscosity and high solid content. The investigation of synthesis conditions on the bond performance showed that the optimal mass proportion between sucrose and citric acid was 25/75, the synthesis temperature was 100 °C, and the synthesis time was 2 h. The wet shear strength of the plywood bonded with SC adhesive, which was synthesized at optimal conditions and satisfied the China National Standard GB/T 9846-2015. The synthesis mechanism was studied by both 13C NMR analysis and HPLC, and the chemical composition manifesting caramelization reaction occurred during the synthesis process. The results of ATR FT-IR indicated the formation of a furan ring, carbonyl, and ether groups in the cured insoluble matter of the SC adhesive, which indicated dehydration condensation as the reaction mechanism between sucrose and citric acid.

Synthesis and Characterization of Sucrose and Ammonium Dihydrogen Phosphate (SADP) Adhesive for Plywood.

The development of eco-friendly adhesives for wood composite products has been a major topic in the field of wood science and product engineering. Although the research on tannin-based and soybean protein-based adhesives has already reached, or at least nears, industrial implementation, we also face a variety of remaining challenges with regards to the push for sustainable adhesives. First, petroleum-derived substances remain a pre-requisite for utilization of said adhesive systems, and also the viscosity of these novel adhesives continues to limit its ability to serve as a drop-in substitute. Within this study, we focus upon the development of an eco-friendly plywood adhesive that does not require any addition of petroleum derived reagents, and the resultant liquid adhesive has both high solid contents as well as a manageably low viscosity at processing temperatures. Specifically, a system based on sucrose and ammonium dihydrogen phosphate (ADP) was synthesized into an adhesive with ~80% solid content and with viscosities ranging from 480-1270 mPa·s. The bonding performance of all adhesive-bound veneer specimens satisfied GB/T 9846-2015 standard at 170 °C hot pressing temperature. To better explain the system's efficiency, in-depth chemical analysis was performed in an effort to understand the chemical makeup of the cured adhesives as well as the components over the time course of curing. Several new structures involving the fixation of nitrogen speak to a novel adhesive molecular network. This research provides a possibility of synthesizing an eco-friendly wood adhesive with a high solid content and a low viscosity by renewable materials, and this novel adhesive system has the potential to be widely utilized in the wood industry.

Complete Genome Characterization of a Novel Infectious Bursal Disease Virus Strain Isolated from a Chicken Farm in China.

Infectious bursal disease (IBD) is a highly infectious disease in chicken, and vaccination is the best way to prevent outbreak of infectious bursal disease virus (IBDV). In this study, we isolated a variant IBDV strain from a chicken farm with vaccinated chickens. The full genome of this IBDV strain was determined and analyzed.