An autonomous laboratory for the accelerated synthesis of novel materials.

To close the gap between the rates of computational screening and experimental realization of novel materials1,2, we introduce the A-Lab, an autonomous laboratory for the solid-state synthesis of inorganic powders. This platform uses computations, historical data from the literature, machine learning (ML) and active learning to plan and interpret the outcomes of experiments performed using robotics. Over 17 days of continuous operation, the A-Lab realized 41 novel compounds from a set of 58 targets including a variety of oxides and phosphates that were identified using large-scale ab initio phase-stability data from the Materials Project and Google DeepMind. Synthesis recipes were proposed by natural-language models trained on the literature and optimized using an active-learning approach grounded in thermodynamics. Analysis of the failed syntheses provides direct and actionable suggestions to improve current techniques for materials screening and synthesis design. The high success rate demonstrates the effectiveness of artificial-intelligence-driven platforms for autonomous materials discovery and motivates further integration of computations, historical knowledge and robotics.

Direct Lithium Extraction from α-Spodumene through Solid-State Reactions for Sustainable Li2CO3 Production.

With increasing battery demand comes a need for diversified Li sources beyond brines. Among all Li-bearing minerals, spodumene is most often used for its high Li content and natural abundance. However, the traditional approach to process spodumene is costly and energy-intensive, requiring the mineral be transformed from its natural α to ß phase at >1000 °C. Acid leaching is then applied, followed by neutralization to precipitate Li2CO3. In this work, we report an alternative method to extract Li directly from α-spodumene, which is performed at lower temperatures and avoids the use of acids. It is shown that Li2CO3 is formed with >90% yield at 750 °C by reacting α-spodumene with Na2CO3 and Al2O3. The addition of Al2O3 is critical to reduce the amount of Li2SiO3 that forms when only Na2CO3 is used, instead providing increased thermodynamic driving force to form NaAlSiO4 and Li2CO3 as the sole products. We find that this reaction is most effective at 4 h, after which volatility limits the yield. Following its extraction, Li2CO3 can be isolated by washing the sample using deionized water. This energy-saving and acid-free route to obtain Li2CO3 directly from spodumene can help meet the growing demand for Li.

COVIDScholar: An automated COVID-19 research aggregation and analysis platform.

The ongoing COVID-19 pandemic produced far-reaching effects throughout society, and science is no exception. The scale, speed, and breadth of the scientific community's COVID-19 response lead to the emergence of new research at the remarkable rate of more than 250 papers published per day. This posed a challenge for the scientific community as traditional methods of engagement with the literature were strained by the volume of new research being produced. Meanwhile, the urgency of response lead to an increasingly prominent role for preprint servers and a diffusion of relevant research through many channels simultaneously. These factors created a need for new tools to change the way scientific literature is organized and found by researchers. With this challenge in mind, we present an overview of COVIDScholar https://covidscholar.org, an automated knowledge portal which utilizes natural language processing (NLP) that was built to meet these urgent needs. The search interface for this corpus of more than 260,000 research articles, patents, and clinical trials served more than 33,000 users at an average of 2,000 monthly active users and a peak of more than 8,600 weekly active users in the summer of 2020. Additionally, we include an analysis of trends in COVID-19 research over the course of the pandemic with a particular focus on the first 10 months, which represents a unique period of rapid worldwide shift in scientific attention.

Dataset of solution-based inorganic materials synthesis procedures extracted from the scientific literature.

The development of a materials synthesis route is usually based on heuristics and experience. A possible new approach would be to apply data-driven approaches to learn the patterns of synthesis from past experience and use them to predict the syntheses of novel materials. However, this route is impeded by the lack of a large-scale database of synthesis formulations. In this work, we applied advanced machine learning and natural language processing techniques to construct a dataset of 35,675 solution-based synthesis procedures extracted from the scientific literature. Each procedure contains essential synthesis information including the precursors and target materials, their quantities, and the synthesis actions and corresponding attributes. Every procedure is also augmented with the reaction formula. Through this work, we are making freely available the first large dataset of solution-based inorganic materials synthesis procedures.

In vitro and in vivo evaluation of hypothermia on pharmacokinetics and pharmacodynamics of nimodipine in rabbits.

Objective To investigate the effect of hypothermia on the pharmacokinetics and pharmacodynamics of nimodipine in rabbits using in vivo and in vitro methods. Methods Five healthy New Zealand rabbits received a single dose of nimodipine (0.5 mg/kg) intravenously under normothermic and hypothermic conditions. Doppler ultrasound was used to monitor cerebral blood flow, vascular resistance, and heart rate. In vitro evaluations of protein binding, hepatocyte uptake and intrinsic clearance of liver microsomes at different temperatures were also conducted. Results Plasma concentrations of nimodipine were significantly higher in hypothermia than in normothermia. Nimodipine improved cerebral blood flow under both conditions, but had a longer effective duration during the hypothermic period. Low temperature decreased the intrinsic clearance of liver microsomes, with no change in protein binding or hepatocyte uptake of nimodipine. Conclusion Nimodipine is eliminated at a slower rate during hypothermia than during normothermia, mainly due to the decreased activity of cytochrome P450 enzymes. This results in elevated system exposure with little enhancement in pharmacological effect.

[Autologous mononuclear bone marrow cell transplantation by intracoronary route for patients with ischemic heart disease: observation of 2-years follow-up].

OBJECTIVE: To investigate the long-term effect and safety of intracoronary autologous bone marrow mononuclear cell (BMMC) transplantation in patients with ischemic heart disease (IHD). METHODS: Seventy-six patients with IHD, 26 patients with acute myocardial infarction (AMI) and 26 patients with chronic ischemic heart failure (CIHF), underwent routine treatment plus intracoronary autologous BMMC transplantation, and 24 patients, including 10 patients with AMI and 14 patients with CIHF underwent routine treatment as controls. Autologous BMMC transplantation was performed via a balloon catheter placed into the infarct-related artery during balloon dilatation by high pressure infusion to occlude the artery, which was performed 6 - 8 times for 2 minutes each with 2-minute interval or via a balloon catheter without occluding the infarct-related artery. Follow-up was conducted for 2 years. RESULTS: The surgery was safety without major periprocedural complications. There were no other new arrhythmias found by Holter recorder during the 2-years follow-up. In the AMI patients receiving BNNC transplantation, the left ventricular ejection fraction (LVEF) 1 and 2 years later increased by 5.79% (P < 0.05), 3.79% (P > 0.05) respectively; but there was no change in left ventricular end diastolic volume (LVEDV) and left ventricular end systolic volume (LVESV). The LVEF 1 and 2 years later of the control group increased by 8.8% and 9.2% respectively (both P < 0.01) and the LVESV 1 and 2 years later decreased by 20.4% and 27.8% respectively (both P < 0.05), the myocardium defect area 2 years later was not significantly different from that 3 months later. The heart function of the control group became markedly worse. CONCLUSION: Autologous BMMC intracoronary transplantation is safe and effective, especially in patients with CIHF.

[The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction].

OBJECTIVE: To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. METHODS: Thirty patients with RIHF (LVEF < 40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0 +/- 0.7) x 10(7) were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received standard medical therapy served as control. Baseline and follow up evaluations included complete clinical evaluations, plasma BNP, ANP, ET-1 measurements, echocardiography, PET, and Holter monitoring. RESULTS: Baseline characteristics were similar between the 2 groups. There were no major periprocedural complications. One patient developed ventricular premature contractions during cell infusion for several seconds and recovered spontaneously. Compared to pre-transplantation, plasma BNP and ET-1 significantly decreased and plasma ANP significantly increased at 7 days post transplantation; 6 minutes walking distance increased from (72.1 +/- 31.5) to (201.6 +/- 23.3) m (P < 0.01), LVEF increased 9.9% (P < 0.001) and FDG-PET revealed vital myocardium area increased (10.3 +/- 3.4)% (P < 0.01) at 3 months after BM-MNCs transplantation. At 6 months follow up, the NYHA class improved from (3.4 +/- 0.1 to 2.4 +/- 0.2, P < 0.001) and no patient died and 1 patient rehospitalized due to lower extremities edema. In control group, LVEF decreased 7.2% compared to baseline (P < 0.001) and was significantly lower than transplantation group at 3 months (P < 0.001). At 6 months follow up, the NYHA class increased from (3.5 +/- 0.1 to 3.9 +/- 0.1, P < 0.05), 2 patients died and 10 patients rehospitalized due to aggravated heart failure. CONCLUSION: Present study demonstrates that intracoronary transplantation of autologous BM-MNCs is safe and effective for treating patients with RIHF after myocardial infarction.

[Transplantation of fetal cardiomyocyte regenerates infarcted myocardium in rats].

OBJECTIVE: To investigate the feasibility and efficiency of fetal cardiomyocyte transplantation into the rat model of myocardial infarction. METHODS: Cardiomyocytes were isolated from aborted human embryos aged 12 - 16 weeks and cultured for 5 days to confirm their viability. Rat model of extensive myocardial infarction (MI) was established in 18 male Wistar rats by ligating the descending anterior branch of left coronary artery and the 18 rats were randomly divided into 2 groups: transplantation group (n = 7, 2 x 10(6) fetal cardiomyocytes were transplanted into the myocardial scar) and culture medium injection group (n = 6, culture medium was injected into the myocardial scar) 5 days after extensive MI was caused. Another 6 rats undergoing sham operation were used as controls. Echocardiography was performed before and 60 +/- 3 days after the implantation to assess the left ventricular (LV) remodeling and cardiac function. Then the rats were killed and their heart were harvested to undergo HE staining, immunohistochemical examination with antibody against human alpha-actin smooth muscle (SMA) isoform, and light microscopy. RESULTS: Light microscopy revealed the presence of engrafted human fetal cardiomyocytes in the infarcted myocardium and the presence of nascent intercalated disks connecting the engrafted fetal cardiomyocytes and the host myocardium. The engrafted fetal cardiomyocytes were SMA positive. Serial echocardiography revealed that cell transplantation prevented scar thinning, LV further dilatation and dysfunction while the control animals developed scar thinning, significant LV dilatation accompanied by progressive deterioration in LV contractility. CONCLUSION: Fetal cardiomyocytes can be implanted and survive in the infarcted myocardial cells, thus preventing the scar thinning, and LV further dilatation and dysfunction.

[Transfection of bone marrow mesenchymal stem cells by adeno-associated virus 2/1 vector].

This study was aimed to investigate the transfection efficacy of recombinant adeno-associated virus 2/1 (rAAV2/1) on bone marrow mesenchymal stem cells (BMMSCs) at different multiplicities of infection (MOI) and time, and effect of transfection on growth of rat BMMSCs. The rat BMMSCs cultured in vitro were transfected by using rAAV2/1 with enhanced green fluorescent protein (rAAV2/1-EGFP) at MOI of 1 x 10(4), 1 x 10(5) and 1 x 10(6); the EGFP expression was observed by fluorescent microscopy at 3, 7 and 14 days. The viability, proliferation multiple, differentiation ability of daughter cells were detected for evaluating the effect of rAAV2/1 on survival, proliferation and differentiation of BMMSCs and the fluorescence index (FI) were determined by flow cytometry. The results indicated that after transfection with rAAV2/1 for 24 hours the green fluorescence in BMMSCs were observed, but also the fluorescence gradually was enhanced along with prolonging of time, and reached to steady level after 7 days; the viability, proliferation multiple, differentiation ability of BMMSCs transfected by rAAV2/1-EGFP at different MOI showed no significant changes at 3,7 and 14 days (p > 0.05), meanwhile at same MOI the proliferation multiple obviously increased in comparison between 7 day vs 3 day and 14 days vs 7 days (p < 0.01). The flow cytometric detection showed that the transfection efficacy of rAAV2/1-EGFP on BMMSCs and FI increased significantly as the multiplicity of infection and culture time increased (p < 0.05). It is concluded that rAAV2/1-EGFP is able to transfect into BMMSCs effectively, but the transfection efficiency and fluorescence index increase significantly along with increase of multiplicity of infection and culture time. rAAV2/1-EGFP do not affect viability, proliferation multiple and differentiation ability of BMMSCs. rAAV2/1 is a kind of active vector for gene transfer to reform BMMSCs.