Transition metal perovskite chalcogenides are a new class of versatile semiconductors with high absorption coefficient and luminescence efficiency. Polycrystalline materials synthesized by an ...iodine‐catalyzed solid‐state reaction show distinctive optical colors and tunable bandgaps across the visible range in photoluminescence, with one of the materials' external efficiency approaching the level of single‐crystal InP and CdSe.
Transition metal perovskite chalcogenides, a class of materials with rich tunability in functionalities, are gaining increased attention as candidate materials for renewable energy applications. ...Perovskite oxides are considered excellent n-type thermoelectric materials. Compared to oxide counterparts, we expect the chalcogenides to possess more favorable thermoelectric properties such as lower lattice thermal conductivity and smaller band gap, making them promising material candidates for high temperature thermoelectrics. Thus, it is necessary to study the thermal properties of these materials in detail, especially thermal stability, to evaluate their potential. In this work, we report the synthesis and thermal stability study of five compounds, α-SrZrS3, β-SrZrS3, BaZrS3, Ba2ZrS4, and Ba3Zr2S7. These materials cover several structural types including distorted perovskite, needle-like, and Ruddlesden–Popper phases. Differential scanning calorimeter and thermogravimetric analysis measurements were performed up to 1200 °C in air. Structural and chemical characterizations such as X-ray diffraction, Raman spectroscopy, and energy dispersive analytical X-ray spectroscopy were performed on all the samples before and after the heat treatment to understand the oxidation process. Our studies show that perovskite chalcogenides possess excellent thermal stability in air at least up to 550 °C.
Metformin has been used as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study ...(UKPDS), metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reduce insulin resistance and enhance peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as important. In the gut, metformin modulates the glucagon-like peptide- 1 (GLP-1) - gut-brain axis and impacts the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has the interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases, and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review, we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease.
Abstract Complex oxides offer rich magnetic and electronic behavior intimately tied to the composition and arrangement of cations within the structure. Rare earth iron garnet films exhibit an ...anisotropy along the growth direction which has long been theorized to originate from the ordering of different cations on the same crystallographic site. Here, we directly demonstrate the three-dimensional ordering of rare earth ions in pulsed laser deposited (Eu x Tm 1-x ) 3 Fe 5 O 12 garnet thin films using both atomically-resolved elemental mapping to visualize cation ordering and X-ray diffraction to detect the resulting order superlattice reflection. We quantify the resulting ordering-induced ‘magnetotaxial’ anisotropy as a function of Eu:Tm ratio using transport measurements, showing an overwhelmingly dominant contribution from magnetotaxial anisotropy that reaches 30 kJ m −3 for garnets with x = 0.5. Control of cation ordering on inequivalent sites provides a strategy to control matter on the atomic level and to engineer the magnetic properties of complex oxides.
The first encounter with influenza virus biases later immune responses. This "immune imprinting," formerly from infection within a few years of birth, is in the United States now largely from ...immunization with a quadrivalent, split vaccine (IIV4 quadrivalent inactivated influenza vaccine). In a pilot study of IIV4 imprinting, we used single-cell cultures, next-generation sequencing, and plasma antibody proteomics to characterize the primary antibody responses to influenza in two infants during their first 2 years of seasonal influenza vaccination. One infant, who received only a single vaccination in year 1, contracted an influenza B virus (IBV) infection between the 2 years, allowing us to compare imprinting by infection and vaccination. That infant had a shift in hemagglutinin (HA)-reactive B cell specificity from largely influenza A virus (IAV) specific in year 1 to IBV specific in year 2, both before and after the year 2 vaccination. HA-reactive B cells from the other infant maintained a more evenly distributed specificity. In year 2, class-switched HA-specific B cell
somatic hypermutation (SHM) levels reached the average levels seen in adults. The HA-reactive plasma antibody repertoires of both infants comprised a relatively small number of antibody clonotypes, with one or two very abundant clonotypes. Thus, after the year 2 boost, both infants had overall B cell profiles that resembled those of adult controls.
Influenza virus is a moving target for the immune system. Variants emerge that escape protection from antibodies elicited by a previously circulating variant ("antigenic drift"). The immune system usually responds to a drifted influenza virus by mutating existing antibodies rather than by producing entirely new ones. Thus, immune memory of the earliest influenza virus exposure has a major influence on later responses to infection or vaccination ("immune imprinting"). In the many studies of influenza immunity in adult subjects, imprinting has been from an early infection, since only in the past 2 decades have infants received influenza immunizations. The work reported in this paper is a pilot study of imprinting by the flu vaccine in two infants, who received the vaccine before experiencing an influenza virus infection. The results suggest that a quadrivalent (four-subtype) vaccine may provide an immune imprint less dominated by one subtype than does a monovalent infection.
The making of BaZrS3 thin films by molecular beam epitaxy (MBE) is demonstrated. BaZrS3 forms in the orthorhombic distorted‐perovskite structure with corner‐sharing ZrS6 octahedra. The single‐step ...MBE process results in films smooth on the atomic scale, with near‐perfect BaZrS3 stoichiometry and an atomically sharp interface with the LaAlO3 substrate. The films grow epitaxially via two competing growth modes: buffered epitaxy, with a self‐assembled interface layer that relieves the epitaxial strain, and direct epitaxy, with rotated‐cube‐on‐cube growth that accommodates the large lattice constant mismatch between the oxide and the sulfide perovskites. This work sets the stage for developing chalcogenide perovskites as a family of semiconductor alloys with properties that can be tuned with strain and composition in high‐quality epitaxial thin films, as has been long‐established for other systems including Si‐Ge, III‐Vs, and II‐VIs. The methods demonstrated here also represent a revival of gas‐source chalcogenide MBE.
BaZrS3 thin films are made by molecular beam epitaxy. The single‐step, gas‐source process results in films smooth on the atomic scale, with near‐perfect BaZrS3 stoichiometry and an atomically‐sharp interface with the LaAlO3 substrate. This work sets the stage for developing chalcogenide perovskites as semiconductors with properties that can be tuned with strain and composition in high‐quality epitaxial films.
Metformin was first used to treat type 2 diabetes in the late 1950s and in 2022 remains the first-choice drug used daily by approximately 150 million people. An accumulation of positive pre-clinical ...and clinical data has stimulated interest in re-purposing metformin to treat a variety of diseases including COVID-19. In polycystic ovary syndrome metformin improves insulin sensitivity. In type 1 diabetes metformin may help reduce the insulin dose. Meta-analysis and data from pre-clinical and clinical studies link metformin to a reduction in the incidence of cancer. Clinical trials, including MILES (Metformin In Longevity Study), and TAME (Targeting Aging with Metformin), have been designed to determine if metformin can offset aging and extend lifespan. Pre-clinical and clinical data suggest that metformin, via suppression of pro-inflammatory pathways, protection of mitochondria and vascular function, and direct actions on neuronal stem cells, may protect against neurodegenerative diseases. Metformin has also been studied for its anti-bacterial, −viral, −malaria efficacy. Collectively, these data raise the question: Is metformin a drug for all diseases? It remains unclear as to whether all of these putative beneficial effects are secondary to its actions as an anti-hyperglycemic and insulin-sensitizing drug, or result from other cellular actions, including inhibition of mTOR (mammalian target for rapamycin), or direct anti-viral actions. Clarification is also sought as to whether data from ex vivo studies based on the use of high concentrations of metformin can be translated into clinical benefits, or whether they reflect a ‘Paracelsus’ effect. The environmental impact of metformin, a drug with no known metabolites, is another emerging issue that has been linked to endocrine disruption in fish, and extensive use in T2D has also raised concerns over effects on human reproduction. The objectives for this review are to: 1) evaluate the putative mechanism(s) of action of metformin; 2) analyze the controversial evidence for metformin's effectiveness in the treatment of diseases other than type 2 diabetes; 3) assess the reproducibility of the data, and finally 4) reach an informed conclusion as to whether metformin is a drug for all diseases and reasons. We conclude that the primary clinical benefits of metformin result from its insulin-sensitizing and antihyperglycaemic effects that secondarily contribute to a reduced risk of a number of diseases and thereby enhancing healthspan. However, benefits like improving vascular endothelial function that are independent of effects on glucose homeostasis add to metformin's therapeutic actions.
•Metformin is a drug with a long history.•A critical review of metformin and its benefits in diabetes and beyond•The mode(s) of action of metformin remains controversial.•Should metformin be repurposed metformin for multiple diseases.•Review of whether metformin is a drug for all reasons.
Exercise is an effective nonpharmacological strategy to alleviate diabetic cardiomyopathy (DCM) through poorly defined mechanisms. FGF21 (fibroblast growth factor 21), a peptide hormone with ...pleiotropic benefits on cardiometabolic homeostasis, has been identified as an exercise responsive factor. This study aims to investigate whether FGF21 signaling mediates the benefits of exercise on DCM, and if so, to elucidate the underlying mechanisms.
The global or hepatocyte-specific FGF21 knockout mice, cardiomyocyte-selective β-klotho (the obligatory co-receptor for FGF21) knockout mice, and their wild-type littermates were subjected to high-fat diet feeding and injection of streptozotocin to induce DCM, followed by a 6-week exercise intervention and assessment of cardiac functions. Cardiac mitochondrial structure and function were assessed by electron microscopy, enzymatic assays, and measurements of fatty acid oxidation and ATP production. Human induced pluripotent stem cell-derived cardiomyocytes were used to investigate the receptor and postreceptor signaling pathways conferring the protective effects of FGF21 against toxic lipids-induced mitochondrial dysfunction.
Treadmill exercise markedly induced cardiac expression of β-klotho and significantly attenuated diabetes-induced cardiac dysfunction in wild-type mice, accompanied by reduced mitochondrial damage and increased activities of mitochondrial enzymes in hearts. However, such cardioprotective benefits of exercise were largely abrogated in mice with global or hepatocyte-selective ablation of FGF21, or cardiomyocyte-specific deletion of β-klotho. Mechanistically, exercise enhanced the cardiac actions of FGF21 to induce the expression of the mitochondrial deacetylase SIRT3 by AMPK-evoked phosphorylation of FOXO3, thereby reversing diabetes-induced hyperacetylation and functional impairments of a cluster of mitochondrial enzymes. FGF21 prevented toxic lipids-induced mitochondrial dysfunction and oxidative stress by induction of the AMPK/FOXO3/SIRT3 signaling axis in human induced pluripotent stem cell-derived cardiomyocytes. Adeno-associated virus-mediated restoration of cardiac SIRT3 expression was sufficient to restore the responsiveness of diabetic FGF21 knockout mice to exercise in amelioration of mitochondrial dysfunction and DCM.
The FGF21-SIRT3 axis mediates the protective effects of exercise against DCM by preserving mitochondrial integrity and represents a potential therapeutic target for DCM.
URL: https://www.
gov; Unique identifier: NCT03240978.
Chalcogenides in the perovskite and related crystal structures ("chalcogenide perovskites" for brevity) may be useful for future optoelectronic and energy-conversion technologies inasmuch as they ...have good excited-state, ambipolar transport properties. In recent years, several studies have suggested that semiconductors in the Ba-Zr-S system have slow non-radiative recombination rates. Here, we present a time-resolved photoluminescence (TRPL) study of excited-state carrier mobility and recombination rates in the perovskite-structured material BaZrS
3
, and the related Ruddlesden-Popper phase Ba
3
Zr
2
S
7
. We measure state-of-the-art single crystal samples, to identify properties free from the influence of secondary phases and random grain boundaries. We model and fit the data using a semiconductor physics simulation, to enable more direct determination of key material parameters than is possible with empirical data modeling. We find that both materials have Shockley-Read-Hall recombination lifetimes on the order of 50 ns and excited-state diffusion lengths on the order of 5 μm at room temperature, which bodes well for ambipolar device performance in optoelectronic technologies including thin-film solar cells.
The rates of excited-state decay through recombination processes determine the usefulness of a semiconductor for ambipolar devices. We find that recombination rates in chalcogenide perovskites are promising for continued progress towards solar cells.
Abstract The synthesis of BaZr(S,Se) 3 chalcogenide perovskite alloys is demonstrated by selenization of BaZrS 3 thin films. The anion‐exchange process produces films with tunable composition and ...band gap without changing the orthorhombic perovskite crystal structure or the film microstructure. The direct band gap is tunable between 1.5 and 1.9 eV. The alloy films made in this way feature one‐hundred‐times stronger photoconductive response and a lower density of extended defects, compared to alloy films made by direct growth. The perovskite structure is stable in high‐selenium‐content thin films with and without epitaxy. The manufacturing‐compatible process of selenization in H 2 Se gas may spur the development of chalcogenide perovskite solar cell technology.
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