FAIR data enabling new horizons for materials research.

The prosperity and lifestyle of our society are very much governed by achievements in condensed matter physics, chemistry and materials science, because new products for sectors such as energy, the environment, health, mobility and information technology (IT) rely largely on improved or even new materials. Examples include solid-state lighting, touchscreens, batteries, implants, drug delivery and many more. The enormous amount of research data produced every day in these fields represents a gold mine of the twenty-first century. This gold mine is, however, of little value if these data are not comprehensively characterized and made available. How can we refine this feedstock; that is, turn data into knowledge and value? For this, a FAIR (findable, accessible, interoperable and reusable) data infrastructure is a must. Only then can data be readily shared and explored using data analytics and artificial intelligence (AI) methods. Making data 'findable and AI ready' (a forward-looking interpretation of the acronym) will change the way in which science is carried out today. In this Perspective, we discuss how we can prepare to make this happen for the field of materials science.

Application of first-row transition metal complexes bearing 1,2,3-triazolylidene ligands in catalysis and beyond.

Triazole-derived N-heterocyclic carbenes, triazolylidenes (trz) have become an interesting alternative to the ubiquitous Arduengo-type imidazole-derived carbenes, in part because they are stronger donors, and in other parts due to their versatile synthesis through different types of click reactions. While the use of trz ligands has initially focused on their coordination to precious metals for catalytic applications, the recent past has seen a growing interest in their impact on first-row transition metals. Coordination of trz ligands to such 3d metals is more challenging due to the orbital mismatch between the carbene and the 3d metal center, which also affects the stability of such complexes. Here we summarize the strategies that have been employed so far to overcome these challenges and to prepare first-row transition metal complexes containing at least one trz ligand. Both properties and reactivities of these trz complexes are comprehensively compiled, with a focus on photophysical properties and, in particular, on the application of these complexes in homogeneous catalysis. The diversity of catalytic transformations entailed with these trz 3d metal complexes as well as the record-high performance in some of the reactions underpins the benefits imparted by trz ligands.

Effects of temporal IFNγ exposure on macrophage phenotype and secretory profile: exploring GMP-Compliant production of a novel subtype of regulatory macrophages (MregIFNγ0) for potential cell therapeutic applications.

BACKGROUND: Macrophages are involved in tissue homeostasis, angiogenesis and immunomodulation. Proangiogenic and anti-inflammatory macrophages (regulatory macrophages, Mreg) can be differentiated in-vitro from CD14+ monocytes by using a defined cell culture medium and a stimulus of IFNγ. AIM OF THE STUDY: To scrutinize the potential impact of temporal IFNγ exposure on macrophage differentiation as such exposure may lead to the emergence of a distinct and novel macrophage subtype. METHODS: Differentiation of human CD14+ monocytes to Mreg was performed using a GMP compliant protocol and administration of IFNγ on day 6. Monocytes from the same donor were in parallel differentiated to MregIFNγ0 using the identical protocol but with administration of IFNγ on day 0. Cell characterization was performed using brightfield microscopy, automated and metabolic cell analysis, transmission electron microscopy, flow cytometry, qPCR and secretome profiling. RESULTS: Mreg and MregIFNγ0 showed no differences in cell size and volume. However, phenotypically MregIFNγ0 exhibited fewer intracellular vesicles/vacuoles but larger pseudopodia-like extensions. MregIFNγ0 revealed reduced expression of IDO and PD-L1 (P < 0.01 for both). They were positive for CD80, CD14, CD16 and CD38 (P < 0.0001vs. Mreg for all), while the majority of MregIFNγ0 did not express CD206, CD56, and CD103 on their cell surface (P < 0.01 vs. Mreg for all). In terms of their secretomes, MregIFNγ0 differed significantly from Mreg. MregIFNγ0 media exhibited reduced levels of ENA-78, Osteopontin and Serpin E1, while the amounts of MIG (CXCL9) and IP10 were increased. CONCLUSION: Exposing CD14+ monocytes to an alternatively timed IFNγ stimulation results in a novel macrophage subtype which possess additional M1-like features (MregIFNγ0). MregIFNγ0 may therefore have the potential to serve as cellular therapeutics for clinical applications beyond those covered by M2-like Mreg, including immunomodulation and tumor treatment.

Stable CAAC-Triazenes: A New Nitrogen Ligand System With Donor and Conformational Flexibility, and With Application in Olefin Activation Catalysis.

N-heterocyclic imines such as pyridylidene amines impart high catalytic activity when coordinated to a transition metal, largely imposed by their electronic flexibility. Here, this donor flexibility has been applied for the first time to CAAC-based systems through the synthesis of CAAC-triazenes. These new ligands offer a larger π-conjugation that extends from the N-heterocyclic carbene through three nitrogens rather than just one, as observed in N-heterocyclic imines. We demonstrate the straightforward synthesis of three new CAAC-triazenes containing different substituents on the terminal triazene nitrogen. These compounds are remarkably stable up to 120 °C without loss of N2 as typically observed with similar triazenes. E-to-Z isomerization within the triazene is instigated by UV light and is partially reversible dependent on the triazene substituent. The quinoline-substituted CAAC-triazene 1-Q has been applied as an L,L'-type ligand in the synthesis of [PdCl2(1-Q)], [PdCl(Me)(1-Q)] and [Pd(Me)(H2O(1-Q)]+. E-to-Z ligand isomerization also occurs when coordinated to PdCl2, providing access to on-metal manipulation. The cationic complex [PdMe(H2O)(1-Q)]+ is a precatalyst for oligomerization of ethylene to form initially 2-butene and subsequently linear and branched C8-C12 products from butene activation. Moreover, isomerization of 1-hexene takes place efficiently with exceptionally low catalyst loading (10 ppm) and up to 74,000 turnover numbers.

Deciphering Iron-Catalyzed C-H Amination with Organic Azides: N2 Cleavage from a Stable Organoazide Complex.

Catalytic C-N bond formation by direct activation of C-H bonds offers wide synthetic potential. En route to C-H amination, complexes with organic azides are critical precursors towards the reactive nitrene intermediate. Despite their relevance, α-N coordinated organoazide complexes are scarce in general, and elusive with iron, although iron complexes are by far the most active catalysts for C-H amination with organoazides. Herein, we report the synthesis of a stable iron α-N coordinated organoazide complex from [Fe(N(SiMe3 )2 )2 ] and AdN3 (Ad=1-adamantyl) and its crystallographic, IR, NMR and zero-field 57 Fe Mössbauer spectroscopic characterization. These analyses revealed that the organoazide is in fast equilibrium between the free and coordinated state (Keq =62). Photo-crystallography experiments showed gradual dissociation of N2 , which imparted an Fe-N bond shortening and correspond to structural snapshots of the formation of an iron imido/nitrene complex. Reactivity of the organoazide complex in solution showed complete loss of N2 , and subsequent formation of a C-H aminated product via nitrene insertion into a C-H bond of the N(SiMe3 )2 ligand. Monitoring this reaction by 1 H NMR spectroscopy indicates the transient formation of the imido/nitrene intermediate, which was supported by Mössbauer spectroscopy in frozen solution.

Air-Stable Coordinatively Unsaturated Ruthenium(II) Complex for Ligand Binding and Catalytic Transfer Hydrogenation of Ketones from Ethanol.

Coordinatively unsaturated complexes are interesting from a fundamental level for their formally empty coordination site and, in particular, from a catalytic perspective as they provide opportunities for substrate binding and transformation. Here, we describe the synthesis of a novel underligated ruthenium complex [Ru(cym)(N,N')]+, 3, featuring an amide-functionalized pyridylidene amide (PYA) as the N,N'-bidentate coordinating ligand. In contrast to previously investigated underligated complexes, complex 3 offers potential for dynamic modifications, thanks to the flexible donor properties of the PYA ligand. Specifically, they allow both for stabilizing the formally underligated metal center in complex 3 through nitrogen π-donation and for facilitating through π-acidic bonding properties the coordination of a further ligand L to the ruthenium center to yield the formal 18 e- complexes [Ru(cym)(N,N')(L)]+ (4: L = P(OMe)3; 5: L = PPh3; 6: L = N-methylimidazole; 7: L = pyridine) and neutral complex [RuCl(cym)(N,N')] 8. Analysis by 1H NMR and UV-vis spectroscopies reveals an increasing Ru-L bond strength along the sequence pyridine <1-methylimidazole < PPh3 < P(OMe)3 with binding constants varying over 3 orders of magnitude with log(Keq) values between 2.8 and 5.7. The flexibility of the Ru(PYA) unit and the ensuing accessibility of saturated and unsaturated species with one and the same ligand are attractive from a fundamental point of view and also for catalytic applications, as catalytic transformations rely on the availability of transiently vacant coordination sites. Thus, while complex 3 does not form stable adducts with O-donors such as ketones or alcohols, it transiently binds these species, as evidenced by the considerable catalytic activity in the transfer hydrogenation of ketones. Notably, and as one of only a few catalysts, complex 3 is compatible with EtOH as a hydrogen source. Complex 3 shows excellent performance in the transfer hydrogenation of pyridyl-containing substrates, in agreement with the poor coordination strength of this functional group to the ruthenium center in 3.

Optimal Chest Compression Point During Pediatric Resuscitation: Implications for Pediatric Resuscitation Practice by CT Scans.

OBJECTIVES: Current European guidelines for pediatric cardiopulmonary resuscitation (CPR) recommend the lower half of the sternum as the chest compression point (CP). In this study, we have used thoracic CT scans to evaluate recommended and optimal CP in relation to cardiac anatomy and structure. DESIGN: Analysis of routinely acquired thoracic CT scans acquired from 2000 to 2020. SETTING: Single-center pediatric department in a German University Hospital. PATIENTS: Imaging data were obtained from 290 patients of 3-16 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We measured and analyzed 14 thoracic metrics in each thoracic CT scan. In 44 of 290 (15.2%) scans, the recommended CP did not match the level of the cardiac ventricles. Anatomically, the optimal CP was one rib or one vertebral body lower than the recommended CP, that is, the optimal CP was more caudal to the level of the body of the sternum in 67 of 290 (23.1%) scans. The recommended compression depth appeared reasonable in children younger than 12 years old. At 12 years old or older, the maximum compression depth of 6 cm is less than or equal to one-third of the thoracic depth. CONCLUSIONS: In this study of thoracic CT scans in children 3-16 years old, we have found that optimal CP for CPR appears to be more caudal than the recommended CP. Therefore, it seems reasonable to prefer to use the lower part of the sternum for CPR chest compressions. At 12 years old or older, a compression depth similar to that used in adults-6 cm limit-may be chosen.

From C-H to C-N Bonds: Three Challenges, Three Catalysts, Three Solutions.

N-heterocycles are key building blocks for many pharmaceutical products. An efficient and sustainable method for the synthesis of this class of compounds consists of the recently established intramolecular C-H amination reaction. Development of new iron-based catalysts for this transformation is of paramount importance. Herein, three major challenges in this field are addressed: the accessibility of the catalyst, the lack of mechanisticunderstanding, and the limited activity and robustness of the catalyst. These challenges are tackled by threedifferent catalysts. The first catalyst is the commercially available FeI2, that shows good activities, but is limitedto substrates with activated C-H bonds. The Fe(HMDS)2 catalyst is used to perfom in-depth mechanistic studies, revealing key intermediates of the C-H amination reaction. The third catalyst, featuring mesoionic carbene ligands, displays unprecedented activities and aminates various C-H bonds.

Characterization of large extracellular vesicles (L-EV) derived from human regulatory macrophages (Mreg): novel mediators in wound healing and angiogenesis?

BACKGROUND: Large extracellular vesicles (L-EV) with a diameter between 1 and 10 µm are released by various cell types. L-EV contain and transport active molecules which are crucially involved in cell to cell communication. We have shown that secretory products of human regulatory macrophages (Mreg) bear pro-angiogenic potential in-vitro and our recent findings show that Mreg cultures also contain numerous large vesicular structures similar to L-EV with so far unknown characteristics and function. AIM OF THIS STUDY: To characterize the nature of Mreg-derived L-EV (L-EVMreg) and to gain insights into their role in wound healing and angiogenesis. METHODS: Mreg were differentiated using blood monocytes from healthy donors (N = 9) and L-EVMreg were isolated from culture supernatants by differential centrifugation. Characterization of L-EVMreg was performed by cell/vesicle analysis, brightfield/transmission electron microscopy (TEM), flow cytometry and proteome profiling arrays. The impact of L-EVMreg on wound healing and angiogenesis was evaluated by means of scratch and in-vitro tube formation assays. RESULTS: Mreg and L-EVMreg show an average diameter of 13.73 ± 1.33 µm (volume: 1.45 ± 0.44 pl) and 7.47 ± 0.75 µm (volume: 0.22 ± 0.06 pl) respectively. Flow cytometry analyses revealed similarities between Mreg and L-EVMreg regarding their surface marker composition. However, compared to Mreg fewer L-EVMreg were positive for CD31 (P < 0.01), CD206 (P < 0.05), CD103 (P < 0.01) and CD45 (P < 0.05). Proteome profiling suggested that L-EVMreg contain abundant amounts of pro-angiogenic proteins (i.e. interleukin-8, platelet factor 4 and serpin E1). From a functional point of view L-EVMreg positively influenced in-vitro wound healing (P < 0.05) and several pro-angiogenic parameters in tube formation assays (all segment associated parameters, P < 0.05; number of meshes, P < 0.05). CONCLUSION: L-EVMreg with regenerative and pro-angiogenic potential can be reproducibly isolated from in-vitro cultured human regulatory macrophages. We propose that L-EVMreg could represent a putative therapeutic option for the treatment of chronic wounds and ischemia-associated diseases.

Optimising Electrical Interfacing between the Trimeric Copper Nitrite Reductase and Carbon Nanotubes.

The immobilization of copper-containing nitrite reductase (NiR) from Alcaligenes faecalis on functionalised multi-walled carbon nanotube (MWCNT) electrodes is reported. It is demonstrated that this immobilization is mainly driven by hydrophobic interactions, promoted by the modification of MWCNTs with adamantyl groups. Direct electrochemistry shows high bioelectrochemical reduction of nitrite at the redox potential of NiR with high current density of 1.41 mA cm-2 . Furthermore, the desymmetrization of the trimer upon immobilization induces an independent electrocatalytic behavior for each of the three enzyme subunits, corroborated by an electron-tunneling distance dependence.

Pincer Platinum(II) Hydrides: High Stability Imparted by Donor-Flexible Pyridylidene Amide Ligands and Evidence for Adduct Formation before Protonation.

Donor-flexible ligands are an emerging class of noninnocent ligands. Their ability to adapt their donating strength toward a metal center has had numerous catalytic advantages yet has never been utilized to stabilize and isolate intermediate complexes within these processes. We demonstrate through the use of a pincer ligand containing two donor-flexible pyridylidene amide (PYA) arms in coordination with platinum(II) that this ligand adaptability revealed remarkably stable hydride and formate complexes. These are typically fleeting catalytic intermediates within formic acid dehydrogenation and CO2 hydrogenation catalytic cycles. The PYA platinum hydride complexes are indefinitely stable in air, while formate complexes show no sign of ß-hydrogen elimination. This robustness allowed us to investigate hydride protonation as a seemingly simple reaction, though in-depth kinetic analysis reveals a pre-equilibrium step prior to platinum hydride protonation. This initial step has been attributed to adduct formation and is slower than the protonation, and therefore a relevant aspect when designing catalytic cycles for hydrogen release and its microscopic reverse, viz., hydrogen uptake.

Sterically and Electronically Flexible Pyridylidene Amine Dinitrogen Ligands at Palladium: Hemilabile cis/trans Coordination and Application in Dehydrogenation Catalysis.

Ligand design is crucial for the development of new catalysts and materials with new properties. Herein, the synthesis and unique hemilabile coordination properties of new bis-pyridylidene amine (bis-PYE) ligands to palladium, and preliminary catalytic activity of these complexes in formic acid dehydrogenation are described. The synthetic pathway to form cationic complexes [Pd(bis-PYE)Cl(L)]X with a cis-coordinated N,N-bidentate bis-PYE ligand is flexible and provides access to a diversity of PdII complexes with different ancillary ligands (L=pyridine, DMAP, PPh3 , Cl, P(OMe)3 ). The 1 H NMR chemical shift of the trans-positioned PYE N-CH3 unit is identified as a convenient and diagnostic handle to probe the donor properties of these ancillary ligands and demonstrates the electronic flexibility of the PYE ligand sites. In the presence of a base, the originally cis-coordinated bis-PYE ligand adopts a N,N,N-tridentate coordination mode with the two PYE units in mutual trans position. This cis-trans isomerization is reverted in presence of an acid, demonstrating a unique structural and steric flexibility of the bis-PYE ligand at palladium in addition to its electronic adaptability. The palladium complexes are active in formic acid dehydrogenation to H2 and CO2 . The catalytic performance is directly dependent on the ligand bonding mode, the nature of the ancillary ligand, the counteranion, and additives. The most active system features a bidentate bis-PYE ligand, PPh3 as ancillary ligand and accomplishes turnover frequencies up to 525 h-1 in the first hour and turnover numbers of nearly 1000, which is the highest activity reported for palladium-based catalysts to date.

Pincer and Macrocyclic Pyridylidene Amide (PYA) AuIII Complexes.

Gold-based homogeneous catalysis is dominated by redox neutral AuI systems. Redox-active gold-based catalysts are less common, principally because of redox cycles between AuI and AuIII being hampered by unfavorable potentials. We report gold(III) complexes containing pincer-based, donor-flexible pyridylidene amide (PYA) ligands to address these issues. These complexes act as electron reservoirs through two limiting resonance structures consisting of either soft, imine coordination sites or harder, zwitterionic amide donors. We further alter the donor properties by using the ortho-, meta-, and para-pyridylidene amide variants of the PYA pincer arms. These bis-PYA pincer ligands exhibited a high contribution of amide coordination in the solid-state of the gold(III) complexes; however, the solution data suggests a high contribution from the neutral L-type resonance forms. This L-type contribution, primarily shown through cyclic voltammetry studies, prevents reversible gold(III) reduction and also disfavors abstraction of the ancillary chloride ligand. Furthermore, a novel macrocyclic-PYA ligand is introduced, which shows secondary metal-ligand interactions.

Repetitive application of remote ischemic conditioning (RIC) in patients with peripheral arterial occlusive disease (PAOD) as a non-invasive treatment option: study protocol for a randomised controlled clinical trial.

BACKGROUND: The best medical treatment (BMT) for most patients with early stage of peripheral arterial occlusive disease (PAOD) is often limited to gait training and pharmacological therapy besides endovascular surgery. The application of remote ischemic conditioning (RIC) has been described as a promising experimental strategy for the improvement of therapeutic outcome in cardiovascular disease but has not proven beneficial effects in clinical practice and treatment of PAOD yet. METHODS: Here we describe a prospective, randomized trial for the evaluation of possible effects of repeated application of RIC in patients with PAOD. This monocentric study will enrol 200 participants distributed to an intervention group receiving RIC + BMT and a control group only receiving BMT for four weeks. Patients are at least 18 years of age and have diagnosed PAOD Fontaine stage II b. Pain-free and total walking distance will be measured via treadmill test (primary endpoints). In addition, ankle-brachial index (ABI) and quality of life (QoL) will be assessed using the SF-36 and VascuQoL-6 questionnaire. Moreover, evaluation of markers for atherosclerosis, angiogenic profiling and mononuclear cell characterization will be performed using biochemical assays, proteome profiling arrays and flow cytometry (secondary endpoints). DISCUSSION: Our prospective, randomized monocentric trial is the first of its kind to analyse the effects of chronic and repetitive treatment with RIC in patients with PAOD and might provide important novel information on the molecular mechanisms associated with RIC in PAOD patients. TRIAL REGISTRATION: Prospectively registered in the German Clinical Trials Register (Deutsche Register Klinischer Studien) Registration number: DRKS00025735; Date of registration: 01.07.2021.

An Iron-Mesoionic Carbene Complex for Catalytic Intramolecular C-H Amination Utilizing Organic Azides.

The synthesis of N-heterocycles is of paramount importance for the pharmaceutical industry. They are often synthesized through atom economic and environmentally unfriendly methods, generating significant waste. A less explored, but greener, alternative is the synthesis through the direct intramolecular C-H amination utilizing organic azides. Few examples exist by using this method, but many are limited due to the required use of stoichiometric amounts of Boc2O. Herein, we report a homoleptic C,O-chelating mesoionic carbene-iron complex, which is the first iron-based complex that does not require the addition of any protecting groups for this transformation and that is active also in strong donor solvents such as THF or even DMSO. The achieved turnover number is an order of magnitude higher than any other reported catalytic system. A variety of C-H bonds were activated, including benzylic, primary, secondary, and tertiary. By following the reaction over time, we determined the presence of an initiation period. Kinetic studies showed a first-order dependence on substrate concentration and half-order dependence on catalyst concentration. Intermolecular competition reactions with deuterated substrate showed no KIE, while separate reactions with deuterium-labeled substrate resulted in a KIE of 2.0. Moreover, utilizing deuterated substrate significantly decreased the initiation period of the catalysis. Preliminary mechanistic studies suggest a unique mechanism involving a dimeric iron species as the catalyst resting state.

First experiments with a water-jet plasma X-ray source driven by the novel high-power-high-repetition rate L1 Allegra laser at ELI Beamlines.

ELI Beamlines is a rapidly progressing pillar of the pan-European Extreme Light Infrastructure (ELI) project focusing on the development and deployment of science driven by high-power lasers for user operations. This work reports the results of a commissioning run of a water-jet plasma X-ray source driven by the L1 Allegra laser, outlining the current capabilities and future potential of the system. The L1 Allegra is one of the lasers developed in-house at ELI Beamlines, designed to be able to reach a pulse energy of 100 mJ at a 1 kHz repetition rate with excellent beam properties. The water-jet plasma X-ray source driven by this laser opens opportunities for new pump-probe experiments with sub-picosecond temporal resolution and inherent synchronization between pump and probe pulses.

Effects of remote ischemic preconditioning (RIPC) and chronic remote ischemic preconditioning (cRIPC) on levels of plasma cytokines, cell surface characteristics of monocytes and in-vitro angiogenesis: a pilot study.

Remote ischemic preconditioning (RIPC) protects the heart against myocardial ischemia/reperfusion (I/R) injury and recent work also suggested chronic remote ischemic conditioning (cRIPC) for cardiovascular protection. Based on current knowledge that systemic immunomodulatory effects of RIPC and the anti-inflammatory capacity of monocytes might be involved in cardiovascular protection, the aim of our study was to evaluate whether RIPC/cRIPC blood plasma is able to induce in-vitro angiogenesis, identify responsible factors and evaluate the effects of RIPC/cRIPC on cell surface characteristics of circulating monocytes. Eleven healthy volunteers were subjected to RIPC/cRIPC using a blood pressure cuff inflated to > 200 mmHg for 3 × 5 min on the upper arm. Plasma and peripheral blood monocytes were isolated before RIPC (Control), after 1 × RIPC (RIPC) and at the end of 1 week of daily RIPC (cRIPC) treatment. Plasma concentrations of potentially pro-angiogenic humoral factors (CXCL5, Growth hormone, IGFBP3, IL-1α, IL-6, Angiopoietin 2, VEGF, PECAM-1, sTie-2, IL-8, MCSF) were measured using custom made multiplex ELISA systems. Tube formation assays for evaluation of in-vitro angiogenesis were performed with donor plasma, monocyte conditioned culture media as well as IL-1α, CXCL5 and Growth hormone. The presence of CD14, CD16, Tie-2 and CCR2 was analyzed on monocytes by flow cytometry. Employing in-vitro tube formation assays, several parameters of angiogenesis were significantly increased by cRIPC plasma (number of nodes, P < 0.05; number of master junctions, P < 0.05; number of segments, P < 0.05) but were not influenced by culture medium from RIPC/cRIPC treated monocytes. While RIPC/cRIPC treatment did not lead to significant changes of the median plasma concentrations of any of the selected potentially pro-angiogenic humoral factors, in-depth analysis of the individual subjects revealed differences in plasma levels of IL-1α, CXCL5 and Growth hormone after RIPC/cRIPC treatment in some of the volunteers. Nevertheless, the positive effects of RIPC/cRIPC plasma on in-vitro angiogenesis could not be mimicked by the addition of the respective humoral factors alone or in combination. While monocyte conditioned culture media did not affect in-vitro tube formation, flow cytometry analyses of circulating monocytes revealed a significant increase in the number of Tie-2 positive and a decrease of CCR2 positive monocytes after RIPC/cRIPC (Tie-2: cRIPC, P < 0.05; CCR2: RIPC P < 0.01). Cardiovascular protection may be mediated by RIPC and cRIPC via a regulation of plasma cytokines as well as changes in cell surface characteristics of monocytes (e.g. Tie-2). Our results suggest that a combination of humoral and cellular factors could be responsible for the RIPC/cRIPC mediated effects and that interindividual variations seem to play a considerable part in the RIPC/cRIPC associated mechanisms.

Epitaxial BaSnO3thin films with low dislocation density grown on lattice matched LaInO3substrates.

The use of LaInO3with (110) surface orientation was investigated as a novel orthorhombic substrate for the epitaxial growth of semiconducting BaSnO3thin films. On the basis of reflection high-energy electron diffraction, energy dispersive x-ray analysis and inductively coupled plasma-optical emission spectrometry measurements, we revealed that slight Ba doping of LaInO3crystals is beneficial to stabilize the substrate surface, which facilitates the epitaxial growth of well-ordered BaSnO3thin films by pulsed laser deposition. Fully strained BaSnO3films without misfit dislocations found by means of transmission electron microscopy were achieved due to the negligible lattice mismatch between BaSnO3film and Ba-doped LaInO3substrate. Electric properties of La-doped BaSnO3films exhibit a Hall-mobility of 69 cm2V-1s-1at room temperature and 99 cm2V-1s-1at 20 K at a constant charge carrier density of 3.8·1019cm-3.

Strategies to Overcome the Barrier of Ischemic Microenvironment in Cell Therapy of Cardiovascular Disease.

The transplantation of various immune cell types are promising approaches for the treatment of ischemic cardiovascular disease including myocardial infarction (MI) and peripheral arterial disease (PAD). Major limitation of these so-called Advanced Therapy Medicinal Products (ATMPs) is the ischemic microenvironment affecting cell homeostasis and limiting the demanded effect of the transplanted cell products. Accordingly, different clinical and experimental strategies have been evolved to overcome these obstacles. Here, we give a short review of the different experimental and clinical strategies to solve these issues due to ischemic cardiovascular disease.

Sodium Glucose Co-Transporter 2 Inhibitors Ameliorate Endothelium Barrier Dysfunction Induced by Cyclic Stretch through Inhibition of Reactive Oxygen Species.

SGLT-2i's exert direct anti-inflammatory and anti-oxidative effects on resting endothelial cells. However, endothelial cells are constantly exposed to mechanical forces such as cyclic stretch. Enhanced stretch increases the production of reactive oxygen species (ROS) and thereby impairs endothelial barrier function. We hypothesized that the SGLT-2i's empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) exert an anti-oxidative effect and alleviate cyclic stretch-induced endothelial permeability in human coronary artery endothelial cells (HCAECs). HCAECs were pre-incubated with one of the SGLT-2i's (1 µM EMPA, 1 µM DAPA and 3 µM CANA) for 2 h, followed by 10% stretch for 24 h. HCAECs exposed to 5% stretch were considered as control. Involvement of ROS was measured using N-acetyl-l-cysteine (NAC). The sodium-hydrogen exchanger 1 (NHE1) and NADPH oxidases (NOXs) were inhibited by cariporide, or GKT136901, respectively. Cell permeability and ROS were investigated by fluorescence intensity imaging. Cell permeability and ROS production were increased by 10% stretch; EMPA, DAPA and CANA decreased this effect significantly. Cariporide and GKT136901 inhibited stretch-induced ROS production but neither of them further reduced ROS production when combined with EMPA. SGLT-2i's improve the barrier dysfunction of HCAECs under enhanced stretch and this effect might be mediated through scavenging of ROS. Anti-oxidative effect of SGLT-2i's might be partially mediated by inhibition of NHE1 and NOXs.