Ligand-Mediated Band Engineering in Bottom-Up Assembled SnTe Nanocomposites for Thermoelectric Energy Conversion.

The bottom-up assembly of colloidal nanocrystals is a versatile methodology to produce composite nanomaterials with precisely tuned electronic properties. Beyond the synthetic control over crystal domain size, shape, crystal phase, and composition, solution-processed nanocrystals allow exquisite surface engineering. This provides additional means to modulate the nanomaterial characteristics and particularly its electronic transport properties. For instance, inorganic surface ligands can be used to tune the type and concentration of majority carriers or to modify the electronic band structure. Herein, we report the thermoelectric properties of SnTe nanocomposites obtained from the consolidation of surface-engineered SnTe nanocrystals into macroscopic pellets. A CdSe-based ligand is selected to (i) converge the light and heavy bands through partial Cd alloying and (ii) generate CdSe nanoinclusions as a secondary phase within the SnTe matrix, thereby reducing the thermal conductivity. These SnTe-CdSe nanocomposites possess thermoelectric figures of merit of up to 1.3 at 850 K, which is, to the best of our knowledge, the highest thermoelectric figure of merit reported for solution-processed SnTe.

Watershed phenomena during extracorporeal life support and their clinical impact: a systematic in vitro investigation.

AIMS: Extracorporeal life support (ECLS) during acute cardiac failure restores haemodynamic stability and provides life-saving cardiopulmonary support. Unfortunately, all common cannulation strategies and remaining pulmonary blood flow increase left-ventricular afterload and may favour pulmonary congestion. The resulting disturbed pulmonary gas exchange and a residual left-ventricular action can contribute to an inhomogeneous distribution of oxygenated blood into end organs. These complex flow interactions between native and artificial circulation cannot be investigated at the bedside: only an in vitro simulation can reveal the underlying activities. Using an in vitro mock circulation loop, we systematically investigated the impact of heart failure, extracorporeal support, and cannulation routes on the formation of flow phenomena and flow distribution in the arterial tree. METHODS AND RESULTS: The mock circulation loop consisted of two flexible life-sized vascular models (aorta and vena cava) driven by two paracorporeal assist devices, resistance elements, and compliance reservoirs to mimic the circulatory system. Several large-bore antegrade and retrograde access ports allowed connection to an ECLS system for extracorporeal support. With four degrees of extracorporeal support-that for cardiac failure, early recovery, late recovery, and weaning-we investigated aortic blood flow velocity, blood flow, and mixing zones using colour-coded Doppler ultrasound in the aorta and its corresponding branches. Full retrograde extracorporeal support (3-4 L/min) perfused major portions of the aorta but did not reach the supra-aortic branches and ascending aorta, resulting in an area in the thoracic aorta demonstrating nearly stagnant blood flow velocities during cardiogenic shock and early recovery (0 ± 4 cm/s; -10 ± 15 cm/s, respectively) confined by two watersheds at the aortic isthmus and renal artery origin. Even increased ECLS flow was unable to shift the watershed towards the aortic arch. Antegrade support resulted in homogeneous flow distribution during all stages of cardiac failure but created a markedly negative flow vector in the ascending aorta during cardiogenic shock and early recovery with increased afterload. CONCLUSIONS: Our systematic fluid-mechanical analysis confirms the clinical assumption that despite restoring haemodynamic stability, extracorporeal support generates an inhomogeneous distribution of oxygenated blood with an inadequate supply to end organs and increased left-ventricular afterload with absent ventricular unloading. End-organ supply may be monitored by near-infrared spectroscopy, but an obviously non-controllable watershed emphasizes the need for additional measures: pre-pulmonary oxygenation with a veno-arterial-venous ECLS configuration can allow a transpulmonary passage of oxygenated blood, providing improved end-organ supply.

Cited4 is a sex-biased mediator of the antidiabetic glitazone response in adipocyte progenitors.

Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context-specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone-dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta-adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.

Jak-TGFß cross-talk links transient adipose tissue inflammation to beige adipogenesis.

The transient activation of inflammatory networks is required for adipose tissue remodeling including the "browning" of white fat in response to stimuli such as ß3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFß signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFß signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by ß3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.