Unraveling the Luminescence Quenching Mechanism in Strong and Weak Quantum-Confined CsPbBr3 Triggered by Triarylamine-Based Hole Transport Layers.

Luminescence quenching by hole transport layers (HTLs) is one of the major issues in developing efficient perovskite light-emitting diodes (PeLEDs), which is particularly prominent in blue-emitting devices. While a variety of material systems have been used as interfacial layers, the origin of such quenching and the type of interactions between perovskites and HTLs are still ambiguous. Here, we present a systematic investigation of the luminescence quenching of CsPbBr3 by a commonly employed hole transport polymer, poly[(9,9-dioctylfluorenyl-2,7diyl)-co-(4,4'-(N-(4-sec-butylphenyl) diphenylamine)] (TFB), in LEDs. Strong and weak quantum-confined CsPbBr3 (nanoplatelets (NPLs)/nanocrystals (NCs)) are rationally selected to study the quenching mechanism by considering the differences in their morphology, energy level alignments, and quantum confinement. The steady-state and time-resolved Stern-Volmer plots unravel the dominance of dynamic and static quenching at lower and higher concentrations of TFB, respectively, with a maximum quenching efficiency of 98%. The quenching rate in NCs is faster than that in NPLs owing to their longer PL lifetimes and weak quantum confinement. The ultrafast transient absorption results support these dynamics and rule out the involvement of Forster or Dexter energy transfer. Finally, the 1D 1H and 2D nuclear overhauser effect spectroscopy nuclear magnetic resonance (NOESY NMR) study confirms the exchange of native ligands at the NCs surface with TFB, leading to dark CsPbBr3-TFB ensemble formation accountable for luminescence quenching. This highlights the critical role of the triarylamine functional group on TFB (also the backbone of many HTLs) in the quenching process. These results shed light on the underlying reasons for the luminescence quenching in PeLEDs and will help to rationally choose the interfacial layers for developing efficient LEDs.

Effect of Connectivity on the Carrier Transport and Recombination Dynamics of Perovskite Quantum-Dot Networks.

Quantum-dot (QD) solids are being widely exploited as a solution-processable technology to develop photovoltaic, light-emission, and photodetection devices. Charge transport in these materials is the result of a compromise between confinement at the individual QD level and electronic coupling among the different nanocrystals in the ensemble. While this is commonly achieved by ligand engineering in colloidal-based systems, ligand-free QD assemblies have recently emerged as an exciting alternative where nanostructures can be directly grown into porous matrices with optical quality as well as control over their connectivity and, hence, charge transport properties. In this context, we present a complete photophysical study comprising fluence- and temperature-dependent time-resolved spectroscopy to study carrier dynamics in ligand-free QD networks with gradually varying degrees of interconnectivity, which we achieve by changing the average distance between the QDs. Analysis of the photoluminescence and absorption properties of the QD assemblies, involving both static and time-resolved measurements, allows us to identify the weight of the different recombination mechanisms, both radiative and nonradiative, as a function of QD connectivity. We propose a picture where carrier diffusion, which is needed for any optoelectronic application and implies interparticle transport, gives rise to the exposure of carriers to a larger defect landscape than in the case of isolated QDs. The use of a broad range of fluences permits extracting valuable information for applications demanding either low- or high-carrier-injection levels and highlighting the relevance of a judicious design to balance recombination and diffusion.

Compromiso cardiovascular en pacientes con síndrome inflamatorio pediátrico multisistémico, asociado a infección por SARS-CoV-2 / Cardiovascular involvement in pediatric patients with SARS-CoV-2 associated to multisystemic inflammatory syndrome

INTRODUCCION: El Síndrome Inflamatorio Pediátrico Multisistémico (PIMS) ha emergido como una nueva enfermedad en niños, secundaria a infección por SARSCoV-2. Se caracteriza por presentar compromiso multiorgánico con parámetros inflamatorios elevados y manifestaciones clínicas graves, siendo el corazón el órgano más severamente comprometido. OBJETIVO: Describir las características clínicas y de laboratorio de 23 pacientes con diagnóstico de PIMS con compromiso cardiovascular hospitalizados en un centro único. MÉTODO: Se efectuó un estudio retrospectivo analizando los hallazgos clínicos y de laboratorio junto a las manifestaciones cardiovasculares que presentaron estos pacientes. RESULTADOS: 23/29 pacientes con PIMS (78%) presentaron manifestaciones digestivas y mucocutáneas. Las manifestaciones cardiovasculares fueron: Síndrome Kawasaki y "Kawasaki like" sin compromiso coronario en 15/23 (65%) y con compromiso coronario en 3 (13%). Shock en 9 pacientes (39%), injuria miocárdica- miocarditis en 8 (35%) y derrame pericárdico en 13 (56%). Trastornos del ritmo cardíaco se observaron en 6 pacientes (26%). La terapia más utilizada fue inmunoglobulina y corticoides. 18 /23 requirieron manejo en unidades de intermedio y/o intensivo. Un 70% de los pacientes se recuperó del compromiso cardiovascular antes del alta. CONCLUSIÓN: El compromiso cardiovascular en PIMS es la complicación más frecuente de esta enfermedad, que se acompaña de manifestaciones inmunológicas y hematológicas graves lo que hace necesario un tratamiento multidisciplinario para un mejor manejo de estos pacientes.

INTRODUCTION: Pediatric Multisystemic Inflammatory Syndrome (PIMS) has emerged as a new disease in children, secondary to SARSCoV-2 infection. It is characterized by multi-organ involvement with elevated inflammatory parameters and severe clinical manifestations, the heart being the organ most severely involved. OBJETIVE: to describe the clinical and laboratory characteristics of 23 patients diagnosed with PIMS with cardiovascular involvement hospitalized in a single center. METHOD: We conducted a retrospective study in which we analyzed the clinical and laboratory findings along with the cardiovascular manifestations presented by these patients. Results: 23/29 patients with PIMS and cardiovascular involvement were selected, 78% had digestive and mucocutaneous manifestations. Cardiovascular manifestations consisted of KawasakiKawasaki like syndrome without coronary involvement in 15/23 (65%) and coronary involvement in 3 (13%). Nine patients developed shock (39%), 8 (35%) myocardial injury in and 13 (56%) pericardial effusion.. Heart rhythm disorders were observed in 6 patients (26%). The main therapy was immunoglobulin and corticosteroids. 18 /23 required management in intermediate and/or intensive care unit. 70% of patients recovered from cardiovascular involvement before discharge. CONCLUSION: Cardiovascular involvement in PIMS is the most frequent complication of this disease, but it is associated with severe immunological and hematological manifestations, which makes necessary a multidisciplinary treatment for a better management

N-Acetyl-2-Aminofluorene (AAF) Processing in Adult Rat Hepatocytes in Primary Culture Occurs by High-Affinity Low-Velocity and Low-Affinity High-Velocity AAF Metabolite-Forming Systems.

N-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been described extensively, yet little is known about its biochemical processing, growth cycle expression, and pharmacological properties inside living hepatocytes-the principal cellular targets of this hepatocarcinogen. In this report, primary monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3 H]-N-acetyl-2-aminofluorene were used to extend previous observations of metabolic activation of AAF by highly differentiated, proliferation-competent hepatocytes in long-term cultures. AAF metabolism proceeded by zero-order kinetics. Hepatocytes processed significant amounts of procarcinogen (≈12 µg AAF/106 cells/day). Five ring-hydroxylated and one deacetylated species of AAF were secreted into the culture media. Extracellular metabolite levels varied during the growth cycle (days 0-13), but their rank quantitative order was time invariant: 5-OH-AAF > 7-OH-AAF > 3-OH-AAF > N-OH-AAF > aminofluorene (AF) > 1-OH-AAF. Lineweaver-Burk analyses revealed two principal classes of metabolism: System I (high-affinity and low-velocity), Km[APPARENT] = 1.64 × 10-7 M and VMAX[APPARENT] = 0.1 nmol/106 cells/day and System II (low-affinity and high-velocity), Km[APPARENT] = 3.25 × 10-5 M and VMAX[APPARENT] = 1000 nmol/106 cells/day. A third system of metabolism of AAF to AF, with Km[APPARENT] and VMAX[APPARENT] constants of 9.6 × 10-5 M and 4.7 nmol/106 cells/day, was also observed. Evidence provided in this report and its companion paper suggests selective roles and intracellular locations for System I- and System II-mediated AAF metabolite formation during hepatocarcinogenesis, although some of the molecules and mechanisms responsible for multi-system processing remain to be fully defined.

High-Affinity Low-Capacity and Low-Affinity High-Capacity N-Acetyl-2-Aminofluorene (AAF) Macromolecular Binding Sites Are Revealed During the Growth Cycle of Adult Rat Hepatocytes in Primary Culture.

Long-term cultures of primary adult rat hepatocytes were used to study the effects of N-acetyl-2-aminofluorene (AAF) on hepatocyte proliferation during the growth cycle; on the initiation of hepatocyte DNA synthesis in quiescent cultures; and, on hepatocyte DNA replication following the initiation of DNA synthesis. Scatchard analyses were used to identify the pharmacologic properties of radiolabeled AAF metabolite binding to hepatocyte macromolecules. Two classes of growth cycle-dependent AAF metabolite binding sites-a high-affinity low-capacity site (designated Site I) and a low-affinity high-capacity site (designated Site II)-associated with two spatially distinct classes of macromolecular targets, were revealed. Based upon radiolabeled AAF metabolite binding to purified hepatocyte genomic DNA or to DNA, RNA, proteins, and lipids from isolated nuclei, Site IDAY 4 targets (KD[APPARENT] ≈ 2-4×10-6 M and BMAX[APPARENT] ≈ 6 pmol/106 cells/24 h) were consistent with genomic DNA; and with AAF metabolized by a nuclear cytochrome P450. Based upon radiolabeled AAF binding to total cellular lysates, Site IIDAY 4 targets (KD[APPARENT] ≈ 1.5×10-3 M and BMAX[APPARENT] ≈ 350 pmol/106 cells/24 h) were consistent with cytoplasmic proteins; and with AAF metabolized by cytoplasmic cytochrome P450s. DNA synthesis was not inhibited by concentrations of AAF that saturated DNA binding in the neighborhood of the Site I KD. Instead, hepatocyte DNA synthesis inhibition required higher concentrations of AAF approaching the Site II KD. These observations raise the possibility that carcinogenic DNA adducts derived from AAF metabolites form below concentrations of AAF that inhibit replicative and repair DNA synthesis.

Characterization of energy and performance of swine fed a novel corn-soybean extruded product.

BACKGROUND: A novel extruded product was characterized with a metabolism and lactation trial to establish the product's energy content, and its effects on lactating sow performance. The product was composed of a 60:40 corn-soybean blend, which was then extruded. This product containing the co-extruded 60:40 corn-soybean blend was commercially developed and is used extensively in swine diets in southwest Minnesota. GE of dietary treatments were determined by isoperibol bomb calorimetry. Twelve barrows (59.9 ± 1.4 kg), were used to determine the digestible and metabolizable energy of the extruded product. DE of treatments was determined by subtracting fecal energy from GE provided to barrows by each respective treatment. ME was determined by subtracting urinary energy from calculated digestible energy. Sixty-three sows were used for the lactation trial. Three dietary treatments were utilized: CONTROL (an industry standard diet); PRODUCT (contained the product, vitamins and minerals); OIL (matched the lysine:ME ratio of PRODUCT by addition of soy oil). Sow weight, backfat thickness at the right and left last ribs, body condition score, number of piglets, and litter weights were recorded on the date of farrowing (d 0), (d 9), and at weaning. Blood and milk samples were obtained at weaning, and blood was analyzed for plasma urea nitrogen (PUN), milk was analyzed for total protein and fat content. RESULTS: On a dry-matter basis, the test diet provided 3,908 kcal/kg DE and 3,833 kcal/kg ME, which was significantly greater than the basal diet, which provided 3,633 kcal/kg DE and 3,567 kcal/kg ME (P < 0.0001). These data were used to establish the DE and ME of the product, which were 3,882 kcal/kg and 3,798 kcal/kg, respectively, on an as-fed basis. No effect of diet was observed for changes in sow backfat (RBF P = 0.24; LBF P = 0.07) or body condition score (P = 0.12) during lactation. Milk total protein (P = 0.69), fat (P = 0.66), PUN, average piglet gain (P = 0.55) and piglet mortality (P = 0.70) did not differ between treatments. CONCLUSIONS: While the novel extruded product was higher in energy content than traditional feedstuffs, it resulted in the same lactational sow performance. Thus, the co-extruded corn-soybean product is a reasonable inclusion in sow lactation diets.

Ectopic expression of CD74 in Ikkß-deleted mouse hepatocytes.

CD74, a Type II membrane glycoprotein and MHC class II chaperone involved in antigen processing, is normally expressed by cells associated with the immune system. CD74 also forms heterodimers with CD44 to generate receptors to macrophage migration inhibitory factor (MIF), a proinflammatory cytokine. Following targeted Alb-Cre-mediated deletion of Ikkß in Ikkß(Δhep) mice (Ikkß(F/F):Alb-Cre, a strain highly susceptible to chemically induced hepatotoxicity and hepatocarcinogenesis), CD74 is expressed abundantly by adult hepatocytes throughout liver acini, albeit more intensely in midzonal-to-centrilobular regions. By comparison, CD74 expression is not observed in Ikkß(F/F) hepatocytes, nor is it augmented in the livers of Ikkß(+/+):Alb-Cre mice; CD74 is barely detectable in cultured embryonic fibroblasts from Ikkß(-/-) mice. Microarray profiling shows that constitutive CD74 expression in Ikkß(Δhep) hepatocytes is accompanied by significantly augmented expression of CD44 and key genes associated with antigen processing and host defense, including MHC class II I-Aα, I-Aß, and I-Eß chains, CIITA and CD86. Taken together, these observations suggest that Ikkß(Δhep) hepatocytes might express functional capacities for class II-restricted antigen presentation and heightened responsiveness to MIF-signaling, and also suggest further roles for intrahepatocellular IKKß in the suppression or inactivation of molecules normally associated with the formation and differentiation of cells of the immune system.

Hypothesis: Targeted Ikkß deletion upregulates MIF signaling responsiveness and MHC class II expression in mouse hepatocytes.

Macrophage migration inhibitory factor (MIF) is causally related to the pathogenesis of chronic liver disease but its hepatocellular mechanisms of action are largely unknown. Scattered reports in the literature hint at functional connections between the expression of MIF and major histocompatibility complex (MHC) Class II molecules. Not surprisingly, these relationships have not yet been explored in hepatocytes because MIF and MHC Class II cell surface receptors are commonly expressed by other cell types including various antigen presenting cells of the immune system. On the other hand, mounting evidence suggests that heteromeric MIF receptors share a common molecule with intracellular MHC Class II complexes, viz., CD74, which also serves as the MHC Class II chaperone; and, while it is unclear what cancer-related role(s) MHC Class II receptors might play, increasing evidence suggests that MIF and CD74 are also implicated in the biology of hepatocellular carcinoma. These reports are provocative for two reasons: firstly, IkkßΔhep mice carrying hepatocyte-targeted deletions of Ikkß, an IκB kinase complex subunit required for the activation of the transcription factor NF-κB (nuclear factor-κB), have been shown to display heightened susceptibilities to hepatotoxins and chemical hepatocarcinogens; secondly, microarray profiling observations indicate that IkkßΔhep hepatocytes constitutively and "ectopically" overexpress genes, particularly CD74, CD44 (a MIF-receptor subunit) and MHC Class II I-A/E ß and I-A α chains, and gene families that regulate host immune process and immune defense responses. These findings together suggest that IkkßΔhep mice might express functional MIF and MHC Class II receptors, leading to increased hepatocellular sensitivity to MIF signaling as well as to the unusual property of antigen presentation; both functions might contribute to the heightened liver disease phenotypes of IkkßΔhep mice. The findings raise questions about the potential existence of cohorts of human patients with genetic abnormalities of Ikkß that might confer heightened susceptibility to liver disease including hepatocellular carcinoma.

Targeted deletion of hepatocyte Ikkbeta confers growth advantages.

Mice lacking hepatocyte IKKbeta (Ikkbeta(Delta hep)) are defective in TNFalpha-activation of hepatocellular transcription factor NF-kappaB, and highly susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure, Ikkbeta(Delta hep) mice develop more hepatocellular carcinoma (HCC) than control mice due partly to enhanced DEN-induced hepatocyte death. Here we show that Ikkbeta(Delta hep) hepatocytes display growth advantages over normal hepatocytes consisting of precocious PCNA and cyclin D1 expression during liver regeneration (shortened hepatocyte G(0)-->G(1) transitions), and enhanced recovery efficiency, cyclin D1 expression and cell proliferation after plating. Ex vivo deletion of Ikkbeta also accelerates hepatocyte growth. Ikkbeta(Delta hep) hepatocyte proliferative responses show heightened sensitivity to TGFalpha and TNFalpha, and heightened expression of fibronectin, collagens I/III, nidogen, beta-actin and integrin beta1 mRNAs. These findings suggest that altered mitogen signaling and expression of extracellular matrix and its associated components underlie growth advantages. Increased HCC development in Ikkbeta(Delta hep) mice may also be caused by growth advantages of surviving Ikkbeta-deleted hepatocytes.

Immune-privileged embryonic Swiss mouse STO and STO cell-derived progenitor cells: major histocompatibility complex and cell differentiation antigen expression patterns resemble those of human embryonic stem cell lines.

Embryonic mouse STO (S, SIM; T, 6-thioguanine resistant; O, ouabain resistant) and 3(8)21-enhanced green fluorescent protein (EGFP) cell lines exhibit long-term survival and hepatic progenitor cell behaviour after xenogeneic engraftment in non-immunosuppressed inbred rats, and were previously designated major histocompatibility complex (MHC) class I- and class II-negative lines. To determine the molecular basis for undetectable MHC determinants, the expression and haplotype of H-2K, H-2D, H-2L and I-A proteins were reassessed by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequencing, RNA hybridization, immunoblotting, quantitative RT-PCR (QPCR), immunocytochemistry and flow cytometry. To detect cell differentiation (CD) surface antigens characteristic of stem cells, apoptotic regulation or adaptive immunity that might facilitate progenitor cell status or immune privilege, flow cytometry was also used to screen untreated and cytokine [interferon (IFN)-gamma]-treated cultures. Despite prior PCR genotyping analyses suggestive of H-2q haplotypes in STO, 3(8)21-EGFP and parental 3(8)21 cells, all three lines expressed H-2K cDNA sequences identical to those of d-haplotype BALB/c mice, as well as constitutive and cytokine-inducible H-2K(d) determinants. In contrast, apart from H-2L(d[LOW]) display in 3(8)21 cells, H-2Dd, H-2Ld and I-Ad determinants were undetectable. All three lines expressed constitutive and cytokine-inducible CD34; however, except for inducible CD117([LOW]) expression in 3(8)21 cells, no expression of CD45, CD117, CD62L, CD80, CD86, CD90.1 or CD95L/CD178 was observed. Constitutive and cytokine-inducible CD95([LOW]) expression was detected in STO and 3(8)21 cells, but not in 3(8)21-EGFP cells. MHC (class I(+[LOW])/class II-) and CD (CD34+/CD80-/CD86-/CD95L-) expression patterns in STO and STO cell-derived progenitor cells resemble patterns reported for human embryonic stem cell lines. Whether these patterns reflect associations with mechanisms that are regulatory of immune privilege or functional tissue-specific plasticity is unknown.

Embryonic mouse STO cell-derived xenografts express hepatocytic functions in the livers of nonimmunosuppressed adult rats.

Cells derived from embryonic mouse STO cell lines differentiate into hepatocytes when transplanted into the livers of nonimmunosuppressed dipeptidylpeptidase IV (DPPIV)-negative F344 rats. Within 1 day after intrasplenic injection, donor cells moved rapidly into the liver and were found in intravascular and perivascular sites; by 1 month, they were intrasinusoidal and also integrated into hepatic plates with approximately 2% efficiency and formed conjoint bile canaliculi. Neither donor cell proliferation nor host inflammatory responses were observed during this time. Detection of intrahepatic mouse COX1 mitochondrial DNA and mouse albumin mRNA in recipient rats indicated survival and differentiation of donor cells for at least 3 months. Mouse COX1 targets were also detected intrahepatically 4-9 weeks after STO cell injection into nonimmunosuppressed wild-type rats. In contrast to STO-transplanted rats, mouse DNA or RNA was not detectable in untreated or mock-transplanted rats or in rats injected with donor cell DNA. In cultured STO donor cells, DPPIV and glucose-6-phosphatase activities were observed in small clusters; in contrast, mouse major histocompatibility complex class I H-2Kq, H-2Dq, and H-2Lq and class II I-Aq markers were undetectable in vitro before or after interferon gamma treatment. Together with H-2K allele typing, which confirmed the Swiss mouse origin of the donor cells, these observations indicate that mouse-derived STO cell lines can differentiate along hepatocytic lineage and engraft into rat liver across major histocompatibility barriers.