Engineering Metal Halide Perovskite Nanocrystals with BODIPY Dyes for Photosensitization and Photocatalytic Applications.

The sensitization of surface-anchored organic dyes on semiconductor nanocrystals through energy transfer mechanisms has received increasing attention owing to their potential applications in photodynamic therapy, photocatalysis, and photon upconversion. Here, we investigate the sensitization mechanisms through visible-light excitation of two nanohybrids based on CsPbBr3 perovskite nanocrystals (NC) functionalized with borondipyrromethene (BODIPY) dyes, specifically 8-(4-carboxyphenyl)-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BDP) and 8-(4-carboxyphenyl)-2,6-diiodo-1,3,5,7-tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (I2-BDP), named as NC@BDP and NC@I2-BDP, respectively. The ability of I2-BDP dyes to extract hot hole carriers from the perovskite nanocrystals is comprehensively investigated by combining steady-state and time-resolved fluorescence as well as femtosecond transient absorption spectroscopy with spectroelectrochemistry and quantum chemical theoretical calculations, which together provide a complete overview of the phenomena that take place in the nanohybrid. Förster resonance energy transfer (FRET) dominates (82%) the photosensitization of the singlet excited state of BDP in the NC@BDP nanohybrid with a rate constant of 3.8 ± 0.2 × 1010 s-1, while charge transfer (64%) mediated by an ultrafast charge transfer rate constant of 1.00 ± 0.08 × 1012 s-1 from hot states and hole transfer from the band edge is found to be mainly responsible for the photosensitization of the triplet excited state of I2-BDP in the NC@I2-BDP nanohybrid. These findings suggest that the NC@I2-BDP nanohybrid is a unique energy transfer photocatalyst for oxidizing α-terpinene to ascaridole through singlet oxygen formation.

Multimodal cell atlas of the ageing human skeletal muscle.

Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

The Dark Side of Lead-Free Metal Halide Nanocrystals: Substituent-Modulated Photocatalytic Activity in Benzyl Bromide Reduction.

We illustrate here the high photocatalytic activity of sustainable lead-free metal halide nanocrystals (NCs), namely, Cs3Sb2Br9 NCs, in the reduction of p-substituted benzyl bromides in the absence of a cocatalyst. The electronic properties of the benzyl bromide substituents and the substrate affinity to the NC surface determine the selectivity in C-C homocoupling under visible light irradiation. This photocatalyst can be reused for at least three cycles and preserves its good performance with a turnover number of ca. 105,000.

Ambra1 haploinsufficiency in CD1 mice results in metabolic alterations and exacerbates age-associated retinal degeneration.

Macroautophagy/autophagy is a key process in the maintenance of cellular homeostasis. The age-dependent decline in retinal autophagy has been associated with photoreceptor degeneration. Retinal dysfunction can also result from damage to the retinal pigment epithelium (RPE), as the RPE-retina constitutes an important metabolic ecosystem that must be finely tuned to preserve visual function. While studies of mice lacking essential autophagy genes have revealed a predisposition to retinal degeneration, the consequences of a moderate reduction in autophagy, similar to that which occurs during physiological aging, remain unclear. Here, we described a retinal phenotype consistent with accelerated aging in mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene. These mice showed protein aggregation in the retina and RPE, metabolic underperformance, and premature vision loss. Moreover, Ambra1+/gt mice were more prone to retinal degeneration after RPE stress. These findings indicate that autophagy provides crucial support to RPE-retinal metabolism and protects the retina against stress and physiological aging.Abbreviations : 4-HNE: 4-hydroxynonenal; AMBRA1: autophagy and beclin 1 regulator 1, AMD: age-related macular degeneration;; GCL: ganglion cell layer; GFAP: glial fibrillary acidic protein; GLUL: glutamine synthetase/glutamate-ammonia ligase; HCL: hierarchical clustering; INL: inner nuclear layer; IPL: inner plexiform layer; LC/GC-MS: liquid chromatography/gas chromatography-mass spectrometry; MA: middle-aged; MTDR: MitoTracker Deep Red; MFI: mean fluorescence intensity; NL: NH4Cl and leupeptin; Nqo: NAD(P)H quinone dehydrogenase; ONL: outer nuclear layer; OPL: outer plexiform layer; OP: oscillatory potentials; OXPHOS: oxidative phosphorylation; PCR: polymerase chain reaction; PRKC/PKCα: protein kinase C; POS: photoreceptor outer segment; RGC: retinal ganglion cells; RPE: retinal pigment epithelium; SI: sodium iodate; TCA: tricarboxylic acid.

Carbon Monoxide Stimulates Both Mitophagy And Mitochondrial Biogenesis to Mediate Protection Against Oxidative Stress in Astrocytes.

Astrocytes are key glial cells for the metabolic and functional support of the brain. Mitochondrial quality control (MQC), in particular the balance between mitophagy and mitochondrial biogenesis, is a major event for the maintenance of cellular homeostasis. Carbon monoxide (CO) is an endogenous gasotransmitter that inhibits cell death and inflammation by targeting mitochondria. It is well established that CO promotes cytoprotection by increasing mitochondrial population and metabolism (oxidative phosphorylation). Thus, it is hypothesized that CO-induced cytoprotection may also be mediated by the balance between mitophagy and mitochondrial biogenesis. Herein, the carbon monoxide releasing molecule-A1 (CORM-A1) was used in primary cultures of astrocytes to assess CO role on mitochondrial turnover. PINK1/Parkin-dependent mitophagy was stimulated by CORM-A1 following 1 h of treatment. While at 24 h after treatment, CORM-A1 increased mitochondrial population, which may indicate mitochondrial biogenesis. In fact, mitochondrial biogenesis was confirmed by the enhancement of PGC-1α expression that upregulates several mitochondrial transcription factors. Furthermore, inhibition of mitophagy by knocking down PINK1 expression reverted CO-induced mitochondrial biogenesis, indicating that mitochondrial turnover is dependent on modulation of mitophagy. Finally, CORM-A1 prevented astrocytic cell death induced by oxidative stress in a mitophagy-dependent manner. In fact, whenever PINK1 was knocked down, CORM-A1-induced cytoprotection was lost. In summary, CORM-A1 stimulates mitochondrial turnover, which in turn prevents astrocytic cell death. CO cytoprotection depends on increasing mitochondrial population and on eliminating dysfunctional mitochondria.

Mitochondrial dynamics maintain muscle stem cell regenerative competence throughout adult life by regulating metabolism and mitophagy.

Skeletal muscle regeneration depends on the correct expansion of resident quiescent stem cells (satellite cells), a process that becomes less efficient with aging. Here, we show that mitochondrial dynamics are essential for the successful regenerative capacity of satellite cells. The loss of mitochondrial fission in satellite cells-due to aging or genetic impairment-deregulates the mitochondrial electron transport chain (ETC), leading to inefficient oxidative phosphorylation (OXPHOS) metabolism and mitophagy and increased oxidative stress. This state results in muscle regenerative failure, which is caused by the reduced proliferation and functional loss of satellite cells. Regenerative functions can be restored in fission-impaired or aged satellite cells by the re-establishment of mitochondrial dynamics (by activating fission or preventing fusion), OXPHOS, or mitophagy. Thus, mitochondrial shape and physical networking controls stem cell regenerative functions by regulating metabolism and proteostasis. As mitochondrial fission occurs less frequently in the satellite cells in older humans, our findings have implications for regeneration therapies in sarcopenia.

Revisiting the nontemplate approach for the synthesis of highly green emissive hybrid perovskite nanocrystals: platelets or spheres?

The long-standing debate about the morphology of colloidal methylammonium lead bromide perovskites nanocrystals, manufactured by our nontemplate synthetic strategy reported in 2014, is now resolved; specifically, the highest green emissive single nanoplatelets (of up to 93%) with long-term chemical and photochemical stability have been obtained after suitable purification steps.

Stem cell aging in the skeletal muscle: The importance of communication.

Adult stem cells sustain tissue homeostasis and regeneration; their functional decline is often linked to aging, which is characterized by the progressive loss of physiological functions across multiple tissues and organs. The resident stem cells in skeletal muscle, termed satellite cells, are normally quiescent but activate upon injury to reconstitute the damaged tissue. In this review, we discuss the current understanding of the molecular processes that contribute to the functional failure of satellite cells during aging. This failure is due not only to intrinsic changes but also to extrinsic factors, most of which are still undefined but originate from the muscle tissue microenvironment of the satellite cells (the niche), or from the systemic environment. We also highlight the emerging applications of the powerful single-cell sequencing technologies in the study of skeletal muscle aging, particularly in the heterogeneity of the satellite cell population and the molecular interaction of satellite cells and other cell types in the niche. An improved understanding of how satellite cells communicate with their environment, and how this communication is perturbed with aging, will be helpful for defining countermeasures against loss of muscle regenerative capacity in sarcopenia.

Ruddlesden-Popper Hybrid Lead Bromide Perovskite Nanosheets of Phase Pure n=2: Stabilized Colloids Stored in the Solid State.

Ruddlesden-Popper lead halide perovskite (RP-LHP) nano-nanostructures can be regarded as self-assembled quantum wells or superlattices of 3D perovskites with an intrinsic quantum well thickness of a single or a few (n=2-4) lead halide layers; the quantum wells are separated by organic layers. They can be scaled down to a single quantum well dimension. Here, the preparation of highly (photo)chemical and colloidal stable hybrid LHP nanosheets (NSs) of ca. 7.4 µm lateral size and 2.5 nm quantum well height (thereby presenting a deep blue emission at ca. 440 nm), is reported for the first time. The NSs are close-lying and they even interconnect when deposited on a substrate. Their synthesis is based on the use of the p-toluenesulfonic acid/dodecylamine (pTS/DDA) ligand pair and their (photo)chemical stability and photoluminescence is enhanced by adding EuBr2 nanodots (EuNDs). Strikingly, they can be preserved as a solid and stored for at least one year. The blue emissive colloid can be recovered from the solid as needed by simply dispersing the powder in toluene and then using it to prepare solid films, making them very promising candidates for manufacturing devices.

Intencionalidad del embarazo y cuidados prenatales en Uruguay / Pregnancy intention and antenatal care services in Uruguay / Intencionalidade da gravidez e cuidado pré-natal no Uruguai

Resumen: Introducción: desde hace algunos años el número de embarazos no intencionales en Uruguay ronda el 40%; esta cifra es alta en comparación con otros países que también tienen baja fecundidad y da cuenta de las dificultades de acceso y uso eficaz de métodos anticonceptivos modernos. Además, varios estudios evidencian que los embarazos no intencionales están vinculados con cuidados prenatales insuficientes y peores desempeños de los recién nacidos respecto a los nacimientos resultantes de embarazos intencionales. Objetivo: analizar la asociación entre intencionalidad de los embarazos y los cuidados prenatales en Uruguay a partir del estudio de su incidencia sobre la captación temprana del embarazo y las prácticas no saludables durante la gestación (fumar y tomar alcohol). Método: se consideran los nacimientos no intencionales y a destiempo (no buscados en ese momento) como dos grupos de tratamiento y se comparan con el grupo de nacimientos intencionales. Se examina el efecto neto de la intencionalidad del embarazo sobre las prácticas de salud durante la gestación utilizando técnicas de Propensity Score Matching (PSM). Se utilizan datos provenientes de la Encuesta de Nutrición, Desarrollo Infantil y Salud (ENDIS), un estudio de panel que recoge información desde 2013 de madres con hijos de entre 0 y 3 años en hogares ubicados en localidades urbanas de Uruguay (mayores a 5.000 habitantes). Resultados: antes de realizar el emparejamiento por PSM, las diferencias entre grupos de intención de embarazos fueron significativas para captación temprana y haber fumado, mientras que haber bebido alcohol no se asoció a diferencias significativas entre grupos de intención de los embarazos.

Summary: Introduction: in Uruguay, the number of unintended pregnancies has been around 40% for several years. This is rather a high percentage if compared to other countries who also have low fertility rates and evidences difficulties in access to modern contraceptive methods or using them effectively. Likewise, several studies evidence unintended pregnancies are related to insufficient antenatal care services and worse outcome in the new-borns when compared to births resulting from intentional pregnancies. Objective: to study the relationship between pregnancy intentionality and antenatal care services in Uruguay, based on an analysis of its impact on the early engagement of pregnancies and non-healthy practices during pregnancy (smoking and alcohol consumption). Method: unintended and untimely births (not sought at that time) were included in the study as two treatment groups, and they are compared to the group of intentional births. The net effect of pregnancy intention on health practices during pregnancy was examined using the de Propensity Score Matching (PSM) techniques. We used data delivered by the Nutrition, Child Development and Health Survey, a panel study that has been collecting information from mothers of children between 0 and 3 years old who live in urban localities of Uruguay (with over 5,000 inhabitants) since 2013. Results: Prior to the PSM matching, the differences in early engagement and smoking were significant between pregnancy intention groups, whereas alcohol consumption was not associated to significant differences between pregnancy intention groups.

Resumo: Introdução: há anos, o número de gestações não intencionais no Uruguai gira em torno de 40%; este número é alto em comparação com outros países que também têm baixa fecundidade e explica as dificuldades de acesso e uso de métodos anticoncepcionais modernos. Além disso, diversos estudos mostram que a gravidez não intencional está associada ao pré-natal insuficiente e piores parâmetros do recém-nascido em comparação com o nascimento decorrente da gravidez intencional. Objetivos: analisar a associação entre intencionalidade da gravidez e assistência pré-natal no Uruguai, a partir do estudo de sua incidência na detecção precoce da gravidez e práticas não saudáveis durante a gravidez (tabagismo e etilismo). Método: os nascimentos não intencionais e prematuros (não desejados no momento) são considerados dois grupos de tratamento e comparados com o grupo de partos intencionais. O efeito líquido da intencionalidade da gravidez sobre as práticas de saúde durante a gravidez é examinado usando técnicas de correspondência de pontuação de propensão (PSM). São utilizados os dados da Pesquisa de Nutrição, Desenvolvimento Infantil e Saúde (ENDIS), um estudo de painel que coleta informações desde 2013 de mães com filhos de 0 a 3 anos em domicílios localizados em áreas urbanas do Uruguai (mais de 5.000 habitantes). Resultados: antes de realizar a comparação por PSM, as diferenças entre os grupos de intenção de gravidez foram significativas para recrutamento precoce e tabagismo, enquanto ter bebido álcool não foi associado a diferenças significativas entre os grupos de intenção de gravidez.

The synergy between the CsPbBr3 nanoparticle surface and the organic ligand becomes manifest in a demanding carbon-carbon coupling reaction.

We demonstrate here the suitability of CsPbBr3 nanoparticles as photosensitizers for a demanding photoredox catalytic homo- and cross-coupling of alkyl bromides at room temperature by merely using visible light and an electron donor, thanks to the cooperative action between the nanoparticle surface and organic capping.

Assessing Autophagy in Muscle Stem Cells.

The skeletal muscle tissue in the adult is relatively stable under normal conditions but retains a striking ability to regenerate by its resident stem cells (satellite cells). Satellite cells exist in a quiescent (G0) state; however, in response to an injury, they reenter the cell cycle and start proliferating to provide sufficient progeny to form new myofibers or undergo self-renewal and returning to quiescence. Maintenance of satellite cell quiescence and entry of satellite cells into the activation state requires autophagy, a fundamental degradative and recycling process that preserves cellular proteostasis. With aging, satellite cell regenerative capacity declines, correlating with loss of autophagy. Enhancing autophagy in aged satellite cells restores their regenerative functions, underscoring this proteostatic activity's relevance for tissue regeneration. Here we describe two strategies for assessing autophagic activity in satellite cells from GFP-LC3 reporter mice, which allows direct autophagosome labeling, or from non-transgenic (wild-type) mice, where autophagosomes can be immunostained. Treatment of GFP-LC3 or WT satellite cells with compounds that interfere with autophagosome-lysosome fusion enables measurement of autophagic activity by flow cytometry and immunofluorescence. Thus, the methods presented permit a relatively rapid assessment of autophagy in stem cells from skeletal muscle in homeostasis and in different pathological scenarios such as regeneration, aging or disease.

Las trayectorias de las mujeres sin hijos en Uruguay / Life-course trajectories of childless women in Uruguay / As trajetórias das mulheres sem filhos no Uruguai

El objetivo de este trabajo es analizar la población de mujeres uruguayas que finalizan su vida reproductiva sin hijos. Además de cuantificar el fenómeno, se busca responder las siguientes preguntas: ¿qué rasgos socioeconómicos las caracterizan?; ¿cuáles son las trayectorias típicas que conducen a la nuliparidez?; ¿en qué medida es el resultado de aspiraciones reproductivas frustradas o de la voluntad de no tener hijos? Para responder estas preguntas, se utiliza una estrategia de métodos combinados que integra datos cuantitativos y cualitativos. Los resultados muestran que la proporción de nulíparas descendió aproximadamente de 25% a 10%, entre las nacidas entre 1900 y 1960, y que en los datos más recientes se detecta un incipiente incremento. Además, hay una mayor proporción de nulíparas entre las mujeres de nivel educativo alto. Finalmente, la tipologización de trayectorias hacia la nuliparidez definitiva reafirma la heterogeneidad de caminos y atributos: aunque se identificaron trayectorias guiadas por la intención de no tener hijos, un conjunto importante de mujeres llega a la nuliparidez como una consecuencia no buscada de la postergación de la maternidad.

O objetivo deste artigo é estudar as mulheres uruguaias que terminam sua vida reprodutiva sem filhos. Além de quantificar o fenômeno, procura-se responder às seguintes questões: quais são seus principais traços socioeconômicos? Quais são as trajetórias típicas que levam essas mulheres a não se tornarem mães? Até que ponto essa situação é o resultado de aspirações reprodutivas frustradas e até que ponto da vontade de não ter filhos? A estratégia metodológica é baseada na combinação de informações quantitativas e qualitativas, utilizando métodos mistos. Os resultados evidenciam que a proporção de mulheres nulíparas, ao final do ciclo reprodutivo, diminuiu de aproximadamente 25% para 10%, entre as nascidas em 1900-1960, sendo que nos dados mais recentes é detectado um aumento incipiente. Além disso, há uma maior proporção de mulheres sem filhos entre as mulheres de alto nível educacional. Por fim, a tipologização das trajetórias que levam à nuliparidade definitiva reafirma a heterogeneidade de caminhos e atributos: embora tenham sido identificadas trajetórias guiadas pela intenção de não ter filhos, um importante grupo de mulheres chega ao final da vida reprodutiva como uma consequência não intencional do adiamento da maternidade.

This paper aims to analyze Uruguayan women who end their reproductive life span without having children. In addition to quantifying the phenomenon, it seeks to answer the following questions: Which are their main socioeconomic traits? What are the typical trajectories that lead to childlessness? To what extent is it the outcome of unsatisfied reproductive aspirations and to what extent of the will to not have any children? We use a mixed methods approach integrating quantitative and qualitative data. Our results show that the proportion of childless women dropped from approximately 25% to 10% among those born in 1900-1960, and that the most recent data show an incipient increase. In addition, there is a higher proportion of childless women among those with a high level of education. Finally, our typology of trajectories towards definitive childlessness confirms the diversity of paths and traits: although trajectories guided by the intention of not having children were identified, a significant number of women reach childlessness as an unintended consequence of the postponement of motherhood.

Ultrathin lead bromide perovskite platelets spotted with europium(ii) bromide dots.

We describe here the preparation of a novel nanohybrid comprising a two-layer cesium lead bromide nanoplatelet, [CsPbBr3]PbBr4 NPL, containing europium(ii) bromide (EuBr2) nanodots, by ultrasound/heating treatment of toluene dispersions of the CsPbBr3 nanomaterial in the presence of EuBr2 nanodots. The hybrid nanoplatelets exhibit strong excitonic and narrow emission peaks characteristic of ultrathin NPLs at 430 and 436 nm, respectively.

Acyl-CoA-Binding Protein Is a Lipogenic Factor that Triggers Food Intake and Obesity.

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were elevated in obese patients and reduced in anorexia nervosa. In mice, systemic injection of ACBP protein inhibited autophagy, induced lipogenesis, reduced glycemia, and stimulated appetite as well as weight gain. We designed three approaches to neutralize ACBP, namely, inducible whole-body knockout, systemic administration of neutralizing antibodies, and induction of antiACBP autoantibodies in mice. ACBP neutralization enhanced autophagy, stimulated fatty acid oxidation, inhibited appetite, reduced weight gain in the context of a high-fat diet or leptin deficiency, and accelerated weight loss in response to dietary changes. In conclusion, neutralization of ACBP might constitute a strategy for treating obesity and its co-morbidities.

Colloids of Naked CH3NH3PbBr3 Perovskite Nanoparticles: Synthesis, Stability, and Thin Solid Film Deposition.

A novel preparation of lead halide, CH3NH3PbBr3, perovskite nanoparticle solid films from colloidal "naked" nanoparticles, that is, dispersible nanoparticles without any surfactant, is reported. The colloids are obtained by simply adding potassium ions, whose counterions are both more lipophilic and less coordinating than bromide ions, to the perovskite precursor solutions (CH3NH3Br/PbBr2 in dimethylformamide) following the reprecipitation strategy. The naked nanoparticles exhibit a low tendency to aggregate in solution, and they effectively self-assembled on a substrate by centrifugation of the colloid, leading to homogeneous nanoparticle solid films with arbitrary thickness. These results are expected to spur further the interest in lead halide perovskites due to the new opportunities offered by these films.

Standard Assays for the Study of Autophagy in the Ex Vivo Retina.

Autophagy is a catabolic pathway that mediates the degradation and recycling of intracellular components, and is a key player in a variety of physiological processes in cells and tissues. Recent studies of autophagy in the eye suggest that this pathway is fundamental for the preservation of retinal homeostasis. Given its accessible location outside the brain, the retina is an ideal organ in which to study the central nervous system and a wide range of neuronal processes, from development to neurodegeneration. Here we review several methods used to assess autophagy in the retina in both physiological and pathological conditions.