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Background and ObjectivesReal-time quaking-induced conversion (RT-QuIC) assay detects misfolded α-synuclein (AS) in the skin and CSF of patients with the synucleinopathies Parkinson disease and dementia with Lewy bodies. Isolated REM sleep behavior disorder (IRBD) constitutes the prodromal stage of these synucleinopathies. We aimed to compare the ability of RT-QuIC to identify AS in the skin and CSF of patients with IRBD.MethodsThis was a cross-sectional study where consecutive patients with polysomnographic-confirmed IRBD and age-matched controls without RBD underwent skin biopsy and lumbar puncture the same day. Three-millimeter skin punch biopsies were obtained bilaterally in the cervical region from dorsal C7 and C8 dermatomes and in distal legs. RT-QuIC assessed AS in these 6 skin sites and the CSF.ResultsWe recruited 91 patients with IRBD and 41 controls. In the skin, sensitivity to detect AS was 76.9% (95% CI 66.9–85.1), specificity 97.6% (95% CI 87.1–99.9) positive predictive value 98.6% (95% CI 91.0–99.8), negative predictive value 65.6% (95% CI 56.6–73.6), and accuracy 83.3% (95% CI 75.9–89.3). In the CSF, the sensitivity was 75.0% (95% CI 64.6–83.6), the specificity was 97.5% (95% CI 86.8–99.9), the positive predictive value was 98.5% (95% CI 90.5–99.8), the negative predictive value was 63.9% (95% CI 55.2–71.9), and the accuracy was 82.0% (95% CI 74.3–88.3). Results in the skin and CSF samples showed 99.2% agreement. Compared with negative patients, RT-QuIC AS-positive patients had a higher likelihood ratio of prodromal Parkinson disease (p< 0.001) and showed more frequently hyposmia (p< 0.001), dopamine transporter imaging single-photon emission CT deficit (p= 0.002), and orthostatic hypotension (p= 0.014). No severe or moderate adverse effects were reported. There was no difference between the percentage of participants reporting mild adverse events secondary to skin biopsy or lumbar puncture (9.1% vs 17.2%;p= 0.053). One hundred and ten (83%) and 104 (80%) participants, respectively, stated they would accept to undergo skin biopsy and lumbar puncture again for research purposes.DiscussionOur study in IRBD shows that (1) RT-QuIC detects AS in the skin and CSF with similar high sensitivity, specificity, and agreement, (2) AS RT-QuIC positivity is associated with supportive features and biomarkers of synucleinopathy, and (3) skin punch biopsy and lumbar puncture have comparable mild adverse effects, tolerance, and acceptance. RT-QuIC in the skin or CSF might represent a patient selection strategy for future neuroprotective trials targeting AS in IRBD.Classification of EvidenceThis study provides Class III evidence that RT-QuIC–detected AS in the skin and CSF distinguishes patients with IRBD from controls.

The search for molecules to be targeted that are involved in apoptosis resistance/increased survival and pathogenesis of onco-hematological malignancies is ongoing since these diseases are still not completely understood. Over the years, a good candidate has been identified in the Heat Shock Protein of 70kDa (HSP70), a molecule defined as “the most cytoprotective protein ever been described”. HSP70 is induced in response to a wide variety of physiological and environmental insults, allowing cells to survive lethal conditions. This molecular chaperone has been detected and studied in almost all the onco-hematological diseases and is also correlated to poor prognosis and resistance to therapy. In this review, we give an overview of the discoveries that have led us to consider HSP70 as a therapeutic target for mono- or combination-therapies in acute and chronic leukemias, multiple myeloma and different types of lymphomas. In this excursus, we will also consider HSP70 partners, such as its transcription factor HSF1 or its co-chaperones whose druggability could indirectly affect HSP70. Finally, we will try to answer the question asked in the title of this review considering that, despite the effort made by research in this field, HSP70 inhibitors never reached the clinic.

Mixed-halide mixed-cation hybrid perovskites are among the most promising perovskite compositions for application in a variety of optoelectronic devices due to their high performance, low cost, and bandgap-tuning capabilities. Instability pathways such as those driven by ionic migration, however, continue to hinder their further progress. Here, an operando variable-pitch synchrotron grazing-incidence wide-angle X-ray scattering technique is used to track the surface and bulk structural changes in mixed-halide mixed-cation perovskite solar cells under continuous load and illumination. By monitoring the evolution of the material structure, it is demonstrated that halide remixing along the electric field and illumination direction during operation hinders phase segregation and limits device instability. Correlating the evolution with directionality- and depth-dependent analyses, it is proposed that this halide remixing is induced by an electrostrictive effect acting along the substrate out-of-plane direction. However, this stabilizing effect is overwhelmed by competing halide demixing processes in devices exposed to humid air or with poorer starting performance. The findings shed new light on understanding halide de- and re-mixing competitions and their impact on device longevity. These operando techniques allow real-time tracking of the structural evolution in full optoelectronic devices and unveil otherwise inaccessible insights into rapid structural evolution under external stress conditions.

Mixed lead-tin halide perovskites have sufficiently low bandgaps (∼1.2 eV) to be promising absorbers for perovskite-perovskite tandem solar cells. Previous reports on lead-tin perovskites have typically shown poor optoelectronic properties compared to neat lead counterparts: short photoluminescence lifetimes (

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

Here we use time-resolved and steady-state optical spectroscopy on state-of-the-art low- and high-bandgap perovskite films for tandems to quantify intrinsic recombination rates and absorption coefficients. We apply these data to calculate the limiting efficiency of perovskite-silicon and all-perovskite two-terminal tandems employing currently available bandgap materials as 42.0 % and 40.8 % respectively. By including luminescence coupling between sub-cells, i.e. the re-emission of photons from the high-bandgap sub-cell and their absorption in the low-bandgap sub-cell, we reveal the stringent need for current matching is relaxed when the high-bandgap sub-cell is a luminescent perovskite compared to calculations that do not consider luminescence coupling. We show luminescence coupling becomes important in all-perovskite tandems when charge carrier trapping rates are < 10$^{6}$ s$^{-1}$ (corresponding to carrier lifetimes longer than 1 $��$s at low excitation densities) in the high-bandgap sub-cell, which is lowered to 10$^{5}$ s$^{-1}$ in the better-bandgap-matched perovskite-silicon cells. We demonstrate luminescence coupling endows greater flexibility in both sub-cell thicknesses, increased tolerance to different spectral conditions and a reduction in the total thickness of light absorbing layers. To maximally exploit luminescence coupling we reveal a key design rule for luminescent perovskite-based tandems: the high-bandgap sub-cell should always have the higher short-circuit current. Importantly, this can be achieved by reducing the bandgap or increasing the thickness in the high-bandgap sub-cell with minimal reduction in efficiency, thus allowing for wider, unstable bandgap compositions (>1.7 eV) to be avoided. Finally, we experimentally visualise luminescence coupling in an all-perovskite tandem device stack through cross-section luminescence images., 20 pages, 5 figures

Simple Summary The use of ibrutinib has changed the management and clinical history of patients with multiple-treated chronic lymphocytic leukemia (CLL). Nevertheless, an increasing number of patients develop resistance to treatment, with mechanisms still to be fully clarified. Since HSP70 plays a pivotal role in mediating the survival and the progression of CLL, we herein addressed the role of HSP70 and its regulator HSF1 in the development of ibrutinib-mediated resistance. We found an increase in both proteins when the treatment was failing, and thus the disease was progressing. This suggests the involvement of HSP70 in mechanisms of drug resistance. Moreover, we demonstrated that the use, at different levels, of HSP70/HSF1 axis inhibitors could represent a novel rational therapeutic approach to overcome ibrutinib resistance in those patients who relapsed after this type of treatment. Abstract The Btk inhibitor ibrutinib has significantly changed the management of chronic lymphocytic leukemia (CLL) patients. Despite its clinical efficacy, relapses occur, and outcomes after ibrutinib failure are poor. Although BTK and PLCγ2 mutations have been found to be associated with ibrutinib resistance in a fair percentage of CLL patients, no information on resistance mechanisms is available in patients lacking these mutations. The heat shock protein of 70 kDa (HSP70) and its transcription factor heat shock factor 1 (HSF1) play a role in mediating the survival and progression of CLL, as well as taking part in drug resistance in various cancers. We demonstrated that resveratrol and related phenols were able to induce apoptosis in vitro in leukemic cells from CLL untreated patients by acting on the HSP70/HSF1 axis. The same was achieved in cells recovered from 13 CLL patients failing in vivo ibrutinib treatment. HSP70 and HSF1 levels decreased following in vitro treatment, correlating to apoptosis induction. We suggest an involvement of HSP70/HSF1 axis in controlling resistance to ibrutinib in CLL cells, since their inhibition is effective in inducing in vitro apoptosis in cells from ibrutinib refractory patients. The targeting of HSP70/HSF1 axis could represent a novel rational therapeutic strategy for CLL, also for relapsing patients.

Luminescent colloidal CdSe nanorings are a new type of semiconductor structure that have attracted interest due to the potential for unique physics arising from their non-trivial toroidal shape. However, the exciton properties and dynamics of these materials with complex topology are not yet well understood. Here, we use a combination of femtosecond vibrational spectroscopy, temperature-resolved photoluminescence (PL), and single particle measurements to study these materials. We find that on transformation of CdSe nanoplatelets to nanorings, by perforating the center of platelets, the emission lifetime decreases and the emission spectrum broadens due to ensemble variations in the ring size and thickness. The reduced PL quantum yield of nanorings (~10%) compared to platelets (~30%) is attributed to an enhanced coupling between: (i) excitons and CdSe LO-phonons at 200 cm-1 and (ii) negatively charged selenium-rich traps which give nanorings a high surface charge (~-50 mV). Population of these weakly emissive trap sites dominates the emission properties with an increased trap emission at low temperatures relative to excitonic emission. Our results provide a detailed picture of the nature of excitons in nanorings and the influence of phonons and surface charge in explaining the broad shape of the PL spectrum and the origin of PL quantum yield losses. Furthermore, they suggest that the excitonic properties of nanorings are not solely a consequence of the toroidal shape but are also a result of traps introduced by puncturing the platelet center., Comment: 38 pages, 10 figures

Imaging techniques, like electroluminescence and dark lock-in thermography, are valuable quality control tools as they yield quantitative and spatially resolved information about the device. In this paper, we isolated some of the conductive foil–cell interconnections of back-contact solar cells to study the appearance of these intentional failures in electroluminescence, dark lock-in thermography, and series resistance images. It has been found that isolated emitter-to-foil contacts are clearly visible in the three imaging techniques, as they show characteristic features that deviate from the features typical of functioning emitter-to-foil dots. Isolated base-to-foil contacts are instead invisible in the images obtained by electroluminescence and only hardly visible in the images obtained by the other two techniques. Only after a large amount of contacts are isolated, a local current redistribution or drastic series resistance increase is noticeable. Two graphical methods for the automatic identification of isolated emitter-to-foil contacts in electroluminescence, dark lock-in thermography, and series resistance images were also designed, showing a success rate of 97% in the investigated cells. Such techniques could represent useful tools for implementation in inline quality control processes. Moreover, the techniques and conclusions drawn in this paper can be extended to a large number of other conventional and emerging photovoltaic technologies.

International audience; Celebrating 10 years from the technological revolution brought about by the first report of halide perovskite solar cells, Symposium G of the EMRS Spring Meeting 2019 was dedicated to the memory of the late George C. Papavassiliou (Figure 1), a vibrant pioneer in the early days of the field during the 1990s. The Symposium, entitled "Halide Perovskites: low dimensions for devices", to reflect the important potential of these tunable semiconductors in technology, was designed with the intention of bringing together researchers from across all breadths and lengths of the field. From the discovery of new materials to the study of their photophysical properties-from both theory and experiment viewpoints-to more technical studies related to the implementation of perovskites into functional devices, the Symposium highlighted most aspects of the perovskite research that have been actively studied to date. In this respect, the symposium proved successful in providing key opportunities for discussions on progress in new material development as well as to introduce new potential applications beyond optoelectronics, with energy-related developments standing out. Among the 12 invited talks the 56 oral presentations and its 38 poster presentations (including a joint session with Symposium B-Emerging photovoltaics: strategies for more stable devices), the Symposium delivered lively discussion stimulated by the invited researchers who delineated the different themes of the Symposium. B. Lounis showed how the exciton-phonon coupling operates in perovskites, presenting an excellent account on the photo-physics of halide perovskite nanocrystals at the single-particle level 1. On a more applied topic, M. Bodnarchuk explained the intricacies of the synthesis and emission tuning of colloidal perovskite nanocrystals, showing how much the interface interactions between the inorganic perovskite and the organic surfactants can influence the properties, and proposed innovative methodologies on how to control the interactions 2. On the "phonon problem", R. Schaller presented a "high-throughput" study of many perovskite derivatives, experimentally pinpointing the anharmonic nature of the phonons that derive from the dynamically disordered nature of the crystal lattice 3. P. Plochocka covered the excitons present in the perovskites and highlighted very vividly how to manipulate excitons using (enormous) magnetic fields and extract useful information on their binding energy and lifetimes within the perovskite structure 4. Shifting the dimensionality to perovskite nanowires, the presentation of E. Horvath introduced many innovative methods to produce functional perovskite nanowires that can be shaped "at will" to various morphologies, by manipulating the substrate pattern and the surface conditions 5. Figure I.

International audience; Grain size in polycrystalline halide perovskite films is known to have an impact on the optoelectronic properties of the films, but its influence on their soft structural properties and phase transitions is unclear. Here, temperature-dependent X-ray diffraction, absorption, and macro- and micro-photoluminescence measurements are used to investigate the tetragonal to orthorhombic phase transition in thin methylammonium lead iodide films with grain sizes ranging from the micrometer scale down to the tens of nanometer scale. It is shown that the phase transition nominally at approximate to 150 K is increasingly suppressed with decreasing grain size and, in the smallest grains, the first evidence of a phase transition is only seen at temperatures as low as approximate to 80 K. With decreasing grain size, an increasing magnitude of the hysteresis is also seen in the structural and optoelectronic properties when cooling to, and then upon heating from, 100 K. This work reveals the remarkable sensitivity of the optoelectronic, physical, and phase properties to the local environment of the perovskite structure, which will have large ramifications for phase and defect engineering in operating devices.

Halide perovskites are emerging as valid alternatives to conventional photovoltaic active materials owing to their low cost and high device performances. This material family also shows exceptional tunability of properties by varying chemical components, crystal structure, and dimensionality, providing a unique set of building blocks for new structures. Here, highly stable self-assembled lead–tin perovskite heterostructures formed between low bandgap 3D and higher bandgap 2D components are demonstrated. A combination of surface-sensitive X-ray diffraction, spatially resolved photoluminescence, and electron microscopy measurements is used to reveal that microstructural heterojunctions form between high bandgap 2D surface crystallites and lower bandgap 3D domains. Furthermore, in situ X-ray diffraction measurements are used during film formation to show that an ammonium thiocyanate additive delays formation of the 3D component and thus provides a tunable lever to substantially increase the fraction of 2D surface crystallites. These novel heterostructures will find use in bottom cells for stable tandem photovoltaics with a surface 2D layer passivating the 3D material, or in energy transfer devices requiring controlled energy flow from localized surface crystallites to the bulk.

For neat Pb perovskites, two-dimensional (2D) hybrid perovskites, where n layers of inorganic material are separated by a long-chain organic cation, generally exhibit greater stability but have lower photovoltaic performance characteristics, motivating the study of 2D/3D mixed-dimension systems to realize both high efficiency and stability. In this Letter, we demonstrate such optimal compromise between performance and stability using formamidinium, cesium, and t-butylammonium as A-site cations with Pb:Sn mixed-metal low-band-gap perovskites. Perovskite solar cells based on n = 4 and 5 lead–tin perovskites achieved power conversion efficiencies of up to 9.3 and 10.6%, respectively, and correspondingly retained 47 and 29% of their initial efficiency during storage in nitrogen for 2000 h. A similar stability trend for n = 4 over n = 5 was also observed for unencapsulated devices during continuous operation under a combined air atmosphere and temperature for 10 h, resulting in improved stability over the 3D lead–tin counterpart.

Mixed-halide lead perovskites have attracted significant attention in the field of photovoltaics and other optoelectronic applications due to their promising bandgap tunability and device performance. Here, the changes in photoluminescence and photoconductance of solution-processed triple-cation mixed-halide (Cs0.06MA0.15FA0.79)Pb(Br0.4I0.6)3 perovskite films (MA: methylammonium, FA: formamidinium) are studied under solar-equivalent illumination. It is found that the illumination leads to localized surface sites of iodide-rich perovskite intermixed with passivating PbI2 material. Time- and spectrally resolved photoluminescence measurements reveal that photoexcited charges efficiently transfer to the passivated iodide-rich perovskite surface layer, leading to high local carrier densities on these sites. The carriers on this surface layer therefore recombine with a high radiative efficiency, with the photoluminescence quantum efficiency of the film under solar excitation densities increasing from 3% to over 45%. At higher excitation densities, nonradiative Auger recombination starts to dominate due to the extremely high concentration of charges on the surface layer. This work reveals new insight into phase segregation of mixed-halide mixed-cation perovskites, as well as routes to highly luminescent films by controlling charge density and transfer in novel device structures.

Light-emitting diodes based on halide perovskites have recently reached external quantum efficiencies of over 20%. However, the performance of visible perovskite light-emitting diodes has been hindered by non-radiative recombination losses and limited options for charge-transport materials that are compatible with perovskite deposition. Here, we report efficient, green electroluminescence from mixed-dimensional perovskites deposited on a thin (~1 nm) lithium fluoride layer on an organic semiconductor hole-transport layer. The highly polar dielectric interface acts as an effective template for forming high-quality bromide perovskites on otherwise incompatible hydrophobic charge-transport layers. The control of crystallinity and dimensionality of the perovskite layer is achieved by using tetraphenylphosphonium chloride as an additive, leading to external photoluminescence quantum efficiencies of around 65%. With this approach, we obtain light-emitting diodes with external quantum efficiencies of up to 19.1% at high brightness (>1,500 cd m−2). Green perovskite light-emitting diodes with external quantum efficiencies of up to 19.1% at high brightness can be created by depositing an ultrathin layer of strongly polar lithium fluoride between the perovskite and hole-transport layers.

International audience; Luminescent colloidal CdSe nanorings are a recently developed type of semiconductor structure that have attracted interest due to the potential for rich physics arising from their non-trivial toroidal shape. However, the exciton properties and dynamics of these materials with complex topology are not yet well understood. Here, we use a combination of femtosecond vibrational spectroscopy, temperature