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Background: The mechanisms at the basis of depression are still matter of debate, but several studies in the literature suggest common pathways with dementia (genetic predispositions, metabolic and inflammatory mechanisms, neuropathological changes) and other geriatric syndromes., Aims: To evaluate the role of cortisol (as marker of the HPA, hypothalamus-pituitary-adrenal axis hyperactivity) in elderly subjects with depressive symptoms (by the means of the AGICO, AGIng and COrtisol, study), in relationship to the presence of the major geriatric syndromes., Methods: The AGICO study enrolled patients from ten Geriatric Units in Italy. Every subject received a comprehensive geriatric assessment or CGA (including the Mini Mental State Examination or MMSE, Geriatric Depression Scale or GDS and Cornell Scale for Depression in Dementia or CSDD), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal), a CGA-derived frailty index (FI) and a modified measure of allostatic load (AL)., Results: The MMSE scores were significantly and inversely related to the values of GDS (p < 0.001) and CSDD (p < 0.05), respectively. The patients with depressive symptoms (GDS/CSDD > 8) showed significantly increased disability, MetS, inflammation, FI and AL and significantly reduced MMSE and renal function. The diurnal and nocturnal urinary cortisol levels in the patients with depressive symptoms (GDS/CSDD > 8) were higher with respects to controls (p < 0.05 for nocturnal difference)., Discussion: The AGICO study showed that the stress response is activated in the patients with depression., Conclusion: The depression in elderly patient should be reconsidered as a systemic disease, with coexisting major geriatric syndromes (disability, dementia, frailty) and combined pathogenetic mechanisms (metabolic syndrome, impaired renal function, low-grade inflammation, and allostatic load). Cortisol confirmed its role as principal mediator of the aging process in both dementia and metabolic syndrome., (© 2024. The Author(s).)

A supramolecular approach based on self-assembled structures allows the formation of large structured co-assemblies based on chiral and achiral compounds with original physicochemical features. In this contribution, an achiral and hydrophobic porphyrin was co-assembled at the air-water interface with mesoscopic silica nano-helices dispersed in the water subphase of a Langmuir trough without covalent bond formation. This procedure allowed transferring the porphyrin/nano-helix co-assemblies on a solid support within a thin hybrid layer. The interaction between the two species was characterized using spectroscopic techniques and atomic force microscopy. As evidenced by the circular dichroism measurements performed directly on solid films, tunable chirality was induced to the porphyrin aggregates according to the chirality of the silica nano-helices. When the co-assemblies were transferred on surface plasmon resonance (SPR) slides and exposed to aqueous solutions of histidine enantiomers, selective chiral discrimination was observed which was determined by the matching/mismatching between the chirality of the analyte and the helicity of the nano-helical structure.

The ability of olfaction to distinguish odors is based on many different properties deriving from the molecular structure, including chirality. Even if the electronic nose (e-nose) concept has been widely used in strict analogy with biological systems to implement sensor arrays that recognize and distinguish complex odor matrices, the fabrication of an enantioselective e-nose remains a challenge. This paper introduces an array of quartz microbalances (QMB) functionalized with sensitive materials made of a combination of achiral receptors and silica nanohelices grafted by chiral and achiral porphyrins. In this combination, nanohelices provide a chiral template for the spatial arrangement of porphyrins, while porphyrins act as receptors that can interact differently with analytes. Remarkably, even if single sensors show scarce enantioselectivity, the signals of the overall array achieve recognition of the chiral identity of the five diverse enantiomeric pairs tested when the data are processed with proper multivariate algorithms. Such an innovative and generalizable approach is expected to enable the formation of an extensive library of readily integrable chiral receptors in enantioselective sensor arrays, potentially revolutionizing diverse fields such as agrochemicals, medicine, and environmental sciences., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background Aims: Dendritic cells (DCs) are professional antigen-presenting cells of the mammalian immune system. Ex vivo differentiated DCs represent a unique Advanced Therapy Medicinal Product (ATMP), used in several clinical trials as personalized cancer immunotherapy. The therapy's reliability depends on its capacity to produce high-quality mature DCs (mDCs) in compliance with Good Manufacturing Practices., Aims: From March 2010 to December 2023, 103 patients were enrolled in multiple clinical trials at the Immuno-Gene Therapy Factory at IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori". Six hundred forty-two doses were produced, and the manufacturing process was implemented to optimize production. Our study is a retrospective analysis focusing on the quality control results., Methods: We retrospectively analyzed the results of the quality control tests carried out on each produced batch, evaluating viability, purity and phenotype of mDCs and their quality in terms of microbiological safety. The data obtained are given with median and interquartile range., Results: The batches were found to be microbiologically safe in terms of sterility, mycoplasma, and endotoxins. An increase in DC maturation markers was found. The release criteria checks showed a high percentage of viability and purity was maintained during the production process., Conclusions: Our findings have confirmed that the measures implemented have ensured the safety of the products and have contributed to the establishing a robust "Pharmaceutical Quality System." This has enabled many safe mDCs to be produced for clinical trials., Competing Interests: Declaration of competing interest None., (Copyright © 2024 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.)

For advanced therapy medicinal products, the development and validation of potency assays are required, in accordance with international guidelines, to characterise the product and obtain reliable and consistent data. Our purpose was to validate the killing assay for the evaluation of autologous anti-CD19 chimeric antigen receptor (CAR) T potency. We used CD4 + and CD8 + lymphocytes or anti-CD19 CAR-T cells as effector cells and REH (CD19 +) or MOLM-13 (CD19 -) cell lines as target cells. After co-culturing target and effector cells (1:1 ratio) for 24 h, samples were labelled with 7-AAD, anti-CD3 and anti-CD19 antibodies and the frequency of CD19 + dead cells was evaluated by flow cytometry. In order to verify the CAR-T specificity for the CD19 + target, the co-culture between CAR-T and REH or MOLM-13 at different effector-to-target ratios was scheduled. Moreover, not transduced CD4 + and CD8 + lymphocytes were tested in comparison with CAR-T from the same donor to demonstrate the assay specificity. Linearity and accuracy were evaluated, and established acceptance criteria were compiled for both parameters (r 2  ≥ 0.97 for linearity and average relative error ≤ 10% for accuracy). Furthermore, the method was considered robust when performed between 23 and 25 h of co-culture, and the intra-assay, inter-assay and inter-day precision was obtained. Finally, in order to verify the inter-analyst precision, the test was executed by three different operators and the intra-class correlation coefficient was > 0.4 in both cases. In conclusion, we consider this CAR-T potency assay as validated and usable in all steps of product development and quality control., (© 2024. The Author(s).)

Background: The rejuvenation and restoration of a well-defined jawline contour are crucial for enhancing facial aesthetics in both men and women. Within the jawline aesthetic unit (mandibular angle), the masseter muscle plays a significant role, as it is responsible for mandibular masticatory movements. We propose a new approach using ultrasound-guided intramuscular fat transfer to enhance the mandibular angle and jawline., Methods: The multicenter study included 20 patients from three countries (Peru, Brazil, and Mexico). After fat harvesting, the ultrasound-guided masseteric fat transfer was performed with a 1.5-mm Viaro cannula from an incision beneath the ear lobule. The fat was then injected intramuscularly into the masseter at each side of the mandibular angle., Results: Masseter ultrasound-guided fat transfer was performed on 10 men and 10 women between 2021 and 2022. The patients had a mean age of 34.4 ± 6.39 years and a mean body mass index of 22.39 ± 2.59 kg per m 2 . The mean injected volume was 5.83 mL and 5.58 mL on the right and left sides, respectively. Muscle thickness increased in patients immediately postsurgery, but decreased after 1 month. The muscle remained significantly thicker on each side than the presurgery measurements in patients regardless of gender (both P < 0.0001)., Conclusions: Ultrasound-guided intramuscular fat transfer is a safe and reproducible technique for enhancing the jawline contour at the mandibular angle. We believe that it could be a more durable solution than other procedures, although further evaluation of long-term results is necessary., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The development of chiral receptors for discriminating the configuration of the analyte of interest is increasingly urgent in view of monitoring pollution in water and waste liquids. Here, we investigate an easy protocol to immobilize the desired non-water-soluble receptors inside a water-dispersible chiral nanoplatform made of silica. This approach induces chirality in the receptors and Here, we investigate an easy protocol to immobilize the desired non-water-soluble receptors inside a water-dispersible chiral nanoplatform made of silica. This approach induces chirality in the receptors and makes the dye@nanohelix system disperse in a suspension of water without aggregation. We noted strong induction and amplification of chiroptical activity in both achiral and chiral (proline-based or hemicucurbituril-based) porphyrin derivatives with and without zinc ions once confined and organized in nanometer silica helices. The results clearly demonstrated that the organization-induced chirality amplification of porphyrins dominates the molecular chirality, and the amplification is more efficient for more flexible porphyrins (especially free-base and achiral).

Enantiorecognition of a chiral analyte usually requires the ability to respond with high specificity to one of the two enantiomers of a chiral compound. However, in most cases, chiral sensors have chemical sensitivity toward both enantiomers, showing differences only in the intensity of responses. Furthermore, specific chiral receptors are obtained with high synthetic efforts and have limited structural versatility. These facts hinder the implementation of chiral sensors in many potential applications. Here, we utilize the presence of both enantiomers of each receptor to introduce a novel normalization that allows the enantio-recognition of compounds even when single sensors are not specific for one enantiomer of a target analyte. For this purpose, a novel protocol that permits the fabrication of a large set of enantiomeric receptor pairs with low synthetic efforts by combining metalloporphyrins with ( R , R )- and ( S , S )-cyclohexanohemicucurbit[8]uril is developed. The potentialities of this approach are investigated by an array of four pairs of enantiomeric sensors fabricated using quartz microbalances since gravimetric sensors are intrinsically non-selective toward the mechanism of interaction of analytes and receptors. Albeit the weak enantioselectivity of single sensors toward limonene and 1-phenylethylamine, the normalization allows the correct identification of these enantiomers in the vapor phase indifferent to their concentration. Remarkably, the achiral metalloporphyrin choice influences the enantioselective properties, opening the way to easily obtain a large library of chiral receptors that can be implemented in actual sensor arrays. These enantioselective electronic noses and tongues may have a potential striking impact in many medical, agrochemical, and environmental fields.

In this work, we have described the synthesis and characterization of novel zinc (II) phthalocyanine bearing four 2-(2,4-dichloro-benzyl)-4-(1,1,3,3-tetramethyl-butyl)-phenoxy substituents on the peripheral positions. The compound was characterized by elemental analysis and different spectroscopic techniques, such as FT-IR, 1 H NMR, MALDI-TOF, and UV-Vis. The Zn (II) phthalocyanine shows excellent solubility in organic solvents such as dichloromethane (DCM), n-hexane, chloroform, tetrahydrofuran (THF), and toluene. Photochemical and electrochemical characterizations of the complex were performed by UV-Vis, fluorescence spectroscopy, and cyclic voltammetry. Its good solubility allows a direct deposition of this compound as film, which has been tested as a solid-state sensing material in gravimetric chemical sensors for gas detection, and the obtained results indicate its potential for qualitative discrimination and quantitative assessment of various volatile organic compounds, among them methanol, n-hexane, triethylamine (TEA), toluene and DCM, in a wide concentration range.

Reflectance anisotropy spectroscopy (RAS) has been largely used to investigate organic compounds: Langmuir-Blodgett and Langmuir-Schaeffer layers, the organic molecular beam epitaxy growth in situ and in real time, thin and ultrathin organic films exposed to volatiles, in ultra-high vacuum (UHV), in controlled atmosphere and even in liquid. In all these cases, porphyrins and porphyrin-related compounds have often been used, taking advantage of the peculiar characteristics of RAS with respect to other techniques. The technical modification of a RAS spectrometer (CD-RAS: circular dichroism RAS) allows us to investigate the circular dichroism of samples instead of the normally studied linear dichroism: CD-RAS measures (in transmission mode) the anisotropy of the optical properties of a sample under right and left circularly polarized light. Although commercial spectrometers exist to measure the circular dichroism of substances, the "open structure" of this new spectrometer and its higher flexibility in design makes it possible to couple it with UHV systems or other experimental configurations. The importance of chirality in the development of organic materials (from solutions to the solid state, as thin layers deposited-in liquid or in vacuum-on transparent substrates) could open interesting possibilities to a development in the investigation of the chirality of organic and biological layers. In this manuscript, after the detailed explanation of the CD-RAS technique, some calibration tests with chiral porphyrin assemblies in solution or deposited in solid film are reported to demonstrate the quality of the results, comparing curves obtained with CD-RAS and a commercial spectrometer.

Introduction: Physical rehabilitation restores lost function and promotes brain plasticity in people with Multiple Sclerosis (MS). Research groups worldwide are testing the therapeutic effects of combining non-invasive neuromodulation with physical therapy (PT) to further improve functional outcomes in neurological disorders but with mixed results. Whether such devices enhance function is not clear. We present the rationale and study design for a randomized controlled trial evaluating if there is additional benefit to the synergistic pairing of translingual neurostimulation (TLNS) with PT to improve walking and balance in MS., Methods and Analysis: A parallel group [PT + TLNS or PT + Sham], quadruple-blinded, randomized controlled trial. Participants (N = 52) with gait and balance deficits due to relapsing-remitting or progressive MS, who are between 18 and 70 years of age, will be recruited through patient registries in Newfoundland & Labrador and Saskatchewan, Canada. All participants will receive 14 weeks of PT while wearing either a TLNS or sham device. Dynamic Gait Index is the primary outcome. Secondary outcomes include fast walking speed, subjective ratings of fatigue, MS impact, and quality of life. Outcomes are assessed at baseline (Pre), after 14 weeks of therapy (Post), and 26 weeks (Follow Up). We employ multiple methods to ensure treatment fidelity including activity and device use monitoring. Primary and secondary outcomes will be analyzed using linear mixed-effect models. We will control for baseline score and site to test the effects of Time (Post vs. Follow-Up), Group and the Group x Time interaction as fixed effects. A random intercept of participant will account for the repeated measures in the Time variable. Participants must complete the Post testing to be included in the analysis., Ethics and Dissemination: The Human Research Ethics Boards in Newfoundland & Labrador (HREB#2021.085) & Saskatchewan (HREB Bio 2578) approved the protocol. Dissemination avenues include peer-reviewed journals, conferences and patient-oriented communications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was supported by an Independent Investigator –led Grant from Helius Medical, the company that makes the PoNS units. They and their employees had no involvement in the design and conduct of this study. Helius Medical technologies provided the PoNS™ (both TLNS and sham) devices. They have no involvement in data collection, analysis or reporting., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Arm contouring usually represents a challenge for the surgeon due to zones with high risk of irregularities/asymmetries, the variable degree of skin laxity, and the differences between patient/gender preferences. In men, the bigger and muscular the arms the better, while women tend to prefer a slim and soft silhouette., Methods: We performed arm cadaveric dissections and also searched our records for patients who underwent fat grafting of the arm in addition to HD2, from January 2016 to May 2022 at a single center in Bogotá, Colombia., Results: Two hundred eighty-nine consecutive patients (275 men and 14 women) underwent high-definition lipoplasty/HD2 plus fat grafting of the biceps (72 muscles), the triceps (46 muscles), the deltoids (426 muscles), or a combination of them. Mean age was 39 and 36 years for men and women, respectively. Range of the fat graft volume was 30-150 ml. No major complications were reported. Follow-up period ranged from 2 to 24 months. Most patients were satisfied with the results., Conclusions: Men usually seek an overall well-toned and muscular extremity, while women tend to prefer a slim but also athletic contour. Such outcomes can be achieved through intramuscular fat grafting of the biceps, triceps, and deltoids. The proper recognition of the pedicles and a precise surgical technique will ensure both its safety and the reproducibility of the results., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

One big challenge of body contouring surgery is the liposculpture of the lower limbs, probably because of the imperative symmetry and the risk of contour irregularities. We are reporting our experience in fat grafting of the thighs and calves for men and women undergoing dynamic definition liposculpture., Methods: We did cadaveric dissections of the vastus lateralis, vastus medialis, rectus femoris, and gastrocnemius muscles and identified each of their primary pedicles. We also performed fat grafting of these muscles in the contralateral virgin cadaveric specimen. We searched our records for patients who underwent fat grafting of the lower extremity in addition to dynamic definition liposculpture, from January 2016 to May 2022 at a single center in Bogotá, Colombia., Results: Seventy-three consecutive patients met the inclusion criteria (26 men and 47 women). We grafted 102 gastrocnemius muscles, 86 vastus medialis muscles, 98 vastus lateralis muscles, and 22 rectus femoris muscles. Mean age was 34 and 41 years for men and women, respectively. Range of the fat graft volume was 50-200 mL. No complications were recorded related to fat grafting. Almost all patients were satisfied with the procedure (89%). Follow-up period ranged from 2 to 36 months., Conclusions: Fat grafting of the lower limb muscles should be considered an alternative operative technique to enhance volume and athletic appearance of this body segment. Based on cadaveric dissections and clinical evidence, our technique is considered reliable and reproducible with remarkable outcomes and a very low complication rate., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The aesthetics for the male posterior torso remain a topic not fully studied in body contouring surgery, neither the lipoinjection of its muscles have been considered before. As a result, we carried out a retrospective cohort study including patients who underwent fat grafting of either the trapezius or the latissimus dorsi muscles as part of dynamic definition liposculpture (HD2)., Methods: We performed cadaveric dissections to support the fat grafting technique for both the trapezius and the latissimus dorsi muscles. We also searched our records for patients who underwent fat grafting of these muscles in addition to HD2 from January 2016 to November 2021 at a single center in Bogotá, Colombia., Results: Thirty-five consecutive patients met the inclusion criteria. In total, 22 (63%) and 7 (20%) of 35 underwent fat grafting at the trapezius and the latissimus dorsi muscles alone, respectively, and 6 out of 35 (17%) of both. Mean age is 39 years (range = 22-63). All patients were men. No complications were recorded related to fat grafting. Almost all patients were satisfied with the procedure (97%). Follow-up period ranged from 2 to 48 months., Conclusions: Liposuction might not be enough to achieve the ideal V-shape of the men's back in some cases; hence, fat grafting of the power muscles becomes the best option. Recognition of the main neurovascular pedicle, proper preoperative markings, and a correct surgical technique ensure both the safety and the reproducibility of the technique., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Perovskite solar cells (PSCs) and modules are driving the energy revolution in the coming photovoltaic field. In the last 10 years, PSCs reached efficiency close to the silicon photovoltaic technology by adopting low-cost solution processes. Despite this, the noble metal (such as gold and silver) used in PSCs as a counter electrode made these devices costly in terms of energy, CO 2 footprint, and materials. Carbon-based perovskite solar cells (C-PSCs) and modules use graphite/carbon-black-based material as the counter electrode. The formulation of low-cost carbon-based inks and pastes makes them suitable for large area coating techniques and hence a solid technology for imminent industrialization. Here, we want to present the upscaling routes of carbon-counter-electrode-based module devices in terms of materials formulation, architectures, and manufacturing processes in order to give a clear vision of the scaling route and encourage the research in this green and sustainable direction.

Conjugating the porphyrin ring with an amino acid via amide linkage represents a straightforward way for conferring both amphiphilicity and chirality to the macrocycle. Proline residue is a good choice in this context since its conformational rigidity allows for porphyrin assembling where molecular chirality is efficiently transferred and amplified using properly honed aqueous environments. Herein, we describe the evolution of the studies carried out by our group to achieve chiral systems from some porphyrin-proline derivatives, both in solution and in the solid state. The discussion focuses on some fundamental aspects reflecting on the final molecular architectures obtained, which are related to the nature of the appended group (stereochemistry and charge), the presence of a metal ion coordinated to the porphyrin core and the bulk solvent properties. Indeed, fine-tuning the mentioned parameters enables the achievement of stereospecific structures with distinctive chiroptical and morphological features. Solid films based on these chiral systems were also obtained and their recognition abilities in gaseous and liquid phase are here described.

Background: In the aging process, the cumulative exposure to stress with increased cortisol levels is considered to be associated to the senescence itself and its related disorders., Aims: To evaluate the role of cortisol in elderly subjects, with or without dementia, by the means of the AGICO study., Methods: The AGICO study enrolled patients from ten Geriatric Units in Italy in 2012-2017 (Study Director Prof Paolo Falaschi, S. Andrea Hospital of Rome). Every subject received a comprehensive geriatric assessment (including the Mini-Mental State Examination, MMSE), the neurological examination (with a computed tomography scan or magnetic resonance imaging of the brain), the assessment of the metabolic syndrome (MetS), the evaluation of the cortisol activity by two consecutive urine collections (diurnal and nocturnal)., Results: The MMSE was inversely related to the standardized diurnal and nocturnal urinary cortisol levels (p < 0.025 and p < 0.01, respectively) and the age was positively related (p < 0.01 and p < 0.001, respectively). The ratio between the standardized diurnal and nocturnal urinary cortisol levels was 1.50 ± 1.2 (mean ± standard deviation) and it was not modified by the age or dementia. The standardized diurnal and nocturnal urinary cortisol levels were significantly higher in patients with dementia (MMSE < 24) (p < 0.01). In the analysis of the subgroups with MetS, the highest concentrations of diurnal and nocturnal cortisol were found in patients with both dementia and MetS (p < 0.025 and p < 0.01, respectively)., Discussion: The AGICO study showed that the stress response significantly and progressively increases with age., Conclusion: The cortisol increase in aging is related to the presence of both dementia and metabolic syndrome., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Natalizumab is a humanized monoclonal antibody used for treatment of highly active relapsing-remitting multiple sclerosis (MS). With more than 15 years of post-marketing experience with natalizumab in Canada, several real-world studies have shown the long-term efficacy and safety of natalizumab. In addition, risk stratification/mitigation strategies for progressive leukoencephalopathy (PML), an adverse effect associated with natalizumab based on the John Cunningham virus (JCV) index; treatment duration beyond 24 months; and prior exposure to immunosuppressant drugs have been developed., Methods: A group of neurologists from various MS clinics across Canada met in September 2021 to update the 2015 Canadian practice recommendations for the use of natalizumab in persons with MS (PwMS)., Results: The recommendations focused on the long-term efficacy and safety data from real-world studies, patient selection according to JCV index criteria, risk management strategies for PML (including extended interval dosing), and options for switching to currently available disease-modifying therapies for MS., Conclusions: The recommendations of clinical neurologists seek to optimize the management of PwMS who may benefit from treatment with natalizumab., (Crown Copyright © 2022. Published by Elsevier B.V. All rights reserved.)

Advanced therapy medical products (ATMPs) are rapidly growing as innovative medicines for the treatment of several diseases. Hence, the role of quality analytical tests to ensure consistent product safety and quality has become highly relevant. Several clinical trials involving dendritic cell (DC)-based vaccines for cancer treatment are ongoing at our institute. The DC-based vaccine is prepared via CD14+ monocyte differentiation. A fresh dose of 10 million DCs is administered to the patient, while the remaining DCs are aliquoted, frozen, and stored in nitrogen vapor for subsequent treatment doses. To evaluate the maintenance of quality parameters and to establish a shelf life of frozen vaccine aliquots, a stability program was developed. Several parameters of the DC final product at 0, 6, 12, 18, and 24 months were evaluated. Our results reveal that after 24 months of storage in nitrogen vapor, the cell viability is in a range between 82% and 99%, the expression of maturation markers remains inside the criteria for batch release, the sterility tests are compliant, and the cell costimulatory capacity unchanged. Thus, the data collected demonstrate that freezing and thawing do not perturb the DC vaccine product maintaining over time its functional and quality characteristics.

Cationic porphyrins exhibit an amazing variety of binding modes and inhibition mechanisms of 20S proteasome. Depending on the spatial distribution of their electrostatic charges, they can occupy different sites on α rings of 20S proteasome by exploiting the structural code responsible for the interaction with regulatory proteins. Indeed, they can act as competitive or allosteric inhibitors by binding at the substrate gate or at the grooves between the α subunits, respectively. Moreover, the substitution of a charged moiety in the peripheral arm with a hydrophobic moiety revealed a "new" 20S functional state with higher substrate affinity and catalytic efficiency. In the present study, we expand our structure-activity relationship (SAR) analysis in order to further explore the potential of this versatile class of 20S modulators. Therefore, we have extended the study to additional macrocyclic compounds, displaying different structural features, comparing their interaction behavior on the 20S proteasome with previously investigated compounds. In particular, in order to evaluate how the introduction of a peptidic chain can affect the affinity and the interacting mechanism of porphyrins, we investigate the MTPyApi, a porphyrin derivatized with an Arg-Pro-rich antimicrobial peptide. Moreover, to unveil the role played by the porphyrin core, this was replaced with a corrole scaffold, a "contracted" version of the tetrapyrrolic ring due to the lack of a methine bridge. The analysis has been undertaken by means of integrated kinetic, Nuclear Magnetic Resonance, and computational studies. Finally, in order to assess a potential pharmacological significance of this type of investigation, a preliminary attempt has been performed to evaluate the biological effect of these molecules on MCF7 breast cancer cells in dark conditions, envisaging that porphyrins may indeed represent a powerful tool for the modulation of cellular proteostasis.

To produce clothes made with engineered fabrics to monitor the physiological parameters of workers, strain sensors were produced by depositing two different types of water-based inks (P1 and P2) suitably mixed with graphene nanoplatelets (GNPs) on a fabric. We evaluated the biocompatibility of fabrics with GNPs (GNP fabric) through in vitro and in vivo assays. We investigated the effects induced on human keratinocytes by the eluates extracted from GNP fabrics by the contact of GNP fabrics with cells and by seeding keratinocytes directly onto the GNP fabrics using a cell viability test and morphological analysis. Moreover, we evaluated in vivo possible adverse effects of the GNPs using the model system Caenorhabditis elegans . Cell viability assay, morphological analysis and Caenorhabditis elegans tests performed on smart fabric treated with P2 (P2GNP fabric) did not show significant differences when compared with their respective control samples. Instead, a reduction in cell viability and changes in the membrane microvilli structure were found in cells incubated with smart fabric treated with P1. The results were helpful in determining the non-toxic properties of the P2GNP fabric. In the future, therefore, graphene-based ink integrated into elastic fabric will be developed for piezoresistive sensors.

Optical chemical sensors are widely applied in many fields of modern analytical practice, due to their simplicity in preparation and signal acquisition, low costs, and fast response time. Moreover, the construction of most modern optical sensors requires neither wire connections with the detector nor sophisticated and energy-consuming hardware, enabling wireless sensor development for a fast, in-field and online analysis. In this review, the last five years of progress (from 2017 to 2021) in the field of optical chemical sensors development for persistent organic pollutants (POPs) is provided. The operating mechanisms, the transduction principles and the types of sensing materials employed in single selective optical sensors and in multisensory systems are reviewed. The selected examples of optical sensors applications are reported to demonstrate the benefits and drawbacks of optical chemical sensor use for POPs assessment.

An easy and fast method to achieve chiral porphyrin films on glass is herein reported. The on-surface formation of organized supramolecular architectures with distinctive and remarkable chiroptical features strictly depends on the macrocycles used, the solvent chosen for the casting deposition, and most importantly, on the roughness of the glass slide. Dynamic light scattering studies performed on 10 -4 -10 -6  M porphyrin solutions revealed the presence of small porphyrin aggregates, whose size and number increase depending on the initial concentration. Once transferred on surface, these protoaggregates act as nucleation seeds for the following, self-assembling into larger structures upon solvent evaporation, with a process driven by a fine balance between intermolecular and molecule-substrate interactions. The described method represents a straightforward way to fabricate porphyrin-based chiral surfaces onto a transparent and economic substrate in few minutes. The results obtained can be particularly promising for the development of sensors based on stereoselective optical active films, targeting the detection of chiral analytes of practical relevance, such as the so-called emerging pollutants released in the environment from agrochemical, food, and pharmaceutical manufacturing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Magna, Traini, Naitana, Bussetti, Domenici, Paradossi, Venanzi, Di Natale, Paolesse, Monti and Stefanelli.)