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Antonio Ianniciello,1 Emilio Attena,2 Gerardo Carpinella,3 Ambra Uccello,4 Ciro Mauro,3 Vincenzo Russo1 1Department of Medical Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, Naples, Italy; 2Cardiology Unit, Monaldi and Cotugno Hospital, Naples, Italy; 3Cardiology Unit, Cardarelli Hospital, Naples, Italy; 4Cardiology Unit, Marcianise Hospital, Caserta Health Authority, Caserta, ItalyCorrespondence: Vincenzo Russo, Department of Medical Translational Sciences, University of Campania “Luigi Vanvitelli”, Monaldi Hospital, Piazzale E. Ruggieri, Naples, 80131, Italy, Email vincenzo.russo@unicampania.itAbstract: We described the case of a 68-year-old COVID-19 patient with hypertension and dyslipidemia who discontinued the cardiovascular medications during hospitalization and experienced a late onset occurrence of concomitant ST-elevation myocardial infarction and ischemic stroke at resolution of SARS-CoV-2 pneumonia.Keywords: COVID-19, stroke, myocardial infarction, thrombotic events, discontinuation, cardiovascular therapies

Abstract Supporting cell proliferation through nucleotide biosynthesis is an essential requirement for cancer cells. Hence, inhibition of folate-mediated one carbon (1C) metabolism, which is required for nucleotide synthesis, has been successfully exploited in anti-cancer therapy. Here, we reveal that mitochondrial folate metabolism is upregulated in patient-derived leukaemic stem cells (LSCs). We demonstrate that inhibition of mitochondrial 1C metabolism through impairment of de novo purine synthesis has a cytostatic effect on chronic myeloid leukaemia (CML) cells. Consequently, changes in purine nucleotide levels lead to activation of AMPK signalling and suppression of mTORC1 activity. Notably, suppression of mitochondrial 1C metabolism increases expression of erythroid differentiation markers. Moreover, we find that increased differentiation occurs independently of AMPK signalling and can be reversed through reconstitution of purine levels and reactivation of mTORC1. Of clinical relevance, we identify that combination of 1C metabolism inhibition with imatinib, a frontline treatment for CML patients, decreases the number of therapy-resistant CML LSCs in a patient-derived xenograft model. Our results highlight a role for folate metabolism and purine sensing in stem cell fate decisions and leukaemogenesis.

Abstract Macrophages are fundamental cells of the innate immune system that support normal haematopoiesis and play roles in both anti-cancer immunity and tumour progression. Here we use a chimeric mouse model of chronic myeloid leukaemia (CML) and human bone marrow (BM) derived macrophages to study the impact of the dysregulated BM microenvironment on bystander macrophages. Utilising single-cell RNA sequencing (scRNA-seq) of Philadelphia chromosome (Ph) negative macrophages we reveal unique subpopulations of immature macrophages residing in the CML BM microenvironment. CML exposed macrophages separate from their normal counterparts by reduced expression of the surface marker CD36, which significantly reduces clearance of apoptotic cells. We uncover aberrant production of CML-secreted factors, including the immune modulatory protein lactotransferrin (LTF), that suppresses efferocytosis, phagocytosis, and CD36 surface expression in BM macrophages, indicating that the elevated secretion of LTF is, at least partially responsible for the supressed clearance function of Ph- macrophages.

Extensive efforts in providing upper limb amputees with sensory feedback have primarily focused on the restoration of tactile capabilities, while challenges in evoking proprioceptive sensations have been poorly addressed. Previously, an human–machine interface (HMI) was proposed based on permanent magnets implanted in residual muscles of an amputee, namely the myokinetic interface, to control robotic limb prostheses. Besides control, implanted magnets offer an unprecedent opportunity to trigger musculotendon proprioceptors via untethered selective vibrations. Herein, the challenge of tracking multiple moving magnets is addressed (e.g., following muscle contractions) while being vibrated by controlled magnetic fields produced by external coils. Results demonstrate the viability of a real‐time (RT) system capable of simultaneously tracking and vibrating multiple moving magnets within a three‐dimensional workspace. Highly selective torsional vibrations in the frequency span eliciting movement illusions (70, 80, and 90 Hz) are achieved on two moving magnets, with efficiencies above 0.82 (over 80% of spectral power at the desired frequency). Tracking accuracy and precision remain robust to the coil magnetic field, with position median errors below 1.2 mm and median displacement errors below 0.95 mm. This study represents a crucial step towards the development of a bench system to study proprioception in humans.

Abstract Background Fruit and vegetables are highly perishable. In an era where reducing food waste is absolutely essential, packaging is important for maintaining the postharvest quality of these fresh products. Research is working to reduce the use of synthetic materials, not safe for the environment and human health. In this perspective, chitosan emerges as a viable solution for this purpose, as it is biodegradable, biocompatible and also safe for food application. The growing interest in using insects as a source of chitin has allowed for increased exploitation of insect-based waste products to recover valuable materials, such as biopolymers. The black soldier fly (Hermetia illucens L.) is the most widely reared species in Europe for feed production and waste management. Results In this work, fresh mature apricots (Prunus armeniaca L.), nectarines (Prunus persica vulgaris Mill.) and yellow peaches (Prunus persica var. laevis Gray) were coated with 0.5% and 1% chitosan from the pupal exuviae of Hermetia illucens, applied by spraying and stored at room temperature or 4 °C until they decay. Then, to validate the effectiveness of chitosan as a polymer for fruit preservation, several parameters including pH, TSS and weight loss were evaluated. Conclusions The results showed that chitosan derived from the black soldier fly is as effective as or better than the commercially available crustacean chitosan in maintaining more stable some storage parameters in fresh apricots, nectarines and peaches. Thus, insects, especially Hermetia illucens, are confirmed as a viable alternative source of the polymer. Graphical Abstract

Abstract Deregulated oxidative metabolism is a hallmark of leukaemia. While tyrosine kinase inhibitors (TKIs) such as imatinib have increased survival of chronic myeloid leukaemia (CML) patients, they fail to eradicate disease-initiating leukemic stem cells (LSCs). Whether TKI-treated CML LSCs remain metabolically deregulated is unknown. Using clinically and physiologically relevant assays, we generate multi-omics datasets that offer unique insight into metabolic adaptation and nutrient fate in patient-derived CML LSCs. We demonstrate that LSCs have increased pyruvate anaplerosis, mediated by increased mitochondrial pyruvate carrier 1/2 (MPC1/2) levels and pyruvate carboxylase (PC) activity, in comparison to normal counterparts. While imatinib reverses BCR::ABL1-mediated LSC metabolic reprogramming, stable isotope-assisted metabolomics reveals that deregulated pyruvate anaplerosis is not affected by imatinib. Encouragingly, genetic ablation of pyruvate anaplerosis sensitises CML cells to imatinib. Finally, we demonstrate that MSDC-0160, a clinical orally-available MPC1/2 inhibitor, inhibits pyruvate anaplerosis and targets imatinib-resistant CML LSCs in robust pre-clinical CML models. Collectively these results highlight pyruvate anaplerosis as a persistent and therapeutically targetable vulnerability in imatinib-treated CML patient-derived samples.

Abstract Chitosan was produced from Hermetia illucens pupal exuviae by heterogeneous and homogeneous deacetylation. Tomato fruits (Solanum lycopersicum), that are one of the most grown and consumed food throughout the world, were coated with 0.5 and 1% chitosan, applied by dipping or spraying, and stored at room temperature or 4 °C, for a storage period of 30 days. Statistical analysis give different results depending on the analysed parameters: heterogeneous chitosan, indeed, had a better effect than the homogenous one in maintaining more stable physico-chemical parameters, while the homogenous chitosan improved the total phenols, flavonoids and antioxidant activity. Chitosan coatings applied by spraying were more effective in all the analyses. Chitosan derived from H. illucens always performed similarly to the commercial chitosan. However, a general better performance of insect-derived chitosan on the concentration of phenolics and flavonoids, and the antioxidant activity was observed as compared to the commercial one. Chitosan coating has already been successfully used for preservation of fresh fruits, as alternative to synthetic polymers, but this is the first investigation of chitosan produced from an insect for this application. These preliminary results are encouraging regarding the validation of the insect H. illucens as a source of chitosan.

Summary: The ability of chitosan produced from pupal exuviae of Hermetia illucens to retard the decay of the local strawberry (Fragaria x ananassa) cultivar Melissa was investigated for the first time in this paper. The results demonstrated the effectiveness of insect chitosan compared to the commercial polymer in preserving and enhancing, at the same time, some physicochemical parameters (weight loss, pH and soluble solids content) and nutraceutical properties (total polyphenol content, total flavonoid content and total antioxidant activity) of strawberries stored at RT, 4°C and at mixed storage conditions (4°C + RT). Moreover, chitosan from H. illucens was also effective in reducing fungal decay and improving fruit shelf life. The obtained results confirm that insect chitosan, particularly deriving from H. illucens pupal exuviae, can be a viable alternative to crustacean one in safeguarding postharvest fruits.

Abstract Growing antimicrobial resistance has prompted researchers to identify new natural molecules with antimicrobial potential. In this perspective, attention has been focused on biopolymers that could also be functional in the medical field. Chitin is the second most abundant biopolymer on Earth and with its deacetylated derivative, chitosan, has several applications in biomedical and pharmaceutical fields. Currently, the main source of chitin is the crustacean exoskeleton, but the growing demand for these polymers on the market has led to search for alternative sources. Among these, insects, and in particular the bioconverter Hermetia illucens, is one of the most bred. Chitin can be extracted from larvae, pupal exuviae and dead adults of H. illucens, by applying chemical methods, and converted into chitosan. Fourier-transformed infrared spectroscopy confirmed the identity of the chitosan produced from H. illucens and its structural similarity to commercial polymer. Recently, studies showed that chitosan has intrinsic antimicrobial activity. This is the first research that investigated the antibacterial activity of chitosan produced from the three developmental stages of H. illucens through qualitative and quantitative analysis, agar diffusion tests and microdilution assays, respectively. Our results showed the antimicrobial capacity of chitosan of H. illucens, opening new perspectives for its use in the biological area.

Extensive efforts in providing upper limb amputees with sensory feedback have primarily focused on the restoration of tactile capabilities, while challenges in evoking proprioceptive sensations have been poorly addressed. Previously, an human–machine interface (HMI) was proposed based on permanent magnets implanted in residual muscles of an amputee, namely the myokinetic interface, to control robotic limb prostheses. Besides control, implanted magnets offer an unprecedent opportunity to trigger musculotendon proprioceptors via untethered selective vibrations. Herein, the challenge of tracking multiple moving magnets is addressed (e.g., following muscle contractions) while being vibrated by controlled magnetic fields produced by external coils. Results demonstrate the viability of a real‐time (RT) system capable of simultaneously tracking and vibrating multiple moving magnets within a three‐dimensional workspace. Highly selective torsional vibrations in the frequency span eliciting movement illusions (70, 80, and 90 Hz) are achieved on two moving magnets, with efficiencies above 0.82 (over 80% of spectral power at the desired frequency). Tracking accuracy and precision remain robust to the coil magnetic field, with position median errors below 1.2 mm and median displacement errors below 0.95 mm. This study represents a crucial step towards the development of a bench system to study proprioception in humans. [ABSTRACT FROM AUTHOR]

Background: Sialidosis is a rare autosomal recessive disease caused by NEU1 mutations, leading to neuraminidase deficiency and accumulation of sialic acid-containing oligosaccharides and glycopeptides into the tissues. Sialidosis is divided into two clinical entities, depending on residual enzyme activity, and can be distinguished according to age of onset, clinical features, and progression. Type 1 sialidosis is the milder, late-onset form, also known as non-dysmorphic sialidosis. It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As a rare condition, the diagnosis is often only made after few years from onset, and the clinical management might prove difficult. Furthermore, the information in the literature on the long-term course is scarce. Case presentations: We describe a comprehensive clinical, neuroradiological, ophthalmological, and electrophysiological history of four unrelated patients affected by type 1 sialidosis. The long-term care and novel clinical and neuroradiological insights are discussed. Discussion and conclusions: We report the longest follow-up (up to 30 years) ever described in patients with type 1 sialidosis. During the course, we observed a high degree of motor and speech disability with preserved cognitive functions. Among the newest antiseizure medication, perampanel (PER) was proven to be effective in controlling myoclonus and tonic–clonic seizures, confirming it is a valid therapeutic option for these patients. Brain magnetic resonance imaging (MRI) disclosed new findings, including bilateral gliosis of cerebellar folia and of the occipital white matter. In addition, a newly reported variant (c.914G > A) is described.

Discovered over fifty years ago, autophagy is a double-edged blade. On one hand, it regulates cellular energy sources by “cannibalization” of its own cellular components, feeding on proteins and other unused cytoplasmic factors. On the other, it is a recycling process that removes dangerous waste from the cytoplasm keeping the cell clean and healthy. Failure of the autophagic machinery is translated in dysfunction of the immune response, in aging, and in the progression of pathologies such as Parkinson disease, diabetes, and cancer. Further investigation identified autophagy with a protective role in specific types of cancer, whereas in other cases it can promote tumorigenesis. Evidence shows that treatment with chemotherapeutics can upregulate autophagy in order to maintain a stable intracellular environment promoting drug resistance and cell survival. Leukemia, a blood derived cancer, represents one of the malignancies in which autophagy is responsible for drug treatment failure. Inhibition of autophagy is becoming a strategic target for leukemic stem cell (LSC) eradication. Interestingly, the latest findings demonstrate that LSCs show higher levels of mitochondrial metabolism compared to normal stem cells. With this review, we aim to explore the links between autophagy and metabolism in the hematopoietic system, with special focus on primitive LSCs.