Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric Modulation of GSK-3β as a New Therapeutic Approach in Limb Girdle Muscular Dystrophy R1 Calpain 3-Related

Limb-girdle muscular dystrophy R1 calpain 3-related (LGMDR1) is an autosomal recessive muscular dystrophy produced by mutations in the CAPN3 gene. It is a rare disease and there is no cure or treatment for the disease while the pathophysiological mechanism by which the absence of calpain 3 provokes the dystrophy in muscles is not clear. However, key proteins implicated in Wnt and mTOR signaling pathways, which regulate muscle homeostasis, showed a considerable reduction in their expression and in their phosphorylation in LGMDR1 patients’ muscles. Finally, the administration of tideglusib and VP0.7, ATP non-competitive inhibitors of glycogen synthase kinase 3β (GSK-3β), restore the expression and phosphorylation of these proteins in LGMDR1 cells, opening the possibility of their use as therapeutic options.
Further Characterization of Intrastriatal Lipopolysaccharide Model of Parkinson’s Disease in C57BL/6 Mice

Parkinson’s disease (PD) is the most common movement disorder, characterized by progressive degeneration of the nigrostriatal pathway, which consists of dopaminergic cell bodies in substantia nigra and their neuronal projections to the striatum. Moreover, PD is associated with an array of non-motor symptoms such as olfactory dysfunction, gastrointestinal dysfunction, impaired regulation of the sleep-wake cycle, anxiety, depression, and cognitive impairment. Inflammation and concomitant oxidative stress are crucial in the pathogenesis of PD. Thus, this study aimed to model PD via intrastriatal injection of the inflammagen lipopolysaccharide (LPS)to investigate if the lesion causes olfactory and motor impairments, inflammation, oxidative stress, and alteration in synaptic proteins in the olfactory bulb, striatum, and colon. Ten µg of LPS was injected unilaterally into the striatum of 27 male C57BL/6 mice, and behavioural assessment was conducted at 4 and 8 weeks post-treatment, followed by tissue collection. Intrastriatal LPS induced motor impairment in C57BL/6 mice at 8 weeks post-treatment evidenced by reduced latency time in the rotarod test. LPS also induced inflammation in the striatum characterized by increased expression of microglial marker Iba-1 and astrocytic marker GFAP, with degeneration of dopaminergic neuronal fibres (reduced tyrosine hydroxylase immunoreactivity), and reduction of synaptic proteins and DJ-1 protein. Additionally, intrastriatal LPS induced inflammation, oxidative stress and alterations in synaptic proteins within the olfactory bulb, although this did not induce a significant impairment in olfactory function. Intrastriatal LPS induced mild inflammatory changes in the distal colon, accompanied by increased protein expression of 3-nitrotyrosine-modified proteins. This model recapitulated the major features of PD such as motor impairment and degeneration of dopaminergic neuronal fibres in the striatum, as well as some pathological changes in the olfactory bulb and colon; thus, this model could be suitable for understanding clinical PD and testing neuroprotective strategies.
Biological Activity of Naturally Derived Naphthyridines

Marine and terrestrial environments are rich sources of various bioactive substances, which have been used by humans since prehistoric times. Nowadays, due to advances in chemical sciences, new substances are still discovered, and their chemical structures and biological properties are constantly explored. Drugs obtained from natural sources are used commonly in medicine, particularly in cancer and infectious diseases treatment. Naphthyridines, isolated mainly from marine organisms and terrestrial plants, represent prominent examples of naturally derived agents. They are a class of heterocyclic compounds containing a fused system of two pyridine rings, possessing six isomers depending on the nitrogen atom’s location. In this review, biological activity of naphthyridines obtained from various natural sources was summarized. According to previous studies, the naphthyridine alkaloids displayed multiple activities, i.a. , antiinfectious, anticancer, neurological, psychotropic, affecting cardiovascular system, and immune response. Their wide range of activity makes them a fascinating object of research with prospects for use in therapeutic purposes.
Mental Health and Psychological Wellbeing during the COVID-19 Lockdown: A Longitudinal Study in the Balearic Islands (Spain)

Confining the entire population to a lockdown after the outbreak of SARS-CoV-2 was an unprecedented measure designed to protect the health of those living in Spain. The objective of the present study is to assess the evolution of mental health and psychological wellbeing during lockdown. To do this, we carried out a longitudinal study, via an online survey over the eight weeks of lockdown (weekly assessments). Sociodemographic variables were recorded, along with data related to COVID-19, psychological wellbeing (anxiety, depression, psychotropic drugs, consultations made to improve mood or anxiety), life satisfaction, and self-perceived health. A total of 681 individuals participated in the study, 76.8% were women; the mean age was 43 years old (SD = 12.7). Initially, high scores were reported for anxiety, depression, and the number of consultations to improve mood, but these decreased significantly over the study period. The reverse seems to be true for life satisfaction, perceived good health, and intake of psychotropic drugs. We also identified groups whose psychological wellbeing was more susceptible to the effects of lockdown. Women, those worried about their jobs after the pandemic, and those afraid of being infected were the most affected individuals. More generally, after the initial negative effect on psychological wellbeing, various indicators improved over the lockdown period.
Magnetic Particle Imaging: Current and Future Applications, Magnetic Nanoparticle Synthesis Methods and Safety Measures

Magnetic nanoparticles (MNPs) have a wide range of applications; an area of particular interest is magnetic particle imaging (MPI). MPI is an imaging modality that utilizes superparamagnetic iron oxide particles (SPIONs) as tracer particles to produce highly sensitive and specific images in a broad range of applications, including cardiovascular, neuroimaging, tumor imaging, magnetic hyperthermia and cellular tracking. While there are hurdles to overcome, including accessibility of products, and an understanding of safety and toxicity profiles, MPI has the potential to revolutionize research and clinical biomedical imaging. This review will explore a brief history of MPI, MNP synthesis methods, current and future applications, and safety concerns associated with this newly emerging imaging modality.
Label-Free Electrochemical Sensor Based on Manganese Doped Titanium Dioxide Nanoparticles for Myoglobin Detection: Biomarker for Acute Myocardial Infarction

A label free electrochemical sensor based on pure titanium oxide and manganese (Mn)-doped titanium oxide (TiO2) nanoparticles are fabricated and characterized for the sensitive detection of myoglobin (Mb) levels to analyze the cardiovascular infarction. Pristine and Mn-doped TiO2 nanoparticles were synthesized via the sol-gel method and characterized in order to understand their structure, morphologies, composition and optical properties. The structural properties revealed that the pure- and doped-TiO2 nanoparticles possess different TiO2 planes. FTIR studies confirm the formation of metal oxide nanoparticles by exhibiting a well-defined peak in the range of 600–650 cm−1. The values of the optical band gap, estimated from UV-Vis spectroscopy, are decreased for the Mn-doped TiO2 nanoparticles. UV-Vis spectra in the presence of myoglobin (Mb) indicated interaction between the TiO2 nanoparticles and myoglobin. The SPE electrodes were then fabricated by printing powder film over the working electrode and tested for label-free electrochemical detection of myoglobin (Mb) in the concentration range of 0–15 nM Mb. The fabricated electrochemical sensor exhibited a high sensitivity of 100.40 μA-cm−2/nM with a lowest detection limit of 0.013 nM (0.22 ng/mL) and a response time of ≤10 ms for sample S3. An interference study with cyt-c and Human Serum Albumin (HSA) of the sensors show the selective response towards Mb in 1:1 mixture.
Perspectivity of bifunctional chelating agents in chemical, biological and biomedical applications

Bifunctional chelating agents (BFCs) are molecules with dual functional units, one for conjugation and another for chelation. Their initial applications in targeted radioimaging and radiotherapy have spurred their exploration towards extensive utility in different chemical and biochemical applications during the last two decades. The designing of core structure and conjugative unit of BFCs vary by their area of application. Different chelating agents varying from simple acyclic to complex macrocyclic units have been studied and bifunctionalized. Herein, evolution of designed BFCs and their application in nuclear medicine, magnetic resonance imaging (MRI), heterogeneous catalysis, homogenous catalysis using ionic liquids, fluorescence spectroscopy, luminescence (bio)imaging, chromatography and treatment of nuclear waste have been reviewed. Further, future prospects of these molecules in various applications have been analyzed.
A Grain-Scale Study of Mojave Mars Simulant (MMS-1)

Space exploration has attracted significant interest by government agencies and the scientific community in recent years in an attempt to explore possible scenarios of settling of facilities on the Moon and Mars surface. One of the important components in space exploration is related with the understanding of the geophysical and geotechnical characteristics of the surfaces of planets and their natural satellites and because of the limitation of available extra-terrestrial samples, many times researchers develop simulants, which mimic the properties and characteristics of the original materials. In the present study, characterization at the grain-scale was performed on the Mojave Mars Simulant (MMS-1) with emphasis on the frictional behavior of small size samples which follow the particle-to-particle configuration. Additional characterization was performed by means of surface composition and morphology analysis and the crushing behavior of individual grains. The results from the study present for the first time the micromechanical tribological response of Mars simulant, and attempts were also made to compare the behavior of this simulant with previously published results on other types of Earth and extra-terrestrial materials. Despite some similarities between Mars and Moon simulants, the unique characteristics of the MMS-1 samples resulted in significant differences and particularly in severe damage of the grain surfaces, which was also linked to the dilation behavior at the grain-scale.
Comparative Study of the Properties of Plasticized Polylactic Acid with Maleinized Hemp Seed Oil and a Novel Maleinized Brazil Nut Seed Oil

In this study, for the first time, Brazil nut seed oil was chemically modified with maleic anhydride to obtain maleinized Brazil nut seed oil (MBNO). The same process was developed to obtain maleinized hemp seed oil (MHO). The use of MBNO and MHO was studied as bio-based plasticizers by incorporating them with different contents ranging from 0 to 10 phr in a polylactic acid (PLA) matrix. By means of mechanical, thermal and thermomechanical characterization techniques, the properties of the different formulations were studied to evaluate the plasticizing effect of the MBNO and MHO. With the addition of both plasticizers, a significant increase in ductile properties was observed, reaching an increase in elongation at break of 643% with 7.5 phr MBNO and 771% with 10 phr MHO compared to neat PLA. In addition, it has been observed that the mechanical resistant properties do not decrease, since the oils enhance the crystallization of PLA by increasing the free volume between its chains and counteracting the effect. Finally, a disintegration test was carried out under thermophilic conditions at 58 °C for 27 days, demonstrating that the incorporation of MHO and MBNO does not significantly affect the biodegradability of neat PLA.
Imaging Quality Control, Methodology Harmonization and Clinical Data Management in Stress Echo 2030

Stress echo (SE) 2030 study is an international, prospective, multicenter cohort study that will include >10,000 patients from ≥20 centers from ≥10 countries. It represents the logical and chronological continuation of the SE 2020 study, which developed, validated, and disseminated the “ABCDE protocol” of SE, more suitable than conventional SE to describe the complex vulnerabilities of the contemporary patient within and beyond coronary artery disease. SE2030 was started with a recruitment plan from 2021 to 2025 (and follow-up to 2030) with 12 subprojects (ranging from coronary artery disease to valvular and post-COVID-19 patients). With these features, the study poses particular challenges on quality control assurance, methodological harmonization, and data management. One of the significant upgrades of SE2030 compared to SE2020 was developing and implementing a Research Electronic Data Capture (REDCap)-based infrastructure for interactive and entirely web-based data management to integrate and optimize reproducible clinical research data. The purposes of our paper were: first, to describe the methodology used for quality control of imaging data, and second, to present the informatic infrastructure developed on RedCap platform for data entry, storage, and management in a large-scale multicenter study.
Antibiotic Prophylaxis or Granulocyte-Colony Stimulating Factor Support in Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Simple Summary Effective anti-infective strategies are of crucial importance in patients with multiple myeloma undergoing high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT). We compare, for the first time, antibiotic prophylaxis versus granulocyte-colony stimulating factor (G-CSF) support as anti-infective strategies in this specific setting, including 353 individual cases of HDT/ASCT. We show similar efficacy in preventing infectious complications regarding antibiotic prophylaxis and G-CSF. Furthermore, we demonstrate that G-CSF support is associated with a shorter duration of inpatient stay and a lower rate of emerging multidrug resistant bacteria, especially vancomycin-resistant Enterococcus faecium. Therefore, G-CSF support should be the preferred anti-infective strategy in patients with multiple myeloma receiving HDT/ASCT. Abstract We compare, in this manuscript, antibiotic prophylaxis versus granulocyte-colony stimulating factor (G-CSF) support as anti-infective strategies, in patients with multiple myeloma (MM), undergoing high-dose therapy followed by autologous stem cell transplantation (HDT/ASCT). At our institution, antibiotic prophylaxis after HDT/ASCT in MM was stopped in January 2017 and replaced by G-CSF support in March 2017. Consecutive MM patients who received HDT/ASCT between March 2016 and July 2018 were included in this single-center retrospective analysis. In total, 298 patients and 353 individual cases of HDT/ASCT were evaluated. In multivariate analyses, G-CSF support was associated with a significantly shortened duration of severe leukopenia < 1/nL (p < 0.001, hazard ratio (HR) = 16.22), and hospitalization (estimate = −0.19, p < 0.001) compared to antibiotic prophylaxis. Rates of febrile neutropenia, need of antimicrobial therapy, transfer to intensive care unit, and death, were similar between the two groups. Furthermore, antibiotic prophylaxis was associated with a significantly increased risk for the development of multidrug resistant bacteria especially vancomycin-resistant Enterococcus faecium compared to G-CSF support (odds ratio (OR) = 17.38, p = 0.01). Stop of antibiotic prophylaxis as an anti-infective strategy was associated with a reduction in overall resistance rates of bacterial isolates. These results indicate that G-CSF support should be the preferred option in MM patients undergoing HDT/ASCT.
Cell membrane–camouflaged liposomes for tumor cell–selective glycans engineering and imaging in vivo

Significance Cell-surface glycans are dynamic indicators reporting cell physiological state and pathological processes including occurrence and progression of disease (e.g., cancer). For precise cancer diagnosis and treatment, however, it’s difficult to selectively visualize glycans of different cancer cells or cancer subtypes. Herein, we demonstrate the feasibility of cancer cell membrane–camouflaged azidosugar liposomes for cancer cell–selective metabolic glycoengineering. The biomimetic liposomes inherit the cell selectivity to homotypic cancer cells. Therefore, they cannot only realize selective glycan imaging of different cancer cells and breast cancer subtypes but can also sense lung metastasis of tumors. The strategy is also applicable to the use of tumor tissue–derived cell membranes, implying the clinical prospects for personalized medicine. The dynamic change of cell-surface glycans is involved in diverse biological and pathological events such as oncogenesis and metastasis. Despite tremendous efforts, it remains a great challenge to selectively distinguish and label glycans of different cancer cells or cancer subtypes. Inspired by biomimetic cell membrane–coating technology, herein, we construct pH-responsive azidosugar liposomes camouflaged with natural cancer-cell membrane for tumor cell–selective glycan engineering. With cancer cell–membrane camouflage, the biomimetic liposomes can prevent protein corona formation and evade phagocytosis of macrophages, facilitating metabolic glycans labeling in vivo. More importantly, due to multiple membrane receptors, the biomimetic liposomes have prominent cell selectivity to homotypic cancer cells, showing higher glycan-labeling efficacy than a single-ligand targeting strategy. Further in vitro and in vivo experiments indicate that cancer cell membrane–camouflaged azidosugar liposomes not only realize cell-selective glycan imaging of different cancer cells and triple-negative breast cancer subtypes but also do well in labeling metastatic tumors. Meanwhile, the strategy is also applicable to the use of tumor tissue–derived cell membranes, which shows the prospect for individual diagnosis and treatment. This work may pave a way for efficient cancer cell–selective engineering and visualization of glycans in vivo.
Search for Novel Lead Inhibitors of Yeast Cytochrome bc1, from Drugbank and COCONUT

In this work we introduce a novel filtering and molecular modeling pipeline based on a fingerprint and descriptor similarity procedure, coupled with molecular docking and molecular dynamics (MD), to select potential novel quoinone outside inhibitors (QoI) of cytochrome bc1 with the aim of determining the same or different chromophores to usual. The study was carried out using the yeast cytochrome bc1 complex with its docked ligand (stigmatellin), using all the fungicides from FRAC code C3 mode of action, 8617 Drugbank compounds and 401,624 COCONUT compounds. The introduced drug repurposing pipeline consists of compound similarity with C3 fungicides and molecular docking (MD) simulations with final QM/MM binding energy determination, while aiming for potential novel chromophores and perserving at least an amide (R1HN(C=O)R2) or ester functional group of almost all up to date C3 fungicides. 3D descriptors used for a similarity test were based on the 280 most stable Padel descriptors. Hit compounds that passed fingerprint and 3D descriptor similarity condition and had either an amide or an ester group were submitted to docking where they further had to satisfy both Chemscore fitness and specific conformation constraints. This rigorous selection resulted in a very limited number of candidates that were forwarded to MD simulations and QM/MM binding affinity estimations by the ORCA DFT program. In this final step, stringent criteria based on (a) sufficiently high frequency of H-bonds; (b) high interaction energy between protein and ligand through the whole MD trajectory; and (c) high enough QM/MM binding energy scores were applied to further filter candidate inhibitors. This elaborate search pipeline led finaly to four Drugbank synthetic lead compounds (DrugBank) and seven natural (COCONUT database) lead compounds—tentative new inhibitors of cytochrome bc1. These eleven lead compounds were additionally validated through a comparison of MM/PBSA free binding energy for new leads against those obtatined for 19 QoIs.
Impact of Digitalization on Customers’ Well-Being in the Pandemic Period: Challenges and Opportunities for the Retail Industry

Order increases, supply chain disruptions, changing customer behavior, store closures, and more that have been caused by the coronavirus epidemic (COVID-19) will undoubtedly affect the online commerce forms of business. The coronavirus pandemic has a significant impact on digitalization and customer experience and well-being in mobile commerce. Since the beginning of the coronavirus pandemic, online sales and the number of online shoppers using wireless internet-enabled devices have increased tremendously. The article develops, an experimental study that captures COVID-19 and digital commerce’s impact in terms of customers’ experience and well-being during the pandemic period. The study explores the synergy between technology evolution and the effects of the COVID-19 pandemic on customers’ behavior based on survey data collection and the technology acceptance model (TAM). The results reveal that, for millennials, digital commerce seems to be the typical way of shopping and paying in the pandemic period since the oldest generations adopted in a smaller proportion the use of mobile devices for shopping and payments. Besides, retailers are confronted with great challenges raised by millennials’ expectations. The result confirms four of the six hypotheses based on the technology acceptance model (TAM). As a result, it shows that the easiness of use, trust, mobility, and customer involvement influences the behavioral intention of the customer to use mobile commerce, and that usefulness and customization does not influence the behavioral intention.
An Electrochemical Ti3C2Tx Aptasensor for Sensitive and Label-Free Detection of Marine Biological Toxins

Saxitoxin (STX) belongs to the family of marine biological toxins, which are major contaminants in seafood. The reference methods for STX detection are mouse bioassay and chromatographic analysis, which are time-consuming, high costs, and requirement of sophisticated operation. Therefore, the development of alternative methods for STX analysis is urgent. Electrochemical analysis is a fast, low-cost, and sensitive method for biomolecules analysis. Thus, in this study, an electrolyte-insulator-semiconductor (EIS) sensor based on aptamer-modified two-dimensional layered Ti3C2Tx nanosheets was developed for STX detection. The high surface area and rich functional groups of MXene benefited the modification of aptamer, which had specific interactions with STX. Capacitance-voltage (C-V) and constant-capacitance (ConCap) measurement results indicated that the aptasensor was able to detect STX with high sensitivity and good specificity. The detection range was 1.0 nM to 200 nM and detection limit was as low as 0.03 nM. Moreover, the aptasensor was found to have a good selectivity and two-week stability. The mussel tissue extraction test suggested the potential application of this biosensor in detecting STX in real samples. This method provides a convenient approach for low-cost, rapid, and label-free detection of marine biological toxins.