Miracle-dz/UniFAR-FTUs huggingface dataset:
Structures and topological defects in pressure-driven lyotropic chromonic liquid crystals

Significance Many driven and active nematic fluids exhibit complex microstructures, but their characteristics and dynamics are poorly understood. We explore the structures emerging in a pressure-driven nematic lyotropic chromonic liquid crystal in a microfluidic channel. We show that twist-type topological defects spontaneously emerge under flow. Our single-shot quantitative polarization imaging method allows us to quantify the fluctuations of these defects, which we show to reflect the tumbling character of the liquid crystal. We report how the defect size is governed by the balance between nucleation and annihilation forces, a balance that can be tuned by the flow rate. Such control over the microstructure opens pathways for using these nematic materials in optical devices and to control assembly of biological systems. Lyotropic chromonic liquid crystals are water-based materials composed of self-assembled cylindrical aggregates. Their behavior under flow is poorly understood, and quantitatively resolving the optical retardance of the flowing liquid crystal has so far been limited by the imaging speed of current polarization-resolved imaging techniques. Here, we employ a single-shot quantitative polarization imaging method, termed polarized shearing interference microscopy, to quantify the spatial distribution and the dynamics of the structures emerging in nematic disodium cromoglycate solutions in a microfluidic channel. We show that pure-twist disclination loops nucleate in the bulk flow over a range of shear rates. These loops are elongated in the flow direction and exhibit a constant aspect ratio that is governed by the nonnegligible splay-bend anisotropy at the loop boundary. The size of the loops is set by the balance between nucleation forces and annihilation forces acting on the disclination. The fluctuations of the pure-twist disclination loops reflect the tumbling character of nematic disodium cromoglycate. Our study, including experiment, simulation, and scaling analysis, provides a comprehensive understanding of the structure and dynamics of pressure-driven lyotropic chromonic liquid crystals and might open new routes for using these materials to control assembly and flow of biological systems or particles in microfluidic devices.
Kynurenine Monooxygenase Expression and Activity in Human Astrocytomas

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. The enzyme indoleamine-2,3-dioxygenase (IDO), which participates in the rate-limiting step of tryptophan catabolism through the kynurenine pathway (KP), is associated with poor prognosis in patients with GBM. The metabolites produced after tryptophan oxidation have immunomodulatory properties that can support the immunosuppressor environment. In this study, mRNA expression, protein expression, and activity of the enzyme kynurenine monooxygenase (KMO) were analyzed in GBM cell lines (A172, LN-18, U87, U373) and patient-derived astrocytoma samples. KMO mRNA expression was assessed by real-time RT-qPCR, KMO protein expression was evaluated by flow cytometry and immunofluorescence, and KMO activity was determined by quantifying 3-hydroxykynurenine by HPLC. Heterogenous patterns of both KMO expression and activity were observed among the GBM cell lines, with the A172 cell line showing the highest KMO expression and activity. Higher KMO mRNA expression was observed in glioma samples than in patients diagnosed with only a neurological disease; high KMO mRNA expression was also observed when using samples from patients with GBM in the TCGA program. The KMO protein expression was localized in GFAP+ cells in tumor tissue. These results suggest that KMO is a relevant target to be explored in glioma since it might play a role in supporting tumor metabolism and immune suppression.
Impact of the Introduction of Accreditation Standards on the Satisfaction of Patients in Cardiology Departments

Background: It can be presumed that introducing accreditation standards and obtaining national accreditation by a hospital should translate into increased patient satisfaction. The aim was to analyze the impact of introducing accreditation standards on patient satisfaction in cardiology departments. Methods: 1080 patients, who were hospitalized in four cardiological wards (W1–W4) between 2009–2015, were asked to complete a 22-item questionnaire that assessed the level of their satisfaction with their medical care. 58 questionnaires were excluded because of incomplete data. The hospital was accredited in 2013. Results: In 3 of the 4 wards, a statistically higher total score (the patient was more satisfied) in the period after the accreditation (2013–2015) compared to the period before the accreditation (2009–2012) was as follows: W1 (80.37 ± 6.54 vs. 83.85 ± 5.9; p = 0.0004), W2 (79.95 ± 7.62 vs. 81.46 ± 8.2: p = 0.0376), W4: (78.84 ± 7.94 vs. 84.91 ± 5.57; p = 0.0376); in one ward, there was no statistical difference: W3 (80.11 ± 8.42 vs. 81.07 ± 8.15; p = 0.3284). A significant difference was found in the number of points for the total assessment that were collected for all of the analyzed departments throughout the entire period (2009–2015)–W1: p = 0.0032; W2: p = 0.0176; W3: p = 0.0313 and W4: p < 0.0001). The medium-term rate of the change of the total score decreased after the accreditation. Conclusion: Preparing a hospital for a national accreditation program brought significant benefits for patients in a long-term observation.
COSMOtherm as an Effective Tool for Selection of Deep Eutectic Solvents Based Ready-To-Use Extracts from Graševina Grape Pomace

The aim of this work is to develop an industrially suitable process for the sustainable waste disposal in wine production. The proposed process involves the development of an environmentally friendly method for the isolation of biologically active compounds from Graševina grape pomace according to the green extraction principles, in order to obtain a ready-to-use extract. In this process, deep eutectic solvents (DES) were used as extraction solvents. Aiming to save time in selecting the optimal DES that would provide the most efficient Graševina pomace polyphenols extraction, the user-friendly software COSMOtherm was used and 45 DES were screened. Moreover, the prepared extracts were chemically and biologically characterized to confirm their safety for human application. Computational and experimental results proved the applicability of COSMOtherm in the selection of the optimal DES for the environmentally friendly preparation of the ready-to-use extract from Graševina grape pomace with expected application in the cosmetic industry.
Exposomes to Exosomes: Exosomes as Tools to Study Epigenetic Adaptive Mechanisms in High-Altitude Humans

Humans on earth inhabit a wide range of environmental conditions and some environments are more challenging for human survival than others. However, many living beings, including humans, have developed adaptive mechanisms to live in such inhospitable, harsh environments. Among different difficult environments, high-altitude living is especially demanding because of diminished partial pressure of oxygen and resulting chronic hypobaric hypoxia. This results in poor blood oxygenation and reduces aerobic oxidative respiration in the mitochondria, leading to increased reactive oxygen species generation and activation of hypoxia-inducible gene expression. Genetic mechanisms in the adaptation to high altitude is well-studied, but there are only limited studies regarding the role of epigenetic mechanisms. The purpose of this review is to understand the epigenetic mechanisms behind high-altitude adaptive and maladaptive phenotypes. Hypobaric hypoxia is a form of cellular hypoxia, which is similar to the one suffered by critically-ill hypoxemia patients. Thus, understanding the adaptive epigenetic signals operating in in high-altitude adjusted indigenous populations may help in therapeutically modulating signaling pathways in hypoxemia patients by copying the most successful epigenotype. In addition, we have summarized the current information about exosomes in hypoxia research and prospects to use them as diagnostic tools to study the epigenome of high-altitude adapted healthy or maladapted individuals.
Combined Hurdle Technologies Using UVC Waterproof LED for Inactivating Foodborne Pathogens on Fresh-Cut Fruits

This study investigated the combined bactericidal efficacy of slightly acidic electrolyzed water (SAEW), fumaric acid (FA), and ultravioletC waterproof light-emitting diodes (UVC W-LED) for the control of Staphylococcus aureus and Listeria monocytogenes in fresh-cut fruits. Cherry tomato, grape, apple, and pineapple were inoculated with S. aureus and L. monocytogenes and then washed with 30 ppm SAEW containing 0.5% FA in a container equipped with two UVC W-LEDs. Behaviors of S. aureus and L. monocytogenes and quality properties of fresh-cut fruits were monitored after storage at 10 °C and 15 °C for 7 days. The most effective reductions of S. aureus (1.65 log CFU/g) and L. monocytogenes (2.63 log CFU/g) were observed in the group with the combined treatment of SAEW + FA and UVC W-LED. At 10 °C and 15 °C, populations of both pathogens in the combined treatment group were lower than those in a control. Combined treatment showed no negative effect on moisture retention in the fruit. Moreover, visual changes were less significant than in the control. These results demonstrate that the combined treatment can improve the microbial safety and the quality of fruits. If it is properly used in the sanitizing step of the fresh produce industry, a positive effect can be expected.
Decline in telomere length with increasing age across nonhuman vertebrates: A meta‐analysis

The prediction that telomere length (TL) shortens with increasing age is a major element in considering the role of telomeres as a key player in evolution. While telomere attrition is found in humans both in vitro and in vivo, the increasing number of studies reporting diverse age‐specific patterns of TL challenges the hypothesis of a universal decline of TL with increasing age. Here, we performed a meta‐analysis to estimate the relationship between TL and age across 175 estimates encompassing 98 species of vertebrates. We found that, on average, TL does decline with increasing age during adulthood. However, this decline was weak and variable across vertebrate classes, and we also found evidence for a publication bias that might weaken our current evidence of decreasing TL with increasing age. We found no evidence for a faster decline in TL with increasing age when considering the juvenile stage (from birth to age at first reproduction) compared to the adult stage. Heterogeneity in TL ageing rates was explained by the method used to measure telomeres: detectable TL declines with increasing age were found only among studies using TRF with in‐gel hybridisation and qFISH methods, but not in studies using qPCR and Southern blot‐based TRF methods. While we confirmed that TL declines with increasing age in most adult vertebrates, our results identify an influence of telomere measurement methodology, which highlights the need to examine more thoroughly the effect of the method of measurement on TL estimates.
Expanding the Search for Sperm Transmission Elements in the Mitochondrial Genomes of Bivalve Mollusks

Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) in bivalve mollusks is one of the most notable departures from the paradigm of strict maternal inheritance of mtDNA among metazoans. Recently, work on the Mediterranean mussel Mytilus galloprovincialis suggested that a nucleotide motif in the control region of this species, known as the sperm transmission element (STE), helps protect male-transmitted mitochondria from destruction during spermatogenesis. Subsequent studies found similar, yet divergent, STE motifs in other marine mussels. Here, we extend the in silico search for mtDNA signatures resembling known STEs. This search is carried out for the large unassigned regions of 157 complete mitochondrial genomes from within the Mytiloida, Veneroida, Unionoida, and Ostreoida bivalve orders. Based on a sliding window approach, we present evidence that there are additional putative STE signatures in the large unassigned regions of several marine clams and freshwater mussels with DUI. We discuss the implications of this finding for interpreting the origin of doubly uniparental inheritance in ancestral bivalve mollusks, as well as potential future in vitro and in silico studies that could further refine our understanding of the early evolution of this unusual system of mtDNA inheritance.
A Transcriptome Community-and-Module Approach of the Human Mesoconnectome

Graph analysis allows exploring transcriptome compartments such as communities and modules for brain mesostructures. In this work, we proposed a bottom-up model of a gene regulatory network to brain-wise connectome workflow. We estimated the gene communities across all brain regions from the Allen Brain Atlas transcriptome database. We selected the communities method to yield the highest number of functional mesostructures in the network hierarchy organization, which allowed us to identify specific brain cell functions (e.g., neuroplasticity, axonogenesis and dendritogenesis communities). With these communities, we built brain-wise region modules that represent the connectome. Our findings match with previously described anatomical and functional brain circuits, such the default mode network and the default visual network, supporting the notion that the brain dynamics that carry out low- and higher-order functions originate from the modular composition of a GRN complex network
Removal of Ammonium Ions from Aqueous Solutions Using Weathered Halloysite

This study investigated the use of weathered halloysite as an ion exchange material for ammonium removal from water. The study was conducted under static and dynamic conditions. The influence of such parameters as the preliminary concentration of ammonium ions, dose of halloysite, and pH was examined in periodic studies. The ion exchange capacity of weathered halloysite under various regeneration conditions such as concentration, excess of regeneration solution and the pH at which the regeneration was performed was also determined. The effect of flow velocity, initial NH4+-ions concentration was studied in column tests and the weathered halloysite’s ion -exchange capacity was also determined. The best results of ammonium ion removal were obtained at pH 6. The equilibrium isotherms were described using the Langmuir and Freundlich models. The results of periodic studies show a good fit for the data of both models, with Langmuir isotherms reflecting the removal of ammonium ions better. A good match for the data (R2 > 0.99) was provided by a pseudo second-order kinetic model. The obtained results indicate that a properly prepared halloysite can be a useful mineral for the removal of dangerous substances, such as ammonium ions, present in natural waters.
Routes for Potassium Ions across Mitochondrial Membranes: A Biophysical Point of View with Special Focus on the ATP-Sensitive K+ Channel

Potassium ions can cross both the outer and inner mitochondrial membranes by means of multiple routes. A few potassium-permeable ion channels exist in the outer membrane, while in the inner membrane, a multitude of different potassium-selective and potassium-permeable channels mediate K+ uptake into energized mitochondria. In contrast, potassium is exported from the matrix thanks to an H+/K+ exchanger whose molecular identity is still debated. Among the K+ channels of the inner mitochondrial membrane, the most widely studied is the ATP-dependent potassium channel, whose pharmacological activation protects cells against ischemic damage and neuronal injury. In this review, we briefly summarize and compare the different hypotheses regarding the molecular identity of this patho-physiologically relevant channel, taking into account the electrophysiological characteristics of the proposed components. In addition, we discuss the characteristics of the other channels sharing localization to both the plasma membrane and mitochondria.
Recent Advances in BTK Inhibitors for the Treatment of Inflammatory and Autoimmune Diseases

Bruton’s tyrosine kinase (BTK) plays a crucial role in B-cell receptor and Fc receptor signaling pathways. BTK is also involved in the regulation of Toll-like receptors and chemokine receptors. Given the central role of BTK in immunity, BTK inhibition represents a promising therapeutic approach for the treatment of inflammatory and autoimmune diseases. Great efforts have been made in developing BTK inhibitors for potential clinical applications in inflammatory and autoimmune diseases. This review covers the recent development of BTK inhibitors at preclinical and clinical stages in treating these diseases. Individual examples of three types of inhibitors, namely covalent irreversible inhibitors, covalent reversible inhibitors, and non-covalent reversible inhibitors, are discussed with a focus on their structure, bioactivity and selectivity. Contrary to expectations, reversible BTK inhibitors have not yielded a significant breakthrough so far. The development of covalent, irreversible BTK inhibitors has progressed more rapidly. Many candidates entered different stages of clinical trials; tolebrutinib and evobrutinib are undergoing phase 3 clinical evaluation. Rilzabrutinib, a covalent reversible BTK inhibitor, is now in phase 3 clinical trials and also offers a promising future. An analysis of the protein–inhibitor interactions based on published co-crystal structures provides useful clues for the rational design of safe and effective small-molecule BTK inhibitors.
The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Δψm) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.
Clinical Risk Constellations for the Development of Bipolar Disorders

The early recognition of psychiatric disorders has been a focus of research in the last decades and has led to improvements in clinical care, especially in the area of early psychosis. Like non-affective psychosis, bipolar disorders are often diagnosed with a delay that can lead to long periods of untreated illness and impact long-term outcomes. This article presents the rationale for early recognition in bipolar disorder and presents the current evidence for the identification of risk factors, their assessment and validity in predicting the onset of bipolar disorder.
Crystal Structure of Poly(lactic acid) Stereocomplex: Random Packing Model of PDLA and PLLA Chains As Studied by X-ray Diffraction Analysis

The crystal structure model of stereocomplex between poly(l-lactic acid) (PLLA) and poly(d-lactic acid) (PDLA) with the L/D ratio of 50/50 was proposed by several groups [the space group P1 model by Okihara et al. (1991) and R3c or R3c model by Cartier et al. (1997)], among which the model of the space group R3c (or R3c) had been currently recognized as the most preferable one. However, the thus apparently established model cannot explain such an important experimental fact that the stereocomplex is formed not only for the PLLA/PDLA blend of the L/D ratio 50/50 but also for the blends with the L/D ratio of 70/30–30/70. We have proposed here a new model with the space group P3, which can cover the SC structures of the L/D ratio in the range of 70/30–50/50–30/70. This model can show the more quantitative reproducibility of the observed X-ray diffraction data for both the hkl and 000l reflection profiles. In particular the experimental observation of the 0003 reflection is inconsistent with the previous mo.
Computational Insight on the Interaction of Common Blood Proteins with Gold Nanoparticles

Protein interactions with engineered gold nanoparticles (AuNPs) and the consequent formation of the protein corona are very relevant and poorly understood biological phenomena. The nanoparticle coverage affects protein binding modalities, and the adsorbed protein sites influence interactions with other macromolecules and cells. Here, we studied four common blood proteins, i.e., hemoglobin, serum albumin, α1-antiproteinase, and complement C3, interacting with AuNPs covered by hydrophobic 11-mercapto-1-undecanesulfonate (MUS). We use Molecular Dynamics and the Martini coarse−grained model to gain quantitative insight into the kinetics of the interaction, the physico-chemical characteristics of the binding site, and the nanoparticle adsorption capacity. Results show that proteins bind to MUS−capped AuNPs through strong hydrophobic interactions and that they adapt to the AuNP surfaces to maximize the contact surface, but no dramatic change in the secondary structure of the proteins is observed. We suggest a new method to calculate the maximum adsorption capacity of capped AuNPs based on the effective surface covered by each protein, which better represents the realistic behavior of these systems.