bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Characterization of Human Meibomian Glands, Free Sebaceous Glands, and Hair-Associated Sebaceous Glands Based on Biomarkers, Analysis of Secretion Composition, and Gland Morphology
Authors: Liu Yuqiuhe , Butovich Igor A. , Garreis Fabian , Zahn Ingrid , Scholz Michael , Gaffling Simone , Jabari Samir , Dietrich Jana , Paulsen Friedrich
Published: March 2024

Meibomian gland dysfunction (MGD) is one of the main causes of dry eye disease. To better understand the physiological functions of human meibomian glands (MGs), the present study compared MGs with free sebaceous glands (SGs) and hair-associated SGs of humans using morphological, immunohistochemical, and liquid chromatography—mass spectrometry (LCMS)-based lipidomic approaches. Eyelids with MGs, nostrils, lips, and external auditory canals with free SGs, and scalp with hair-associated SGs of body donors were probed with antibodies against cytokeratins (CK) 1, 8, 10, and 14, stem cell markers keratin 15 and N-cadherin, cell–cell contact markers desmoglein 1 (Dsg1), desmocollin 3 (Dsc3), desmoplakin (Dp), plakoglobin (Pg), and E-cadherin, and the tight junction protein claudin 5. In addition, Oil Red O staining (ORO) was performed in cryosections. Secretions of MGs as well as of SGs of nostrils, external auditory canals, and scalps were collected from healthy volunteers, analyzed by LCMS, and the data were processed using various multivariate statistical analysis approaches. Serial sections of MGs, free SGs, and hair-associated SGs were 3D reconstructed and compared. CK1 was expressed differently in hair-associated SGs than in MGs and other free SGs. The expression levels of CK8, CK10, and CK14 in MGs were different from those in hair-associated SGs and other free SGs. KRT15 was expressed differently in hair-associated SGs, whereas N-cadherin was expressed equally in all types of glands. The cell–cell contact markers Dsg1, Dp, Dsc3, Pg, and E-cadherin revealed no differences. ORO staining showed that lipids in MGs were more highly dispersed and had larger lipid droplets than lipids in other free SGs. Hair-associated SGs had a smaller number of lipid droplets. LCMS revealed that the lipid composition of meibum was distinctively different from that of the sebum of the nostrils, external auditory canals, and scalp. The 3D reconstructions of the different glands revealed different morphologies of the SGs compared with MGs which are by far the largest type of glands. In humans, MGs differ in their morphology and secretory composition and show major differences from free and hair-associated SGs. The composition of meibum differs significantly from that of sebum from free SGs and from hair-associated SGs. Therefore, the MG can be considered as a highly specialized type of holocrine gland that exhibits all the histological characteristics of SGs, but is significantly different from them in terms of morphology and lipid composition.
Anti-Inflammatory Action of Resveratrol in the Central Nervous System in Relation to Glucose Concentration—An In Vitro Study on a Blood–Brain Barrier Model
Authors: Komorowska Justyna , Wątroba Mateusz , Bednarzak Małgorzata , Grabowska Anna D. , Szukiewicz Dariusz
Published: March 2024

Unbalanced blood glucose levels may cause inflammation within the central nervous system (CNS). This effect can be reversed by the action of a natural neuroprotective compound, resveratrol (RSV). The study aimed to investigate the anti-inflammatory effect of RSV on astrocyte cytokine profiles within an in vitro model of the blood–brain barrier (BBB) under varying glucose concentrations (2.2, 5.0, and 25.0 mmol/L), corresponding to hypo-, normo-, and hyperglycemia. The model included co-cultures of astrocytes (brain compartment, BC) and endothelial cells (microvascular compartment, MC), separated by 0.4 µm wide pores. Subsequent exposure to 0.2 μM LPS in the brain compartment (BC) and 50 μM RSV in the microvascular compartment (MC) of each well was carried out. Cytokine levels (IL-1 α, IL-1 β, IL-2, IL-4, IL-6, IL-8) in the BC were assessed using a Multi-Analyte ELISArray Kit before and after the addition of LPS and RSV. Statistical analysis was performed to determine significance levels. The results demonstrated that RSV reduced the concentration of all studied cytokines in the BC, regardless of glucose levels, with the most substantial decrease observed under normoglycemic conditions. Additionally, the concentration of RSV in the BC was highest under normoglycemic conditions compared to hypo- and hyperglycemia. These findings confirm that administration of RSV in the MC exerts anti-inflammatory effects within the BC, particularly under normoglycemia-simulating conditions. Further in vivo studies, including animal and human research, are warranted to elucidate the bioavailability of RSV within the central nervous system (CNS).
Beyond Quadruple Therapy and Current Therapeutic Strategies in Heart Failure with Reduced Ejection Fraction: Medical Therapies with Potential to Become Part of the Therapeutic Armamentarium
Authors: Kourek Christos , Briasoulis Alexandros , Papamichail Adamantia , Xanthopoulos Andrew , Tsougos Elias , Farmakis Dimitrios , Paraskevaidis Ioannis
Published: March 2024

Heart failure with reduced ejection fraction (HFrEF) is a complex clinical syndrome with significant morbidity and mortality and seems to be responsible for approximately 50% of heart failure cases and hospitalizations worldwide. First-line treatments of patients with HFrEF, according to the ESC and AHA guidelines, include β-blockers, angiotensin receptor/neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, and mineralocorticoid receptor antagonists. This quadruple therapy should be initiated during hospital stay and uptitrated to maximum doses within 6 weeks after discharge according to large multicenter controlled trials. Quadruple therapy improves survival by approximately 8 years for a 55-year-old heart failure patient. Additional therapeutic strategies targeting other signaling pathways such as ivabradine, digoxin, and isosorbide dinitrate and hydralazine combination for African Americans, as well as adjunctive symptomatic therapies, seem to be necessary in the management of HFrEF. Although second-line medications have not achieved improvements in mortality, they seem to decrease heart failure hospitalizations. There are novel medical therapies including vericiguat, omecamtiv mecarbil, genetic and cellular therapies, and mitochondria-targeted therapies. Moreover, mitraclip for significant mitral valve regurgitation, ablation in specific atrial fibrillation cases, omecamtiv mecarbil are options under evaluation in clinical trials. Finally, the HeartMate 3 magnetically levitated centrifugal left ventricular assist device (LVAD) has extended 5-year survival for stage D HF patients who are candidates for an LVAD.
PVI-Net: Point–Voxel–Image Fusion for Semantic Segmentation of Point Clouds in Large-Scale Autonomous Driving Scenarios
Authors: Wang Zongshun , Li Ce , Ma Jialin , Feng Zhiqiang , Xiao Limei
Published: March 2024

In this study, we introduce a novel framework for the semantic segmentation of point clouds in autonomous driving scenarios, termed PVI-Net. This framework uniquely integrates three different data perspectives—point clouds, voxels, and distance maps—executing feature extraction through three parallel branches. Throughout this process, we ingeniously design a point cloud–voxel cross-attention mechanism and a multi-perspective feature fusion strategy for point images. These strategies facilitate information interaction across different feature dimensions of perspectives, thereby optimizing the fusion of information from various viewpoints and significantly enhancing the overall performance of the model. The network employs a U-Net structure and residual connections, effectively merging and encoding information to improve the precision and efficiency of semantic segmentation. We validated the performance of PVI-Net on the SemanticKITTI and nuScenes datasets. The results demonstrate that PVI-Net surpasses most of the previous methods in various performance metrics.
DNA Barcoding Supports “Color-Pattern’’-Based Species of Stictochironomus from China (Diptera: Chironomidae)
Authors: Song Chao , Chen Guanyu , Wang Le , Lei Teng , Qi Xin
Published: March 2024

The genus Stictochironomus (Diptera: Chironomidae) has an almost worldwide distribution, with more than 30 species. However, species delimitation and identification based on the markings on the wings and legs are controversial and uncertain. In this study, we focused on color patterns to review the adults of the genus from China, and two new species (S. trifuscipes sp. nov. and S. quadrimaculatus sp. nov.) are described and figured. DNA barcodes can accurately separate the two new species with specific color patterns. However, heterospecific individuals form a monophyletic cluster in the phylogeny tree. For example, S. maculipennis (Meigen) and S. pictulus (Meigen), which have a lower interspecific genetic divergence, form a single clade. Sequences with the same species name but with high intraspecific distance form more than one phylogenetic clade, such as S. sticticus (Fabricius) of three clades, S. pictulus of four clades, S. akizukii (Tokunaga) and S. juncaii Qi, Shi, and Wang of two clades, might have potential cryptic species diversity. Species delimitation analysis using ASAP, PTP, and GMYC clearly delineated them as separate species. Consequently, color patterns are a good diagnostic characteristic for species delimitation in Stictochironomus. The distance-based analysis shows that a threshold of 4.5–7.7% is appropriate for species delimitation in Stictochironomus. Additionally, an updated key including color pattern variation for male adults of known Stictochironomus species from China is provided.
The Application of Radiomics and AI to Molecular Imaging for Prostate Cancer
Authors: Tapper William , Carneiro Gustavo , Mikropoulos Christos , Thomas Spencer A. , Evans Philip M. , Boussios Stergios
Published: March 2024

Molecular imaging is a key tool in the diagnosis and treatment of prostate cancer (PCa). Magnetic Resonance (MR) plays a major role in this respect with nuclear medicine imaging, particularly, Prostate-Specific Membrane Antigen-based, (PSMA-based) positron emission tomography with computed tomography (PET/CT) also playing a major role of rapidly increasing importance. Another key technology finding growing application across medicine and specifically in molecular imaging is the use of machine learning (ML) and artificial intelligence (AI). Several authoritative reviews are available of the role of MR-based molecular imaging with a sparsity of reviews of the role of PET/CT. This review will focus on the use of AI for molecular imaging for PCa. It will aim to achieve two goals: firstly, to give the reader an introduction to the AI technologies available, and secondly, to provide an overview of AI applied to PET/CT in PCa. The clinical applications include diagnosis, staging, target volume definition for treatment planning, outcome prediction and outcome monitoring. ML and AL techniques discussed include radiomics, convolutional neural networks (CNN), generative adversarial networks (GAN) and training methods: supervised, unsupervised and semi-supervised learning.
Deinstitutionalization as Reparative Justice: A Commentary on the Guidelines on Deinstitutionalization, including in Emergencies
Authors: Minkowitz Tina
Published: March 2024

In this paper, I argue that the Committee on the Rights of Persons with Disabilities Guidelines on Deinstitutionalization, Including in Emergencies function as an instrument and template for reparative justice towards persons still in institutions and survivors of institutionalization. The Guidelines construct deinstitutionalization as a reparative process at both the systemic and individual levels, as well as calling for the creation of reparation and redress mechanisms. I examine the entire body of the Guidelines, highlight their reparative content, and point out where the text may fall short of this perspective and how the shortcomings might be remedied. This paper is grounded in the situation of psychiatric institutionalization and the concerns of people subjected to that system, emphasizing issues faced by this constituency and its human rights concerns for redress and legal and societal change. The issues addressed include the following: the strengthening of normative standards with regard to the abolition of psychiatric institutionalization and forced interventions and the obligation to immediately end these violations; a policy shift towards the de-medicalization of psychosocial disability; the implications of reparative justice in diminishing the role and authority of those that have operated institutions including the mental health system; the role of adult persons with disabilities as members of families and the role played by some family members in institutionalization; issues to be considered in designing reparations processes and mechanisms. Following some introductory remarks, this paper is structured to follow the outline of the Guidelines, quoting the text with interspersed comments and ending with a brief conclusion.
Electrical and Electro-Thermal Characteristics of (Carbon Black-Graphite)/LLDPE Composites with PTC Effect
Authors: Lungulescu Eduard-Marius , Stancu Cristina , Setnescu Radu , Notingher Petru V. , Badea Teodor-Adrian
Published: March 2024

Electrical properties and electro-thermal behavior were studied in composites with carbon black (CB) or hybrid filler (CB and graphite) and a matrix of linear low-density polyethylene (LLDPE). LLDPE, a (co)polymer with low crystallinity but with high structural regularity, was less studied for Positive Temperature Coefficient (PTC) applications, but it would be of interest due to its higher flexibility as compared to HDPE. Structural characterization by scanning electron microscopy (SEM) confirmed a segregated structure resulted from preparation by solid state powder mixing followed by hot molding. Direct current (DC) conductivity measurements resulted in a percolation threshold of around 8% (w) for CB/LLDPE composites. Increased filler concentrations resulted in increased alternating current (AC) conductivity, electrical permittivity and loss factor. Resistivity-temperature curves indicate the dependence of the temperature at which the maximum of resistivity is reached (Tmax(R)) on the filler concentration, as well as a differentiation in the Tmax(R) from the crystalline transition temperatures determined by DSC. These results suggest that crystallinity is not the only determining factor of the PTC mechanism in this case. This behavior is different from similar high-crystallinity composites, and suggests a specific interaction between the conductive filler and the polymeric matrix. A strong dependence of the PTC effect on filler concentration and an optimal concentration range between 14 and 19% were also found. Graphite has a beneficial effect not only on conductivity, but also on PTC behavior. Temperature vs. time experiments, revealed good temperature self-regulation properties and current and voltage limitation, and irrespective of the applied voltage and composite type, the equilibrium superficial temperature did not exceed 80 °C, while the equilibrium current traversing the sample dropped from 22 mA at 35 V to 5 mA at 150 V, proving the limitation capacities of these materials. The concentration effects revealed in this work could open new perspectives for the compositional control of both the self-limiting and interrupting properties for various low-temperature applications.
One-Step Synthesis of TiO2/SiO2-np Nanocomposite Photocatalytic Multilayer Films: Effect of Incorporation Time Sequences of SiO2 Nanoparticles during the TiO2 Film Growth
Authors: Lai Shutong , Aubry Eric , Sublemontier Olivier , Briois Pascal
Published: March 2024

In this article, the TiO2/SiO2-np nanocomposite multilayer films were synthesized in a single step by reactive magnetron sputtering combined with a nanoparticle aerosol jet. The SiO2 nanoparticles (SiO2-np) were introduced into a growing TiO2 thin film with different time sequences during deposition for a fixed duration. The SiO2-np acting as impurities are introduced into the TiO2 to willingly disturb its growth and to cause growth defects in order to increase the specific surface area of the photocatalytic film. In reason of the non-photoactive properties of the SiO2 nanoparticles, their introduction allows us to study only the effects induced on the film morphology, microstructure, and photocatalytic properties by their incorporation. The fractographies and topographies reveal strong changes in the morphologies depending on the time sequence of the nanoparticle introduction in the thin films. The introduction of SiO2-np from the beginning of the TiO2 film growth leads to the formation of high and large growth defects resulting in a highly diffusive surface. In addition, XRD analysis shows that the crystallite size tends to decrease as the composite film layer gets closer to the surface. Their photocatalytic performance is obtained by following the degradation of orange G dye under UV-visible irradiation. The photocatalytic performance is not only related to the specific surface area of the catalyst film, and the coverage of the photoactive phase on the surface, but also to the crystal quality of the photoactive phase. Furthermore, the samples exhibit good photostability, maintaining the same activity after four degradation cycles. In the specific case of TiO2/SiO2-np, it is demonstrated that the introduction of the nanoparticles only at the beginning of the film growth is more efficient than a continuous introduction. This result suggests that this original process allows the use of a relevant strategy for the nanoparticle introduction according to the required functionality.
Freeze–Thaw Damage Characterization of Cement-Stabilized Crushed Stone Base with Skeleton Dense Gradation
Authors: Xiao Rui , An Baoping , Wu Fei , Wang Wensheng , Sui Yi , Wang Yinghan
Published: March 2024

The skeleton dense graded cement-stabilized crushed stone base is a widely used material for road construction. However, this material is susceptible to freeze–thaw damage, which can lead to degradation and failure, for which there is still a lack of an in-depth understanding of the freeze–thaw damage characteristics. This study aims to assess the mechanical performance and the freeze–thaw damage characteristics of the cement-stabilized crushed stone base with skeleton dense gradation based on a mechanical test and acoustic technology in a laboratory. There is a gradually increasing trend in the mass loss rate of the base material with an increase in freeze–thaw cycles. The curve steepens significantly after 15 cycles, following a parabola-fitting pattern relationship. The compressive strength of the cement-stabilized crushed stone base also decreased with a parabola-fitting pattern, and the decrease rate may accelerate as the freeze–thaw cycles increase. The resilience modulus of the base material decreased with increasing freeze–thaw cycles, following a parabolic trend. This suggests that the material’s resistance to freeze–thaw damage decreases with increasing cycles. The ultrasonic wave velocity decreased with increasing freeze–thaw cycles, exhibiting a parabolic trend. This decline can be attributed to microcracks and defects developing within the material, offering insights for monitoring and predicting its service life. The damage progression of the cement-stabilized crushed stone base was found to occur in three stages: initial, stationary, and failure. The duration of stage I increased with freeze–thaw cycles, while the duration of stage III decreased. The findings provide valuable insights into the mechanisms and processes of freeze–thaw damage in a cement-stabilized crushed stone base with skeleton dense gradation.
Thermogravimetric/Thermal–Mass Spectroscopy Insight into Oxidation Propensity of Various Mechanochemically Made Kesterite Cu2ZnSnS4 Nanopowders
Authors: Lejda Katarzyna , Partyka Janusz , Janik Jerzy F.
Published: March 2024

Thermogravimetry coupled with thermal analysis and quadrupole mass spectroscopy TGA/DTA-QMS were primarily used to assess the oxidation susceptibility of a pool of nanocrystalline powders of the semiconductor kesterite Cu2ZnSnS4 for prospective photovoltaic applications, which were prepared via the mechanochemically assisted synthesis route from two different precursor systems. Each system, as confirmed by XRD patterns, yielded first the cubic polytype of kesterite with defunct semiconductor properties, which, after thermal annealing at 500 °C under neutral gas atmosphere, was converted to the tetragonal semiconductor polytype. The TGA/DTA-QMS determinations up to 1000 °C were carried out under a neutral argon Ar atmosphere and under a dry, oxygen-containing gas mixture of O2:Ar = 1:4 (vol.). The mass spectroscopy data confirmed that under each of the gas atmospheres, a distinctly different, multistep evolution of such oxygen-bearing gaseous compounds as sulfur oxides SO2/SO3, carbon dioxide CO2, and water vapor H2O was taking place. The TGA/DTA changes in correlation with the nature of evolving gases helped in the elucidation of the plausible chemistry linked to kesterite oxidation, both in the stage of nanopowder synthesis/storage at ambient air conditions and during forced oxidation up to 1000 °C in the dry, oxygen-containing gas mixture.
Higher C-Reactive Protein to Albumin Ratio Portends Long-Term Mortality in Patients with Chronic Heart Failure and Reduced Ejection Fraction
Authors: Tanık Veysel Ozan , Akdeniz Evliya , Çınar Tufan , Şimşek Barış , İnan Duygu , Kıvrak Ahmet , Karabağ Yavuz , Çağdaş Metin , Kalkan Kamuran , Karabay Can Yücel , Özlek Bülent
Published: March 2024

Background and Objectives: In this study, we aimed to investigate the prognostic value of the C-reactive protein to albumin ratio (CAR) for all-cause mortality in patients with chronic heart failure with reduced ejection fraction (HFrEF). Materials and Methods: In total, 404 chronic HFrEF patients were included in this observational and retrospective study. The CAR value of each patient included in this analysis was calculated. We stratified the study population into tertiles (T1, T2, and T3) according to CAR values. The primary outcome of the analysis was to determine all-cause mortality. Results: The median follow-up period in our study was 30 months. In the follow-up, 162 (40%) patients died. The median value of CAR was higher in patients who did not survive during the follow-up [6.7 (IQR = 1.6–20.4) vs. 0.6 (IQR = 0.1–2.6), p < 0.001]. In addition, patients in the T3 tertile (patients with the highest CAR) had a higher rate of all-cause mortality [n = 90 cases (66.2%), p < 0.001]. Multivariate Cox regression analysis revealed that CAR was an independent predictor of mortality in patients with HFrEF (hazard ratio: 1.852, 95% confidence interval: 1.124–2.581, p = 0.005). In a receiver operating characteristic curve analysis, the optimal cut-off value of CAR was >2.78, with a sensitivity of 66.7% and specificity of 76%. Furthermore, older age, elevated N-terminal pro-brain natriuretic peptide levels, and absence of a cardiac device were also independently associated with all-cause death in HFrEF patients after 2.5 years of follow-up. Conclusions: The present study revealed that CAR independently predicts long-term mortality in chronic HFrEF patients. CAR may be used to predict mortality among these patients as a simple and easily obtainable inflammatory marker.
Machine Learning to Predict Enzyme–Substrate Interactions in Elucidation of Synthesis Pathways: A Review
Authors: Salas-Nuñez Luis F. , Barrera-Ocampo Alvaro , Caicedo Paola A. , Cortes Natalie , Osorio Edison H. , Villegas-Torres Maria F. , González Barrios Andres F.
Published: March 2024

Enzyme–substrate interactions play a fundamental role in elucidating synthesis pathways and synthetic biology, as they allow for the understanding of important aspects of a reaction. Establishing the interaction experimentally is a slow and costly process, which is why this problem has been addressed using computational methods such as molecular dynamics, molecular docking, and Monte Carlo simulations. Nevertheless, this type of method tends to be computationally slow when dealing with a large search space. Therefore, in recent years, methods based on artificial intelligence, such as support vector machines, neural networks, or decision trees, have been implemented, significantly reducing the computing time and covering vast search spaces. These methods significantly reduce the computation time and cover broad search spaces, rapidly reducing the number of interacting candidates, as they allow repetitive processes to be automated and patterns to be extracted, are adaptable, and have the capacity to handle large amounts of data. This article analyzes these artificial intelligence-based approaches, presenting their common structure, advantages, disadvantages, limitations, challenges, and future perspectives.
Fabrication of a Microfluidic Test Device with a 3D Printer and Its Combination with the Loop Mediated Isothermal Amplification Method to Detect Streptococcus pyogenes
Authors: Kirkoyun Uysal Hayriye , Eryildiz Meltem , Demirci Mehmet
Published: March 2024

New rapid, reliable, and cost-effective alternative systems are needed for the rapid diagnosis of Streptococcus pyogenes. The aim of this study was to fabricate a microfluidic test device to detect Streptococcus pyogenes by combining the Loop-mediated isothermal amplification method via a 3D printer. Microfluidic test devices were designed in CATIA V5 Release 16 software, and data were directly transferred to a 3D printer and produced using the FDM method with biocompatible PLA filament. The S. pyogenes ATCC 19615 and different ATCC strains was used. Following identification by classical culture methods, a 0.5 McFarland suspension was prepared from the colonies, and DNA isolation was performed from this liquid by a boiling method. S. pyogenes specific speB gene was used to desing LAMP primer sets in PrimerExplorer V5 software and tested on a microfluidic device. LAMP reactions were performed on microfluidic device and on a microcentrifuge tube separately. Both results were analyzed using the culture method as the standard method to diagnostic values. Melting curve analysis of the amplicons of the LAMP reactions performed on a LightCycler 480 system to detect amplification. Among the 50 positive and 100 negative samples, only four samples were found to be false negative by LAMP reaction in a microcentrifuge tube, while eight samples were found to be false negative by LAMP reaction on a microfluidic device. Six samples were found to be false positive by the LAMP reaction in the microcentrifuge tube, while ten samples were found to be false positive by the LAMP reaction on a microfluidic chip. The sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP reactions performed in the microcentrifuge tube and on the microfluidic device were 92–84%, 94–90%, 88.46–80.77%, and 95.92–91.84%, respectively. The limit of detection (LOD) was found to be the same as 1.5 × 102 CFU/mL and the limit of quantification (LOQ) values of the LAMP reactions were performed on the microcentrifuge tube and on the microfluidic device were 2.46 × 102–7.4 × 102 CFU/mL, respectively. Cohen’s kappa (κ) values of the LAMP reactions were performed on the microcentrifuge tube and on the microfluidic device were 0.620–0.705, respectively. In conclusion, our data showed that the LAMP method can be combined with microfluidic test device to detect S. pyogenes, this microfluidic device can be manufactured using 3D printers and results are close to gold standard methods. These devices can be combined with LAMP reactions to detect different pathogens where resources are limited and rapid results are required.
Regioselectively Carboxylated Cellulose Nanofibril Models from Dissolving Pulp: C6 via TEMPO Oxidation and C2,C3 via Periodate–Chlorite Oxidation
Authors: Guo Mengzhe , Ede James D. , Sayes Christie M. , Shatkin Jo Anne , Stark Nicole , Hsieh You-Lo
Published: March 2024

Regioselective C6 and C2,C3 carboxylated cellulose nanofibrils (CNFs) have been robustly generated from dissolving pulp, a readily available source of unmodified cellulose, via stoichiometrically optimized 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO)-mediated and sequential sodium periodate-sodium chlorite (PC) oxidation coupled with high-speed blending. Both regioselectively optimized carboxylated CNF series possess the widest ranges of comparable charges (0.72–1.48 mmol/g for T-CNFs vs. 0.72–1.10 mmol/g for PC-CNFs), but similar ranges of thickness (1.3–2.4 nm for T-CNF, 1.8–2.7 nm PC-CNF), widths (4.6–6.6 nm T-CNF, 5.5–5.9 nm PC-CNF), and lengths (254–481 nm T-CNF, 247–442 nm PC-CNF). TEMPO-mediated oxidation is milder and one-pot, thus more time and process efficient, whereas the sequential periodate–chlorite oxidation produces C2,C3 dialdehyde intermediates that are amenable to further chemical functionalization or post-reactions. These two well-characterized regioselectively carboxylated CNF series represent coherent cellulose nanomaterial models from a single woody source and have served as references for their safety study toward the development of a safer-by-design substance evaluation tool.
Effect of Aromatic Herbs and Spices Present in the Mediterranean Diet on the Glycemic Profile in Type 2 Diabetes Subjects: A Systematic Review and Meta-Analysis
Authors: Garza María Carmen , Pérez-Calahorra Sofía , Rodrigo-Carbó Carmen , Sánchez-Calavera María Antonia , Jarauta Estíbaliz , Mateo-Gallego Rocío , Gracia-Rubio Irene , Lamiquiz-Moneo Itziar
Published: March 2024

Background: The Mediterranean Diet (MedDiet) is the dietary pattern par excellence for managing and preventing metabolic diseases, such as Type 2 Diabetes (T2DM). The MedDiet incorporates spices and aromatic herbs, which are abundant sources of bioactive compounds. The aim of this study was to analyze the effect of all aromatic herbs and spices included in the MedDiet, such as black cumin, clove, parsley, saffron, thyme, ginger, black pepper, rosemary, turmeric, basil, oregano, and cinnamon, on the glycemic profile in T2DM subjects. Methods: PubMed, Web of Science, and Scopus databases were searched for interventional studies investigating the effect of these aromatic herbs and spices on the glycemic profile in T2DM subjects. Results: This systematic review retrieved 6958 studies, of which 77 were included in the qualitative synthesis and 45 were included in the meta-analysis. Our results showed that cinnamon, turmeric, ginger, black cumin, and saffron significantly improved the fasting glucose levels in T2DM subjects. The most significant decreases in fasting glucose were achieved after supplementation with black cumin, followed by cinnamon and ginger, which achieved a decrease of between 27 and 17 mg/dL. Conclusions: Only ginger and black cumin reported a significant improvement in glycated hemoglobin, and only cinnamon and ginger showed a significant decrease in insulin.
A Comparative Review of Key Isothiocyanates and Their Health Benefits
Authors: Olayanju Julia B. , Bozic Dragica , Naidoo Uma , Sadik Omowunmi A.
Published: March 2024

Isothiocyanates are biologically active products resulting from the hydrolysis of glucosinolates predominantly present in cruciferous vegetables belonging to the Brassicaceae family. Numerous studies have demonstrated the diverse bioactivities of various isothiocyanates, encompassing anticarcinogenic, anti-inflammatory, and antioxidative properties. Nature harbors distinct isothiocyanate precursors, glucosinolates such as glucoraphanin and gluconastrin, each characterized by unique structures, physical properties, and pharmacological potentials. This comprehensive review aims to consolidate the current understanding of Moringa isothiocyanates, mainly 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate), comparing this compound with other well-studied isothiocyanates such as sulforaphane and phenyl ethyl isothiocyanates. The focus is directed toward elucidating differences and similarities in the efficacy of these compounds as agents with anticancer, anti-inflammatory, and antioxidative properties.
Opposing Effects of Nutritional Supply on Bone Health at Different Ages: Based on the National Health and Nutrition Examination Survey Database
Authors: Wei Jieqiong , Zhang Yaxi , Yuan Yuehan , Li Min , Zhai Bingfang , Chen Jihua
Published: March 2024

(1) Background: Nutrients play an essential role in bone health, whether in achieving peak bone mineral density (BMD) or maintaining bone health. This study explores the relationship between nutrient supply and femoral bone health at different ages. (2) Methods: A total of 5603 participants meeting the inclusion and exclusion criteria were included in this study using the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2010, 2013 to 2014, and 2017 to 2018. Femoral bone mineral density and bone status were dependent variables, and dietary nutrient intake and nutrient intake status were independent variables. The relationship between dietary nutrient intake and bone mineral density was explored, and the importance of nutrients affecting bone status was analyzed through a neural network model. At the same time, we investigated the relationship between nutrient intake and bone status. (3) Results: The peak of age and femoral bone mineral density appeared at 20 years old in our study. After grouping by age, logistic regression analysis showed that before 20 years old, without adjusting other variables, high-fat diet was more likely to have normal bone mass than appropriate fat diet (OR: 4.173, 95%CI: 1.007–17.289). After adjusting for all demographic factors, niacin intake (OR: 1.062, 95%CI: 1.019–1.108) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.627, 95%CI: 0.408–0.965) was not. After 20 years old, after adjusting for carbohydrate, protein, vitamin B6, niacin, dietary fat, vitamin B2, and vitamin B12, vitamin B2 intake (OR: 1.153, 95%CI: 1.04–1.278) was beneficial for normal bone mass, while vitamin B6 intake (OR: 0.842, 95%CI: 0.726–0.976) was not. After adjusting for all confounding factors, vitamin B2 intake (OR: 1.288, 95%CI: 1.102–1.506) was beneficial for normal bone mass. In addition, we found that even if there was no statistical significance, the effects of high-fat diet on bone mass were different at different ages. (4) Conclusions: By conducting an in-depth analysis of the NHANES database, this study reveals that dietary factors exert divergent effects on bone health across different age groups, implying the necessity of implementing tailored dietary strategies to maintain optimal bone health at distinct life stages.
How to Suppress Mineral Loss and Stimulate Anabolism in Postmenopausal Bones with Appropriate Timing of Exercise and Nutrients
Authors: Borer Katarina T.
Published: March 2024

Background. Bone Health and Osteoporosis Foundation (BHOF) reports that as of 2023, approximately 10 million of older Americans have osteoporosis and another 44 million have low bone density. Osteoporosis is a serious handicap for the elderly and, in particular, for estrogen-deficient postmenopausal women, as it increases the risk of debilitating bone weakness and fractures. The BHOF recommendations for prevention of osteopenia, osteoporosis and bone fractures are to perform weight-bearing and muscle-strengthening exercises and to take recommended amounts of daily calcium and vitamin D. Methods. The purpose of this review is to describe and discuss recent evidence-based research on how to effectively utilize timing of exercise and calorie intake for stimulation of postmenopausal bone anabolism, and to provide this new information in the form of specific and actionable recommendations. Results. The five evidence-based recommendations are as follows: 1. Select an appropriate circadian time of day for exercise; 2. Increase walking speed to raise the movement momentum; 3. Eat a weight-maintenance meal one or two hours before the exercise bout; 4. Sustain the duration of walking activity (impulse) for 40 to 45 min; and 5. Repeat effective exercise stimulus 7 to 8 h after the first one to double the anabolic effect. Osteogenesis can also be increased with subthreshold mechanical loading, where needed, under several special circumstances. Conclusions. This review should provide pragmatic actionable pointers on how to utilize the idiosyncratic bone responsiveness to timing of movement and meals to prevent osteoporosis and encourage research toward a better understanding of how bone detects adequacy of a mechanical stimulus and determines duration of necessary rest to recover its sensitivity to mechanical stimulation and nutrients.
Circadian Syndrome Is Associated with Dietary Patterns among Middle-Older Americans: The Health and Retirement Study
Authors: Aljahdali Abeer Ali , Shi Zumin
Published: March 2024

Population aging is a global demographic characteristic of the 21st century, and healthy eating is a core component of healthy aging. However, limited evidence is available among older adults for associations between diet quality and circadian syndrome (CircS). Thus, this study examined associations between dietary patterns and CircS among a representative sample of middle-older adults in the US. The sample comprised middle-older adults enrolled in the 2016 core wave of the Health and Retirement Study (HRS) and one of its sub-studies, the 2013 Health Care and Nutrition Study (HCNS). A food frequency questionnaire was used to quantify habitual food intake and identify dietary patterns using a factor analysis. CircS was defined based on the existence of ≥4 components of metabolic syndrome and indicators of sleep disorders and depression. A total of 4253 middle-older adults with a mean age (SD) of 65.4 (10.0) years were included in the study. The prevalence of CircS was 35.9%. Comparing extreme quartiles of the “Prudent Pattern”, the odds ratio (95% CI) for CircS was 0.72 (0.55–0.94), and it was 1.47 (1.10–1.95) for the “Western Pattern”. The “Western Pattern” was positively associated while the “Prudent Pattern” was inversely associated with the odds of CircS among middle-older adults.
The Influence of High-Dose Parenteral Vitamin C on the Incidence and Severity of Postoperative Pulmonary Complications in Cardiac Surgery with Extracorporeal Circulation: A Randomized Controlled Trial
Authors: Karadžić Kočica Milica , Ristić Arsen , Soldatović Ivan , Lazović Dejan , Čumić Jelena , Grujić Miloš , Karan Radmila , Terzić Duško , Palibrk Ivan , Kočica Mladen , Marković Dejan
Published: March 2024

Cardiac surgery (CS) with extracorporeal circulation (ECC), induces intense oxidative stress (OS) and systemic inflammatory response (SIR), which may seriously affect postoperative lung function. We aimed to test if high parenteral (200 mg/kg/24 h) daily doses of Vitamin C (VitC), given within 48 h after the beginning of the operation, may reduce the incidence and severity of postoperative pulmonary complications (PPCs) in CS patients. This single-center, prospective, randomized, single-blinded, interventional trial included 150 patients, assigned to control Group A (n = 75) and interventional Group B (n = 75). Group B intraoperatively received one-fourth (i.e., 50 mg/kg) of the planned daily Vit C dose, divided into three equal parts and diluted in 10 mL of normal saline, while Group A received an equal volume of normal saline at the same time frames (i.e., the induction of anesthesia, aortic cross-clamp release, and sternal closure). After 6 h from the first intraoperative dose, the following regimen was applied: Group B: 50 mg/kg, 30 min i.v. infusion of VitC in 50 mL of normal saline, every 6 h, for the next 48 h, and Group A: 30 min i.v. infusion of an equal volume of normal saline every 6 h, for the next 48 h. Modified Kroenke’s score was used to determine the incidence and severity of PPCs. The overall incidence of PPCs was 36.7% and was significantly lower in Group B (13.3% vs. 60.0%, p < 0.001). The PPCs severity score was also significantly lower in Group B (1 vs. 3, p < 0.001). In addition, patients from Group B had significantly less damaged lungs, better postoperative renal function, shorter ICU stays, fewer ICU re-admissions, and lower hospital mortality. No VitC-related adverse effects were recorded. High parenteral daily VitC doses given within 48 h after the beginning of CS are safe and effective in reducing the incidence and severity of PPCs. A multicenter RCT is needed to confirm these results.
Application of Liquid Chromatography Coupled to Mass Spectrometry for Direct Estimation of the Total Levels of Adenosine and Its Catabolites in Human Blood
Authors: Šofranko Jakub , Mitro Peter , Lazúrová Zora , Péč Martin Jozef , Bolek Tomáš , Péčová Renata , Dohál Matúš , Samoš Matej , Murín Radovan
Published: March 2024

Adenosine is a multifunctional nucleoside with several roles across various levels in organisms. Beyond its intracellular involvement in cellular metabolism, extracellular adenosine potently influences both physiological and pathological processes. In relation to its blood level, adenosine impacts the cardiovascular system, such as heart beat rate and vasodilation. To exploit the adenosine levels in the blood, we employed the liquid chromatography method coupled with mass spectrometry (LC–MS). Immediately after collection, a blood sample mixed with acetonitrile solution that is either enriched with 13C-labeled adenosine or a newly generated mixture is transferred into the tubes containing the defined amount of 13C-labeled adenosine. The 13C-enriched isotopic adenosine is used as an internal standard, allowing for more accurate quantification of adenosine. This novel protocol for LC–MS-based estimation of adenosine delivers a rapid, highly sensitive, and reproducible means for quantitative estimation of total adenosine in blood. The method also allows for quantification of a few catabolites of adenosine, i.e., inosine, hypoxanthine, and xanthine. Our current setup did not allow for the detection or quantifying of uric acid, which is the final product of adenosine catabolism. This advancement provides an analytical tool that has the potential to enhance our understanding of adenosine’s systemic impact and pave the way for further investigations into its intricate regulatory mechanisms.
Acheta domesticus: A Natural Source of Anti-Skin-Aging Ingredients for Cosmetic Applications
Authors: Yeerong Kankanit , Chantawannakul Panuwan , Anuchapreeda Songyot , Rades Thomas , Müllertz Anette , Chaiyana Wantida
Published: March 2024

Acheta domesticus is an edible insect, rich in nutritional value and considered a sustainable protein source. This study aimed to investigate the potential application of A. domesticus extracts for anti-skin-aging purposes. The extracts were prepared by maceration at ambient temperature with 95% ethanol or hexane and maceration in gentle heat (45 °C) with 95% v/v ethanol or DI water. The extracts were examined for total protein, phenolic, and flavonoid contents. Protein molecular weight distribution was analyzed. The safety of the extracts was investigated in terms of irritation and cytotoxicity. Biological activities relevant to the inhibition of skin aging were evaluated, including increasing transforming growth factor-beta 1 (TGF-β1) expression and inhibitory activities on collagenase and hyaluronidase. The aqueous extract from maceration in gentle heat had the highest total protein content (63 ± 1% w/w), total phenolic content (0.48 ± 0.03 mg GAE/g extract), TGF-β1 stimulating activities (33 ± 2 pg/mL), and collagenase inhibition (with a half maximal inhibitory concentration of 26 ± 1 µg/mL) among various extracts investigated. It caused no irritation to the hen’s egg chorioallantoic membrane and showed no cytotoxicity to human dermal fibroblasts and peripheral blood mononuclear cells. Therefore, aqueous A. domesticus extract is proposed as an innovative natural anti-skin-aging ingredient.
Gut Microbiota Metabolites: Unveiling Their Role in Inflammatory Bowel Diseases and Fibrosis
Authors: Bernardi Francesca , D’Amico Ferdinando , Bencardino Sarah , Faggiani Ilaria , Fanizza Jacopo , Zilli Alessandra , Parigi Tommaso Lorenzo , Allocca Mariangela , Danese Silvio , Furfaro Federica
Published: March 2024

In recent years, there has been a growing focus on the intricate interplay between the gut microbiota and host health, specifically in the context of inflammatory bowel diseases (IBDs). The gut microbiota produces a diverse array of metabolites, influencing the host’s immune response and tissue homeostasis. Noteworthy metabolites, such as short-chain fatty acids, bile acids, and indoles, exert significant effects on intestinal inflammation and fibrosis. This review integrates current research findings to clarify the mechanisms through which gut microbiota metabolites contribute to the progression of IBD and fibrosis, offering insights into potential therapeutic targets and strategies for managing these intricate gastrointestinal conditions. The unraveling of the complex relationship between gut microbiota metabolites and inflammatory processes holds promise for the development of targeted interventions that could lead to more effective and personalized treatment approaches for individuals affected by IBD and subsequent intestinal fibrosis.
Anti-Cholinergic Effects of the Phenolic Extract from the Astragalus crenatus Plant: A Computational and Network Pharmacology Study
Authors: Lekmine Sabrina , Benslama Ouided , Tahraoui Hichem , Ola Mohammad Shamsul , Laouani Aicha , Kadi Kenza , Martín-García Antonio Ignacio , Ali Ahmad
Published: March 2024

Investigations into cholinesterase inhibition have received attention from researchers in recent years for the treatment of Alzheimer’s disease. Cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), hold pivotal significance in Alzheimer’s disease (AD) treatment. In this study, we utilized the ethanolic extract of Astragalus crenatus followed by liquid chromatography–electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to separate and identify at least 21 compounds in the extract. Rosmarinic acid exhibited the highest concentration (96.675 ± 1.3 mg/g extract), succeeded by hesperidin (79.613 ± 1.2 mg/g extract), hesperetin (75.102 ± 1.4 mg/g extract), rutin (68.156 ± 1.6 mg/g extract), chlorogenic acid (67.645 ± 1.5 mg/g extract), fisetin (66.647 ± 2.3 mg/g extract), and hyperoside (63.173 ± 1.5 mg/g extract). A. crenatus extract efficiently inhibited both AChE and BChE activities in a dosage-dependent manner. Molecular docking was employed to scrutinize the anticholinesterase mechanisms of the identified phytocompounds. Notably, a network pharmacology analysis was executed for the most efficacious compound. Based on binding energies, hesperidin emerged as the most potent inhibitor against both AChE and BChE, exhibiting scores of −10.5 Kcal/mol and −9.8 Kcal/mol, respectively. Due to its dual inhibition of AChE and BChE activities, hesperidin from Astragalus crenatus holds promise for the development of novel therapeutics aimed at neurological disorders, particularly AD.