bluuebunny/crossref_metadata_2025 huggingface dataset:
The Acute Antiallodynic Effect of Tolperisone in Rat Neuropathic Pain and Evaluation of Its Mechanism of Action
Authors: Lakatos Péter P. , Karádi Dávid Árpád , Galambos Anna Rita , Essmat Nariman , Király Kornél , Laufer Rudolf , Geda Orsolya , Zádori Zoltán S. , Tábi Tamás , Al-Khrasani Mahmoud , Szökő Éva
Published: August 2022

Current treatment approaches to manage neuropathic pain have a slow onset and their use is largely hampered by side-effects, thus there is a significant need for finding new medications. Tolperisone, a centrally acting muscle relaxant with a favorable side effect profile, has been reported to affect ion channels, which are targets for current first-line medications in neuropathic pain. Our aim was to explore its antinociceptive potency in rats developing neuropathic pain evoked by partial sciatic nerve ligation and the mechanisms involved. Acute oral tolperisone restores both the decreased paw pressure threshold and the elevated glutamate level in cerebrospinal fluid in neuropathic rats. These effects were comparable to those of pregabalin, a first-line medication in neuropathy. Tolperisone also inhibits release of glutamate from rat brain synaptosomes primarily by blockade of voltage-dependent sodium channels, although inhibition of calcium channels may also be involved at higher concentrations. However, pregabalin fails to affect glutamate release under our present conditions, indicating a different mechanism of action. These results lay the foundation of the avenue for repurposing tolperisone as an analgesic drug to relieve neuropathic pain.
Curcumin Sensitises Cancerous Kidney Cells to TRAIL Induced Apoptosis via Let-7C Mediated Deregulation of Cell Cycle Proteins and Cellular Metabolism
Authors: Obaidi Ismael , Blanco Fernández Alfonso , McMorrow Tara
Published: August 2022

Targeted therapies are the most attractive options in the treatment of different tumours, including kidney cancers. Such therapies have entered a golden era due to advancements in research, breakthroughs in scientific knowledge, and a better understanding of cancer therapy mechanisms, which significantly improve the survival rates and life expectancy of patients. The use of tumour necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) as an anticancer therapy has attracted the attention of the scientific community and created great excitement due to its selectivity in targeting cancerous cells with no toxic impacts on normal tissues. However, clinical studies disappointingly showed the emergence of resistance against TRAIL. This study aimed to employ curcumin to sensitise TRAIL-resistant kidney cancerous ACHN cells, as well as to gain insight into the molecular mechanisms of TRAIL sensitization. Curcumin deregulated the expression of apoptosis-regulating micro Ribonucleic Acid (miRNAs), most notably, let-7C. Transfecting ACHN cells with a let-7C antagomir significantly increased the expression of several cell cycle protein, namely beta (β)-catenin, cyclin dependent kinase (CDK)1/2/4/6 and cyclin B/D. Further, it overexpressed the expression of the two key glycolysis regulating proteins including hypoxia-inducible factor 1-alpha (HIF-1α) and pyruvate dehydrogenase kinase 1 (PDK1). Curcumin also suppressed the expression of the overexpressed proteins when added to the antagomir transfected cells. Overall, curcumin targeted ACHN cell cycle and cellular metabolism by promoting the differential expression of let-7C. To the best of our knowledge, this is the first study to mechanistically report the cancer chemosensitisation potential of curcumin in kidney cancer cells via induction of let-7C.
Information Theory as an Experimental Tool for Integrating Disparate Biophysical Signaling Modules
Authors: McMillen Patrick , Walker Sara I. , Levin Michael
Published: August 2022

There is a growing appreciation in the fields of cell biology and developmental biology that cells collectively process information in time and space. While many powerful molecular tools exist to observe biophysical dynamics, biologists must find ways to quantitatively understand these phenomena at the systems level. Here, we present a guide for the application of well-established information theory metrics to biological datasets and explain these metrics using examples from cell, developmental and regenerative biology. We introduce a novel computational tool named after its intended purpose, calcium imaging, (CAIM) for simple, rigorous application of these metrics to time series datasets. Finally, we use CAIM to study calcium and cytoskeletal actin information flow patterns between Xenopus laevis embryonic animal cap stem cells. The tools that we present here should enable biologists to apply information theory to develop a systems-level understanding of information processing across a diverse array of experimental systems.
Histone Deacetylases Cooperate with NF-κB to Support the Immediate Migratory Response after Zebrafish Pronephros Injury
Authors: Zhuang Mingyue , Scholz Alexander , Walz Gerd , Yakulov Toma Antonov
Published: August 2022

Acute kidney injury (AKI) is commonly associated with severe human diseases, and often worsens the outcome in hospitalized patients. The mammalian kidney has the ability to recover spontaneously from AKI; however, little progress has been made in the development of supportive treatments. Increasing evidence suggest that histone deacetylases (HDAC) and NF-κB promote the pathogenesis of AKI, and inhibition of Hdac activity has a protective effect in murine models of AKI. However, the role of HDAC at the early stages of recovery is unknown. We used the zebrafish pronephros model to study the role of epigenetic modifiers in the immediate repair response after injury to the tubular epithelium. Using specific inhibitors, we found that the histone deacetylase Hdac2, Hdac6, and Hdac8 activities are required for the repair via collective cell migration. We found that hdac6, hdac8, and nfkbiaa expression levels were upregulated in the repairing epithelial cells shortly after injury. Depletion of hdac6, hdac8, or nfkbiaa with morpholino oligonucleotides impaired the repair process, whereas the combined depletion of all three genes synergistically suppressed the recovery process. Furthermore, time-lapse video microscopy revealed that the lamellipodia and filopodia formation in the flanking cells was strongly reduced in hdac6-depleted embryos. Our findings suggest that Hdac activity and NF-κB are synergistically required for the immediate repair response in the zebrafish pronephros model of AKI, and the timing of HDAC inhibition might be important in developing supportive protocols in the human disease.
Insulin-like Growth Factor 2 (IGF-2) and Insulin-like Growth Factor Binding Protein 7 (IGFBP-7) Are Upregulated after Atypical Antipsychotics in Spanish Schizophrenia Patients
Authors: Fernández-Pereira Carlos , Penedo Maria Aránzazu , Rivera-Baltanas Tania , Fernández-Martínez Rafael , Ortolano Saida , Olivares José Manuel , Agís-Balboa Roberto Carlos
Published: August 2022

Insulin-like growth factor 2 (IGF-2) and IGF binding protein 7 (IGFBP-7) have been related to schizophrenia (SZ) due to their implication in neurodevelopment. The purpose of this study was to assess whether the alterations in IGF-2 and IGFBP-7 in SZ patients are intrinsically related to the psychiatric disorder itself or are a secondary phenomenon due to antipsychotic treatment. In order to test this hypothesis, we measured plasma IGF-2 and IGFBP-7 in drug-naïve first episode (FE) and multiple episodes or chronic (ME) SZ Caucasian patients who have been following treatment for years. A total of 55 SZ patients (FE = 15, ME = 40) and 45 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the Self-Assessment Anhedonia Scale (SAAS) were employed to check schizophrenic symptomatology and anhedonia, respectively. Plasma IGF-2 and IGFBP-7 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The FE SZ patients had much lower IGF-2, but not IGFBP-7, than controls. Moreover, both IGF-2 and IGFBP-7 significantly increased after atypical antipsychotic treatment (aripiprazole, olanzapine, or risperidone) in these patients. On the other hand, chronic patients showed higher levels of both proteins when compared to controls. Our study suggests that circulatory IGF-2 and IGFBP-7 increase after antipsychotic treatment, regardless of long-term conditions and being lower in drug-naïve FE patients.
Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis
Authors: Kim Won-Tae , Mun Jeong-Yeon , Baek Seung-Woo , Kim Min-Hye , Yang Gi-Eun , Jeong Mi-So , Choi Sun Young , Han Jin-Yeong , Kim Moo Hyun , Leem Sun-Hee
Published: August 2022

Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.
Synthetic and Natural Antifungals—Desirable and Hazardous Effects
Authors: Stojković Dejan , Ivanov Marija , Ćirić Ana
Published: August 2022

The increasing incidence of patients struggling with fungal infections, along with high losses in the production of different foods/crops due to fungal diseases presents a significant burden to healthcare, agronomy, and economies worldwide [...]
X-ray Dark-Field Imaging for Improved Contrast in Historical Handwritten Literature
Authors: Akstaller Bernhard , Schreiner Stephan , Dietrich Lisa , Rauch Constantin , Schuster Max , Ludwig Veronika , Hofmann-Randall Christina , Michel Thilo , Anton Gisela , Funk Stefan
Published: August 2022

If ancient documents are too fragile to be opened, X-ray imaging can be used to recover the content non-destructively. As an extension to conventional attenuation imaging, dark-field imaging provides access to microscopic structural object information, which can be especially advantageous for materials with weak attenuation contrast, such as certain metal-free inks in paper. With cotton paper and different self-made inks based on authentic recipes, we produced test samples for attenuation and dark-field imaging at a metal-jet X-ray source. The resulting images show letters written in metal-free ink that were recovered via grating-based dark-field imaging. Without the need for synchrotron-like beam quality, these results set the ground for a mobile dark-field imaging setup that could be brought to a library for document scanning, avoiding long transport routes for valuable historic documents.
Pathogenesis and Personalized Interventions for Pharmacological Treatment-Resistant Neuropsychiatric Symptoms in Alzheimer’s Disease
Authors: Nagata Tomoyuki , Shinagawa Shunichiro , Inamura Keisuke , Shigeta Masahiro
Published: August 2022

Alzheimer’s disease (AD) is the most common form of dementia, with cognitive impairment as a core symptom. Neuropsychiatric symptoms (NPSs) also occur as non-cognitive symptoms during the disease course, worsening the prognosis. Recent treatment guidelines for NPSs have recommended non-pharmacological treatments as the first line of therapy, followed by pharmacological treatments. However, pharmacological treatment for urgent NPSs can be difficult because of a lack of efficacy or an intolerance, requiring multiple changes in psychotropic prescriptions. One biological factor that might be partly responsible for this difficulty is structural deterioration in elderly people with dementia, which may cause a functional vulnerability affecting the pharmacological response. Other causative factors might include awkward psychosocial interpersonal relations between patients and their caregiver, resulting in distressful vicious circles. Overlapping NPS sub-symptoms can also blur the prioritization of targeted symptoms. Furthermore, consistent neurocognitive reductions cause a primary apathy state and a secondary distorted ideation or perception of present objects, leading to reactions that cannot be treated pharmacologically. The present review defines treatment-resistant NPSs in AD; it may be necessary and helpful for clinicians to discuss the pathogenesis and comprehensive solutions based on three major hypothetical pathophysiological viewpoints: (1) biology, (2) psychosociology, and (3) neurocognition.
Personalized Medicine Workflow in Post-Traumatic Orbital Reconstruction
Authors: Sabelis Juliana F. , Schreurs Ruud , Essig Harald , Becking Alfred G. , Dubois Leander
Published: August 2022

Restoration of the orbit is the first and most predictable step in the surgical treatment of orbital fractures. Orbital reconstruction is keyhole surgery performed in a confined space. A technology-supported workflow called computer-assisted surgery (CAS) has become the standard for complex orbital traumatology in many hospitals. CAS technology has catalyzed the incorporation of personalized medicine in orbital reconstruction. The complete workflow consists of diagnostics, planning, surgery and evaluation. Advanced diagnostics and virtual surgical planning are techniques utilized in the preoperative phase to optimally prepare for surgery and adapt the treatment to the patient. Further personalization of the treatment is possible if reconstruction is performed with a patient-specific implant and several design options are available to tailor the implant to individual needs. Intraoperatively, visual appraisal is used to assess the obtained implant position. Surgical navigation, intraoperative imaging, and specific PSI design options are able to enhance feedback in the CAS workflow. Evaluation of the surgical result can be performed both qualitatively and quantitatively. Throughout the entire workflow, the concepts of CAS and personalized medicine are intertwined. A combination of the techniques may be applied in order to achieve the most optimal clinical outcome. The goal of this article is to provide a complete overview of the workflow for post-traumatic orbital reconstruction, with an in-depth description of the available personalization and CAS options.
An Approach to Assessing Zoo Animal Welfare in a Rarely Studied Species, the Common Cusimanse Crossarchus obscurus
Authors: Free Danielle , Justice William S. M. , Smith Sarah Jayne , Howard Vittoria , Wolfensohn Sarah
Published: August 2022

Objective welfare assessments play a fundamental role in ensuring that positive welfare is achieved and maintained for animals in captivity. The Animal Welfare Assessment Grid (AWAG), a welfare assessment tool, has been validated for use with a variety of both domestic and exotic species. It combines both resource- and animal-based measures but relies heavily on knowledge of the species to effectively assess welfare. Many zoo species are understudied in the wild due to their cryptic nature or habitat choice; therefore, the published literature needs to be supported with captive behavioural observations and zoo records. Here we adapted previously published AWAG templates to assess the welfare of Crossarchus obscurus. A total of 21 factors were identified, and the final template was used to retrospectively score the welfare of two male and two female C. obscurus at Marwell Zoo, UK, validating the use of this process for preparing a welfare assessment for a species where the published literature is scarce.
Wall Fabrication by Direct Energy Deposition (DED) Combining Mild Steel (ER70) and Stainless Steel (SS 316L): Microstructure and Mechanical Properties
Authors: Uralde Virginia , Suarez Alfredo , Aldalur Eider , Veiga Fernando , Ballesteros Tomas
Published: August 2022

Direct energy deposition is gaining much visibility in research as one of the most adaptable additive manufacturing technologies for industry due to its ease of application and high deposition rates. The possibility of combining these materials to obtain parts with variable mechanical properties is an important task to be studied. The combination of two types of steel, mild steel ER70-6 and stainless steel SS 316L, for the fabrication of a wall by direct energy deposition was studied for this paper. The separate fabrication of these two materials was studied for the microstructurally flawless fabrication of bimetallic walls. As a result of the application of superimposed and overlapped strategies, two walls were fabricated and the microstructure, mechanical properties and hardness of the resulting walls are analyzed. The walls obtained with both strategies present dissimilar regions; the hardness where the most present material is ER70-6 is around 380 HV, and for SS 316L, it is around 180 HV. The average values of ultimate tensile strength (UTS) are 869 and 628 MPa, yield strength (YS) are 584 and 389 MPa and elongation at break are 20% and 36%, respectively, in the cases where we have more ER70-6 in the sample than SS 316L. This indicates an important relationship between the distribution of the materials and their mechanical behavior.
The Discrete Dipole Approximation: A Review
Authors: Chaumet Patrick Christian
Published: August 2022

There are many methods for rigorously calculating electromagnetic diffraction by objects of arbitrary shape and permittivity. In this article, we will detail the discrete dipole approximation (DDA) which belongs to the class of volume integral methods. Starting from Maxwell’s equations, we will first present the principle of DDA as well as its theoretical and numerical aspects. Then, we will discuss the many developments that this method has undergone over time and the numerous applications that have been developed to transform DDA in a very versatile method. We conclude with a discussion of the strengths and weaknesses of the DDA and a description of the freely available DDA-based electromagnetic diffraction codes.
Marine Bacterial Ribosomal Peptides: Recent Genomics- and Synthetic Biology-Based Discoveries and Biosynthetic Studies
Authors: Sukmarini Linda
Published: August 2022

Marine biodiversity is represented by an exceptional and ample array of intriguing natural product chemistries. Due to their extensive post-translational modifications, ribosomal peptides—also known as ribosomally synthesized and post-translationally modified peptides (RiPPs)—exemplify a widely diverse class of natural products, endowing a broad range of pharmaceutically and biotechnologically relevant properties for therapeutic or industrial applications. Most RiPPs are of bacterial origin, yet their marine derivatives have been quite rarely investigated. Given the rapid advancement engaged in a more powerful genomics approach, more biosynthetic gene clusters and pathways for these ribosomal peptides continue to be increasingly characterized. Moreover, the genome-mining approach in integration with synthetic biology techniques has markedly led to a revolution of RiPP natural product discovery. Therefore, this present short review article focuses on the recent discovery of RiPPs from marine bacteria based on genome mining and synthetic biology approaches during the past decade. Their biosynthetic studies are discussed herein, particularly the organization of targeted biosynthetic gene clusters linked to the encoded RiPPs with potential bioactivities.
The Impact of Simulated Gastric Acid and Toothbrushing on Surface Characteristics of Resin-Modified Glass-Ionomer Cements
Authors: Tărăboanță Ionuț , Buhățel Dan , Nica Irina , Stoleriu Simona , Ghiorghe Angela Cristina , Pancu Galina , Tărăboanță-Gamen Andra Claudia , Andrian Sorin
Published: August 2022

Background and Objectives: The aim of this in vitro study was to evaluate the effect of simulated gastric acid associated with toothbrushing on the surface condition of three resin-modified glass-ionomer cements (RMGIC). Materials and Methods: One hundred and sixty samples of each material were obtained and included in three study groups according to the tested material: Group I (Ionolux, VOCO GmbH, Cuxhaven, Germany); Group II (Vitremer, 3 M-ESPE, St. Paul, MN, USA); and Group III (Fuji II LC, GC Corporation, Tokyo, Japan). The samples were submersed in hydrochloric acid 0.01 M (pH 3.8) for 3 h and exposed to a toothbrushing procedure at a frequency of 10,000 cycles with medium and hard bristles immediately or 30 min after the acid attack. Profilometric measurements were performed by using a non-contact profilometer (Dektak XT, Bruker, Billerica, MA, USA) in order to assess the surface roughness. ANOVA and Bonferroni post hoc tests were used for the statistical analysis at a significance level of p < 0.05. Results: Exposure of RMGICs to the erosive effect of hydrochloric acid in association with toothbrushing 30 min after the chemical attack increased the surface roughness of all three RMGICs. Exposure of the three tested materials exclusively to the action of hydrochloric acid did not affect the surface roughness. Conclusions: One year of hydrochloric acid challenge associated with one year of toothbrushing with medium-hardness bristles performed 30 min after the acid attack increase the surface roughness of two of the three types of RMGIC tested (Ionolux and Fuji II LC).
The Effects of Cholesterol Oxidation on Erythrocyte Plasma Membranes: A Monolayer Study
Authors: Lechner Bob-Dan , Smith Paul , McGill Beth , Marshall Skye , Trick Jemma L. , Chumakov Andrei P. , Winlove Charles Peter , Konovalov Oleg V. , Lorenz Christian D. , Petrov Peter G.
Published: August 2022

Cholesterol plays a key role in the molecular and mesoscopic organisation of lipid membranes and it is expected that changes in its molecular structure (e.g., through environmental factors such as oxidative stress) may affect adversely membrane properties and function. In this study, we present evidence that oxidation of cholesterol has significant effects on the mechanical properties, molecular and mesoscopic organisation and lipid–sterol interactions in condensed monolayers composed of the main species found in the inner leaflet of the erythrocyte membrane. Using a combination of experimental methods (static area compressibility, surface dilatational rheology, fluorescence microscopy, and surface sensitive X-ray techniques) and atomistic molecular dynamics simulations, we show that oxidation of cholesterol to 7-ketocholesterol leads to stiffening of the monolayer (under both static and dynamic conditions), significant changes in the monolayer microdomain organisation, disruption in the van der Waals, electrostatic and hydrophobic interactions between the sterol and the other lipid species, and the lipid membrane hydration. Surface sensitive X-ray techniques reveal that, whilst the molecular packing mode is not significantly affected by cholesterol oxidation in these condensed phases, there are subtle changes in membrane thickness and a significant decrease in the coherence length in monolayers containing 7-ketocholesterol.
3D Printed Microfluidic Bioreactors Used for the Preferential Growth of Bacterial Biofilms through Dielectrophoresis
Authors: Csapai Alexandra , Toc Dan A. , Popa Florin , Tosa Nicoleta , Pascalau Violeta , Costache Carmen , Botan Alexandru , Popa Catalin O.
Published: August 2022

A realistic modelling of the way biofilms form and evolve in time requests a dynamic approach. In this study, the proposed route uses continuous-flow bioreactors under controlled flow rates and temperature in the culture medium containing bacteria or fungi. 3D printed, Polylactic acid (PLA), flow-based bioreactors with integrated copper electrodes were used to investigate the effect of dielectrophoresis on the formation and growth of Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 27853, and Klebsiella pneumoniae ATCC 13883 biofilms. Bacterial suspensions of 1McF turbidity have been prepared and circulated through the bioreactors. At the same time, a 30 V potential difference was applied on the system. The effect of the non-uniform electric field induced upon the bacterial cells was determined using quantitative methods, such as an adjusted microtiter plate technique, as well as spectral domain optical coherence tomography (SD-OCT) images. The morphology and the surface quality of the biofilms were investigated using Scanning Electron Microscopy (SEM) images. The results show that the different bacterial cells present a positive dielectrophoretic behaviour, with the preferential formation of biofilms in the high field gradient region.
Safe and Efficient Recovery Technique of Horizontal Isolated Pillar under Loose Tailings Backfill; A Case Study in a Zinc-Lead Mine
Authors: Feng Fan , Zhang Jiqing , Yan Zhikai , Wu Yedan , Song Yamin , Xie Zhiwei , Cheng Xiang
Published: August 2022

The presence of loose medium backfill above the horizontal pillar will technically hinder the efficient recovery of the pillar since the improper design and preserved roof protection layer height will potentially lead to casualties and equipment damage caused by large area collapse of filled tailings as well as roof fall accidents. In this study, a safe and efficient technique for the recovery of isolated pillars under loose tailings backfill was carried out via field investigation, theoretical analysis, numerical simulation, and analytic hierarchy process using the isolated pillars in the 855 middle sublevel of Hongling Zinc-Lead Mine, Chifeng, Inner Mongolia, as a practical engineering background. Current studies have revealed that the optimal scheme for an isolated horizontal pillar recovered via the cut-and-fill stoping of a drift vertical to ore body strike involves preserving a 1.0-m roof protection layer above the crown pillar combined with a spaced mining extraction sequence. This design minimizes ore dilution and losses during the pillar extraction process under safe operation. Our research results provide theoretical and technical support for the safe and efficient recovery of isolated pillars under loose tailings backfill in similar mines.
Optimum Fleet Selection Using Machine Learning Algorithms—Case Study: Zenouz Kaolin Mine
Authors: Nobahar Pouya , Pourrahimian Yashar , Mollaei Koshki Fereidoun
Published: August 2022

This paper presents the machine learning (ML) method, a novel approach that could be a profitable idea to optimize fleet management and achieve a sufficient output to reduce operational costs, by diminishing trucks’ queuing time and excavators’ idle time, based on the best selection of the fleet. The performance of this method was studied at the Zenouz kaolin mine to optimize the type of loader and the number of trucks used to supply the processing plant’s ore demands. Accordingly, five years’ data, such as dates, weather conditions, number of trucks, routes, loader types, and daily hauled ore, were collected, adapted, and processed to train the following five practical algorithms: linear regression, decision tree, K-nearest neighbour, random forest, and gradient boosting algorithm. By comparing the results of the algorithms, the gradient boosting decision tree algorithm was determined to be the best fit and predicted test data values with 85% accuracy. Subsequently, 11,322 data were imported into the machine as various scenarios and daily hauled minerals as output results were predicted for each working zone individually. Finally, the data which had the minimum variation from the selected required scheduled value, and its related data concerning loader type and the number of demanded trucks, were indicated for each day of the working year.
Screen Printing of Surface-Modified Barium Titanate/Polyvinylidene Fluoride Nanocomposites for High-Performance Flexible Piezoelectric Nanogenerators
Authors: Li Hai , Lim Sooman
Published: August 2022

Piezoelectric energy harvesters are appealing for the improvement of wearable electronics, owing to their excellent mechanical and electrical properties. Herein, screen-printed piezoelectric nanogenerators (PENGs) are developed from triethoxy(octyl)silane-coated barium titanate/polyvinylidene fluoride (TOS-BTO/PVDF) nanocomposites with excellent performance based on the important link between material, structure, and performance. In order to minimize the effect of nanofiller agglomeration, TOS-coated BTO nanoparticles are anchored onto PVDF. Thus, composites with well-distributed TOS-BTO nanoparticles exhibit fewer defects, resulting in reduced charge annihilation during charge transfer from inorganic nanoparticles to the polymer. Consequently, the screen-printed TOS-BTO/PVDF PENG exhibits a significantly enhanced output voltage of 20 V, even after 7500 cycles, and a higher power density of 15.6 μW cm−2, which is 200 and 150% higher than those of pristine BTO/PVDF PENGs, respectively. The increased performance of TOS-BTO/PVDF PENGs is due to the enhanced compatibility between nanofillers and polymers and the resulting improvement in dielectric response. Furthermore, as-printed devices could actively adapt to human movements and displayed excellent detection capability. The screen-printed process offers excellent potential for developing flexible and high-performance piezoelectric devices in a cost-effective and sustainable way.
Enhancement of the Green H2 Production by Using TiO2 Composite Polybenzimidazole Membranes
Authors: Díaz-Abad Sergio , Rodrigo Manuel , Sáez Cristina , Lobato Justo
Published: August 2022

This study reports the hydrogen production using TiO2 based composite polybenzimidazole membranes through the SO2 depolarized electrolysis that requires lower energy input than the direct water electrolysis. Composite membranes prepared and studied in this work showed very promising results in terms of proton conductivity, chemical stability, and crossover. Thus, a reduction in SO2 crossover was observed with the increase of the concentration of TiO2, obtaining reductions as high as 42% with the 3.0 wt% TiO2-PBI membrane at 120 °C. Higher hydrogen production rates and Faradaic efficiencies were achieved by all the composite membranes, with an optimum for the 1.0 wt% TiO2-PBI membrane (with this membrane, the production of hydrogen increased a 53% at 110 °C and a 49% at 120 °C as compared with the standard PBI membrane), demonstrated the benefit of the use of composite membranes with respect to the standard one for green hydrogen production.
The Dark Side of Iron: The Relationship between Iron, Inflammation and Gut Microbiota in Selected Diseases Associated with Iron Deficiency Anaemia—A Narrative Review
Authors: Malesza Ida J. , Bartkowiak-Wieczorek Joanna , Winkler-Galicki Jakub , Nowicka Aleksandra , Dzięciołowska Dominika , Błaszczyk Marta , Gajniak Paulina , Słowińska Karolina , Niepolski Leszek , Walkowiak Jarosław , Mądry Edyta
Published: August 2022

Iron is an indispensable nutrient for life. A lack of it leads to iron deficiency anaemia (IDA), which currently affects about 1.2 billion people worldwide. The primary means of IDA treatment is oral or parenteral iron supplementation. This can be burdened with numerous side effects such as oxidative stress, systemic and local-intestinal inflammation, dysbiosis, carcinogenic processes and gastrointestinal adverse events. Therefore, this review aimed to provide insight into the physiological mechanisms of iron management and investigate the state of knowledge of the relationship between iron supplementation, inflammatory status and changes in gut microbiota milieu in diseases typically complicated with IDA and considered as having an inflammatory background such as in inflammatory bowel disease, colorectal cancer or obesity. Understanding the precise mechanisms critical to iron metabolism and the awareness of serious adverse effects associated with iron supplementation may lead to the provision of better IDA treatment. Well-planned research, specific to each patient category and disease, is needed to find measures and methods to optimise iron treatment and reduce adverse effects.
Association between Obesity, Overweight, Elevated Waist Circumference, and Insulin Resistance Markers among Brazilian Adolescent Students
Authors: Deusdará Rodolfo , de Moura Souza Amanda , Szklo Moyses
Published: August 2022

(1) Background: There is still controversy concerning the most effective and efficient strategy to identify insulin resistance in adolescents. We estimated the level of fasting insulin (fasting insulin equivalent, FIeq) that would replicate the strength of the associations of obesity, overweight, and waist circumference with two insulin resistance markers: triglyceride/high-density lipoprotein (TG/HDL) and triglyceride/glucose (TyG); (2) Methods: We studied approximately 38,000 adolescents aged 12 to 17 years, sampled from a multicenter Brazilian school-based survey, The Study of Cardiovascular Risk Factors in Adolescents (Portuguese acronym, ERICA), conducted in 2013–2014. Fasting insulin equivalents for adiposity variables were calculated by dividing the beta coefficient of each adiposity measure by the fasting insulin beta coefficient from linear regression analysis according to age (12–14, 15–17 years old) and sex, and adjusted by smoking, alcohol consumption, physical inactivity, sedentary behavior, socioeconomic status, and Tanner stage; (3) Results: The FIeqs for obesity were greater than those for overweight and elevated waist circumference for both TG/HDL and TyG in early adolescence. The FIeqs for elevated WC were greater than those for obesity and overweight in adolescents aged 15 to 17 years; (4) Conclusions: Our study suggests that WC measurements might be useful to identify adolescents with insulin resistance, particularly in late adolescence.
Impact of Clarified Apple Juices with Different Processing Methods on Gut Microbiota and Metabolomics of Rats
Authors: Xu Lei , Yang Shini , Wang Kewen , Lu Anjing , Wang Xue , Xu Zhenzhen
Published: August 2022

The consumption of processed foods has increased compared to that of fresh foods in recent years, especially due to the coronavirus disease 2019 pandemic. Here, we evaluated the health effects of clarified apple juices (CAJs, devoid of pectin and additives) processed to different degrees, including not-from-concentrate (NFC) and from-concentrate (FC) CAJs. A 56-day experiment including a juice-switch after 28 days was designed. An integrated analysis of 16S rRNA sequencing and untargeted metabolomics of cecal content were performed. In addition, differences in the CAJs tested with respect to nutritional indices and composition of small-molecule compounds were analyzed. The NFC CAJ, which showed a higher phenolic content resulting from the lower processing degree, could improve microbiota diversity and influence its structure. It also reduced bile acid and bilirubin contents, as well as inhibited the microbial metabolism of tryptophan in the gut. However, we found that these effects diminished with time by performing experiment extension and undertaking juice-switching. Our study provides evidence regarding the health effects of processed foods that can potentially be applied to public health policy decision making. We believe that NFC juices with a lower processing degree could potentially be healthier than FC juice.
The Influence of Sociodemographic Factors, Lifestyle, and Risk Perception on Dietary Patterns in Pregnant Women Living in Highly Contaminated Areas: Data from the NEHO Birth Cohort
Authors: Ruggieri Silvia , Drago Gaspare , Panunzi Simona , Rizzo Giulia , Tavormina Elisa Eleonora , Maltese Sabina , Cibella Fabio
Published: August 2022

During pregnancy, maternal nutrition and lifestyle play a critical role in influencing fetal development and newborn health outcomes. The aim of this study is to investigate the factors influencing the adherence to dietary patterns in pregnant women living in highly contaminated areas, and whether women with higher environmental risk perception manifest different nutritional behaviors during pregnancy. Food consumption data on 816 pregnant women from the Neonatal Environment and Health Outcomes (NEHO) residential birth cohort were analyzed. Dietary patterns were computed by principal component analysis. A multinomial logistic regression was also applied to identify sociodemographic, lifestyle, and pregnancy-related determinants of adherence to dietary patterns during pregnancy. Three patterns of food consumption—explaining 24.9% of the total variance—were identified as “prudent”, “high energy”, and “vegetarian” patterns. Results suggest that food choices during pregnancy follow a social gradient and align with other health behaviors during pregnancy: older, better educated, and physically active women with higher risk perception are more likely to follow healthier dietary patterns. Knowledge about what is eaten can contribute to dietary choices. Interventions to improve the prenatal nutrition knowledge of pregnant women are needed, especially concerning younger mothers and those with lower educational levels.
Synthesis, Characterisation and Mechanism of Action of Anticancer 3-Fluoroazetidin-2-ones
Authors: Malebari Azizah M. , Duffy Morales Gabriela , Twamley Brendan , Fayne Darren , Khan Mohemmed Faraz , McLoughlin Eavan C. , O’Boyle Niamh M. , Zisterer Daniela M. , Meegan Mary J.
Published: August 2022

The stilbene combretastatin A-4 (CA-4) is a potent microtubule-disrupting agent interacting at the colchicine-binding site of tubulin. In the present work, the synthesis, characterisation and mechanism of action of a series of 3-fluoro and 3,3-difluoro substituted β-lactams as analogues of the tubulin-targeting agent CA-4 are described. The synthesis was achieved by a convenient microwave-assisted Reformatsky reaction and is the first report of 3-fluoro and 3,3-difluoro β-lactams as CA-4 analogues. The β-lactam compounds 3-fluoro-4-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxy phenyl)azetidin-2-one 32 and 3-fluoro-4-(3-fluoro-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)azetidin-2-one) 33 exhibited potent activity in MCF-7 human breast cancer cells with IC50 values of 0.075 µM and 0.095 µM, respectively, and demonstrated low toxicity in non-cancerous cells. Compound 32 also demonstrated significant antiproliferative activity at nanomolar concentrations in the triple-negative breast cancer cell line Hs578T (IC50 0.033 μM), together with potency in the invasive isogenic subclone Hs578Ts(i)8 (IC50 = 0.065 μM), while 33 was also effective in MDA-MB-231 cells (IC50 0.620 μM). Mechanistic studies demonstrated that 33 inhibited tubulin polymerisation, induced apoptosis in MCF-7 cells, and induced a downregulation in the expression of anti-apoptotic Bcl2 and survivin with corresponding upregulation in the expression of pro-apoptotic Bax. In silico studies indicated the interaction of the compounds with the colchicine-binding site, demonstrating the potential for further developing novel cancer therapeutics as microtubule-targeting agents.
Revisiting Cerebrospinal Fluid Flow Direction and Rate in Physiologically Based Pharmacokinetic Model
Authors: Hirasawa Makoto , de Lange Elizabeth C. M.
Published: August 2022

The bidirectional pulsatile movement of cerebrospinal fluid (CSF), instead of the traditionally believed unidirectional and constant CSF circulation, has been demonstrated. In the present study, the structure and parameters of the CSF compartments were revisited in our comprehensive and validated central nervous system (CNS)-specific, physiologically based pharmacokinetic (PBPK) model of healthy rats (LeiCNS-PK3.0). The bidirectional and site-dependent CSF movement was incorporated into LeiCNS-PK3.0 to create the new LeiCNS-PK“3.1” model. The physiological CSF movement rates in healthy rats that are unavailable from the literature were estimated by fitting the PK data of sucrose, a CSF flow marker, after intra-CSF administration. The capability of LeiCNS-PK3.1 to describe the PK profiles of other molecules was compared with that of the original LeiCNS-PK3.0 model. LeiCNS-PK3.1 demonstrated superior description of the CSF PK profiles of a range of small molecules after intra-CSF administration over LeiCNS-PK3.0. LeiCNS-PK3.1 also retained the same level of predictability of CSF PK profiles in cisterna magna after intravenous administration. These results support the theory of bidirectional and site-dependent CSF movement across the entire CSF space over unidirectional and constant CSF circulation in healthy rats, pointing out the need to revisit the structures and parameters of CSF compartments in CNS-PBPK models.
Poly(methacrylate citric acid) as a Dual Functional Carrier for Tumor Therapy
Authors: Yu Bo , Shen Yiping , Zhang Xuejie , Ding Lijuan , Meng Zheng , Wang Xiaotong , Han Meihua , Guo Yifei , Wang Xiangtao
Published: August 2022

Owing to its pH-sensitive property and chelating Cu2+ effect, poly(methacrylate citric acid) (PCA) can be utilized as a dual functional nanocarrier to construct a nanodelivery system. Negatively charged carboxyl groups can interact with positively charged antineoplastic drugs through electrostatic interaction to form stable drug nanoparticles (NPs). Through drug experimental screening, doxorubicin (DOX) was selected as the model drug, PCA/DOX NPs with a diameter of 84 nm were prepared, and the drug-loading content was 68.3%. PCA/DOX NPs maintained good stability and a sustained release profile. Cell experiments presented that PCA/DOX NPs could inhibit effectively the growth of 4T1 cells; the IC50 value was decreased by approximately 15-fold after incubation for 72 h. The cytotoxicity toward H9C2 was decreased significantly. Moreover, based on its ability to efficiently adsorb copper ions, PCA showed good vascular growth inhibition effect in vitro. Furthermore, animal experiments showed that PCA/DOX NPs presented stronger anticancer effects than DOX; the tumor inhibition rate was increased by 1.5-fold. Myocardial toxicity experiments also confirmed that PCA reduced the cardiotoxicity of DOX. In summary, PCA/DOX NPs show good antitumor efficacy and low toxicity, and have good potential for clinical application.
Under the Umbrella of Clinical Pharmacology: Inflammatory Bowel Disease, Infliximab and Adalimumab, and a Bridge to an Era of Biosimilars
Authors: Petric Zvonimir , Goncalves Joao , Paixao Paulo
Published: August 2022

Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders—Crohn’s disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety. To ease the burden of IBD and other severe diseases, biosimilars have emerged as a cost-effective alternative to an originator product. According to the current knowledge, biosimilars of IFX and ADL in IBD patients are shown to be as safe and effective as their originators. The future of biosimilars, in general, is promising due to the potential of making the health care system more sustainable. However, their use is accompanied by misconceptions regarding their effectiveness and safety, as well as by controversy regarding their interchangeability. Hence, until a scientific consensus is achieved, scientific data on the long-term effectiveness and safety of biosimilars are needed.
Low-Cost and Recyclable Photocatalysts: Metal Oxide/Polymer Composites Applied in the Catalytic Breakdown of Dyes
Authors: Borjigin Timur , Schmitt Michael , Morlet-Savary Fabrice , Xiao Pu , Lalevée Jacques
Published: August 2022

Novel metal oxide/polymer composite photocatalysts prepared by photocuring with common metal oxide particles (ZnO or CeO2) and acrylic ester monomers have been investigated for the first time. Metal oxide particles were fully integrated with the acrylate polymer network based on the crosslink of poly ethylene glycol diacrylate (noted below as Poly-PEG) by photopolymerization upon mild light source (LED@405 nm) irradiation. The prepared metal/oxide composite showed excellent performance in the photodegradation of Acid Black dye (used as a benchmark pollutant) in an aqueous environment. Indeed, under UV lamp irradiation for 60 min, the degradation of Acid Black reached 59% and 56%, in the presence of 10 wt% ZnO/Poly-PEG and 3 wt% CeO2/poly PEG, respectively. Markedly, the new reported photocatalysts have offered much better performance over the conventional TiO2 photocatalytic material used as a control (39% degradation using 1 wt% TiO2/poly PEG). In turn, the new proposed metal oxide/polymer composites were further characterized by a range of analytical characterization methods, including the swelling test, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), dynamic mechanical analysis (DMA), UV–visible diffuse reflectance spectroscopy, and electron spin resonance analysis. The results showed that the new photocatalysts demonstrated excellent water adsorption properties, high-temperature resistance, and excellent recyclability, which were very suitable for wide application and in line with the concept of green chemistry.
Supramolecular Polycaprolactone-Based Polyurethanes with Thermally Activated Shape-Memory Behavior
Authors: Muscas Fabio , Sessini Valentina , Peponi Laura , López Antonio Julio , Ureña Alejandro , Navarro Rodrigo , Marcos-Fernández Ángel
Published: August 2022

In this work, using supramolecular polyurethanes theories, two polycaprolactone-based polyurethanes with 2-ureido-4-[1H]-pyrimidinone (UPy) motifs capable of forming quadruple hydrogen bonds were synthetized and characterized, focusing our attention on their capability to show thermally activated shape-memory response. In particular, 1H NMR analyses confirmed the chemical structure of the supramolecular polyurethanes, while DSC showed their totally amorphous morphology. DMTA in tensile mode was used to study their thermally activated shape-memory properties. In our case, the UPy units are the switching domains while the network formed by the segregated hard segments is the permanent domain obtained materials with excellent shape-memory response at both 100 and 85 °C. These materials are promising for multi-responsive materials where bio-based and potentially recyclable polymers with excellent shape-memory properties are needed.