bluuebunny/crossref_metadata_2025 huggingface dataset:
The Mechanical Properties and Degradation Behavior of 3D-Printed Cellulose Nanofiber/Polylactic Acid Composites
Authors: Zhang Zhongsen , Cao Bingyan , Jiang Ning
Published: September 2023

Polylactic acid (PLA) has been widely used in many fields because of its good biodegradability, biocompatibility, and renewability. This work studied the degradation behavior and mechanical properties of cellulose nanofiber (CNF)/PLA composites. In vitro degradation experiments of 3D-printed samples were conducted at elevated temperatures, and the degradation characteristics were evaluated by mechanical tests, gel permeation chromatography (GPC), differential scanning calorimetric (DSC), and scanning electron microscope (SEM). The results indicated that the addition of CNF (0.5 wt%) accelerated the degradation rate of PLA. The decreases in number average molecular weight (Mn) and weight average molecular weight (Mw) of composites were 7.96% and 4.91% higher than that of neat PLA, respectively. Furthermore, the tensile modulus of composites was 18.4% higher than that of neat PLA, while the strength was 7.4% lower due to poor interfacial bonding between CNF and PLA. A mapping relationship between accelerated and normal degradation showed that the degradation experienced during 60 days at 37 °C was equivalent to that undergone during 14 days at 50 °C; this was achieved by examining the alteration in Mn. Moreover, the degradation process caused a notable deformation in the samples due to residual stress generated during the 3D printing process. This study provided valuable insights for investigating the in vitro degradation behavior of 3D-printed products.
Fracture Behavior of Concrete under Chlorine Salt Attack Exposed to Freeze–Thaw Cycles Environment
Authors: Li Wenhao , Hu Shaowei
Published: September 2023

Fracture behavior is one of the key properties to study concrete cracking under sodium chloride attack exposed to the freeze–thaw cycles environment, which is frequently neglected. In this paper, 24 single edge notch beam specimens and 24 cubes were poured. The corresponding freeze–thaw cycles test in sodium chloride solution, standard cube compressive strength of concrete test, and three-point-bending tests were carried out. The research revealed that the fracture toughness, fracture energy, relative dynamic modulus of elasticity, and standard cube compressive strength were decreased by increasing freeze–thaw cycles under sodium chloride attack, and the damage degree of concrete caused by sodium chloride solution was deeper than that of pure water. In particular, there existed good linear correlation between the fracture behavior and imposed freeze–thaw damage for various solution. Accordingly, a more reliable damage model using fracture control parameters as damage factors was proposed.
Using Traffic Sensors in Smart Cities to Enhance a Spatio-Temporal Deep Learning Model for COVID-19 Forecasting
Authors: Muñoz-Organero Mario
Published: September 2023

Respiratory viruses, such as COVID-19, are spread over time and space based on human-to-human interactions. Human mobility plays a key role in the propagation of the virus. Different types of sensors in smart cities are able to continuously monitor traffic-related human mobility, showing the impact of COVID-19 on traffic volumes and patterns. In a similar way, traffic volumes measured by smart traffic sensors provide a proxy variable to capture human mobility, which is expected to have an impact on new COVID-19 infections. Adding traffic data from smart city sensors to machine learning models designed to estimate upcoming COVID-19 incidence values should provide optimized results compared to models based on COVID-19 data alone. This paper proposes a novel model to extract spatio-temporal patterns in the spread of the COVID-19 virus for short-term predictions by organizing COVID-19 incidence and traffic data as interrelated temporal sequences of spatial images. The model is trained and validated with real data from the city of Madrid in Spain for 84 weeks, combining information from 4372 traffic measuring points and 143 COVID-19 PCR test centers. The results are compared with a baseline model designed for the extraction of spatio-temporal patterns from COVID-19-only sequences of images, showing that using traffic information enhances the results when forecasting a new wave of infections (MSE values are reduced by a 70% factor). The information that traffic data has on the spread of the COVID-19 virus is also analyzed, showing that traffic data alone is not sufficient for accurate COVID-19 forecasting.
Degenerated Boundary Layers and Long-Wave Low-Frequency Motion in High-Contrast Elastic Laminates
Authors: Aghalovyan Lenser A. , Ghulghazaryan Lusine G. , Kaplunov Julius , Prikazchikov Danila
Published: September 2023

The effect of high contrast on the multiscale behaviour of elastic laminates is studied. Mathematical modelling in this area is of significant interest for a variety of modern applications, including but not limited to advanced sandwich structures and photovoltaic panels. As an example, the antiplane shear of a symmetric, three-layered plate is considered. The problem parameters expressing relative thickness, stiffness and density are assumed to be independent. The high contrast may generally support extra length and time scales corresponding to degenerated boundary layers and propagating long-wave low-frequency vibration modes. The main focus is on the relation between these two phenomena. The developed multiparametric approach demonstrates that those do not always appear simultaneously. The associated explicit estimates on contrast parameters are established. In addition, the recent asymptotic extension of the classical Saint-Venant’s principle is adapted for calculating the contribution of the degenerate boundary layer or long-wave low-frequency propagation mode. The peculiarity of the limiting absorption principle in application to layered media is also addressed.
Actinoquinazolinone, a New Quinazolinone Derivative from a Marine Bacterium Streptomyces sp. CNQ-617, Suppresses the Motility of Gastric Cancer Cells
Authors: Pulat Sultan , Kim Da-Ae , Hillman Prima F. , Oh Dong-Chan , Kim Hangun , Nam Sang-Jip , Fenical William
Published: September 2023

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial–mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.
Activation of a Silent Polyketide Synthase SlPKS4 Encoding the C7-Methylated Isocoumarin in a Marine-Derived Fungus Simplicillium lamellicola HDN13-430
Authors: Yu Jing , Liu Xiaolin , Ma Chuanteng , Li Chen , Zhang Yuhan , Che Qian , Zhang Guojian , Zhu Tianjiao , Li Dehai
Published: September 2023

Coumarins, isocoumarins and their derivatives are polyketides abundant in fungal metabolites. Although they were first discovered over 50 years ago, the biosynthetic process is still not entirely understood. Herein, we report the activation of a silent nonreducing polyketide synthase that encodes a C7-methylated isocoumarin, similanpyrone B (1), in a marine-derived fungus Simplicillium lamellicola HDN13-430 by heterologous expression. Feeding studies revealed the host enzymes can change 1 into its hydroxylated derivatives pestapyrone A (2). Compounds 1 and 2 showed moderate radical scavenging activities with ED50 values of 67.4 µM and 104.2 µM. Our discovery fills the gap in the enzymatic elucidation of naturally occurring C7-methylated isocoumarin derivatives.
Polymeric Inclusion Membranes Based on Ionic Liquids for Selective Separation of Metal Ions
Authors: Hernández-Fernández Adrián , Iniesta-López Eduardo , Ginestá-Anzola Anahí , Garrido Yolanda , Pérez de los Ríos Antonia , Quesada-Medina Joaquín , Hernández-Fernández Francisco José
Published: September 2023

In this work, poly(vinyl chloride)-based polymeric ionic liquid inclusion membranes were used in the selective separation of Fe(III), Zn(II), Cd(II), and Cu(II) from hydrochloride aqueous solutions. The ionic liquids under study were 1-octyl-3-methylimidazolium hexafluorophosphate, [omim+][PF6−] and methyl trioctyl ammonium chloride, [MTOA+][Cl−]. For this purpose, stability studies of different IL/base polymer compositions against aqueous phases were carried out. Among all polymer inclusion membranes studied, [omim+][PF6−]/PVC membranes at a ratio of 30/70 and [MTOA+][Cl−]/PVC membranes at a ratio of 70/30 were able to retain up to 82% and 48% of the weight of the initial ionic liquid, respectively, after being exposed to a solution of metal ions in 1 M HCl for 2048 h (85 days). It was found that polymer inclusion membranes based on the ionic liquid methyl trioctyl ammonium chloride allowed the selective separation of Zn(II)/Cu(II) and Zn(II)/Fe(III) mixtures with separation factors of 1996, 606 and, to a lesser extent but also satisfactorily, Cd(II)/Cu(II) mixtures, with a separation factor of 112. Therefore, selecting the appropriate ionic liquid/base polymer mixture makes it possible to create polymeric inclusion membranes capable of selectively separating target metal ions.
The Battle for Survival: The Role of RNA Non-Canonical Tails in the Virus–Host Interaction
Authors: Wen Xianghui , Irshad Ahsan , Jin Hua
Published: September 2023

Terminal nucleotidyltransferases (TENTs) could generate a ‘mixed tail’ or ‘U-rich tail’ consisting of different nucleotides at the 3′ end of RNA by non-templated nucleotide addition to protect or degrade cellular messenger RNA. Recently, there has been increasing evidence that the decoration of virus RNA terminus with a mixed tail or U-rich tail is a critical way to affect viral RNA stability in virus-infected cells. This paper first briefly introduces the cellular function of the TENT family and non-canonical tails, then comprehensively reviews their roles in virus invasion and antiviral immunity, as well as the significance of the TENT family in antiviral therapy. This review will contribute to understanding the role and mechanism of non-canonical RNA tailing in survival competition between the virus and host.
In Search of Complementary Extraction Methods for Comprehensive Coverage of the Escherichia coli Metabolome
Authors: Gould Henry , Cheung William , Finnigan James D. , Muñoz-Muñoz José , Charnock Simon J. , Black Gary W.
Published: September 2023

Escherichia coli is an invaluable research tool for many fields of biology, in particular for the production of recombinant enzymes. However, the activity of many such recombinant enzymes cannot be determined using standard biochemical assays, as often, the relevant substrates are not known, or the products produced are not detectable. Today, the biochemical footprints of such unknown enzyme activities can be revealed via the analysis of the metabolomes of the recombinant E. coli clones in which they are expressed, using sensitive technologies such as mass spectrometry. However, before any metabolites can be identified, it is necessary to achieve as high a coverage of the potential metabolites present within E. coli as possible. We have therefore analyzed a wide range of different extraction methods against the cell free extracts of various recombinant E. coli clones. The results were analyzed to determine the minimum number of extractions that achieved high recovery and coverage of metabolites. Two methods were selected for further analysis due to their ability to produce not only high numbers of ions, but also wide mass coverage and a high degree of complementarity. One extraction method uses acetonitrile and water, in a 4:1 ratio, which is then dried down and reconstituted in the chromatography running buffer prior to injection onto the chromatography column, and the other extraction method uses a combination of methanol, water and chloroform, in a 3:1:1 ratio, which is injected directly onto the chromatography column. These two extraction methods were shown to be complementary to each other, as regards the respective metabolites extracted, and to cover a large range of metabolites.
Effect of the Textures and Particle Sizes of Limestone on the Quicklime Reaction Activity
Authors: Zhu Minjie , Wu Jing , Yang Zehao , Zhu Yong , Rong Quan , Wen Qingfu
Published: September 2023

Quicklime is not only an important raw material for the steel and nano-calcium carbonate industries but also a key carrier for capturing carbon dioxide in the fight against global warming, and its reaction activity plays a vital role in these processes. Recent studies have found that quicklime produced from limestones with similar chemical compositions under the same production process has significantly different reaction activities, which indicates that something other than the chemical composition of limestone affects quicklime reaction activity. To explore the factors affecting quicklime reaction activity, this study analyzed the textures and calcite particle size of limestone collected from different areas of Guangxi, China, and measures the quicklime reaction activity with different calcination times. It has been found that: (1) limestone with a clastic texture is preferred to that with a crystalline texture (including transition type) in yielding quicklime with higher reaction activity; and (2) for limestone with a clastic texture, fine-grained limestone tends to produce the same or higher quicklime reaction activity with lower energy consumption.
The Impacts of Molybdenum Exploration on Cd and Zn Contents in Surface Water: Evidence from a Molybdenum Mine in the Xiaoqinling Mountains
Authors: Yang Min , Fu Weishun , Chen Huaqing , Zhang Xin , Zhao Aning , Xu Youning
Published: September 2023

In order to study the impact of molybdenum ore development in a large molybdenum mining area in the Xiaoqinling Mountains on the water and sediment quality of the Wenyu stream, surface water, sediment, and surrounding rock samples were collected, and the Cd and Zn contents were analyzed. The pollution status and ecological risk degree of river water and sediment samples in the Wenyu stream watershed were evaluated using the single element pollution index method, geoaccumulation index method, Hakanson potential ecological risk assessment method, potentially toxic elements (PTEs) health risk assessment, and PTEs pollution comprehensive index method. Finally, the impact of mining development on the contents of Cd and Zn in the Wenyu stream were discussed, and the sources of pollution were identified. The study revealed that the levels of Cd and Zn in 23 water samples collected from the primary channel of the Wenyu stream were markedly higher compared to the unaffected contrast area. Similarly, the concentrations of Cd and Zn in the 17 sediment samples were significantly elevated compared to the average values in the reference area. These findings indicated that The Wenyu stream was heavily impacted by the molybdenum mining activities, resulting in a high ecological risk associated with the sediment in the primary channel. Acid mine drainage in the mining area, sediment release activities, and atmospheric dust fall are considered to be the main sources of PTEs polluting the Wenyu stream watershed. Relevant personnel should complete a thorough river water quality investigation and perform ecological environment restoration so as to ensure sustainable economic development.
Synthesis and Characterization of New Pyrano[2,3-c]pyrazole Derivatives as 3-Hydroxyflavone Analogues
Authors: Urbonavičius Arminas , Krikštolaitytė Sonata , Bieliauskas Aurimas , Martynaitis Vytas , Solovjova Joana , Žukauskaitė Asta , Arbačiauskienė Eglė , Šačkus Algirdas
Published: September 2023

In this paper, an efficient synthetic route from pyrazole-chalcones to novel 6-aryl-5-hydroxy-2-phenylpyrano[2,3-c]pyrazol-4(2H)-ones as 3-hydroxyflavone analogues is described. The methylation of 5-hydroxy-2,6-phenylpyrano[2,3-c]pyrazol-4(2H)-one with methyl iodide in the presence of a base yielded a compound containing a 5-methoxy group, while the analogous reaction of 5-hydroxy-2-phenyl-6-(pyridin-4-yl)pyrano[2,3-c]pyrazol-4(2H)-one led to the zwitterionic 6-(N-methylpyridinium)pyrano[2,3-c]pyrazol derivative. The treatment of 5-hydroxy-2,6-phenylpyrano[2,3-c]pyrazol-4(2H)-one with triflic anhydride afforded a 5-trifloylsubstituted compound, which was further used in carbon–carbon bond forming Pd-catalyzed coupling reactions to yield 5-(hetero)aryl- and 5-carbo-functionalized pyrano[2,3-c]pyrazoles. The excited-state intramolecular proton transfer (ESIPT) reaction of 5-hydroxypyrano[2,3-c]pyrazoles from the 5-hydroxy moiety to the carbonyl group in polar protic, polar aprotic, and nonpolar solvents was observed, resulting in well-resolved two-band fluorescence. The structures of the novel heterocyclic compounds were confirmed by 1H-, 13C-, 15N-, and 19F-NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data.
Synthesis and Optimization of Cs2B′B″X6 Double Perovskite for Efficient and Sustainable Solar Cells
Authors: Yao Ruijia , Zhou Tingxue , Ji Shilei , Liu Wei , Li Xing’ao
Published: September 2023

Hybrid perovskite materials with high light absorption coefficients, long diffusion lengths, and high mobility have attracted much attention, but their commercial development has been seriously hindered by two major problems: instability and lead toxicity. This has led to lead-free halide double perovskite becoming a prominent competitor in the photovoltaic field. For lead-free double perovskites, Pb2+ can be heterovalent, substituted by non-toxic metal cations as a double perovskite structure, which promotes the flexibility of the composition. However, the four component elements and low solubility in the solvent result in synthesis difficulties and phase impurity problems. And material phase purity and film quality are closely related to the number of defects, which can limit the photoelectric performance of solar cells. Therefore, based on this point, we summarize the synthesis methods of Cs2B′B″X6 double perovskite crystals and thin films. Moreover, in the application of solar cells, the existing research mainly focuses on the formation process of thin films, band gap adjustment, and surface engineering to improve the quality of films and optimize the performance of devices. Finally, we propose that Cs2B′B″X6 lead-free perovskites offer a promising pathway toward developing highly efficient and stable perovskite solar cells.
Indole-Based Compounds as Potential Drug Candidates for SARS-CoV-2
Authors: Girgis Adel S. , Panda Siva S. , Kariuki Benson M. , Bekheit Mohamed S. , Barghash Reham F. , Aboshouk Dalia R.
Published: September 2023

The COVID-19 pandemic has posed a significant threat to society in recent times, endangering human health, life, and economic well-being. The disease quickly spreads due to the highly infectious SARS-CoV-2 virus, which has undergone numerous mutations. Despite intense research efforts by the scientific community since its emergence in 2019, no effective therapeutics have been discovered yet. While some repurposed drugs have been used to control the global outbreak and save lives, none have proven universally effective, particularly for severely infected patients. Although the spread of the disease is generally under control, anti-SARS-CoV-2 agents are still needed to combat current and future infections. This study reviews some of the most promising repurposed drugs containing indolyl heterocycle, which is an essential scaffold of many alkaloids with diverse bio-properties in various biological fields. The study also discusses natural and synthetic indole-containing compounds with anti-SARS-CoV-2 properties and computer-aided drug design (in silico studies) for optimizing anti-SARS-CoV-2 hits/leads.
Design, Synthesis, Antitumour Evaluation, and In Silico Studies of Pyrazolo-[1,5-c]quinazolinone Derivatives Targeting Potential Cyclin-Dependent Kinases
Authors: Zheng Danyang , Yang Chenqi , Li Xiaogang , Liu Dong , Wang Yan , Wang Xuesong , Zhang Xueying , Tan Yinfeng , Zhang Yuchen , Li Youbin , Xu Junyu
Published: September 2023

An efficient, straightforward, and metal-free methodology to rapidly access functionalised pyrazolo-[1,5-c]quinazolinones via a [3 + 2] dipolar cycloaddition and regioselective ring expansion process was developed. The synthesised compounds were characterised by methods such as NMR, HRMS, and HPLC. The in vitro antiproliferative activity against A549 cells (non-small cell lung cancer) was significant for compounds 4i, 4m, and 4n with IC50 values of 17.0, 14.2, and 18.1 μM, respectively. In particular, compounds 4t and 4n showed inhibitory activity against CDK9/2. Predicted biological target and molecular modelling studies suggest that the compound 4t may target CDKs for antitumour effects. The synthesised derivatives were considered to have moderate drug-likeness and sufficient safety in silico. In summary, a series of pyrazolo-[1,5-c]quinazolinone derivatives with antitumour activity is reported for the first time. We provide not only a simple and efficient synthetic method but also helpful lead compounds for the further development of novel cyclin-dependent kinase (CDK) inhibitors.
Terpenoid Glucosides from Gentiana macrophylla That Attenuate TNF-α Induced Pulmonary Inflammation in A549 Cells
Authors: Huang Pei-Qi , Luo Yong-Xin , Zhang Yu-Jia , Li Zhi-Xuan , Wen Yan , Zhang Kun , Li Dong-Li , Jin Jing-Wei , Wu Ri-Hui , Gan Li-She
Published: September 2023

Four previously undescribed terpenoid glucosides, including one sesquiterpenoid di-glucoside (1), two new iridoid glucosides (2, 3), and a new triterpenoid tri-glucoside (4), were isolated from a 70% ethanol extract of the root of Gentiana macrophylla (Gentianaceae), along with eight known terpenoids. Their structures were determined by spectroscopic techniques, including 1D, 2D NMR, and HRMS (ESI), as well as chemical methods. The absolute configuration of compound 1 was determined by quantum chemical calculation of its theoretical electronic circular dichroism (ECD) spectrum. The sugar moieties of all the new compounds were confirmed to be D-glucose by GC analysis after acid hydrolysis and acetylation. Anti-pulmonary inflammation activity of the iridoids were evaluated on a TNF-α induced inflammation model in A549 cells. Compound 2 could significantly alleviate the release of proinflammatory cytokines IL-1β and IL-8 and increase the expression of anti-inflammatory cytokine IL-10.
Possibilities and Limitations of ICP-Spectrometric Determination of the Total Content of Tin and Its Inorganic and Organic Speciations in Waters with Different Salinity Levels—Part 2: Separate Determination of Inorganic and Organic Speciations of Tin
Authors: Temerdashev Zaual , Abakumov Pavel , Bolshov Mikhail , Abakumova Darya , Pupyshev Alexander
Published: September 2023

In this study, determination of the inorganic and organic forms of tin in waters of different salinities is considered. The possibility of the separation of speciations of tin using liquid–liquid extraction (LLE); precipitation with fluorides, iodides, ammonia, and iron (III) chloride; and sorption of organotin compounds (OTCs) was studied. The LLE and analyte precipitation methods proved to be ineffective. Inorganic and organic forms of tin were separated by the sorption of OTCs using silica gel sorbent Diapak C18. Under optimized conditions, a technique for the separate determination of the forms of tin in natural waters was developed. The technique combines hydride generation and microwave mineralization of solutions followed by ICP spectrometry. The inorganic forms of tin were determined after their solid-phase separation from organotin compounds. The lower limits of analyte quantification were 0.03 μg/L (ICP-MS) and 0.05 μg/L (ICP-OES), which provide separate determinations of inorganic and organic forms of tin in waters with different salinities. The content of OTCs in water was determined by subtracting the inorganic concentration from the total concentration of tin. The technique will allow a comprehensive assessment of the toxicological impact of tin speciations on the aquatic ecosystem.
All Roads Lead to the Gut: The Importance of the Microbiota and Diet in Migraine
Authors: Spekker Eleonóra , Nagy-Grócz Gábor
Published: September 2023

Migraine, a prevalent neurological condition and the third most common disease globally, places a significant economic burden on society. Despite extensive research efforts, the precise underlying mechanism of the disease remains incompletely comprehended. Nevertheless, it is established that the activation and sensitization of the trigeminal system are crucial during migraine attacks, and specific substances have been recognized for their distinct involvement in the pathomechanism of migraine. Recently, an expanding body of data indicates that migraine attacks can be prevented and treated through dietary means. It is important to highlight that the various diets available pose risks for patients without professional guidance. This comprehensive overview explores the connection between migraine, the gut microbiome, and gastrointestinal disorders. It provides insight into migraine-triggering foods, and discusses potential diets to help reduce the frequency and severity of migraine attacks. Additionally, it delves into the benefits of using pre- and probiotics as adjunctive therapy in migraine treatment.
Effects of Bovine Lactoferrin on the Maintenance of Respiratory and Systemic Physical Conditions in Healthy Adults—A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Oda Hirotsugu , Kubo Shutaro , Tada Asuka , Yago Takumi , Sugita Chihiro , Yoshida Hiroki , Toida Tatsunori , Tanaka Miyuki , Kurokawa Masahiko
Published: September 2023

Objectives: We investigated the effects of bovine lactoferrin (LF) on the maintenance of the respiratory and systemic physical conditions. Methods: A randomized, double-blind, placebo-controlled trial was conducted. Healthy adults at Kyushu University of Health and Welfare ingested a placebo or bovine LF (200 mg/day) for 12 weeks. The primary endpoints were the total respiratory and systemic symptom scores. The secondary endpoint was the activity of plasmacytoid dendritic cells (pDCs) in peripheral blood. Results: A total of 157 subjects were randomized (placebo, n = 79; LF, n = 78), of whom, 12 dropped out. The remaining 145 participants were included in the full analysis set (placebo group, n = 77; LF group, n = 68). The total scores for respiratory and systemic symptoms during the intervention were significantly lower in the LF group than in the placebo group. The expression of CD86 and HLA-DR on pDCs was significantly higher in the LF group than in the placebo group at week 12. Adverse events were comparable between the groups, and no adverse drug reactions were observed. Conclusions: These results suggest that orally ingested LF supports the normal immune system via maintaining pDC activity, and maintains respiratory and systemic physical conditions in healthy adults.
Ghrelin as a Biomarker of “Immunometabolic Depression” and Its Connection with Dysbiosis
Authors: Gajewska Agata , Strzelecki Dominik , Gawlik-Kotelnicka Oliwia
Published: September 2023

Ghrelin, a gastrointestinal peptide, is an endogenous ligand of growth hormone secretagogue receptor 1a (GHSR1a), which is mainly produced by X/A-like cells in the intestinal mucosa. Beyond its initial description as a growth hormone (GH) secretagogue stimulator of appetite, ghrelin has been revealed to have a wide range of physiological effects, for example, the modulation of inflammation; the improvement of cardiac performance; the modulation of stress, anxiety, taste sensation, and reward-seeking behavior; and the regulation of glucose metabolism and thermogenesis. Ghrelin secretion is altered in depressive disorders and metabolic syndrome, which frequently co-occur, but it is still unknown how these modifications relate to the physiopathology of these disorders. This review highlights the increasing amount of research establishing the close relationship between ghrelin, nutrition, microbiota, and disorders such as depression and metabolic syndrome, and it evaluates the ghrelinergic system as a potential target for the development of effective pharmacotherapies.
The Relationship between Social Media Use and Body Image in Lebanese University Students
Authors: Karam Joanne M. , Bouteen Carol , Mahmoud Yara , Tur Josep A. , Bouzas Cristina
Published: September 2023

Well-being is not only defined as being physically healthy; multiple factors can affect a person’s well-being. Social media is strongly correlated with the body dissatisfaction of an individual. High exposure to lean and toned body shapes has created new standards and “idealized” body types. The aim of this article was to assess the relationship between social media and body image among university students in Lebanon. Data were obtained from 292 university students (median age: 22 years), selected from different Lebanese regions by using convenience sampling. Demographic data, social media addiction, body satisfaction, levels of physical activity, eating behaviors, and ultimate well-being were expressed as median and interquartile range. People who relied more on social media were younger than those who did not. Individuals addicted to social media had higher odds of having moderate and marked body image concerns. A significant association was found between social media addiction and emotional overeating, food responsiveness, and feeling hunger. These findings stress the need for rising regional and national awareness among social media users, especially the younger ones, and the implementation of intervention and prevention techniques to help prevent body image dissatisfaction, disordered eating patterns, and the alteration of overall well-being.
The Effects of Dietary Chromium Supplementation along with Discontinuing a High-Fat Diet on the Microbial Enzymatic Activity and the Production of SCFAs in the Faeces of Rats
Authors: Juśkiewicz Jerzy , Ognik Katarzyna , Fotschki Joanna , Napiórkowska Dorota , Cholewińska Ewelina , Grzelak-Błaszczyk Katarzyna , Krauze Magdalena , Fotschki Bartosz
Published: September 2023

The present study assessed the changes in faecal microbial activity in obese Wistar rats fed high-fat or low-fat diets supplemented with various forms of chromium (picolinate or nanoparticles). The 18-week study was divided into two phases: an introductory period (9 weeks; obesity status induction via a high-fat diet) and an experimental period (9 weeks; maintained on a high-fat diet or switched to a low-fat diet and Cr supplementation). During the experimental period (10–18 weeks of feeding), samples of fresh faeces were collected on chosen days. The bacterial enzymatic activity and short-chain fatty acids (SCFAs) concentration were assessed to characterise the dynamism of the changes in faecal microbial metabolic activity under the applied dietary treatments. The results indicated that faecal microbial metabolic activity displayed several adaptation mechanisms in response to modifications in dietary conditions, and a beneficial outcome resulted from a pro-healthy dietary habit change, that is, switching from a high-fat to a low-fat diet. Dietary supplementation with chromium nanoparticles further modulated the aforementioned microbial activity, i.e., diminished the extracellular and total enzymatic activities, while the effect of chromium picolinate addition was negligible. Both the high-fat diet and the addition of chromium nanoparticles reduced SCFA concentrations and increased the faecal pH values.
Genetically Predicted Levels of Serum Metabolites and Risk of Sarcopenia: A Mendelian Randomization Study
Authors: Sha Tingting , Wang Ning , Wei Jie , He Hongyi , Wang Yilun , Zeng Chao , Lei Guanghua
Published: September 2023

Metabolites’ connection to sarcopenia through inflammation and mitochondrial dysfunction is presumed, but their impact remains unclear due to limitations in conventional observational studies caused by confounding bias and reverse causation. We conducted a Mendelian randomization (MR) analysis to elucidate the association of serum metabolites with sarcopenia and its related traits, i.e., appendicular lean mass and grip strength. Genetic instruments to proxy the serum metabolites were extracted from the most comprehensive genome-wide association study on the topic published so far. The corresponding summary statistics for the associations of genetic instruments with outcomes were calculated from the UK Biobank (n = 324,976 participants). The primary analyses were assessed by an inverse-variance weighted (IVW) method. The weighted median and MR-PRESSO methods were used as sensitive analyses. Fourteen genetically predicted serum metabolites were associated with the risk of sarcopenia (PIVW < 0.05). Two metabolites showed the overlapped association with sarcopenia and its related traits, which were isovalerylcarnitine (sarcopenia: odds ratio [OR] = 4.00, 95% confidence interval [CI] = 1.11~14.52, PIVW = 0.034; appendicular lean mass: β = −0.45 kg, 95% CI = −0.81~−0.09, PIVW = 0.015; grip strength: β = −1.51 kg, 95% CI = −2.31~−0.71, PIVW = 2.19 × 10−4) and docosapentaenoate (sarcopenia: OR = 0.16, 95% CI = 0.03~0.83, PIVW = 0.029; appendicular lean mass: β = −0.45 kg, 95% CI = 0.08~0.81, PIVW = 0.016). Twenty-seven metabolites were suggestive associated with appendicular lean mass or grip strength. This MR study provided evidence for the potential effects of metabolites on sarcopenia.
Adipose Tissue Dynamics: Cellular and Lipid Turnover in Health and Disease
Authors: Palacios-Marin Ivonne , Serra Dolors , Jimenez-Chillarón Josep , Herrero Laura , Todorčević Marijana
Published: September 2023

The alarming increase in obesity and its related metabolic health complications, such as type 2 diabetes, has evolved into a global pandemic. Obesity is mainly characterized by excessive accumulation of adipose tissue, primarily due to an imbalance between energy intake and expenditure. Prolonged positive energy balance leads to the expansion of existing adipocytes (hypertrophy) and/or an increase in preadipocyte and adipocyte number (hyperplasia) to accommodate excess energy intake. However, obesity is not solely defined by increases in adipocyte size and number. The turnover of adipose tissue cells also plays a crucial role in the development and progression of obesity. Cell turnover encompasses the processes of cell proliferation, differentiation, and apoptosis, which collectively regulate the overall cell population within adipose tissue. Lipid turnover represents another critical factor that influences how adipose tissue stores and releases energy. Our understanding of adipose tissue lipid turnover in humans remains limited due to the slow rate of turnover and methodological constraints. Nonetheless, disturbances in lipid metabolism are strongly associated with altered adipose tissue lipid turnover. In obesity, there is a decreased rate of triglyceride removal (lipolysis followed by oxidation), leading to the accumulation of triglycerides over time. This review provides a comprehensive summary of findings from both in vitro and in vivo methods used to study the turnover of adipose cells and lipids in metabolic health and disease. Understanding the mechanisms underlying cellular and lipid turnover in obesity is essential for developing strategies to mitigate the adverse effects of excess adiposity.
Injectable Thermosensitive Hyaluronic Acid Hydrogels for Chondrocyte Delivery in Cartilage Tissue Engineering
Authors: Chen Chih-Hao , Kao Hao-Hsi , Lee Yen-Chen , Chen Jyh-Ping
Published: September 2023

In this study, we synthesize a hyaluronic acid-g-poly(N-isopropylacrylamide) (HPN) copolymer by grafting the amine-terminated poly(N-isopropylacrylamide) (PNIPAM-NH2) to hyaluronic acid (HA). The 5% PNIPAM-NH2 and HPN polymer solution is responsive to temperature changes with sol-to-gel phase transition temperatures around 32 °C. Compared with the PNIPAM-NH2 hydrogel, the HPN hydrogel shows higher water content and mechanical strength, as well as lower volume contraction, making it a better choice as a scaffold for chondrocyte delivery. From an in vitro cell culture, we see that cells can proliferate in an HPN hydrogel with full retention of cell viability and show the phenotypic morphology of chondrocytes. In the HPN hydrogel, chondrocytes demonstrate a differentiated phenotype with the upregulated expression of cartilage-specific genes and the enhanced secretion of extracellular matrix components, when compared with the monolayer culture on tissue culture polystyrene. In vivo studies confirm the ectopic cartilage formation when HPN was used as a cell delivery vehicle after implanting chondrocyte/HPN in nude mice subcutaneously, which is shown from a histological and gene expression analysis. Taken together, the HPN thermosensitive hydrogel will be a promising injectable scaffold with which to deliver chondrocytes in cartilage-tissue-engineering applications.
The First Physiologically Based Pharmacokinetic (PBPK) Model for an Oral Vaccine Using Alpha-Tocopherol as an Adjuvant
Authors: Saldanha Leonor , Vale Nuno
Published: September 2023

Oral vaccines represent many advantages compared to standard vaccines. They hold a simple method of administration and manufacturing process. In addition to these, the way they can induce immune responses makes these a promising technology for the pharmaceutical industry and represents a new hope to society. Physiologically based pharmacokinetics (PBPK) has been used in support of drug development to predict the pharmacokinetics of the compound, considering the patient’s physiology. Despite PBPK studies now being widely used, there are very few models in the literature that support vaccine development. Therefore, the goal of this article was to determine how PBPK could support vaccine development. The first PBPK model for an oral vaccine using alpha-tocopherol as a vaccine adjuvant was built. LogP is the parameter that influences the delivery of alpha-tocopherol into the tissues more. Having a high LogP means it accumulates in adipose tissue and is slowly metabolized. The ideal formulation to include alpha-tocopherol in an oral vaccine would incorporate nanoparticles in a capsule, and the dosage of the compound would be 150 mg in a volume of 200 mL. This article aims to determine if alpha-tocopherol, as a well-known adjuvant for intramuscular injection vaccines, could be used as an adjuvant to oral vaccines. This model was built considering the conditions and requirements needed for designing an oral vaccine. This implies making sure the antigen and adjuvants reach the main target by overcoming the challenges of the gastrointestinal tract. The main parameters that would need to be included in a formulation using alpha-tocopherol as an adjuvant were determined.
Computational Insight of Phase Transformation and Drug Release Behaviour of Doxycycline-Loaded Ibuprofen-Based In-Situ Forming Gel
Authors: Puyathorn Napaphol , Tamdee Poomipat , Sirirak Jitnapa , Okonogi Siriporn , Phaechamud Thawatchai , Chantadee Takron
Published: September 2023

This research investigates the gel formation behaviour and drug-controlling performance of doxycycline-loaded ibuprofen-based in-situ forming gels (DH-loaded IBU-based ISGs) for potential applications in periodontal treatment. The investigation begins by exploring the physical properties and gel formation behaviour of the ISGs, with a particular focus on determining their sustained release capabilities. To gain a deeper understanding of the molecular interactions and dynamics within the ISGs, molecular dynamic (MD) simulations are employed. The effects of adding IBU and DH on reducing surface tension and water tolerance properties, thus affecting molecular properties. The phase transformation phenomenon is observed around the interface, where droplets of ISGs move out to the water phase, leading to the precipitation of IBU around the interface. The optimization of drug release profiles ensures sustained local drug release over seven days, with a burst release observed on the first day. Interestingly, different organic solvents show varying abilities to control DH release, with dimethyl sulfoxide (DMSO) demonstrating superior control compared to N-Methyl-2-pyrrolidone (NMP). MD simulations using AMBER20 software provide valuable insights into the movement of individual molecules, as evidenced by root-mean-square deviation (RMSD) values. The addition of IBU to the system results in the retardation of IBU molecule movement, particularly evident in the DMSO series, with the diffusion constant value of DH reducing from 1.2452 to 0.3372 and in the NMP series from 0.3703 to 0.2245 after adding IBU. The RMSD values indicate a reduction in molecule fluctuation of DH, especially in the DMSO system, where it decreases from over 140 to 40 Å. Moreover, their radius of gyration is influenced by IBU, with the DMSO system showing lower values, suggesting an increase in molecular compactness. Notably, the DH-IBU configuration exhibits stable pairing through H-bonding, with a higher amount of H-bonding observed in the DMSO system, which is correlated with the drug retardation efficacy. These significant findings pave the way for the development of phase transformation mechanistic studies and offer new avenues for future design and optimization formulation in the ISG drug delivery systems field.
A Promising Approach: Magnetic Nanosystems for Alzheimer’s Disease Theranostics
Authors: Chaparro Catarina I. P. , Simões Beatriz T. , Borges João P. , Castanho Miguel A. R. B. , Soares Paula I. P. , Neves Vera
Published: September 2023

Among central nervous system (CNS) disorders, Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and a major cause of dementia worldwide. The yet unclear etiology of AD and the high impenetrability of the blood–brain barrier (BBB) limit most therapeutic compounds from reaching the brain. Although many efforts have been made to effectively deliver drugs to the CNS, both invasive and noninvasive strategies employed often come with associated side effects. Nanotechnology-based approaches such as nanoparticles (NPs), which can act as multifunctional platforms in a single system, emerged as a potential solution for current AD theranostics. Among these, magnetic nanoparticles (MNPs) are an appealing strategy since they can act as contrast agents for magnetic resonance imaging (MRI) and as drug delivery systems. The nanocarrier functionalization with specific moieties, such as peptides, proteins, and antibodies, influences the particles’ interaction with brain endothelial cell constituents, facilitating transport across the BBB and possibly increasing brain penetration. In this review, we introduce MNP-based systems, combining surface modifications with the particles’ physical properties for molecular imaging, as a novel neuro-targeted strategy for AD theranostics. The main goal is to highlight the potential of multifunctional MNPs and their advances as a dual nanotechnological diagnosis and treatment platform for neurodegenerative disorders.
Integrated Continuous Wet Granulation and Drying: Process Evaluation and Comparison with Batch Processing
Authors: Forster Seth P. , Dippold Erin , Haser Abbe , Emanuele Daniel , Meier Robin
Published: September 2023

The pharmaceutical industry is in the midst of a transition from traditional batch processes to continuous manufacturing. However, the challenges in making this transition vary depending on the selected manufacturing process. Compared with other oral solid dosage processes, wet granulation has been challenging to move towards continuous processing since traditional equipment has been predominantly strictly batch, instead of readily adapted to material flow such as dry granulation or tablet compression, and there have been few equipment options for continuous granule drying. Recently, pilot and commercial scale equipment combining a twin-screw wet granulator and a novel horizontal vibratory fluid-bed dryer have been developed. This study describes the process space of that equipment and compares the granules produced with batch high-shear and fluid-bed wet granulation processes. The results of this evaluation demonstrate that the equipment works across a range of formulations, effectively granulates and dries, and produces granules of similar or improved quality to batch wet granulation and drying.
A Single–Multi-Path Combinatorial RMSA Algorithm with Least Resource Consumption in Semi-Filterless Optical Networks
Authors: Yuan Junling , Xie Yanyan , Wang Suhua , Li Xuhong , Zhang Qikun , Zhang Jing
Published: September 2023

Filterless optical networks (FONs) have become a cost-effective solution for optical network deployment due to their low-cost characteristics. However, eliminating active switching elements causes signals to propagate over unintended links, wasting spectral resources. Therefore, semi-filterless optical networks (Semi-FONs) have become a more cost-effective solution. This paper mainly studies the routing, modulation, and spectrum assignment (RMSA) problem in semi-filterless optical networks. It proposes a single–multi-path combination (LR-SMPC) RMSA algorithm with the least resource consumption. The algorithm first obtains the K shortest paths that satisfy the conditions according to the K short path (KSP) algorithm and re-orders the paths according to the resource consumption path re-ordering strategy, selecting the three paths that consume the least resources as the set of candidate paths. Then, based on the single–multi-path combination scheme of the set of candidate paths, the resource consumption of each scheme and the maximum number of available spectrum blocks for each path is calculated, from which the single path or multi-path with the least resource consumption is selected to serve the request. We perform simulation experiments on two network topologies using Poisson traffic models and compare them with existing single-path algorithms (S-P), fixed spectrum assignment granularity algorithms (g = 1), and adaptation spectrum assignment algorithms (g adaptation) to evaluate the performance of the proposed algorithm. The simulation results show that the proposed algorithm exhibits better performance in terms of both blocking rate and spectrum utilization.