bluuebunny/crossref_metadata_2025 huggingface dataset:
Temperature and Aging Effects on the Rheological Properties and Performance of Geopolymer-Modified Asphalt Binder and Mixtures
Authors: Hamid Abdulrahman , Baaj Hassan , El-Hakim Mohab
Published: January 2023

Using geopolymer as a modifier for asphalt binders and mixtures gained momentum for investigation in recent decades. Limited research investigations attempted to link the effect of temperature and traffic loading on the rheological properties and performance of geopolymer-modified asphalt binders. The primary objective of this study is to evaluate the effect of fly ash-based geopolymer (GF), styrene-butadiene-styrene (SBS), and the combination of GF with SBS on the rheological properties and performance of asphalt binders at low and intermediate temperatures. The rheological properties and performance of neat and modified asphalt binders (4%GF, 8%GF,12%GF, 2%SBS, and hybrid (2%SBS+8%GF)) were evaluated utilizing dynamic shear rheometer (DSR) and bending beam rheometer (BBR) devices. To evaluate the fatigue resistance of asphalt binders, the linear amplitude sweep (LAS) and viscoelastic continuum damage (VECD) models were applied. The dynamic or complex modulus and moisture damage resistance were measured to investigate the influence of modifiers on the performance of asphalt mixtures. The findings demonstrated that for both unaged and RTFO-aged asphalt binders, additives reduced the temperature sensitivity of both G′ and G″. When the binders were exposed to long-term aging using a pressure aging vessel (PAV), it was noticed that the 8%GF binder became more susceptible to temperature changes. The 2%SBS binder had the lowest creep stiffness compared with the neat and other modifiers, while the hybrid binder exhibited the highest resistance to fatigue distress at different temperatures compared with the other binders. The modified asphalt mixes (8%GF, 2%SBS, and hybrid) achieved the maximum tensile strength (St) compared with the neat asphalt binder, with an increase of more than 80%. The St increased from 580.4 kPa to 740.4 kPa, 884.8 kPa, and 917.4 kPa by utilising the 8%GF, 2%SBS, and hybrid binders, respectively. Furthermore, the modified asphalt mixture exhibited more ability to resist cracking, attaining the highest fracture energy in dry and freeze-thaw conditions.
Novel Photonic Applications of Silicon Carbide
Authors: Ou Haiyan , Shi Xiaodong , Lu Yaoqin , Kollmuss Manuel , Steiner Johannes , Tabouret Vincent , Syväjärvi Mikael , Wellmann Peter , Chaussende Didier
Published: January 2023

Silicon carbide (SiC) is emerging rapidly in novel photonic applications thanks to its unique photonic properties facilitated by the advances of nanotechnologies such as nanofabrication and nanofilm transfer. This review paper will start with the introduction of exceptional optical properties of silicon carbide. Then, a key structure, i.e., silicon carbide on insulator stack (SiCOI), is discussed which lays solid fundament for tight light confinement and strong light-SiC interaction in high quality factor and low volume optical cavities. As examples, microring resonator, microdisk and photonic crystal cavities are summarized in terms of quality (Q) factor, volume and polytypes. A main challenge for SiC photonic application is complementary metal-oxide-semiconductor (CMOS) compatibility and low-loss material growth. The state-of-the-art SiC with different polytypes and growth methods are reviewed and a roadmap for the loss reduction is predicted for photonic applications. Combining the fact that SiC possesses many different color centers with the SiCOI platform, SiC is also deemed to be a very competitive platform for future quantum photonic integrated circuit applications. Its perspectives and potential impacts are included at the end of this review paper.
Adsorptive Removal of Rhodamine B Dye Using Carbon Graphite/CNT Composites as Adsorbents: Kinetics, Isotherms and Thermodynamic Study
Authors: Zghal Sabrine , Jedidi Ilyes , Cretin Marc , Cerneaux Sophie , Abdelmouleh Makki
Published: January 2023

The study of the adsorption efficiency of new carbon/CNT composites was undertaken to remove a cationic dye, Rhodamine B (RhB), from dye-contaminated wastewater. Indeed, we investigated the effect of different experimental parameters such as time, initial concentration of dye and temperature on the adsorption of RhB by the carbon composites (KS44-0 and KS44-20). The results showed that the adsorption uptake increased with the initial concentration and solution temperature while maintaining a relatively constant pH. The presence of the carbon nanotubes provided more active sites for dye removal and improved the adsorption behavior of Rhodamine B dye. The analysis of the experimental data was conducted using model equations, such as Langmuir, Freundlich and Temkin isotherms. As regards the Freundlich isotherm model, it was the best fit for the equilibrium data obtained from the experiments. The applicability of the pseudo-second-order equation could be explained assuming that the overall adsorption rate is limited by the rate of adsorbate transport that occurs on the pore surfaces of adsorbents. Furthermore, the intraparticle diffusion and Bangham models were used to investigate the diffusion mechanism of RhB absorption onto carbon composites. They showed that multiple adsorption stages occurred simultaneously via pore surface diffusion. Concerning the thermodynamic parameters (∆G°, ∆H°, and ∆S°), they were calculated and explained in the mean of the chemical structure of the adsorbate. Negative standard Gibbs free energy change values (ΔG°ads) at all temperatures suggested that the adsorption process was spontaneous, and the positive values of the standard enthalpy change of adsorption (∆H°ads) revealed the reaction to be endothermic. The values of standard enthalpy (ΔH°ads) and activation energy (Ea) indicated that the adsorption process corresponds to physical sorption. The mechanisms for the removal of Rhodamine B dye from wastewater using carbon composite were predicted. RhB is a planar molecule that is readily adsorbed, in which adsorbed molecules are bound by hydrophobic or other weak interactions due to the π-π interactions between the dyes’ aromatic backbones and the hexagonal skeleton of graphite and carbon nanotubes. Thus, the graphite carbon/carbon nanotube composite is believed to play a major role in organic pollutant reduction.
Carbonization of MOF-5/Polyaniline Composites to N,O-Doped Carbon/ZnO/ZnS and N,O-Doped Carbon/ZnO Composites with High Specific Capacitance, Specific Surface Area and Electrical Conductivity
Authors: Savić Marjetka , Janošević Ležaić Aleksandra , Gavrilov Nemanja , Pašti Igor , Nedić Vasiljević Bojana , Krstić Jugoslav , Ćirić-Marjanović Gordana
Published: January 2023

Composites of carbons with metal oxides and metal sulfides have attracted a lot of interest as materials for energy conversion and storage applications. Herein, we report on novel N,O-doped carbon/ZnO/ZnS and N,O-doped carbon/ZnO composites (generally named C-(MOF-5/PANI)), synthesized by the carbonization of metal–organic framework MOF-5/polyaniline (PANI) composites. The produced C-(MOF-5/PANI)s are comprehensively characterized in terms of composition, molecular and crystalline structure, morphology, electrical conductivity, surface area, and electrochemical behavior. The composition and properties of C-(MOF-5/PANI) composites are dictated by the composition of MOF-5/PANI precursors and the form of PANI (conducting emeraldine salt (ES) or nonconducting emeraldine base). The ZnS phase is formed only with the PANI-ES form due to S-containing counter-ions. XRPD revealed that ZnO and ZnS existed as pure wurtzite crystalline phases. PANI and MOF-5 acted synergistically to produce C-(MOF-5/PANI)s with high SBET (up to 609 m2 g−1), electrical conductivity (up to 0.24 S cm−1), and specific capacitance, Cspec, (up to 238.2 F g−1 at 10 mV s−1). Values of Cspec commensurated with N content in C-(MOF-5/PANI) composites (1–10 wt.%) and overcame Cspec of carbonized individual components PANI and MOF-5. By acid etching treatment of C-(MOF-5/PANI), SBET and Cspec increased to 1148 m2 g−1 and 341 F g−1, respectively. The developed composites represent promising electrode materials for supercapacitors.
Effect of Mo Content on Hydrogen Evolution Reaction of 1400 MPa-Grade High-Strength Bolt Steel
Authors: Xiong Xilin , Song Keke , Li Jinxu , Su Yanjing
Published: January 2023

The effect of Mo content of 1400 MPa-grade high-strength bolt steel on hydrogen diffusion behavior and the hydrogen evolution reaction were studied using a hydrogen permeation experiment, potentiodynamic polarization tests, thermal desorption spectroscopy, and the first-principle calculation. Two 1400 MPa-grade high-strength bolt steels with different Mo content were used. Based on the potentiodynamic polarization tests, both steels’ electrochemical behavior was similar in the test range. The hydrogen permeation experiment showed that the process of hydrogen adsorption and absorption was significantly promoted, and hydrogen desorption and recombination were slightly promoted, with the Mo content increasing from 0.70 to 1.09 wt%. The thermal desorption spectroscopy showed the overall reaction of hydrogen permeation and evolution. The increasing Mo content facilitated hydrogen entry behavior and increased the hydrogen content. According to the first-principle calculation and the density functional theory, this phenomenon is induced by the stronger bonding ability of Mo-H than Fe-H. This work could guide the design of 1400 MPa-grade high-strength bolt steel.
An Unsupervised Rapid Network Alignment Framework via Network Coarsening
Authors: Zhang Lei , Qian Feng , Chen Jie , Zhao Shu
Published: January 2023

Network alignment aims to identify the correspondence of nodes between two or more networks. It is the cornerstone of many network mining tasks, such as cross-platform recommendation and cross-network data aggregation. Recently, with the development of network representation learning techniques, researchers have proposed many embedding-based network alignment methods. The effect is better than traditional methods. However, several issues and challenges remain for network alignment tasks, such as lack of labeled data, mapping across network embedding spaces, and computational efficiency. Based on the graph neural network (GNN), we propose the URNA (unsupervised rapid network alignment) framework to achieve an effective balance between accuracy and efficiency. There are two phases: model training and network alignment. We exploit coarse networks to accelerate the training of GNN after first compressing the original networks into small networks. We also use parameter sharing to guarantee the consistency of embedding spaces and an unsupervised loss function to update the parameters. In the network alignment phase, we first use a once-pass forward propagation to learn node embeddings of original networks, and then we use multi-order embeddings from the outputs of all convolutional layers to calculate the similarity of nodes between the two networks via vector inner product for alignment. Experimental results on real-world datasets show that the proposed method can significantly reduce running time and memory requirements while guaranteeing alignment performance.
Current Landscape of Methods to Evaluate Antimicrobial Activity of Natural Extracts
Authors: Gonzalez-Pastor Rebeca , Carrera-Pacheco Saskya E. , Zúñiga-Miranda Johana , Rodríguez-Pólit Cristina , Mayorga-Ramos Arianna , Guamán Linda P. , Barba-Ostria Carlos
Published: January 2023

Natural extracts have been and continue to be used to treat a wide range of medical conditions, from infectious diseases to cancer, based on their convenience and therapeutic potential. Natural products derived from microbes, plants, and animals offer a broad variety of molecules and chemical compounds. Natural products are not only one of the most important sources for innovative drug development for animal and human health, but they are also an inspiration for synthetic biology and chemistry scientists towards the discovery of new bioactive compounds and pharmaceuticals. This is particularly relevant in the current context, where antimicrobial resistance has risen as a global health problem. Thus, efforts are being directed toward studying natural compounds’ chemical composition and bioactive potential to generate drugs with better efficacy and lower toxicity than existing molecules. Currently, a wide range of methodologies are used to analyze the in vitro activity of natural extracts to determine their suitability as antimicrobial agents. Despite traditional technologies being the most employed, technological advances have contributed to the implementation of methods able to circumvent issues related to analysis capacity, time, sensitivity, and reproducibility. This review produces an updated analysis of the conventional and current methods to evaluate the antimicrobial activity of natural compounds.
Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance
Authors: Han Eunkyung , Kim Doyeon , Cho Youngheun , Lee Seonock , Kim Jungho , Kim Hyuncheol
Published: January 2023

Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.
Photochromic and Luminescent Properties of a Salt of a Hybrid Molecule Based on C60 Fullerene and Spiropyran—A Promising Approach to the Creation of Anticancer Drugs
Authors: Khuzin Artur A. , Galimov Dim I. , Khuzina Liliya L.
Published: January 2023

For the first time a pyrrolidinofullerene salt containing a spiropyran group and an ammonium group, capable of reversibly reacting to UV radiation, has been synthesized. Photoinduced reactions of the synthesized compounds were studied using absorption and luminescence spectroscopies, spectral and kinetic characteristics were measured. The hybrid molecule was found to exhibit intrinsic fluorescence even in the spirocyclic form. The C60 derivative showed a higher stability and better spectral and luminescent properties than the precursor.
Construction of Smart Biomaterials for Promoting Diabetic Wound Healing
Authors: Huang Chan , Yuan Weiyan , Chen Jun , Wu Lin-Ping , You Tianhui
Published: January 2023

Diabetes mellitus is a complicated metabolic disease that has become one of the fastest-growing health crises in modern society. Diabetic patients may suffer from various complications, and diabetic foot is one of them. It can lead to increased rates of lower-extremity amputation and mortality, even seriously threatening the life and health of patients. Because its healing process is affected by various factors, its management and treatment are very challenging. To address these problems, smart biomaterials have been developed to expedite diabetic wound closure and improve treatment outcomes. This review begins with a discussion of the basic mechanisms of wound recovery and the limitations of current dressings used for diabetic wound healing. Then, the categories and characteristics of the smart biomaterial scaffolds, which can be utilized as a delivery system for drugs with anti-inflammatory activity, bioactive agency, and antibacterial nanoparticles for diabetic wound treatment were described. In addition, it can act as a responsive system to the stimulus of the pH, reactive oxygen species, and glucose concentration from the wound microenvironment. These results show that smart biomaterials have an enormous perspective for the treatment of diabetic wounds in all stages of healing. Finally, the advantages of the construction of smart biomaterials are summarized, and possible new strategies for the clinical management of diabetic wounds are proposed.
SGLT2 Inhibitors May Restore Endothelial Barrier Interrupted by 25-Hydroxycholesterol
Authors: Pawlos Agnieszka , Broncel Marlena , Woźniak Ewelina , Markiewicz Łukasz , Piastowska-Ciesielska Agnieszka , Gorzelak-Pabiś Paulina
Published: January 2023

SGLT2 (Sodium-glucose Cotransporter-2) inhibitors are newer glucose-lowering drugs with many cardiovascular benefits that are not fully understood yet. Endothelial integrity plays a key role in cardiovascular homeostasis. 25-hydroxycholesterol (25-OHC), which is a proatherogenic stimuli that impairs endothelial barrier functions. VE-cadherin is an endothelial-specific protein crucial in maintaining endothelial integrity. The aim of this study was to assess the influence of SGLT2i on the integrity of endothelial cells interrupted by 25-OHC. We also aimed to evaluate whether this effect is associated with changes in the levels of VE-cadherin. We pre-incubated HUVECs with 10 μg/mL of 25-hydroxycholesterol (25-OHC) for 4 h and then removed it and incubated endothelial cells with 1 μM of empagliflozin, 1 μM canagliflozin, or 1 μM dapagliflozin for 24 h. The control group included HUVECs cultured with the medium or with 25-OHC 10 μg/mL. The integrity of endothelial cells was measured by the RTCA-DP xCELLigence system, and VE-cadherin was assessed in confocal microscopy. Our results show that SGLT2 inhibitors significantly increase endothelial integrity in comparison to medium controls, and they improve endothelial cell integrity interrupted by 25-OHC. This effect is associated with significant improvements in VE-cadherin levels. SGLT2i: empagliflozin, canagliflozin, and dapagliflozin have a beneficial effect on the endothelial cell integrity and VE-cadherin levels reduced by 25-OHC.
Possibilities and Limitations of the Sono-Fenton Process Using Mid-High-Frequency Ultrasound for the Degradation of Organic Pollutants
Authors: Serna-Galvis Efraím A. , Silva-Agredo Javier , Lee Judy , Echavarría-Isaza Adriana , Torres-Palma Ricardo A.
Published: January 2023

Mid-high-frequency ultrasound (200–1000 kHz) eliminates organic pollutants and also generates H2O2. To take advantage of H2O2, iron species can be added, generating a hybrid sono-Fenton process (sF). This paper presents the possibilities and limitations of sF. Heterogeneous (a natural mineral) and homogeneous (Fe2+ and Fe3+ ions) iron sources were considered. Acetaminophen, ciprofloxacin, and methyl orange were the target organic pollutants. Ultrasound alone induced the pollutants degradation, and the dual competing role of the natural mineral (0.02–0.20 g L−1) meant that it had no significant effects on the elimination of pollutants. In contrast, both Fe2+ and Fe3+ ions enhanced the pollutants’ degradation, and the elimination using Fe2+ was better because of its higher reactivity toward H2O2. However, the enhancement decreased at high Fe2+ concentrations (e.g., 5 mg L−1) because of scavenger effects. The Fe2+ addition significantly accelerated the elimination of acetaminophen and methyl orange. For ciprofloxacin, at short treatment times, the degradation was enhanced, but the pollutant complexation with Fe3+ that came from the Fenton reaction caused degradation to stop. Additionally, sF did not decrease the antimicrobial activity associated with ciprofloxacin, whereas ultrasound alone did. Therefore, the chemical structure of the pollutant plays a crucial role in the feasibility of the sF process.
Mechanical Properties of Polypropylene–Cellulose Biocomposites: Molecular Dynamics Simulations Combined with Constant Strain Method
Authors: Möttönen Nea B. , Karttunen Antti J.
Published: January 2023

The use of biocomposites is increasing due to their recyclability, biodegradability, and decreased CO2 emission levels compared to pure polyolefin plastics. Furthermore, suitably engineered biocomposites can provide, for example, superior mechanical properties for various applications. However, the correlations between the atomic-level structure and mechanical properties of most biocomposites are not yet understood. Atomistic molecular dynamics (MD) simulations provide a powerful way to examine the atomic-level structure and mechanical properties of biocomposites. In this study, polypropylene–cellulose biocomposites were examined using maleic anhydride grafted polypropylene (PP-MAH) as a coupling agent. The biocomposites were studied with the Materials Studio program package and COMPASSII force field, using the constant strain approach for mechanical properties. The results were comparable to the experimental literature values, showing that that MD can be applied to study the atomic-level structure–property correlations of polypropylene–cellulose biocomposites.
Influence of InP/ZnS Quantum Dots on Thermodynamic Properties and Morphology of the DPPC/DPPG Monolayers at Different Temperatures
Authors: Wang Juan , Feng Shun , Sheng Qingqing , Liu Ruilin
Published: January 2023

In this work, the effects of InP/ZnS quantum dots modified with amino or carboxyl group on the characteristic parameters in phase behavior, elastic modulus, relaxation time of the DPPC/DPPG mixed monolayers are studied by the Langmuir technology at the temperature of 37, 40 and 45 °C. Additionally, the information on the morphology and height of monolayers are obtained by the Langmuir–Bloggett technique and atomic force microscope technique. The results suggest that the modification of the groups can reduce the compressibility of monolayers at a higher temperature, and the most significant effect is the role of the amino group. At a high temperature of 45 °C, the penetration ability of InP/ZnS-NH2 quantum dots in the LC phase of the mixed monolayer is stronger. At 37 °C and 40 °C, there is no clear difference between the penetration ability of InP/ZnS-NH2 quantum dots and InP/ZnS-COOH quantum dots. The InP/ZnS-NH2 quantum dots can prolong the recombination of monolayers at 45 °C and accelerate it at 37 °C and 40 °C either in the LE phase or in the LC phase. However, the InP/ZnS-COOH quantum dots can accelerate it in the LE phase at all temperatures involved but only prolong it at 45 °C in the LC phase. This work provides support for understanding the effects of InP/ZnS nanoparticles on the structure and properties of cell membranes, which is useful for understanding the behavior about the ingestion of nanoparticles by cells and the cause of toxicity.
Synthesis of Platinum Nanocrystals Dispersed on Nitrogen-Doped Hierarchically Porous Carbon with Enhanced Oxygen Reduction Reaction Activity and Durability
Authors: Li Min , Liu Feng , Pei Supeng , Zhou Zongshang , Niu Kai , Wu Jianbo , Zhang Yongming
Published: January 2023

Platinum-based catalysts are widely used for efficient catalysis of the acidic oxygen reduction reaction (ORR). However, the agglomeration and leaching of metallic Pt nanoparticles limit the catalytic activity and durability of the catalysts and restrict their large-scale commercialization. Therefore, this study aimed to achieve a uniform distribution and strong anchoring of Pt nanoparticles on a carbon support and improve the ORR activity and durability of proton-exchange membrane fuel cells. Herein, we report on the facile one-pot synthesis of a novel ORR catalyst using metal–nitrogen–carbon (M–N–C) bonding, which is formed in situ during the ion exchange and pyrolysis processes. An ion-exchange resin was used as the carbon source containing R-N+(CH3)3 groups, which coordinate with PtCl62− to form nanosized Pt clusters confined within the macroporous framework. After pyrolysis, strong M-N-C bonds were formed, thereby preventing the leaching and aggregation of Pt nanoparticles. The as-synthesized Pt supported on the N-doped hierarchically porous carbon catalyst (Pt/NHPC-800) showed high specific activity (0.3 mA cm−2) and mass activity (0.165 A mgPt−1), which are approximately 2.7 and 1.5 times higher than those of commercial Pt/C, respectively. The electrochemical surface area of Pt/NHPC-800 remained unchanged (~1% loss) after an accelerated durability test of 10,000 cycles. The mass activity loss after ADT of Pt/NHPC-800 was 18%, which is considerably lower than that of commercial Pt/C (43%). Thus, a novel ORR catalyst with highly accessible and homogeneously dispersed Pt-N-C sites, high activity, and durability was successfully prepared via one-pot synthesis. This facile and scalable synthesis strategy for high-efficiency catalysts guides the further synthesis of commercially available ORR catalysts.
Hispidin in the Medicinal Fungus Protects Dopaminergic Neurons from JNK Activation-Regulated Mitochondrial-Dependent Apoptosis in an MPP+-Induced In Vitro Model of Parkinson’s Disease
Authors: Lai Mei-Chou , Liu Wayne-Young , Liou Shorong-Shii , Liu I-Min
Published: January 2023

Degenerative diseases of the brain include Parkinson’s disease (PD), which is associated with moveable signs and is still incurable. Hispidin belongs to polyphenol and originates primarily from the medicinal fungi Inonotus and Phellinus, with distinct biological effects. In the study, MES23.5 cells were induced by 1-methyl-4-phenylpyridinium (MPP+) to build a cell model of PD in order to detect the protective effect of hispdin and to specify the underlying mechanism. Pretreatment of MES23.5 cells with 1 h of hispdin at appropriate concentrations, followed by incubation of 24 h with 2 μmol/L MPP+ to induce cell damage. MPP+ resulted in reactive oxygen species production that diminished cell viability and dopamine content. Mitochondrial dysfunction in MS23.5 cells exposed to MPP+ was observed, indicated by inhibition of activity in the mitochondrial respiratory chain complex I, the collapse of potential in mitochondrial transmembrane, and the liberation of mitochondrial cytochrome c. Enabling C-Jun N-terminal kinase (JNK), reducing Bcl-2/Bax, and enhancing caspase-9/caspase-3/PARP cleavage were also seen by MPP+ induction associated with increased DNA fragmentation. All of the events mentioned above associated with MPP+-mediated mitochondrial-dependent caspases cascades were attenuated under cells pretreatment with hispidin (20 µmol/L); similar results were obtained during cell pretreatment with pan-JNK inhibitor JNK-IN-8 (1 µmol/L) or JNK3 inhibitor SR3576 (25 µmol/L). The findings show that hispidin has neuroprotection against MPP+-induced mitochondrial dysfunction and cellular apoptosis and suggest that hispidin can be seen as an assist in preventing PD.
Microbiota Effect on Trimethylamine N-Oxide Production: From Cancer to Fitness—A Practical Preventing Recommendation and Therapies
Authors: Tacconi Edoardo , Palma Giuseppe , De Biase Davide , Luciano Antonio , Barbieri Massimiliano , de Nigris Filomena , Bruzzese Francesca
Published: January 2023

Trimethylamine N-oxide (TMAO) is a microbial metabolite derived from nutrients, such as choline, L-carnitine, ergothioneine and betaine. Recently, it has come under the spotlight for its close interactions with gut microbiota and implications for gastrointestinal cancers, cardiovascular disease, and systemic inflammation. The culprits in the origin of these pathologies may be food sources, in particular, high fat meat, offal, egg yolk, whole dairy products, and fatty fish, but intercalated between these food sources and the production of pro-inflammatory TMAO, the composition of gut microbiota plays an important role in modulating this process. The aim of this review is to explain how the gut microbiota interacts with the conversion of specific compounds into TMA and its oxidation to TMAO. We will first cover the correlation between TMAO and various pathologies such as dysbiosis, then focus on cardiovascular disease, with a particular emphasis on pro-atherogenic factors, and then on systemic inflammation and gastrointestinal cancers. Finally, we will discuss primary prevention and therapies that are or may become possible. Possible treatments include modulation of the gut microbiota species with diets, physical activity and supplements, and administration of drugs, such as metformin and aspirin.
Human Milk-Derived Levels of let-7g-5p May Serve as a Diagnostic and Prognostic Marker of Low Milk Supply in Breastfeeding Women
Authors: Hicks Steven D. , Chandran Desirae , Confair Alexandra , Ward Anna , Kelleher Shannon L.
Published: January 2023

Low milk supply (LMS) is associated with early breastfeeding cessation; however, the biological underpinnings in the mammary gland are not understood. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally downregulate gene expression, and we hypothesized the profile of miRNAs secreted into milk reflects lactation performance. Longitudinal changes in milk miRNAs were measured using RNAseq in women with LMS (n = 47) and adequate milk supply (AMS; n = 123). Relationships between milk miRNAs, milk supply, breastfeeding outcomes, and infant weight gain were assessed, and interactions between milk miRNAs, maternal diet, smoking status, and BMI were determined. Women with LMS had lower milk volume (p = 0.003), were more likely to have ceased breast feeding by 24 wks (p = 0.0003) and had infants with a lower mean weight-for-length z-score (p = 0.013). Milk production was significantly associated with milk levels of miR-16-5p (R = −0.14, adj p = 0.044), miR-22-3p (R = 0.13, adj p = 0.044), and let-7g-5p (R = 0.12, adj p = 0.046). Early milk levels of let-7g-5p were significantly higher in mothers with LMS (adj p = 0.0025), displayed an interaction between lactation stage and milk supply (p < 0.001), and were negatively related to fruit intake (p = 0.015). Putative targets of let-7g-5p include genes important to hormone signaling, RNA regulation, ion transport, and the extracellular matrix, and down-regulation of two targets (PRLR and IGF2BP1/IMP1) was confirmed in mammary cells overexpressing let-7g-5p in vitro. Our data provide evidence that milk-derived miRNAs reflect lactation performance in women and warrant further investigation to assess their utility for predicting LMS risk and early breastfeeding cessation.
Molecular Mechanism of Fucoidan Nanoparticles as Protector on Endothelial Cell Dysfunction in Diabetic Rats’ Aortas
Authors: Wardani Giftania , Nugraha Jusak , Kurnijasanti Rochmah , Mustafa Mohammad Rais , Sudjarwo Sri Agus
Published: January 2023

Antioxidants have an important role in protecting against diabetes complications such as vascular endothelial cell damage. Fucoidan has strong antioxidant properties, therefore the aim of this study was to investigate the protective mechanism of fucoidan nanoparticles through the pathway of antioxidant activity against streptozotocin-induced diabetic aortic endothelial cell dysfunction in rats. Fucoidan nanoparticles are made utilizing high-energy ball milling. This research consists of five groups, namely: control rats, rats were administered aquadest; diabetic rats, rats were administered streptozotocin (STZ); fucoidan nanoparticle rats, rats were administered STZ and fucoidan nanoparticles. Aortic tissue was collected for the evaluation of ROS (reactive oxygen species), Malondialdehyde (MDA), superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Nuclear factor erythroid-2-related factor 2 (Nrf2), Nitric Oxide (NO), cyclic Guanosine Monophosphate (cGMP), relaxation response of acetylcholine (Ach), and the diameter of the aorta. The size distribution of the fucoidan nanoparticles was 267.2 ± 42.8 nm. Administration of fucoidan nanoparticles decreased the levels of ROS and MDA, and increased the levels of SOD, levels of GPx, Nrf2 expression, NO levels, cGMP expression, the relaxation response of Ach, and lumen diameter of the aorta, which are significantly different when compared with diabetic rats, p < 0.05. In this study, we concluded that the mechanism pathway of fucoidan nanoparticles prevents aortic endothelial cell dysfunction in diabetic rats through antioxidant activity by reducing ROS and MDA and incrementing SOD levels, GPx levels, and Nrf2 expression. All of these can lead to an elevated relaxation response effect of Ach and an increase in the lumen diameter of the aorta, which indicates a protective effect of fucoidan nanoparticles on aortic endothelial cells.
Urinary Risk Profile, Impact of Diet, and Risk of Calcium Oxalate Urolithiasis in Idiopathic Uric Acid Stone Disease
Authors: Siener Roswitha , Löhr Patricia , Hesse Albrecht
Published: January 2023

The role of diet in the pathogenesis of uric acid (UA) nephrolithiasis is incompletely understood. This study investigated the effect of dietary intervention on the risk of UA stone formation under standardized conditions. Twenty patients with idiopathic UA stone disease were included in the study. Dietary intake and 24 h urinary parameters were collected on the usual diet of the patients and a standardized balanced mixed diet. Although urinary UA excretion did not change, the relative supersaturation of UA decreased significantly by 47% under the balanced diet primarily due to the significant increase in urine volume and pH. Urinary pH was below 5.8 in 85% of patients under the usual diet, and in 60% of patients under the balanced diet. The supersaturation of calcium oxalate declined significantly under the balanced diet due to the significant decrease in urinary calcium and oxalate excretion and the increase in urine volume. Dietary intervention is a key component in the management of UA nephrolithiasis. Urinary calcium and oxalate excretion should also be monitored in patients with pure UA calculi to reduce the risk of mixed stone formation with calcium oxalate. Lower urinary pH in UA stone patients can only be partially explained by diet.
Dietary Diversity, Household Food Insecurity and Stunting among Children Aged 12 to 59 Months in N’Djamena—Chad
Authors: Gassara Goudja , Lin Qian , Deng Jing , Zhang Yaxi , Wei Jieqiong , Chen Jihua
Published: January 2023

Background: Household food insecurity is increasingly recognized as a global health problem, particularly in sub-Saharan Africa. This study aimed to contextualize the associations between household food insecurity, dietary diversity and stunting in N’Djamena. Methods: This study is a community-based cross-sectional study, and the SMART (Standardized Monitoring and Assessment of Relief and Transitions) methodology was used to calculate the sample size. A total of 881 households were selected for the survey. A 24-h recall evaluated the dietary diversity score (DDS), the Household Food Insecurity Access Scale (HFIAS) made it possible to assess household food insecurity (HFI), and stunting among children aged 12 to 59 months was assessed by anthropometric measurements. Logistic regression was constructed to determine the association between household food insecurity, dietary diversity, and stunting. The study was conducted from January to March 2022. Results: The prevalence of severe food insecurity was 16.6%, and that of stunting was 25.3%. The mean DDS was 6.5 ± 1.6. Severe food insecurity (OR 2.505, CI: 1.670–3.756) was significantly associated with stunting. The association between DDS and stunting was not significant. Conclusions: This study’s prevalence of household food insecurity and stunting was very high. Household food insecurity and household size were significantly associated with stunting.
Prognostic Significance of Severe Vitamin D Deficiency in Patients with Primary Sclerosing Cholangitis
Authors: Ebadi Maryam , Rider Elora , Tsai Catherine , Wang Sarah , Lytvyak Ellina , Mason Andrew , Montano-Loza Aldo J.
Published: January 2023

Vitamin D deficiency has been linked with adverse events in various liver diseases. The present study aimed to recognize the association between severe vitamin D deficiency and disease progression, hepatobiliary malignancies, liver-related mortality, and the need for liver transplantation in primary sclerosing cholangitis (PSC). Patients with a diagnosis of PSC (n = 354), followed by the autoimmune liver disease clinic at the University of Alberta, were included. Patients with vitamin D levels < 25 nmol/L were defined as severely deficient. Univariate and multivariate analyses were conducted using the Cox proportional hazards regression models. The mean vitamin D level was 59 ± 2 nmol/L, and 63 patients (18%) had a severe vitamin D deficiency. Patients with a severe vitamin D deficiency were 2.5 times more likely to experience hepatobiliary malignancies (HR 2.55, 95% CI, 1.02–6.40, p = 0.046). A severe vitamin D deficiency at diagnosis (HR 1.82, 95% CI, 1.05–3.15, p = 0.03) and persistent deficiencies over time (HR 2.26, 95% CI, 1.17–4.37, p = 0.02) were independently associated with a higher risk of poor clinical liver outcomes. A severe vitamin D deficiency at diagnosis and persistent deficiency at longitudinal assessments were associated with liver-related mortality or the need for liver transplantation.
Ellagic Acid and Its Metabolites as Potent and Selective Allosteric Inhibitors of Liver Pyruvate Kinase
Authors: Battisti Umberto Maria , Gao Chunixa , Akladios Fady , Kim Woonghee , Yang Hong , Bayram Cemil , Bolat Ismail , Kiliclioglu Metin , Yuksel Nursena , Tozlu Ozlem Ozdemir , Zhang Cheng , Sebhaoui Jihad , Iqbal Shazia , Shoaie Saeed , Hacimuftuoglu Ahmet , Yildirim Serkan , Turkez Hasan , Uhlen Mathias , Boren Jan , Mardinoglu Adil , Grøtli Morten
Published: January 2023

Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent a new therapeutic option. However, this breakthrough is complicated by selectivity issues since pyruvate kinase exists in four different isoforms. In this work, we report that ellagic acid (EA) and its derivatives, present in numerous fruits and vegetables, can inhibit PKL potently and selectively. Several polyphenolic analogues of EA were synthesized and tested to identify the chemical features responsible for the desired activity. Molecular modelling studies suggested that this inhibition is related to the stabilization of the PKL inactive state. This unique inhibition mechanism could potentially herald the development of new therapeutics for NAFLD.
Improvement of Dietary Habits among German Medical Students by Attending a Nationwide Online Lecture Series on Nutrition and Planetary Health (“Eat This!”)
Authors: Helbach Anna , Dumm Moritz , Moll Katharina , Böttrich Tim , Leineweber Can Gero , Mueller Wiebke , Matthes Jan , Polidori Maria Cristina
Published: January 2023

Nutrition is a major influential factor in optimizing human health and environmental sustainability. Medical students often do not follow national dietary guideline recommendations. Raising awareness of a healthy lifestyle is important as physicians with healthy lifestyle behaviors are more likely to counsel on nutrition. Our study aims to evaluate a Germany-wide online lecture series on nutritional medicine, “Eat This!”. Before and after the course, 520 medical students who participated and 64 who did not participate in the course (comparison group) filled out an online survey. To assess the students’ dietary habits, a validated FFQ was used. According to this questionnaire, only 31% of the lecture participants consumed enough fruits and 24% consumed enough vegetables, while almost half of the students exceeded the recommended maximum amount of crisps and sweets. After attending the lecture series, guideline adherence with respect to fruits and vegetables showed a significant increase, as did awareness of healthy nutrition and percentage of students with low-risk lifestyle habits. Our results show that low-threshold approaches, such as “Eat This!”, can positively influence the dietary behaviors and lifestyle habits of medical students. This can help future doctors fulfill their role in the fight against the global burden of non-communicable diseases.
The Effect of Hydrolyzed and Fermented Arabinoxylan-Oligo Saccharides (AXOS) Intake on the Middle-Term Gut Microbiome Modulation and Its Metabolic Answer
Authors: Polo Andrea , Albiac Marta Acin , Da Ros Alessio , Ardèvol Vimac Nolla , Nikoloudaki Olga , Verté Fabienne , Di Cagno Raffaella , Gobbetti Marco
Published: January 2023

Although fermentation and hydrolyzation are well-known processes to improve the bioavailability of nutrients and enable the fortification with dietary fibers, the effect of such pre-treatments on the prebiotic features of arabinoxylan-oligosaccharides (AXOS) had not been explored. The middle-term in vitro simulation through the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) demonstrated that the feeding with different formulations (namely oat bran, rye bran and wheat bran) containing hydrolyzed AXOS fermented by lactic acid bacteria significantly increased the synthesis of short-chain fatty acids (SCFA) by colon microbiota, with hydrolyzed and fermented rye bran displaying the highest effect. After two weeks from the interruption of intake, SCFA concentrations significantly decreased but remained still significantly higher compared to the original condition. The microbiome was also affected, with a significant abundance increase in Lactobacillaceae taxon after feeding with all fermented and hydrolyzed formulates. Hydrolyzed and fermented rye bran showed the highest changes. The fungal community, even if it had a lower variety compared to bacteria, was also modulated after feeding with AXOS formulations, with an increase in Candida relative abundance and a decrease in Issatchenkia. On the contrary, the intake of non-hydrolyzed and non-fermented wheat bran did not produce relevant changes of relative abundances. After two weeks from intake interruption (wash out period) such changes were mitigated, and the gut microbiome modulated again to a final structure that was more like the original condition. This finding suggests that hydrolyzed AXOS fermented by lactic acid bacteria could have a more powerful prebiotic effect compared to non-hydrolyzed and non-fermented wheat bran, shaping the colon microbiome and its metabolic answer. However, the intake should be continuous to assure persistent effects. Opening a window into the ecological evolutions and plausible underlying mechanisms, the findings reinforce the perspective to explore more in depth the use of hydrolyzed and fermented AXOS as additional ingredient for bread fortification.
ORAI Calcium Channels: Regulation, Function, Pharmacology, and Therapeutic Targets
Authors: Rubaiy Hussein N.
Published: January 2023

The changes in intracellular free calcium (Ca2+) levels are one of the most widely regulators of cell function; therefore, calcium as a universal intracellular mediator is involved in very important human diseases and disorders. In many cells, Ca2+ inflow is mediated by store-operated calcium channels, and it is recognized that the store-operated calcium entry (SOCE) is mediated by the two partners: the pore-forming proteins Orai (Orai1-3) and the calcium store sensor, stromal interaction molecule (STIM1-2). Importantly, the Orai/STIM channels are involved in crucial cell signalling processes such as growth factors, neurotransmitters, and cytokines via interaction with protein tyrosine kinase coupled receptors and G protein-coupled receptors. Therefore, in recent years, the issue of Orai/STIM channels as a drug target in human diseases has received considerable attention. This review summarizes and highlights our current knowledge of the Orai/STIM channels in human diseases and disorders, including immunodeficiency, myopathy, tubular aggregate, Stormorken syndrome, York platelet syndrome, cardiovascular and metabolic disorders, and cancers, as well as suggesting these channels as drug targets for pharmacological therapeutic intervention. Moreover, this work will also focus on the pharmacological modulators of Orai/STIM channel complexes. Together, our thoughtful of the biology and physiology of the Orai/STIM channels have grown remarkably during the past three decades, and the next important milestone in the field of store-operated calcium entry will be to identify potent and selective small molecules as a therapeutic agent with the purpose to target human diseases and disorders for patient benefit.
A CO2-Responsive Imidazole-Functionalized Fluorescent Material Mediates Cancer Chemotherapy
Authors: Ngan Vo Thuy Thien , Chiou Po-Yen , Ilhami Fasih Bintang , Bayle Enyew Alemayehu , Shieh Yeong-Tarng , Chuang Wei-Tsung , Chen Jem-Kun , Lai Juin-Yih , Cheng Chih-Chia
Published: January 2023

We present a breakthrough in the synthesis and development of functional gas-responsive materials as highly potent anticancer agents suitable for applications in cancer treatment. Herein, we successfully synthesised a stimuli-responsive multifunctional material (I-R6G) consisting of a carbon dioxide (CO2)-sensitive imidazole moiety and spirolactam-containing conjugated rhodamine 6G (R6G) molecule. The resulting I-R6G is highly hydrophobic and non- or weakly fluorescent. Simple CO2 bubbling treatment induces hydrophobic I-R6G to completely dissolve in water and subsequently form self-assembled nanoparticles, which exhibit unique optical absorption and fluorescence behaviours in water and extremely low haemolytic ability against sheep red blood cells. Reversibility testing indicated that I-R6G undergoes reversible CO2/nitrogen (N2)-dependent stimulation in water, as its structural and physical properties can be reversibly and stably switched by alternating cycles of CO2 and N2 bubbling. Importantly, in vitro cellular assays clearly demonstrated that the CO2-protonated imidazole moiety promotes rapid internalisation of CO2-treated I-R6G into cancer cells, which subsequently induces massive levels of necrotic cell death. In contrast, CO2-treated I-R6G was not internalised and did not affect the viability of normal cells. Therefore, this newly created system may provide an innovative and efficient route to remarkably improve the selectivity, safety and efficacy of cancer treatment.
Modeling of Microneedle Arrays in Transdermal Drug Delivery Applications
Authors: Henriquez Francisco , Celentano Diego , Vega Marcela , Pincheira Gonzalo , Morales-Ferreiro J. O.
Published: January 2023

The use of computational tools for the development of technologies in fields such as medicine and engineering has facilitated the process of designing new components and devices for these areas. In this work, two proposals focused on a hollow microneedle array (MNA) for the administration of an analgesic drug are shown and evaluated by means of a computational fluid dynamics (CFD) simulation distributed in three stages. In the first stage, the behavior of lidocaine through the MNA was evaluated as a workflow. Then, the possible entry of the drug into the organism, which was established as a porous aqueous medium, was modeled. Finally, a joint simulation was performed to understand the general behavior in the interaction between the outflow of an MNA and the body to which lidocaine is administered. The input parameters to the simulation were set at a velocity of 0.05 m∙s−1, at a pressure of 2000 Pa, the dominant behavior was defined as laminar flow, and a resistive pressure at the inlet of 400 Pa. Our results indicate that the vertical flow exhibits a better fluid distribution across the MNAs and favorable infiltration behavior, representing better delivery of the analgesic to the skin capillaries.