bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Dynamics Research on Fe Precipitation Behavior of Cu95Fe5 Alloys during Rapid Cooling
Authors: Wang Xufeng , Gao Xufeng , Lai Zhibo , Han Zongen , Li Yungang
Published: February 2024

To investigate structural changes, the Cu95Fe5 alloy system was subjected to cooling rates of 1 × 1013 K/s, 2 × 1012 K/s, 2 × 1011 K/s, and 2 × 1010 K/s using the molecular dynamics simulation method. The results revealed that decreasing the cooling rate caused an increase in the phase transition temperature. Further, the structure of the alloy system exhibited a tendency towards increased stability following cooling at lower cooling rates. The Fe precipitation behavior of the Cu95Fe5 alloys during cooling at the rate of 2 × 1010 K/s was further explored, with the results suggesting that the formation and growth of the Fe cluster is a continuous process governed by the nucleation and growth mechanism. The size and number of Fe clusters formed at different stages were found to be affected by three factors, namely, the interaction force between the Fe atoms, the diffusion ability of the Fe atoms, and the interfacial energy between the Fe cluster and Cu matrix. When the alloy temperature exceeded 1400 K, the accumulation of the Fe atoms was facilitated by their strong interaction. However, the high temperatures and the large diffusion coefficient of the Fe atoms acted as inhibitors to the growth of Fe clusters, despite the intense thermal activities. As the temperature was reduced from 1400 K to 1050 K, the Fe atoms moved with a reduced intensity in a narrower area, and both the number of Fe atoms in the largest cluster and the number of clusters increased due to the action of the interaction force between the Fe atoms. Upon lowering the temperature from 1050 K to 887 K, the size of the largest Fe cluster increased rapidly, while the number of clusters decreased gradually. The growth of the largest Fe cluster could be partly attributed to the diffusion of single Fe atoms into the cluster under the action of the interaction force between the Fe atoms, in addition to the gathering and combination of multiple clusters. When the temperature was lowered from 967 K to 887 K, the diffusion coefficient of the Fe atoms approached 0, indicating that the non-diffusive local structure rearrangements of atoms dominated in the system structure change process. The interface energy governed the combination of the Fe clusters in this stage. At a temperature below 887 K, the alloy crystallized, the activities of the Fe atoms were reduced due to a low temperature, and the movement range of the Fe atoms was small at a fast cooling rate. As such, both the size and number of Fe clusters showed no obvious changes.
Research of a Novel Non-Axisymmetric Side-Compressed Variable Polarity Plasma Arc and Its Pressure Distribution Characteristics
Authors: Zhao Hongxing , Yang Chunli , Fan Chenglei
Published: February 2024

In the keyhole variable polarity plasma arc weldng (VPPAW) process at horizontal position, the metal driven by gravity gathered on one side of the molten pool, and the weld formation is difficult, especially for thick workpiece welding. A specially designed experiment to analyze the influence of gravity on weld formation and a novel nozzle structure with side holes was proposed to generate a novel non-axisymmetric side-compressed plasma arc and redistribute arc pressure. The arc shape and pressure distribution were studied, and the ratio of difference for arc pressure in different directions Rp was introduced to evaluate the effects of non-axisymmetric side compression for the plasma arc. The results indicate that the non-axisymmetric distributed side holes reshape the plasma arc both in the EN and EP phases. The pressure of the non-axisymmetric side-compressed plasma arc decreases relatively strongly in one direction (direction b) and relatively weakly in the other direction (direction a). Rp is significant at 1 mm to 5 mm from the arc center, with a relatively large Rp within this range. The compression effect is enhanced with an increase in welding current or plasma gas flow rate, and Rp increases from 24% to 49% as the plasma gas flow rate increases from 2 L/min to 4.5 L/min. Specially designed validation experiments confirm that the new plasma arc significantly affects the weld formation in keyhole VPPAW process. An aluminum alloy workpiece with 8 mm thickness and no groove preparation was welded by the novel plasma arc in a horizontal welding position, and the weld is well formed.
Compression and Tensile Testing of L-PBF Ti-6Al-4V Lattice Structures with Biomimetic Porosities and Strut Geometries for Orthopedic Implants
Authors: Papazoglou Dimitri P. , Neidhard-Doll Amy T. , Pinnell Margaret F. , Erdahl Dathan S. , Osborn Timothy H.
Published: February 2024

In an effort to contribute to the ongoing development of ASTM standards for additively manufactured metal lattice specimens, particularly within the field of medicine, the compressive and tensile mechanical properties of biomimetic lattice structures produced by laser powder bed fusion (L-PBF) using Ti-6Al-4V feedstock powder were investigated in this research. The geometries and porosities of the lattice structures were designed to facilitate internal bone growth and prevent stress shielding. A thin strut thickness of 200 µm is utilized for these lattices to mimic human cancellous bone. In addition to a thin strut size, two different strut geometries were utilized (cubic and body-centered cubic), along with four different pore sizes (400, 500, 600, and 900 µm, representing 40–90% porosity in a 10 mm cube). A 10 mm3 cube was used for compression testing and an experimental pin-loaded design was implemented for tensile testing. The failure mode for each specimen was examined using scanning electron microscopy (SEM). Lattice structures were compared to the mechanical properties of human cancellous bone. It was found that the elastic modulus of human cancellous bone (10–900 MPa) could be matched for both the tensile (92.7–129.6 MPa) and compressive (185.2–996.1 MPa) elastic modulus of cubic and body-centered cubic lattices. Body-centered cubic lattices exhibited higher compressive properties over cubic, whereas cubic lattices exhibited superior tensile properties. The experimental tensile specimen showed reacquiring failures close to the grips, indicating that a different tensile design may be required for consistent data acquisition in the future.
Geometry-Dependent Elastic Flow Dynamics in Micropillar Arrays
Authors: Ström Oskar E. , Beech Jason P. , Tegenfeldt Jonas O.
Published: February 2024

Regular device-scale DNA waves for high DNA concentrations and flow velocities have been shown to emerge in quadratic micropillar arrays with potentially strong relevance for a wide range of microfluidic applications. Hexagonal arrays constitute another geometry that is especially relevant for the microfluidic pulsed-field separation of DNA. Here, we report on the differences at the micro and macroscopic scales between the resulting wave patterns for these two regular array geometries and one disordered array geometry. In contrast to the large-scale regular waves visible in the quadratic array, in the hexagonal arrays, waves occur in a device-scale disordered zig-zag pattern with fluctuations on a much smaller scale. We connect the large-scale pattern to the microscopic flow and observe flow synchronization that switches between two directions for both the quadratic and hexagonal arrays. We show the importance of order using the disordered array, where steady-state stationary and highly fluctuating flow states persist in seemingly random locations across the array. We compare the flow dynamics of the arrays to that in a device with sparsely distributed pillars. Here, we observe similar vortex shedding, which is clearly observable in the quadratic and disordered arrays. However, the shedding of these vortices couples only in the flow direction and not laterally as in the dense, ordered arrays. We believe that our findings will contribute to the understanding of elastic flow dynamics in pillar arrays, helping us elucidate the fundamental principles of non-Newtonian fluid flow in complex environments as well as supporting applications in engineering involving e.g., transport, sorting, and mixing of complex fluids.
A Review of Reliability in Gate-All-Around Nanosheet Devices
Authors: Wang Miaomiao
Published: February 2024

The gate-all-around (GAA) nanosheet (NS) field-effect-transistor (FET) is poised to replace FinFET in the 3 nm CMOS technology node and beyond, marking the second seminal shift in device architecture across the extensive 60-plus-year history of MOSFET. The introduction of a new device structure, coupled with aggressive pitch scaling, can give rise to reliability challenges. In this article, we present a review of the key reliability mechanisms in GAA NS FET, including bias temperature instability (BTI), hot carrier injection (HCI), gate oxide (Gox) time-dependent dielectric breakdown (TDDB), and middle-of-line (MOL) TDDB. We aim to not only underscore the unique reliability attributes inherent to NS architecture but also provide a holistic view of the status and prospects of NS reliability, taking into account the challenges posed by future scaling.
Effect of Additives on Tribological Performance of Magnetorheological Fluids
Authors: Zhuang Songran , Cao Yongbing , Song Wanli , Zhang Peng , Choi Seung-Bok
Published: February 2024

In this study, nano-diamond (ND) and MoS2 powder are used as additives in a carbonyl iron-based magnetorheological fluid (MRF) to improve its tribological performance. MRFs are prepared by dispersing 35 wt.% of CI particles in silicone oil and adding different proportions (0, 1, 3, or 5 wt.%) of ND and MoS2 additives. Seven kinds of MRFs are made and tested using reciprocating friction and wear tester under different normal loads, and then the friction characteristics are evaluated by analyzing the experimental results. The morphological properties of MRFs and contacting surfaces before and after the tests are also observed using a scanning electron microscope and analyzed via energy-dispersive X-ray spectroscopy. The results show that the appropriate weight percentage of MoS2 additives may decrease the friction coefficient and wear zone. It is also demonstrated from detailed analyses of worn surfaces that the wear mechanism is influenced not only by additives, but also by the applied normal load and magnetic field strength.
Genesis of Gabbroic Hosted Copper Mineralisations in the Albanian Mirdita Zone (Kçira, Thirra)
Authors: Váczi-Lovász Anikó , Kovács Zoltán , Kiss Gabriella B.
Published: February 2024

There is a wide variety of ore deposits in Albania, where 20% of the Cu resources belong to a deposit type of unknown genesis (sulphide-bearing quartz veins in gabbroic rocks). The focus of this paper is on two mineralisations of this type (Kçira and Thirra) in the Mirdita Zone, an ophiolite zone representing the Mesozoic Neotethys Ocean in the Dinarides. Our aim is to understand the ore-forming processes and the genesis of these deposits, which can be used in future exploration projects. According to the petrographical analysis, the host rock suffered propylitic alteration or subgreenschist facies metamorphism. Mineral chemistry of pyrite and epidote suggests a VMS related origin, more precisely, the deeper part of its stockwork feeder zone. The bulk rock geochemical analyses confirms that the mineralisations are classified as mafic-, Cyprus-type VMS deposits. Differences in the geochemical compositions and the corresponding mineralogical observations are attributed to the distinct original geotectonic positions: higher amount of compatible elements (Cr, Ni, V and Cu) occur in Kçira, which formed in a mid-oceanic ridge environment, while incompatible elements (Ag, As, Co and Zn) are more abundant in the Thirra deposit, which formed in a supra-subduction zone setting.
Sustainable Production of Biofuels and Biochemicals via Electro-Fermentation Technology
Authors: Salar-García María José , Ortiz-Martínez Víctor Manuel , Sánchez-Segado Sergio , Valero Sánchez Raúl , Sáez López Antonia , Lozano Blanco Luis Javier , Godínez-Seoane Carlos
Published: February 2024

The energy crisis and climate change are two of the most concerning issues for human beings nowadays. For that reason, the scientific community is focused on the search for alternative biofuels to conventional fossil fuels as well as the development of sustainable processes to develop a circular economy. Bioelectrochemical processes have been demonstrated to be useful for producing bioenergy and value-added products from several types of waste. Electro-fermentation has gained great attention in the last few years due to its potential contribution to biofuel and biochemical production, e.g., hydrogen, methane, biopolymers, etc. Conventional fermentation processes pose several limitations in terms of their practical and economic feasibility. The introduction of two electrodes in a bioreactor allows the regulation of redox instabilities that occur in conventional fermentation, boosting the overall process towards a high biomass yield and enhanced product formation. In this regard, key parameters such as the type of culture, the nature of the electrodes as well as the operating conditions are crucial in order to maximize the production of biofuels and biochemicals via electro-fermentation technology. This article comprises a critical overview of the benefits and limitations of this emerging bio-electrochemical technology and its contribution to the circular economy.
Electrografting of Phenyl Phosphate Layers onto Glassy Carbon for Tuning Catalytic Activity toward the Hydrogen Evolution Reaction
Authors: Atyf Zaynab , Lenne Quentin , Ghilane Jalal
Published: February 2024

In this study, we explored the surface modification of a glassy carbon electrode through the electrografting of 4-Aminophenyl phosphate, which features heteroatoms and ionic properties. The electrochemical grafting process involves reducing in situ-generated diazonium derivatives. The primary objective of this research was to immobilize organic layers and assess their electrochemical and surface properties. Subsequently, the generated surface serves as a template for the electrochemical growth of Pd and Co nanoparticles on functionalized electrodes. The electrocatalytic performances of these hybrid electrodes in driving the hydrogen evolution reaction were investigated. The obtained results indicate an enhancement in the electrocatalytic activity of the modified electrodes, where lower overpotential and higher stability were observed when the catalyst was electrodeposited onto the attached ionic layer. These findings highlight the synergistic effect between the attached phenyl phosphate moieties and electrocatalysts.
Transient Absorption Spectroscopic Investigation of the Photocyclization–Deprotection Reaction of 3′,5′-Dimethoxybenzoin Fluoride
Authors: Liang Runhui , Li Yuanchun , Lo Kin Cheung , Yan Zhiping , Tang Wenjian , Du Lili , Phillips David Lee
Published: February 2024

The 3′,5′-dimethoxybenzoin (DMB) system has been widely investigated as a photoremovable protecting group (PRPG) for the elimination of various functional groups and has been applied in many fields. The photolysis of DMB fluoride leads to a highly efficient photocyclization–deprotection reaction, resulting in a high yield of 3′,5′-dimethoxybenzofuran (DMBF) in a MeCN solution, while there is a competitive reaction that produces DMB in an aqueous solution. The yield of DMB increased as the volume ratio of water increased. To understand the solvent effect of the photolysis of selected DMB-based compounds, a combination of femtosecond to nanosecond transient absorption spectroscopies (fs-TA and ns-TA), nanosecond time-resolved resonance Raman spectroscopy (ns-TR3) and quantum chemical calculation was employed to study the photophysical and photochemical reaction mechanisms of DMB fluoride in different solutions. Facilitated by the bichromophoric nature of DMB fluoride with electron-donating and -withdrawing chromophores, the cyclized intermediates could be found in a pure MeCN solution. The deprotection of a cyclic biradical intermediate results in the simultaneous formation of DMBF and a cyclic cation species. On the other hand, in aqueous solution, fs-TA experiments revealed that α-keto cations could be observed after excitation directly, which could easily produce the DMB through the addition of a hydroxyl within 8.7 ps. This work provides comprehensive photo-deactivation mechanisms of DMB fluoride in MeCN and aqueous conditions and provides critical insights regarding the biomedical application of DMB-based PRPG compounds.
Chemical Composition Antioxidant and Anti-Inflammatory Activities of Myrtus communis L. Leaf Extract: Forecasting ADMET Profiling and Anti-Inflammatory Targets Using Molecular Docking Tools
Authors: Belahcene Samia , Kebsa Widad , Akingbade Tomilola Victor , Umar Haruna Isiyaku , Omoboyowa Damilola Alex , Alshihri Abdulaziz A. , Abo Mansour Adel , Alhasaniah Abdulaziz Hassan , Oraig Mohammed A. , Bakkour Youssef , Leghouchi Essaid
Published: February 2024

Compounds derived from natural sources continue to serve as chemical scaffolds for designing prophylactic/therapeutic options for human healthcare. In this study, we aimed to systematically unravel the chemical profile and antioxidant and anti-inflammatory activities of myrtle methanolic extract (MMEx) using in vitro, in vivo, and in silico approaches. High levels of TPC (415.85 ± 15.52 mg GAE/g) and TFC (285.80 ± 1.64 mg QE/g) were observed. Mass spectrophotometry (GC-MS) analysis revealed the presence of 1,8-cineole (33.80%), α-pinene (10.06%), linalool (4.83%), p-dimethylaminobenzophenone (4.21%), thunbergol (4%), terpineol (3.60%), cis-geranyl acetate (3.25%), and totarol (3.30%) as major compounds. MMEx induced pronounced dose-dependent inhibition in all assays, and the best antioxidant activity was found with H2O2, with an IC50 of 17.81 ± 3.67 µg.mL−1. MMEx showed a good anti-inflammatory effect in vivo by limiting the development of carrageenan-induced paw edema. The pharmacokinetic profiles of the active molecules were determined using the SwissADME website, followed by virtual screening against anti-inflammatory targets including phospholipase A2 (PLA-2), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and NF-κB. A pharmacokinetic study revealed that the molecules have good absorption, distribution, and metabolism profiles, with negative organ toxicity. Among the compounds identified by GC-MS analysis, pinostrobin chalcone, cinnamyl cinnamate, hedycaryol, totarol, and p-dimethylaminobenzophenone were observed to have good binding scores, thus appreciable anti-inflammatory potential. Our study reveals that MMEx from Algerian Myrtus communis L. can be considered to be a promising candidate for alleviating many health complaints associated with oxidative stress and inflammation.
Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial Crop Andrographis paniculate and Its Antiviral Medicinal Parts
Authors: Yu Kuo , Liang Pengjie , Yu Heshui , Liu Hui , Guo Jialiang , Yan Xiaohui , Li Zheng , Li Guoqiang , Wang Ying , Wang Chunhua
Published: February 2024

Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class Ⅰ terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.
Synthesis and Optimization of Ni-Based Nano Metal–Organic Frameworks as a Superior Electrode Material for Supercapacitor
Authors: Manquian Carolina , Navarrete Alberto , Vivas Leonardo , Troncoso Loreto , Singh Dinesh Pratap
Published: February 2024

Metal–organic frameworks (MOFs) are hybrid materials that are being explored as active electrode materials in energy storage devices, such as rechargeable batteries and supercapacitors (SCs), due to their high surface area, controllable chemical composition, and periodic ordering. However, the facile and controlled synthesis of a pure MOF phase without impurities or without going through a complicated purification process (that also reduces the yield) are challenges that must be resolved for their potential industrial applications. Moreover, various oxide formations of the Ni during Ni-MOF synthesis also represent an issue that affects the purity and performance. To resolve these issues, we report the controlled synthesis of nickel-based metal–organic frameworks (NiMOFs) by optimizing different growth parameters during hydrothermal synthesis and by utilizing nickel chloride as metal salt and H2bdt as the organic ligand, in a ratio of 1:1 at 150 °C. Furthermore, the synthesis was optimized by introducing a magnetic stirring stage, and the reaction temperature varied across 100, 150, and 200 °C to achieve the optimized growth of the NiMOFs crystal. The rarely used H2bdt ligand for Ni-MOF synthesis and the introduction of the ultrasonication stage before putting it in the furnace led to the formation of a pure phase without impurities and oxide formation. The synthesized materials were further characterized by powder X-ray diffraction (XRD) technique, scanning electron microscopy (SEM), and UV–vis spectroscopy. The SEM images exhibited the formation of nano NiMOFs having a rectangular prism shape. The average size was 126.25 nm, 176.0 nm, and 268.4 nm for the samples (1:1)s synthesized at 100 °C, 150 °C, and 200 °C, respectively. The electrochemical performances were examined in a three-electrode configuration, in a wide potential window from −0.4 V to 0.55 V, and an electrolyte concentration of 2M KOH was maintained for each measurement. The charge–discharge galvanostatic measurement results in specific capacitances of 606.62 F/g, 307.33 F/g, and 287.42 F/g at a current density of 1 A/g for the synthesized materials at 100 °C, 150 °C, and 200 °C, respectively.
A Review of Benzophenone-Based Derivatives for Organic Light-Emitting Diodes
Authors: Blazevicius Dovydas , Grigalevicius Saulius
Published: February 2024

Organic light-emitting diodes (OLEDs) have garnered considerable attention in academic and industrial circles due to their potential applications in flat-panel displays and solid-state lighting technologies, leveraging the advantages offered by organic electroactive derivatives over their inorganic counterparts. The thin and flexible design of OLEDs enables the development of innovative lighting solutions, facilitating the creation of customizable and contoured lighting panels. Among the diverse electroactive components employed in the molecular design of OLED materials, the benzophenone core has attracted much attention as a fragment for the synthesis of organic semiconductors. On the other hand, benzophenone also functions as a classical phosphor with high intersystem crossing efficiency. This characteristic makes it a compelling candidate for effective reverse intersystem crossing, with potential in leading to the development of thermally activated delayed fluorescent (TADF) emitters. These emitting materials witnessed a pronounced interest in recent years due to their incorporation in metal-free electroactive frameworks and the capability to convert triplet excitons into emissive singlet excitons through reverse intersystem crossing (RISC), consequently achieving exceptionally high external quantum efficiencies (EQEs). This review article comprehensively overviews the synthetic pathways, thermal characteristics, electrochemical behaviour, and photophysical properties of derivatives based on benzophenone. Furthermore, we explore their applications in OLED devices, both as host materials and emitters, shedding light on the promising opportunities that benzophenone-based compounds present in advancing OLED technology.
Effect of Blueberry Supplementation on a Diet-Induced Rat Model of Prediabetes—Focus on Hepatic Lipid Deposition, Endoplasmic Stress Response and Autophagy
Authors: Ferreira Gonçalo , Vieira Pedro , Alves André , Nunes Sara , Preguiça Inês , Martins-Marques Tânia , Ribeiro Tânia , Girão Henrique , Figueirinha Artur , Salgueiro Lígia , Pintado Manuela , Gomes Pedro , Viana Sofia , Reis Flávio
Published: February 2024

Blueberries, red fruits enriched in polyphenols and fibers, are envisaged as a promising nutraceutical intervention in a plethora of metabolic diseases. Prediabetes, an intermediate state between normal glucose tolerance and type 2 diabetes, fuels the development of complications, including hepatic steatosis. In previous work, we have demonstrated that blueberry juice (BJ) supplementation benefits glycemic control and lipid profile, which was accompanied by an amelioration of hepatic mitochondrial bioenergetics. The purpose of this study is to clarify the impact of long-term BJ nutraceutical intervention on cellular mechanisms that govern hepatic lipid homeostasis, namely autophagy and endoplasmic reticulum (ER) stress, in a rat model of prediabetes. Two groups of male Wistar rats, 8-weeks old, were fed a prediabetes-inducing high-fat diet (HFD) and one group was fed a control diet (CD). From the timepoint where the prediabetic phenotype was achieved (week 16) until the end of the study (week 24), one of the HFD-fed groups was daily orally supplemented with 25 g/kg body weight (BW) of BJ (HFD + BJ). BW, caloric intake, glucose tolerance and insulin sensitivity were monitored throughout the study. The serum and hepatic lipid contents were quantified. Liver and interscapular brown and epidydimal white adipose tissue depots (iBAT and eWAT) were collected for histological analysis and to assess thermogenesis, ER stress and autophagy markers. The gut microbiota composition and the short-chain fatty acids (SCFAs) content were determined in colon fecal samples. BJ supplementation positively impacted glycemic control but was unable to prevent obesity and adiposity. BJ-treated animals presented a reduction in fecal SCFAs, increased markers of arrested iBAT thermogenesis and energy expenditure, together with an aggravation of HFD-induced lipotoxicity and hepatic steatosis, which were accompanied by the inhibition of autophagy and ER stress responses in the liver. In conclusion, despite the improvement of glucose tolerance, BJ supplementation promoted a major impact on lipid management mechanisms at liver and AT levels in prediabetic animals, which might affect disease course.
The Immunomodulatory Effects of A2 β-Casein on Immunosuppressed Mice by Regulating Immune Responses and the Gut Microbiota
Authors: Li Xiao , Lu Xingru , Liu Ming , Zhang Yu , Jiang Yujun , Yang Xinyan , Man Chaoxin
Published: February 2024

The aim of this study was to investigate the immunomodulatory effects of A2 β-casein (β-CN) in cyclophosphamide-induced immunosuppressed BALB/c mice. Experiments conducted in vitro revealed that A2 β-CN digestive products have potent immunostimulatory activities. Animal studies demonstrated that A2 β-CN improved the immunological organ index reduction trend caused by cyclophosphamide, reduced the pathological damage to the spleen tissue in immunosuppressed mice, increased the release of IL-17A, IgG, and IgA, and reduced the production of IL-4. By regulating the relative abundance of advantageous bacteria like Oscillospira, Lactobacillus, and Bifidobacteria and harmful bacteria like Coprococcus and Desulfovibrionaceae, A2 β-CN improved gut microbiota disorders in immunosuppressed mice. Moreover, A2 β-CN promoted the production of short-chain fatty acids and increased the diversity of the gut microbiota. Therefore, ingestion of A2 β-CN is beneficial to the host’s immune system and gut health. These findings provide insights for the future application of A2 β-CN-related dairy products.
Zinc Supplementation Enhances the Hematopoietic Activity of Erythropoiesis-Stimulating Agents but Not Hypoxia-Inducible Factor–Prolyl Hydroxylase Inhibitors
Authors: Takahashi Akira
Published: February 2024

Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance hemodialysis who underwent periods of treatment with roxadustat or darbepoetin alfa during the past 3 years were retrospectively observed. Participants who underwent periods with and without zinc supplementation were selected, with nine treated with darbepoetin alfa and nine treated with roxadustat. Similarly to the ESA responsiveness index (ERI), the hematopoietic effect of zinc supplementation was determined by the HIF-PHI responsiveness index (HRI), which was calculated by dividing the HIF-PHI dose (mg/week) by the patient’s dry weight (kg) and hemoglobin level (g/L). Zinc supplementation significantly increased ERI (p < 0.05), but no significant change was observed (p = 0.931) in HRI. Although zinc supplementation did not significantly affect HRI, adequate zinc supplementation is required to alleviate concerns such as vascular calcification and increased serum copper during the use of HIF-PHI.
University Students as Change Agents for Health and Sustainability: A Pilot Study on the Effects of a Teaching Kitchen-Based Planetary Health Diet Curriculum
Authors: Rosenau Nicola , Neumann Uwe , Hamblett Stacey , Ellrott Thomas
Published: February 2024

Global dietary habits are one of the main drivers of climate change. At the same time, they contribute to 11 million premature deaths every year. This raises the question of how the urgently needed transformation of food systems can be realized. Regardless of their degree paths, all university students, in their role as potential future experts and leaders in their fields, can serve as important change agents in society. In this paper, we (a) introduce a university curriculum in a teaching kitchen setting that is based on the planetary health diet (PHD) of the EAT-Lancet Commission, (b) investigate its feasibility, and (c) analyze its effects on the planetary health diet literacy of a pilot cohort of university students enrolled in various degree programs. We developed seven flipped classroom teaching kitchen sessions based on social cognitive theory (SCT), each consisting of a one-hour seminar with student presentations on various nutrition- and sustainability-related key topics, followed by corresponding two-hour hands-on cooking classes. To assess feasibility, specific questions from the official teaching evaluation of the University of Göttingen were analyzed. Changes in self-assessed planetary health diet literacy were measured using a pre- and post-survey. During the pilot phase, 26 students successfully completed the course. A total of 25 participants responded to the teaching evaluation and expressed high satisfaction with the course, the learning outcomes, and the level of demand. A total of 26 participants completed the pre- and post-survey. At the post-intervention, the students rated their planetary health diet literacy as 21 to 98% higher than before their course participation. The findings of this pilot study indicate that the curriculum was well-received and feasible with the target group, and they demonstrate that the course participation increased the university students’ self-assessed ability to disseminate strategies for more sustainable and healthy diets. Through replication at other universities worldwide, the teaching kitchen-based planetary health diet curriculum might foster a social shift towards healthier and more climate-friendly food systems.
Associations of Diet with Health Outcomes in the UK Biobank: A Systematic Review
Authors: Navratilova Hana , Lanham-New Susan , Whetton Anthony , Geifman Nophar
Published: February 2024

The UK Biobank is a cohort study that collects data on diet, lifestyle, biomarkers, and health to examine diet–disease associations. Based on the UK Biobank, we reviewed 36 studies on diet and three health conditions: type 2 diabetes (T2DM), cardiovascular disease (CVD), and cancer. Most studies used one-time dietary data instead of repeated 24 h recalls, which may lead to measurement errors and bias in estimating diet–disease associations. We also found that most studies focused on single food groups or macronutrients, while few studies adopted a dietary pattern approach. Several studies consistently showed that eating more red and processed meat led to a higher risk of lung and colorectal cancer. The results suggest that high adherence to “healthy” dietary patterns (consuming various food types, with at least three servings/day of whole grain, fruits, and vegetables, and meat and processed meat less than twice a week) slightly lowers the risk of T2DM, CVD, and colorectal cancer. Future research should use multi-omics data and machine learning models to account for the complexity and interactions of dietary components and their effects on disease risk.
Efficacy of Butyrate to Inhibit Colonic Cancer Cell Growth Is Cell Type-Specific and Apoptosis-Dependent
Authors: Oncel Sema , Safratowich Bryan D. , Lindlauf James E. , Liu Zhenhua , Palmer Daniel G. , Briske-Anderson Mary , Zeng Huawei
Published: February 2024

Increasing dietary fiber consumption is linked to lower colon cancer incidence, and this anticancer effect is tied to elevated levels of short-chain fatty acids (e.g., butyrate) because of the fermentation of fiber by colonic bacteria. While butyrate inhibits cancer cell proliferation, the impact on cancer cell type remains largely unknown. To test the hypothesis that butyrate displays different inhibitory potentials due to cancer cell type, we determined half-maximal inhibitory concentrations (IC50) of butyrate in HCT116, HT-29, and Caco-2 human colon cancer cell proliferation at 24, 48, and 72 h. The IC50 (mM) butyrate concentrations of HCT116, HT-29, and Caco-2 cells were [24 h, 1.14; 48 h, 0.83; 72 h, 0.86], [24 h, N/D; 48 h, 2.42; 72 h, 2.15], and [24 h, N/D; 48 h, N/D; 72 h, 2.15], respectively. At the molecular level, phosphorylated ERK1/2 and c-Myc survival signals were decreased by (>30%) in HCT116, HT-29, and Caco-2 cells treated with 4 mM butyrate. Conversely, butyrate displayed a stronger potential (>1-fold) for inducing apoptosis and nuclear p21 tumor suppressor in HCT116 cells compared to HT-29 and Caco-2 cells. Moreover, survival analysis demonstrated that a cohort with high p21 gene expression in their colon tissue significantly increased survival time compared to a low-p21-expression cohort of colon cancer patients. Collectively, the inhibitory efficacy of butyrate is cell type-specific and apoptosis-dependent.
Close Adherence to a Mediterranean Diet during Pregnancy Decreases Childhood Overweight/Obesity: A Prospective Study
Authors: Díaz-López Andrés , Rodríguez Espelt Laura , Abajo Susana , Arija Victoria
Published: February 2024

The study of dietary patterns during pregnancy may be of great importance for determining the potential risk of obesity in childhood. We assessed the prospective association between maternal adherence to the Mediterranean diet (MedDiet) during pregnancy and risk of childhood overweight/obesity at 4 years. This prospective analysis involved 272 mother–child pairs from the ECLIPSES study. Maternal diet during pregnancy was assessed using a validated 45-item food-frequency questionnaire and a relative whole-pregnancy MedDiet score (rMedDiet) was calculated. The children’s weight and height were measured at the age of 4. Primary outcome was childhood overweight/obesity based on age- and-sex-specific BMI z-score > 85th percentile using the WHO child growth standards. Mean maternal rMedDiet score in pregnancy was 9.8 (±standard deviation 2.3) and 25.7% of the children were overweight/obese. Significant differences in anthropometric measurements (weight, height, and BMI) were found according to sex, with higher scores for boys. After controlling for potential confounders, greater maternal adherence to rMedDiet during pregnancy was associated with a lower risk of childhood overweight/obesity, highest vs. lowest quartile (OR = 0.34, 95% CI: 0.12–0.90; p-trend 0.037). Similar trends regarding this association (per 1-point increase rMedDiet score) were observed after stratification by advanced maternal age, maternal early pregnancy BMI, education, socioeconomic status, smoking, and gestational weight gain. Our findings suggest that closer adherence to the MedDiet during pregnancy may protect against the risk of offspring overweight/obesity at 4 years. Further research is needed to explore whether associations persist across the life course.
Association of a High Healthy Eating Index Diet with Long-Term Visceral Fat Loss in a Large Longitudinal Study
Authors: Park Sunmin
Published: February 2024

We aimed to investigate the association of a sustainable diet with a long-term reduction in waist circumference (WC) while identifying novel biomarkers for WC reduction (WCR). The participants were recruited initially during 2004–2013 in a large hospital-based cohort, and the follow-up measurements were conducted during 2012–2016. The 65,611 adults aged 45–75 were categorized into WC-loss (n = 22,290) and WC-gain (n = 43,321). Each study investigated demographic, anthropometric, biochemical, genetic, and dietary factors. The modified Healthy Eating Index (MHEI), dietary patterns, and glycemic index were calculated from a validated semi-quantitative food frequency questionnaire. Novel biomarkers influencing WC reduction were identified using machine learning approaches. A WCR was inversely associated with metabolic syndrome (MetS) risk and its components. Daily energy intake did not differ between those with and without WCR. However, MHEI, which represents diet quality, demonstrated a positive association with WCR. Among various dietary patterns, the Asian-style balanced diet (ABD), including more fermented soybeans and less restricted salt than the Diet Approach to Stop Hypertension, was positively associated with WCR. However, an inverse association was observed between the diet that was high in noodle and processed meat consumption and that which was high in rice consumption. However, the PRS for abdominal obesity did not significantly interrupt WCR. The receiver operating characteristic curve in the prediction model for WCR was about 0.86. The biomarkers in the models included MetS components, inflammation index, diet components, alcohol consumption, and smoking status, but not genetic factors. In conclusion, adopting a high-quality diet with a high MHEI like ABD leads to WCR, irrespective of genetic influences. These results could be applied to develop effective strategies for preventing and managing abdominal obesity.
The Human Interference Scoring System (HISS): A New Tool for Quantifying Food Quality Based on Its Level of Processing
Authors: Malamatenios Olivia , Campbell Jessica , Schofield Grant , Zinn Caryn
Published: February 2024

The Human Interference Scoring System (HISS) is a novel food-based diet-quality-classification system based on the existing NOVA method. HISS involves food and fluid allocation into categories from digital imagery based on food processing levels, followed by meal plan analysis using food-servings quantification. The primary purpose of this work was to evaluate the reliability of HISS. Trained nutrition professionals analyzed digital photographs from five hypothetical 24 h food recalls and categorized foods into one of four HISS categories. A secondary purpose was to assess the nutrient composition of the food recalls and other selected foods from the HISS categories. Participants effectively categorized foods into HISS categories, with only minor discrepancies noted. High inter-rater reliability was observed in the outer HISS categories: unprocessed and ultra-processed foods. Ultra-processed items consistently displayed elevated energy, carbohydrates, and sugar compared to unprocessed foods, while unprocessed foods exhibited notably higher dietary fiber. This study introduces the HISS as a potentially useful tool for quantifying a food-quality-based system using digital-photography-based assessments. Its high inter-rater reliability and ability to capture relationships between food processing levels and nutrient composition make it a promising method for assessing dietary habits and food quality.
2023 FDA TIDES (Peptides and Oligonucleotides) Harvest
Authors: Al Shaer Danah , Al Musaimi Othman , Albericio Fernando , de la Torre Beatriz G.
Published: February 2024

A total of nine TIDES (pepTIDES and oligonucleoTIDES) were approved by the FDA during 2023. The four approved oligonucleotides are indicated for various types of disorders, including amyotrophic lateral sclerosis, geographic atrophy, primary hyperoxaluria type 1, and polyneuropathy of hereditary transthyretin-mediated amyloidosis. All oligonucleotides show chemically modified structures to enhance their stability and therapeutic effectiveness as antisense or aptamer oligomers. Some of them demonstrate various types of conjugation to driving ligands. The approved peptides comprise various structures, including linear, cyclic, and lipopeptides, and have diverse applications. Interestingly, the FDA has granted its first orphan drug designation for a peptide-based drug as a highly selective chemokine antagonist. Furthermore, Rett syndrome has found its first-ever core symptoms treatment, which is also peptide-based. Here, we analyze the TIDES approved in 2023 on the basis of their chemical structure, medical target, mode of action, administration route, and common adverse effects.
The Development of a Stable Peptide-Loaded Long-Acting Injection Formulation through a Comprehensive Understanding of Peptide Degradation Mechanisms: A QbD-Based Approach
Authors: Xiong Yingxin , Wang Jiawei , Zhou Xing , Li Xiaohui
Published: February 2024

Quality by design (QbD) serves as a systematic approach to pharmaceutical development, beginning with predefined objectives and emphasizing an understanding of the product based on sound science and risk management. The purpose of this study is to utilize the QbD concept to develop a stable peptide-loaded long-acting injection formulation. An in-depth comprehension of peptide degradation mechanisms was achieved through forced degradation investigations, elucidating (acid) hydrolysis and oxidation as the primary degradation pathways for the peptide ACTY116. The quality built into the product was focused on risk assessment, for which the critical material attributes (CMAs) and critical process parameters (CPPs) associated with the critical quality attributes (CQAs) of each formulation were identified, leading to the development of the corresponding control strategies. CQAs for three LAI (long-acting injectable) formulations were enhanced by taking the right control strategies. The LAI formulation exhibiting the highest stability for ACTY116 was chosen for subsequent pharmacokinetic investigations in rats. The objective of addressing peptide chemical instability and in vivo long-acting release was achieved. For other molecules with susceptible functionalities like amide bonds, amino groups, and hydroxyl groups, the utilization of PLGA-based in situ gel as an LAI formulation for stabilizing molecules provides valuable insights.
The Evolution of Emerging Nanovesicle Technologies for Enhanced Delivery of Molecules into and across the Skin
Authors: Touitou Elka , Natsheh Hiba
Published: February 2024

This review focuses on nanovesicular carriers for enhanced delivery of molecules into and across the skin, from their design to recent emerging technologies. During the last four decades, several approaches have been used aiming to design new nanovesicles, some of them by altering the properties of the classic phospholipid vesicle, the liposome. Phospholipid nanovesicular systems, including the phospholipid soft vesicles as well as the non-phospholipid vesicular carries, are reviewed. The altered nanovesicles have served in the manufacture of various cosmetic products and have been investigated and used for the treatment of a wide variety of skin conditions. The evolution and recent advances of these nanovesicular technologies are highlighted in this review.
4-(Phenylselanyl)-2H-chromen-2-one-Loaded Nanocapsule Suspension—A Promising Breakthrough in Pain Management: Comprehensive Molecular Docking, Formulation Design, and Toxicological and Pharmacological Assessments in Mice
Authors: da Fonseca Caren Aline Ramson , Prado Vinicius Costa , Paltian Jaini Janke , Kazmierczak Jean Carlo , Schumacher Ricardo Frederico , Sari Marcel Henrique Marcondes , Cordeiro Larissa Marafiga , da Silva Aline Franzen , Soares Felix Alexandre Antunes , Oliboni Robson da Silva , Luchese Cristiane , Cruz Letícia , Wilhelm Ethel Antunes
Published: February 2024

Therapies for the treatment of pain and inflammation continue to pose a global challenge, emphasizing the significant impact of pain on patients’ quality of life. Therefore, this study aimed to investigate the effects of 4-(Phenylselanyl)-2H-chromen-2-one (4-PSCO) on pain-associated proteins through computational molecular docking tests. A new pharmaceutical formulation based on polymeric nanocapsules was developed and characterized. The potential toxicity of 4-PSCO was assessed using Caenorhabditis elegans and Swiss mice, and its pharmacological actions through acute nociception and inflammation tests were also assessed. Our results demonstrated that 4-PSCO, in its free form, exhibited high affinity for the selected receptors, including p38 MAP kinase, peptidyl arginine deiminase type 4, phosphoinositide 3-kinase, Janus kinase 2, toll-like receptor 4, and nuclear factor-kappa β. Both free and nanoencapsulated 4-PSCO showed no toxicity in nematodes and mice. Parameters related to oxidative stress and plasma markers showed no significant change. Both treatments demonstrated antinociceptive and anti-edematogenic effects in the glutamate and hot plate tests. The nanoencapsulated form exhibited a more prolonged effect, reducing mechanical hypersensitivity in an inflammatory pain model. These findings underscore the promising potential of 4-PSCO as an alternative for the development of more effective and safer drugs for the treatment of pain and inflammation.