bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling Productivity Reduction and Fuel Consumption in Open-Pit Mining Trucks by Considering the Temporary Deterioration of Mining Roads through Discrete-Event Simulation
Authors: Meneses David , Sepúlveda Felipe D.
Published: February 2023

Open pit mining is based on dynamic operations within the open pit, with the haulage operation being the most decisive in terms of the cost and the overall productivity of the operation. A vital aspect for the success of the haulage operation are the conditions of the roads, which change over time due to wear and tear. The present work aims to model and to evaluate the effect of temporal deterioration affecting mining roads in an open pit mining operation through rolling resistance, using the discrete event simulation (SED) tool to evaluate two key aspects of the operation: productivity and fuel consumption. Additionally, to reverse road deterioration, the assignment of a grader with a variable frequency of use will be modeled through a parallel model. The case study is a 5 km road with a slope of 9.5%, a fleet of 10 trucks, and their capacities of 300 tons, loaded in a 24 h simulation model. The results show that not considering road deterioration can mean an overestimation of productivity of up to 600 Ton/hr, and an overconsumption of 78%. The application of a motor grader could decrease the negative effects of roads deterioration, which depends on the frequency of its assignment. The results show that for the rate of productivity and fuel consumption for every hour of frequency that the motor grader does not do road maintenance, the production loss is 600 tons, and the fuel consumption increases by approximately 1800 L in a day.
Interaction of Some Asymmetrical Porphyrins with U937 Cell Membranes–In Vitro and In Silico Studies
Authors: Mihai Dragos Paul , Boscencu Rica , Manda Gina , Burloiu Andreea Mihaela , Vasiliu Georgiana , Neagoe Ionela Victoria , Socoteanu Radu Petre , Lupuliasa Dumitru
Published: February 2023

The aim of the present study was to assess the effects exerted in vitro by three asymmetrical porphyrins (5-(2-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrin, 5-(2-hydroxyphenyl)-10,15,20-tris-(4-acetoxy-3-methoxyphenyl)porphyrinatozinc(II), and 5-(2-hydroxyphenyl)-10,15,20–tris-(4-acetoxy-3-methoxyphenyl)porphyrinatocopper(II)) on the transmembrane potential and the membrane anisotropy of U937 cell lines, using bis-(1,3-dibutylbarbituric acid)trimethine oxonol (DiBAC4(3)) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH), respectively, as fluorescent probes for fluorescence spectrophotometry. The results indicate the hyperpolarizing effect of porphyrins in the concentration range of 0.5, 5, and 50 μM on the membrane of human U937 monocytic cells. Moreover, the tested porphyrins were shown to increase membrane anisotropy. Altogether, the results evidence the interaction of asymmetrical porphyrins with the membrane of U937 cells, with potential consequences on cellular homeostasis. Molecular docking simulations, and Molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) free energy of binding calculations, supported the hypothesis that the investigated porphyrinic compounds could potentially bind to membrane proteins, with a critical role in regulating the transmembrane potential. Thus, both the free base porphyrins and the metalloporphyrins could bind to the SERCA2b (sarco/endoplasmic reticulum ATPase isoform 2b) calcium pump, while the metal complexes may specifically interact and modulate calcium-dependent (large conductance calcium-activated potassium channel, Slo1/KCa1.1), and ATP-sensitive (KATP), potassium channels. Further studies are required to investigate these interactions and their impact on cellular homeostasis and functionality.
Ugi Four-Component Reactions Using Alternative Reactants
Authors: Hooshmand Seyyed Emad , Zhang Wei
Published: February 2023

The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists’ interest in the field. It has been widely used in the synthesis of diverse heterocycle molecules such as potential drugs, natural product analogs, pseudo peptides, macrocycles, and functional materials. The Ugi-4CRs involve the use of an amine, an aldehyde or ketone, an isocyanide, and a carboxylic acid to produce an α-acetamido carboxamide derivative, which has significantly advanced the field of isocyanide-based MCRs. The so-called intermediate nitrilium ion could be trapped by a nucleophile such as azide, N-hydroxyphthalimide, thiol, saccharin, phenol, water, and hydrogen sulfide instead of the original carboxylic acid to allow for a wide variety of Ugi-type reactions to occur.β In addition to isocyanide, there are alternative reagents for the other three components: amine, isocyanide, and aldehyde or ketone. All these alternative components render the Ugi reaction an aptly diversity-oriented synthesis of a myriad of biologically active molecules and complex scaffolds. Consequently, this review will delve deeper into alternative components used in the Ugi MCRs, particularly over the past ten years.
Metabolites Profiling and In Vitro Biological Characterization of Different Fractions of Cliona sp. Marine Sponge from the Red Sea Egypt
Authors: Hassan Wafaa H. B. , El Sayed Zeinab I. , Al-Wahaibi Lamya H. , Abdel-Aal Mahmoud M. , Abdel-Mageed Wael M. , Abdelsalam Eman , Abdelaziz Sahar
Published: February 2023

Red Sea marine sponges are an important source of biologically active natural products. Therefore, the present study aimed to investigate, for the first time, the components of n-hexane, dichloromethane, and ethyl acetate fractions of Cliona sp. marine sponge collected from the Red Sea, Egypt using UPLC-ESI-MS/MS (Ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry) analysis. The analysis revealed the tentative identification of 23, 16, and 24 compounds from the n-hexane, dichloromethane, and ethyl acetate fractions of Cliona sp., respectively. In addition, the examination of these fractions resulted in the isolation and identification of three sterols and one amino acid. The identification of the isolated compounds was confirmed by 1D and 2D NMR (Nuclear Magnetic Resonance), and MS (Mass spectrometry), and IR (Infrared) spectroscopy. The in vitro cytotoxic, antioxidant, and antimicrobial activities of the total ethanolic extract and its sub-fractions were also evaluated. Interestingly, the ethyl acetate fraction showed potent cytotoxic activity against colon (HCT-116) and human larynx carcinoma (HEP-2) cell lines with IC50 (Half-maximal Inhibitory Concentration) 6.11 ± 0.2 and 12.6 ± 0.9 µg/mL, respectively. However, the dichloromethane fraction showed strong antioxidant activity, with IC50 75.53 ± 3.41 µg/mL. Notably, the total ethanolic extract showed the strongest antibacterial activity against Staphylococcus aureus and Escherichia coli, with MIC (Minimum Inhibitory Concentration) 62.5 ± 0.82 and 125 ± 0.62 µg/mL, respectively, compared to other fractions. In conclusion, this is the first report on the secondary metabolites content and biological activities of Cliona sp. from the Red Sea, Egypt. It also highlights the need for further research on the most active fractions against various cancer cell lines and resistant bacterial and fungal strains. Cliona sp. extract and its fractions could be a potential source of novel and safe natural drugs with a wide range of medicinal and pharmaceutical applications.
Compilation of the Antimicrobial Compounds Produced by Burkholderia Sensu Stricto
Authors: Rodríguez-Cisneros Mariana , Morales-Ruíz Leslie Mariana , Salazar-Gómez Anuar , Rojas-Rojas Fernando Uriel , Estrada-de los Santos Paulina
Published: February 2023

Due to the increase in multidrug-resistant microorganisms, the investigation of novel or more efficient antimicrobial compounds is essential. The World Health Organization issued a list of priority multidrug-resistant bacteria whose eradication will require new antibiotics. Among them, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae are in the “critical” (most urgent) category. As a result, major investigations are ongoing worldwide to discover new antimicrobial compounds. Burkholderia, specifically Burkholderia sensu stricto, is recognized as an antimicrobial-producing group of species. Highly dissimilar compounds are among the molecules produced by this genus, such as those that are unique to a particular strain (like compound CF66I produced by Burkholderia cepacia CF-66) or antimicrobials found in a number of species, e.g., phenazines or ornibactins. The compounds produced by Burkholderia include N-containing heterocycles, volatile organic compounds, polyenes, polyynes, siderophores, macrolides, bacteriocins, quinolones, and other not classified antimicrobials. Some of them might be candidates not only for antimicrobials for both bacteria and fungi, but also as anticancer or antitumor agents. Therefore, in this review, the wide range of antimicrobial compounds produced by Burkholderia is explored, focusing especially on those compounds that were tested in vitro for antimicrobial activity. In addition, information was gathered regarding novel compounds discovered by genome-guided approaches.
A Lewis Acid-Promoted Michael Addition and Ring-Expansion Cascade for the Construction of Nitrogen-Containing Medium-Sized Rings
Authors: Wang Jiaming , Li Jia , Zhao Changgui
Published: February 2023

A Lewis acid-promoted annulation of azadienes and cyclobutamines was developed. This reaction proceeded through Michael addition and ring-expansion cascade, affording the corresponding nitrogen-containing medium-sized rings with a broad scope in moderate to high yields. The catalytic asymmetric version of this reaction has also been explored using a chiral base.
Photocatalytic Inactivation of Co-Culture of E. coli and S. epidermidis Using APTES-Modified TiO2
Authors: Rokicka-Konieczna Paulina , Wanag Agnieszka , Sienkiewicz Agnieszka , Izuma Dylan Shun , Ekiert Ewa , Kusiak-Nejman Ewelina , Terashima Chiaki , Yasumori Atsuo , Fujishima Akira , Morawski Antoni W.
Published: February 2023

The presented work shows the antibacterial activity of TiO2 photocatalysts modified by 3-aminopropyltriethoxysilane (APTES). The APTES-functionalized TiO2 samples were obtained by the solvothermal process followed by calcination. The antibacterial activity of APTES/TiO2 samples was evaluated with two species of bacteria, Escherichia coli and Staphylococcus epidermidis, under artificial solar light (ASL) irradiation. The used bacteria are model organisms characterized by negative zeta potential (approx. −44.2 mV for E. coli and −42.3 mV for S. epidermidis). For the first time, the antibacterial properties of APTES-functionalized TiO2 were evaluated against mono- and co-cultured bacteria. The high antibacterial properties characterized the obtained APTES-modified nanomaterials. The best antibacterial properties were presented in the TiO2-4 h-120 °C-300 mM-Ar-300 °C sample (modified with 300 mM of APTES and calcined at 300 °C). The improvement of the antibacterial properties was attributed to a positive value of zeta potential, high surface area, and porous volume.
Synthesis of Fe-TiO2 and Cu-TiO2 Based Materials by Olive Leaves Biotemplating—Application to Hydrogen Production from Glycerol Photoreforming
Authors: Martín-Gómez Juan , Reca-Expósito Susana , López-Tenllado Francisco J. , Hidalgo-Carrillo Jesús , Marinas Alberto , Urbano Francisco J.
Published: February 2023

Hydrogen production is mainly based on the use of fossil fuels, but currently, many alternative routes are being developed, among which the photo-reforming of oxygenated organic compounds stands out. Recently, several studies have been carried out in order to develop new techniques to create bio-inspired TiO2 structures. One of these is ‘biotemplating’, a process that replicates a biological system in an inorganic TiO2-based structure. In this study, olive by-products—olive leaves—are valorized as a biotemplate for the synthesis of new Fe-TiO2- and Cu-TiO2-based photocatalysts with the aim of improving the replication of the leaf structure and enhancing hydrogen photoproduction. In conclusion, the incorporation of iron and copper decreases the band gap and increases the energetic disorder at the band edges. Moreover, it is verified by SEM and TEM that the metals are not found forming particles but are introduced into the formed TiO2 structure. The accuracy of the internal and external structure replication is improved with the incorporation of Fe in the synthesis, while the incorporation of Cu substantially improves the production of hydrogen, which is multiplied 14 times under UV light and 6 times under sunlight, as compared to a pure TiO2 structure.
Gas Sensing of Laser-Produced Hybrid TiO2-ZnO Nanomaterials under Room-Temperature Conditions
Authors: Mintcheva Neli , Subbiah Dinesh Kumar , Turabayev Marat E. , Gurbatov Stanislav O. , Rayappan John Bosco Balaguru , Kuchmizhak Aleksandr A. , Kulinich Sergei A.
Published: February 2023

The preparation method can considerably affect the structural, morphological, and gas-sensing properties of mixed-oxide materials which often demonstrate superior photocatalytic and sensing performance in comparison with single-metal oxides. In this work, hybrids of semiconductor nanomaterials based on TiO2 and ZnO were prepared by laser ablation of Zn and Ti plates in water and then tested as chemiresistive gas sensors towards volatile organics (2-propanol, acetaldehyde, ethanol, methanol) and ammonia. An infrared millisecond pulsed laser with energy 2.0 J/pulse and a repetition rate of 5 Hz was applied to Zn and Ti metal targets in different ablation sequences to produce two nano-hybrids (TiO2/ZnO and ZnO/TiO2). The surface chemistry, morphology, crystallinity, and phase composition of the prepared hybrids were found to tune their gas-sensing properties. Among all tested gases, sample TiO2/ZnO showed selectivity to ethanol, while sample ZnO/TiO2 sensed 2-propanol at room temperature, both with a detection limit of ~50 ppm. The response and recovery times were found to be 24 and 607 s for the TiO2/ZnO sensor, and 54 and 50 s for its ZnO/TiO2 counterpart, respectively, towards 100 ppm of the target gas at room temperature.
The Effect of Carbon Doping on the Crystal Structure and Electrical Properties of Sb2Te3
Authors: Zhang Jie , Rong Ningning , Xu Peng , Xiao Yuchen , Lu Aijiang , Song Wenxiong , Song Sannian , Song Zhitang , Liang Yongcheng , Wu Liangcai
Published: February 2023

As a new generation of non-volatile memory, phase change random access memory (PCRAM) has the potential to fill the hierarchical gap between DRAM and NAND FLASH in computer storage. Sb2Te3, one of the candidate materials for high-speed PCRAM, has high crystallization speed and poor thermal stability. In this work, we investigated the effect of carbon doping on Sb2Te3. It was found that the FCC phase of C-doped Sb2Te3 appeared at 200 °C and began to transform into the HEX phase at 25 °C, which is different from the previous reports where no FCC phase was observed in C-Sb2Te3. Based on the experimental observation and first-principles density functional theory calculation, it is found that the formation energy of FCC-Sb2Te3 structure decreases gradually with the increase in C doping concentration. Moreover, doped C atoms tend to form C molecular clusters in sp2 hybridization at the grain boundary of Sb2Te3, which is similar to the layered structure of graphite. And after doping C atoms, the thermal stability of Sb2Te3 is improved. We have fabricated the PCRAM device cell array of a C-Sb2Te3 alloy, which has an operating speed of 5 ns, a high thermal stability (10-year data retention temperature 138.1 °C), a low device power consumption (0.57 pJ), a continuously adjustable resistance value, and a very low resistance drift coefficient.
X-ray Activated Nanoplatforms for Deep Tissue Photodynamic Therapy
Authors: Souris Jeffrey S. , Leoni Lara , Zhang Hannah J. , Pan Ariel , Tanios Eve , Tsai Hsiu-Ming , Balyasnikova Irina V. , Bissonnette Marc , Chen Chin-Tu
Published: February 2023

Photodynamic therapy (PDT), the use of light to excite photosensitive molecules whose electronic relaxation drives the production of highly cytotoxic reactive oxygen species (ROS), has proven an effective means of oncotherapy. However, its application has been severely constrained to superficial tissues and those readily accessed either endoscopically or laparoscopically, due to the intrinsic scattering and absorption of photons by intervening tissues. Recent advances in the design of nanoparticle-based X-ray scintillators and photosensitizers have enabled hybridization of these moieties into single nanocomposite particles. These nanoplatforms, when irradiated with diagnostic doses and energies of X-rays, produce large quantities of ROS and permit, for the first time, non-invasive deep tissue PDT of tumors with few of the therapeutic limitations or side effects of conventional PDT. In this review we examine the underlying principles and evolution of PDT: from its initial and still dominant use of light-activated, small molecule photosensitizers that passively accumulate in tumors, to its latest development of X-ray-activated, scintillator–photosensitizer hybrid nanoplatforms that actively target cancer biomarkers. Challenges and potential remedies for the clinical translation of these hybrid nanoplatforms and X-ray PDT are also presented.
Hardware-Intrinsic Physical Unclonable Functions by Harnessing Nonlinear Conductance Variation in Oxide Semiconductor-Based Diode
Authors: Kim Namju , Jeon Seung-Bae , Jang Byung Chul
Published: February 2023

With the advancement of the Internet of Things (IoT), numerous electronic devices are connected to each other and exchange a vast amount of data via the Internet. As the number of connected devices increases, security concerns have become more significant. As one of the potential solutions for security issues, hardware intrinsic physical unclonable functions (PUFs) are emerging semiconductor devices that exploit inherent randomness generated during the manufacturing process. The unclonable security key generated from PUF can address the inherent limitations of conventional electronic systems which depend solely on software. Although numerous PUFs based on the emerging memory devices requiring switching operations have been proposed, achieving hardware intrinsic PUF with low power consumption remains a key challenge. Here, we demonstrate that the process-induced nonlinear conductance variations of oxide semiconductor-based Schottky diodes provide a suitable source of entropy for the implementation of PUF without switching operation. Using a mild oxygen plasma treatment, the surface electron accumulation layer that forms naturally in oxide semiconductor film can be partially eliminated, resulting in a large variation of nonlinearity as an exotic entropy source. The mild plasma-treated Schottky diodes showed near ideal 50% average uniformity and uniqueness, as well as an ideal entropy value without the need for additional hardware area and power costs. These findings will pave the way for the development of hardware intrinsic PUFs to realize energy-efficient cryptographic hardware.
Serum Adipocytokines Profile in Children Born Small and Appropriate for Gestational Age—A Comparative Study
Authors: Zamojska Justyna , Niewiadomska-Jarosik Katarzyna , Wosiak Agnieszka , Gruca Marta , Smolewska Elżbieta
Published: February 2023

Background: Adipose tissue is not only a storage place for fat, but also an endocrine organ, secreting bioactive molecules which influence body metabolism. Such molecules are known as adipocytokines. In the past years the coincidence between adipocytokines and fetal growth restriction disorders was found. The aim of the study was to estimate serum levels of adiponectin, leptin and resistin in children born small for gestational age, compared to children born at an appropriate size for gestational age. Methods: The study consisted of 35 children aged seven to nine years, born SGA (small for gestational age) on term and 25 healthy children (14 girls, 11 boys), born with proper birthweight (AGA—appropriate for gestational age)–control group. Results: Adiponectin and leptin levels were significantly higher in the SGA group compared to the AGA group (p = 0.023, p = 0.018 respectively). The resistin values were comparable in both groups of patients. There was a positive correlation between serum leptin concentration and current body weight in SGA group (r = 0.28; p = 0.108). In turn, adiponectin levels in this group of patients negatively correlated with actual body weight (r = −0.51; p = 0.002). The negative correlation between body mass index and plasma adiponectin levels was found only in children born SGA. SGA children had significantly higher values of diastolic blood pressure. There was negative correlation between serum adiponectin level and systolic blood pressure in SGA children. In the SGA group the phenomenon of catch-up growth was observed in 32 children. Conclusions: Children born SGA have abnormal adipose tissue biomarkers profiles.
Association between Meal Frequency and Weight Status in Spanish Children: A Prospective Cohort Study
Authors: Juton Charlotte , Berruezo Paula , Torres Silvia , Castañer Olga , Según Genís , Fitó Montserrat , Homs Clara , Gómez Santiago F. , Schröder Helmut
Published: February 2023

Childhood obesity is a major international problem, and unhealthy eating habits remain widespread. Increasing the frequency of meals of nutritious food can help children to regulate their appetite and maintain a healthy weight. However, there is scarce prospective evidence on the relationship between the meal frequency and weight outcomes. Therefore, the objective of the present study was to determine the prospective association between the meal frequency, body mass index, and waist circumference in Spanish children. Additionally, we analyzed the impact of the meal frequency on the incidence of excessive weight and abdominal obesity. The study included 1400 children with a mean (SD) age of 10.1 (0.6) and an average follow-up of 15 months. Anthropometric measurements, including the body weight, height, and waist circumference, were measured by trained personnel, and children were asked about whether they usually had the following meals: breakfast, a mid-morning snack, lunch, an afternoon snack, and dinner. Multiple linear regression models revealed a significant (p < 0.05) inverse association between the meal frequency with a standardized BMI (zBMI) and the waist-to-height ratio (WHtR) after adjusting for sex, age, allocation to an intervention group, school, maternal education, physical activity, diet quality, and for the corresponding outcome variable at the baseline. Furthermore, the odds of developing abdominal obesity or excessive weight during the follow-up significantly decreased with an increase in the meal frequency after controlling for the same confounders. In conclusion, a higher meal frequency at the baseline was predictive for a lower zBMI, WHtR, and odds of the incidence of excessive weight and abdominal obesity.
The Role of Omega-3 Polyunsaturated Fatty Acids and Their Lipid Mediators on Skeletal Muscle Regeneration: A Narrative Review
Authors: Jannas-Vela Sebastian , Espinosa Alejandra , Candia Alejandro A. , Flores-Opazo Marcelo , Peñailillo Luis , Valenzuela Rodrigo
Published: February 2023

Skeletal muscle is the largest tissue in the human body, comprising approximately 40% of body mass. After damage or injury, a healthy skeletal muscle is often fully regenerated; however, with aging and chronic diseases, the regeneration process is usually incomplete, resulting in the formation of fibrotic tissue, infiltration of intermuscular adipose tissue, and loss of muscle mass and strength, leading to a reduction in functional performance and quality of life. Accumulating evidence has shown that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their lipid mediators (i.e., oxylipins and endocannabinoids) have the potential to enhance muscle regeneration by positively modulating the local and systemic inflammatory response to muscle injury. This review explores the process of muscle regeneration and how it is affected by acute and chronic inflammatory conditions, focusing on the potential role of n-3 PUFAs and their derivatives as positive modulators of skeletal muscle healing and regeneration.
Anti-Obesity Effect of Auricularia delicate Involves Intestinal-Microbiota-Mediated Oxidative Stress Regulation in High-Fat-Diet-Fed Mice
Authors: Li Lanzhou , Zhai Siyu , Wang Ruochen , Kong Fange , Yang Anhui , Wang Chunyue , Yu Han , Li Yu , Wang Di
Published: February 2023

Auricularia delicate (ADe), an edible fungus belonging to the family Auriculariaceae and order Auriculariales, possesses antimicrobial, hepatoprotective, and antioxidant effects. In this study, after systematic analysis of its composition, ADe was administered to high-fat-diet (HFD)-fed mice to investigate its anti-obesity effect. ADe significantly controlled body weight; alleviated hepatic steatosis and adipocyte hypertrophy; reduced aspartate aminotransferase, total cholesterol, insulin, and resistin; and increased adiponectin levels in HFD-fed mice serum. Based on intestinal microbiota and lipidomics analysis, ADe treatment regulated the composition and abundance of 49 intestinal microorganisms and influenced the abundance of 8 lipid species compared with HFD-fed mice. Based on a correlation analysis of the intestinal microbiota and lipids, Coprococcus showed significant negative associations with ceramide (d18:0 20:0+O), phosphatidylserine (39:4), sphingomyelin (d38:4), and zymosterol (20:2). Moreover, ADe treatment decreased the levels of ROS and MDA and increased the levels of Nrf2, HO-1, and three antioxidant enzymes in HFD-fed mice livers. Collectively, the anti-obesity effect of ADe involves the regulation of oxidative stress and is mediated by the intestinal microbiota. Hence, this study provides a reference for the application of ADe as a candidate food for obesity.
Front-of-Pack Nutrition Labels: Comparing the Nordic Keyhole and Nutri-Score in a Swedish Context
Authors: Pitt Stephanie , Julin Bettina , Øvrebø Bente , Wolk Alicja
Published: February 2023

The extent to which different front-of-pack nutrition labels (FOPNLs) agree or contradict each other has been insufficiently investigated. Considering the 2020 proposal from the European Commission to create a harmonized FOPNL, the aim of this study was to assess agreements and disagreements between two FOPNL schemes—the Keyhole and the Nutri-Score—in a Swedish context. The current Keyhole criteria and the updated Nutri-Score 2022 algorithm were applied to 984 food items and their nutrient compositions, obtained from the food database of the Swedish Food Agency. Agreements (Keyhole-eligible and Nutri-Score A or B; or not Keyhole-eligible and Nutri-Score C, D, or E) and disagreements (Keyhole-eligible and Nutri-Score C, D, or E, or not Keyhole-eligible and Nutri-Score A or B) were calculated as percentages for all items and by food group. An agreement was found for 81% of included items. The lowest level of agreement was found for the groups of flour, grains, and rice (62% agreement) and for plant-based meat and fish analogues (33% agreement). There is generally a good level of agreement between the Keyhole and the Nutri-Score for food items on the Swedish market. Large disagreements found for plant-based meat and fish analogues, and products based on cereals/grains, highlight important considerations for the development of a harmonized FOPNL within Europe.
Effect of Protein Intake Early in Life on Kidney Volume and Blood Pressure at 11 Years of Age
Authors: Parada-Ricart Ester , Ferre Natalia , Luque Veronica , Gruszfeld Dariusz , Gradowska Kinga , Closa-Monasterolo Ricardo , Koletzko Berthold , Grote Veit , Escribano Subías Joaquin
Published: February 2023

High protein intake has been associated with kidney hypertrophy, which is usually reversible; however, when it occurs early in life, it could lead to cell programming with a long-lasting effect. This study aimed to assess whether higher protein ingestion early in life has a persistent effect on kidney volume at 11 years of age, as well as its influence on blood pressure. This is a secondary analysis of a randomized control trial that compared the growth of infants fed with a higher-protein formula versus those fed with a lower-protein formula, with a control group of breastfed infants. Renal ultrasound and anthropometric measurements were assessed at 6 months and 11 years of age. At 11 years, urinary protein, albumin and creatinine, and blood pressure were measured in 232 children. Feeding with a higher-protein formula was associated with a larger kidney volume (β = 8.71, 95%CI 0.09–17.33, p = 0.048) and higher systolic blood pressure (β = 3.43, 95%CI 0.78–6.08, p = 0.011) at 11 years of age. Microalbuminuria was detected in 7% of the patients, with no differences among groups (p = 0.56). The effect of increased protein ingestion early in life may condition kidney volume and blood pressure in later childhood.
Fatigue in Patients on Chronic Hemodialysis: The Role of Indoleamine 2,3-Dioxygenase (IDO) Activity, Interleukin-6, and Muscularity
Authors: Molfino Alessio , Imbimbo Giovanni , Amabile Maria Ida , Ammann Thomas , Lionetto Luana , Salerno Gerardo , Simmaco Maurizio , Chiappini Maria Grazia , Muscaritoli Maurizio
Published: February 2023

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp (p = 0.005), were older (p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients (p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) (p < 0.001), as well as lower hand grip strength (p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW (p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h2 was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity.
Kidney Stone Prevention: Is There a Role for Complementary and Alternative Medicine?
Authors: Cupisti Adamasco , Giannese Domenico , D’Alessandro Claudia , Benedetti Alessia , Panichi Vincenzo , Alfieri Carlo , Castellano Giuseppe , Messa Piergiorgio
Published: February 2023

Complementary and alternative medicine (CAM) is often implemented in kidney stone patients. It consists of preparations including different ingredients, such as herbs, probiotics, and vitamins, often together with alkali, that are classified within the dietary supplementation category. The majority of dietary supplements claiming to treat or prevent kidney stones contain ingredients with conflicting or no scientific evidence to support their claims. Clinicians should advise stone formers that the effects of most supplements are unknown or unstudied in humans and that the absence of evidence does not imply absence of potential harm. Unfortunately, the CAM preparation consists of a mix of different molecules, often including alkali, with different potential mechanisms of action and, even when favorable results are reported, the role of the single molecules cannot be assessed. Despite all these concerns, CAM products remain quite popular among kidney stone patients. The scarce knowledge in this field prevents one from recommending CAM products in daily clinical practice; only a weak suggestion for their use in kidney stone patients may be reasonable.
Efficacy of Fosfomycin-Containing Regimens for Treatment of Bacteremia Due to Pan-Drug Resistant Acinetobacter baumannii in Critically Ill Patients: A Case Series Study
Authors: Assimakopoulos Stelios F. , Karamouzos Vassilis , Eleftheriotis Gerasimos , Lagadinou Maria , Bartzavali Christina , Kolonitsiou Fevronia , Paliogianni Fotini , Fligou Fotini , Marangos Markos
Published: February 2023

Acinetobacter baumannii (AB) has evolved over the last decades as a major problem in carbapenem-resistant gram-negative nosocomial infections, associated with high mortality rates especially in the intensive care unit (ICU). Recent reports highlight the increasing prevalence of resistance to colistin, a last resort therapeutic option for carbapenem-resistant AB. We retrospectively evaluated the characteristics, treatment regimens and outcomes of twenty patients with pan-drug resistant (PDR) AB primary bacteremia hospitalized in the ICU of the University General Hospital of Patras, during a two-year period (October 2020–September 2022). The 28-day mortality reached 50%. Between survivors and non-survivors, no differences were found regarding age, gender, and Charlson comorbidity index (CCI). However, non-survivors had higher APACHE II scores and higher prevalence of septic shock and COVID-19 infection. A significantly higher percentage in the survivor group received Fosfomycin as part of the combination regimen. Inclusion of fosfomycin in the combination therapeutic regimen was associated with significantly better survival as compared to non-fosfomycin-containing regimens. In view of the increasing prevalence of PDR-AB infections in ICUs, its associated high rates of mortality and the lack of effective treatment options, the observed survival benefit with fosfomycin inclusion in the therapeutic regimen merits further validation in larger prospective studies.
Checkpoint Inhibitor-Associated Scleroderma and Scleroderma Mimics
Authors: Macklin Michael , Yadav Sudeep , Jan Reem , Reid Pankti
Published: February 2023

Immune checkpoint inhibitors (ICI) are the standard of care for various malignancies and have been associated with a wide spectrum of complications that are phenotypically akin to primary autoimmune diseases. While the literature on these toxicities is growing, there is a paucity of data regarding ICI-associated scleroderma which can carry significant morbidity and limit the ability to continue effective ICI therapy. Our review aimed to analyze the current literature on ICI-associated systemic scleroderma (ICI-SSc) and key scleroderma mimics. Cases of ICI-SSc had notable differences from primary SSc, such as fewer vascular features and less seropositivity (such as scleroderma-specific antibodies and antinuclear antibodies). We found that patients with a diagnosis of SSc prior to the start of ICI can also experience flares of pre-existing disease after ICI treatment used for their cancer. Regarding scleroderma mimics, several cases of ICI-eosinophilic fasciitis have also been described with variable clinical presentations and courses. We found no cases of scleroderma mimics: ICI-scleromyxedema or ICI-scleroedema. There is a critical need for multi-institutional efforts to collaborate on developing a patient database and conducting robust, prospective research on ICI-scleroderma. This will ultimately facilitate more effective clinical evaluations and management for ICI-scleroderma.
Targeting Some Key Metalloproteinases by Nano-Naringenin and Amphora coffeaeformis as a Novel Strategy for Treatment of Osteoarthritis in Rats
Authors: Shaban Nema S. , Radi Abeer M. , Abdelgawad Mohamed A. , Ghoneim Mohammed M. , Al-Serwi Rasha Hamed , Hassan Randa M. , Mohammed Eman T. , Radi Rania A. , Halfaya Fatma M.
Published: February 2023

Osteoarthritis (OA) represents the highest degenerative disorder. Because cartilage erosion is a common pathological alteration in OA, targeting some key metalloproteinases such as MMP-3, ADAMTS-5 besides their inhibitor TIMP-3 by natural products, could be an effective strategy to protect against osteoarthritis. Forty female Wister rats were categorized into five equal groups. Control, osteoarthritic (OA) (monosodium iodoacetate (MIA) 2 mg/50 µL saline, single intra-articular injection), OA+ indomethacin (2 mg/kg/daily/orally), OA+ nano-naringenin (25 mg/kg/daily/orally), and OA+ Amphora coffeaeformis (772 mg/kg/daily/orally). Treatments were initiated on the 8th day after osteoarthritis induction and continued for 28 days thereafter. Finally, blood and knee joint samples were collected from all rats for biochemical and histopathological evaluations. The current study showed that MIA induced oxidative stress, which resulted in changes in the inflammatory joint markers associated with increased right knee diameter and higher clinical scores for lameness. Amphora coffeaeformis followed by nano-naringenin exhibited a potential anti-arthritic activity by reducing the concentrations of serum MMP-3, ADAMTS-5, and joint MDA and increasing the levels of serum TIMP-3 and joint GSH, similar to indomethacin. The histopathological results confirmed these outcomes. In conclusion, Amphora coffeaeformis and nano-naringenin can be considered as natural therapeutic agents for osteoarthritis owing to their antioxidant and anti-inflammatory activities.
N-butanol Extract of Glycyrrhizae Radix et Rhizoma Inhibits Dengue Virus through Targeting Envelope Protein
Authors: Shi Ling-Zhu , Chen Xi , Cao Hui-Hui , Tian Chun-Yang , Zou Li-Fang , Yu Jian-Hai , Lu Zi-Bin , Zhao Wei , Liu Jun-Shan , Yu Lin-Zhong
Published: February 2023

Background: At present, about half of the world’s population is at risk of being infected with dengue virus (DENV). However, there are no specific drugs to prevent or treat DENV infection. Glycyrrhizae Radix et Rhizome, a well-known traditional Chinese medicine, performs multiple pharmacological activities, including exerting antiviral effects. The aim of this study was to investigate the anti-DENV effects of n-butanol extract from Glycyrrhizae Radix et Rhizome (GRE). Methods: Compounds analysis of GRE was conducted via ultra-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS). The antiviral activities of GRE were determined by the CCK-8 assay, plaque assay, qRT-PCR, Western blotting, and the immunofluorescence assay. The DENV-infected suckling mice model was constructed to explore the antiviral effects of GRE in vivo. Results: Four components in GRE were analyzed by UHPLC-MS/MS, including glycyrrhizic acid, glycyrrhetnic acid, liquiritigenin, and isoliquiritigenin. GRE inhibited the attachment process of the virus replication cycle and reduced the expression of the E protein in cell models. In the in vivo study, GRE significantly relieved clinical symptoms and prolong survival duration. GRE also significantly decreased viremia, reduced the viral load in multiple organs, and inhibited the release of pro-inflammatory cytokines in DENV-infected suckling mice. Conclusions: GRE exhibited significant inhibitory activities in the adsorption stage of the DENV-2 replication cycle by targeting the envelope protein. Thus, GRE might be a promising candidate for the treatment of DENV infection.
Ultrasonically Fabricated Beta-Carotene Nanoemulsion: Optimization, Characterization and Evaluation of Combinatorial Effect with Quercetin on Streptozotocin-Induced Diabetic Rat Model
Authors: Mahadev Manohar , Dubey Akhilesh , Shetty Amitha
Published: February 2023

Diabetes mellitus (D.M.) is a metabolic disease that has affected over 500 million people globally. Bioactive compounds such as β-carotene and Quercetin have gained research interest for their potential antidiabetic properties, and bioactives have reported superior combinatorial effects in several ailments, including D.M. However, poor oral bioavailability has limited their potential application. Thus, the present study was focused on developing ultrasonically fabricated β-Carotene nanoemulsion (βC-NE) by employing capmul as the oil phase, Gelucire 44/14 as surfactant and Acconon MCM C8 as co-surfactant. The 3 factor- 3 level Box-Behnken design (BBD) was applied to optimise the βC-NE and study the impact of selected independent variables such as % Smix (5 to 9%), amplitude (20–30%) and sonication time (2.5–7.5 min) on responses including globule size (G.S.), poly dispersibility Index (PDI) and entrapment efficiency (E.E.). Further, the combinatorial effect of βC-NE with Quercetin Nanoemulsion (QU-NE) in the streptozotocin-induced diabetic rat model was evaluated. The results exhibited that 7% Smix at 25% amplitude for 5 min produced βC-NE with a droplet size of 153.1 ± 12.25 nm, 0.200 ± 0.04 PDI, and 73.25 ± 3.25% E.E. The βC-NE showed superior in-vivo bioavailability by 5.38 folds. The βC-NE, combined with QU-NE, exhibited potential therapeutic benefits in controlling body weight, blood sugar level, lipid levels, and tissue damage markers. Additionally, the pancreatic cells and hepatic cells were well protected. These results demonstrate the potential benefits of βC-NE and QU-NE in combination and recommend them as a substitute strategy for diabetes.
Experimental and Computational Study for the Design of Sulfathiazole Dosage Form with Clay Mineral
Authors: Moreno-Domínguez Eugenia , Borrego-Sánchez Ana , Sánchez-Espejo Rita , Viseras César , Sainz-Díaz Claro Ignacio
Published: February 2023

Sulfathiazole is an antimicrobial belonging to the family of sulfonamides, which were the first antibiotics to be discovered. Sulfathiazole is generally administered orally, and its main disadvantage is that it has low aqueous solubility, requiring high doses for its administration. This fact has led to side effects and the generation of bacterial resistance to the drug over time. The improvement of its solubility would mean not having to administer such high doses in its treatment. At the same time, montmorillonite is a natural, low-cost, non-toxic, biocompatible clay with a high adsorption capacity. It is potentially useful as a nanocarrier to design sulfathiazole dosage forms. In this work, the interaction between the drug and the clay mineral has been studied from an experimental and computational atomistic point of view to improve the drug’s biopharmaceutical profile. The results showed the potential enhancement of the drug solubility due to the correct adsorption of the sulfathiazole in the clay interlayer space. As a result of the inclusion of sulfathiazole in the interlayer of the clay mineral, the solubility of the drug increased by 220% concerning the pristine drug. Experimentally, it was not possible to know the number of drug molecules adsorbed in the interlayer space or the external surface of the carrier. Theoretical studies will enable the knowledge of the stoichiometry of the drug/clay hybrids, with three molecules in the interlayer space being the most favorable process. The resultant basal spacing was in agreement with the experimental results.
Modulation of Skin Inflammatory Responses by Aluminum Adjuvant
Authors: Liao Yanhang , Sun Lixiang , Nie Meifeng , Li Jiacheng , Huang Xiaofen , Heng Shujun , Zhang Wenlu , Xia Tian , Guo Zhuolin , Zhao Qinjian , Zhang Ling-juan
Published: February 2023

Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)—induced atopic dermatitis-like model. We found that injection of a high dose of AS not only suppressed the IMQ-mediated development of T-helper 1 (Th1) and T-helper 17 (Th17) immune responses but also inhibited the IMQ-mediated recruitment and/or activation of neutrophils and macrophages. In contrast, AS injection enhanced MC903-mediated development of the T-helper 2 (Th2) immune response and neutrophil recruitment. Using an in vitro approach, we found that AS treatment inhibited Th1 but promoted Th2 polarization of primary lymphocytes, and inhibited activation of peritoneal macrophages but not bone marrow derived neutrophils. Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.
Blockage of the IL-31 Pathway as a Potential Target Therapy for Atopic Dermatitis
Authors: Orfali Raquel Leao , Aoki Valeria
Published: February 2023

Atopic dermatitis (AD), a pruritic, inflammatory chronic disease with multifactorial pathogenesis, has been a therapeutic challenge. Novel target treatments aim to reduce not only the immunologic dysfunction and microbiome dysbiosis but also the recovery of the damaged skin barrier. The current review focuses on the interleukin 31 (IL-31) pathway and AD and offers an overview of the current clinical studies with monoclonal antibodies blocking this cascade. Pruritus, the key symptom of AD, has substantial participation of the IL-31 complex and activation of relevant signaling pathways. Epidermal keratinocytes, inflammatory cells, and cutaneous peripheral nerves express the interleukin-31 receptor α-chain (IL-31RA), upregulated by Staphylococcus aureus toxins or Th2 cytokines involved in AD. Nemolizumab is a humanized monoclonal antibody that antagonizes IL-31RA, inhibiting the IL-31 cascade and therefore contributing to reducing the pruritus and inflammation and recovering the damaged skin barrier in AD patients. Phases 2 and 3 clinical trials with nemolizumab in AD show a suitable safety profile, with a fast, efficient, and sustained reduction of pruritus and severity scores, especially when associated with topical treatment. Deciphering the full interplay of the IL-31 pathway and AD may expand the potential of nemolizumab as a targeted therapy for AD and other pruritic conditions.
Evaluation of Conventional and Hyaluronic Acid-Coated Thymoquinone Liposomes in an In Vitro Model of Dry Eye
Authors: Landucci Elisa , Mazzantini Costanza , Calvani Maura , Pellegrini-Giampietro Domenico E. , Bergonzi Maria Camilla
Published: February 2023

Dry eye disease (DED) is a common ocular disorder characterized by an inadequate lubrication of the eye by tears leading to inflammation and the alteration of the ocular surface. Current treatments are often limited due to their side effects and ineffectiveness. Thymoquinone (TQ) is a natural compound present in the essential oil of Nigella sativa L., with anti-inflammatory and antioxidant activities. In this study, conventional and hyaluronic acid-coated liposomes were developed to improve TQ activity at ocular level. In the present study, the cytoprotective effects of TQ or TQ liposomes were assessed against oxidative and inflammatory processes in human corneal epithelial cells (HCE-2). Hyperosmolarity conditions (450 mOsm) were used as a model of DED. Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR); COX-2 and Phospho-NF-κB p65 (p-p65) by Western blotting (WB). Moreover, the mitochondrial reactive oxygen species (mtROS) levels were measured by MitoSOX assay. The hyperosmotic treatment induced a significant increase of the proinflammatory genes and proteins expression that were significantly decreased in the liposomes-treated cells. The coincubation with hyaluronic acid-coated liposomes significantly reverted the increase of mtROS production, evidently stimulated by the hyperosmotic stress. Our data suggest that TQ-loaded liposomes have potential as a therapeutic agent in dry eye disease, improving the TQ efficacy.