bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavonoids and Phenolic Acids from Aerial Part of Ajuga integrifolia (Buch.-Ham. Ex D. Don): Anti-Shigellosis Activity and In Silico Molecular Docking Studies
Authors: Tessema Fekade Beshah , Gonfa Yilma Hunde , Asfaw Tilahun Belayneh , Tadesse Tigist Getachew , Tadesse Mesfin Getachew , Bachheti Archana , Pandey Devi Prasad , Wabaidur Saikh M. , Dahlous Kholood A. , Širić Ivan , Kumar Pankaj , Kumar Vinod , Abou Fayssal Sami , Bachheti Rakesh Kumar
Published: January 2023

Shigellosis is one of the major causes of death in children worldwide. Flavonoids and phenolic acids are expected to demonstrate anti-shigellosis activity and anti-diarrheal properties. The aerial part of A. integrifolia is commonly used against diarrhea. This study aimed to identify flavonoids and phenolic acids responsible for this therapeutic purpose. Antioxidant activity, total phenol content, and total flavonoid content were determined. The antibacterial activity of the aerial part against Shigella spp. was also tested using the agar well diffusion method. HPLC analysis was performed using UHPLC-DAD for different extracts of the aerial part. Autodock Vina in the PyRx platform was used to screen responsible components. Ciprofloxacin was used as a reference drug. An enzyme taking part in pyrimidine biosynthesis was used as a target protein. Molecular docking results were visualized using Discovery Studio and LigPlot1.4.5 software. Antioxidant activity, total phenol content, and total flavonoid content are more significant for the aerial part of A. integrifolia. From HPLC analysis, the presence of the flavonoids, quercetin, myricetin, and rutin and the phenolic acids gallic acid, chlorogenic acid, and syringic acid were identified from the aerial part of A. integrifolia. Regarding the antibacterial activity, the aerial part shows considerable activity against Shigella spp. Binding energies, RMSD and Ki values, interaction type, and distance are considered to identify the components most likely responsible for the therapeutic effects and observed activity. Antioxidant activity, total phenol content, and total flavonoid content of the aerial part are in line with anti-shigellosis activity. The top five components that are most likely potentially responsible for therapeutic purposes and anti-shigellosis activity are chlorogenic acid, rutin, dihydroquercetin, dihydromyricetin, and kaempferol.
Proteomic Analysis Reveals the Association between the Pathways of Glutathione and α-Linolenic Acid Metabolism and Lanthanum Accumulation in Tea Plants
Authors: Xue Zhihui , Chen Zhidan , Wang Yankun , Sun Weijiang
Published: January 2023

Lanthanum can affect the growth and development of the tea plant. Tieguanyin (TGY) and Shuixian (SX) cultivars of Camellia sinensis were selected to explore the mechanism underlying the accumulation of lanthanum (tea plants’ most accumulated rare earth element) through proteomics. Roots and fresh leaves of TGY and SX with low- and high-accumulation potential for lanthanum, respectively, were studied; 845 differentially expressed proteins (DEPs) were identified. Gene ontology analysis showed that DEPs were involved in redox processes and related to molecular functions. Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis showed that DEPs were associated with glutathione (GSH) and α-linolenic acid metabolism, plant pathogen interaction, and oxidative phosphorylation. Thirty-seven proteins in the GSH metabolism pathway showed significant differences, wherein 18 GSH S-transferases showed differential expression patterns in the root system. Compared with the control, expression ratios of GST (TEA004130.1) and GST (TEA032216.1) in TGY leaves were 6.84 and 4.06, respectively, after lanthanum treatment; these were significantly higher than those in SX leaves. The LOX2.1 (TEA011765.1) and LOX2.1 (TEA011776.1) expression ratios in the α-linolenic acid metabolic pathway were 2.44 and 6.43, respectively, in TGY roots, which were significantly higher than those in SX roots. The synthesis of specific substances induces lanthanum-associated defense responses in TGY, which is of great significance for plant yield stability.
Molecular Property Prediction of Modified Gedunin Using Machine Learning
Authors: Aly Mohammed , Alotaibi Abdullah Shawan
Published: January 2023

Images of molecules are often utilized in education and synthetic exploration to predict molecular characteristics. Deep learning (DL) has also had an influence on drug research, such as the interpretation of cellular images as well as the development of innovative methods for the synthesis of organic molecules. Although research in these areas has been significant, a comprehensive review of DL applications in drug development would be beyond the scope of a single Account. In this study, we will concentrate on a single major area where DL has influenced molecular design: the prediction of molecular properties of modified gedunin using machine learning (ML). AI and ML technologies are critical in drug research and development. In these other words, deep learning (DL) algorithms and artificial neural networks (ANN) have changed the field. In short, advances in AI and ML present a good potential for rational drug design and exploration, which will ultimately benefit humanity. In this paper, long short-term memory (LSTM) was used to convert a modified gedunin SMILE into a molecular image. The 2D molecular representations and their immediately visible highlights should then provide adequate data to predict the subordinate characteristics of atom design. We aim to find the properties of modified gedunin using K-means clustering; RNN-like ML tools. To support this postulation, neural network (NN) clustering based on the AI picture is used and evaluated in this study. The novel chemical developed via profound learning has long been predicted on characteristics. As a result, LSTM with RNNs allow us to predict the properties of molecules of modified gedunin. The total accuracy of the suggested model is 98.68%. The accuracy of the molecular property prediction of modified gedunin research is promising enough to evaluate extrapolation and generalization. The model suggested in this research requires just seconds or minutes to calculate, making it faster as well as more effective than existing techniques. In short, ML can be a useful tool for predicting the properties of modified gedunin molecules.
The Role of Molecular Structure in Monte Carlo Simulations of the Secondary Electron Yield and Backscattering Coefficient from Methacrylic Acid
Authors: Wiciak-Pawłowska Katarzyna , Winiarska Anna , Taioli Simone , Dapor Maurizio , Franz Małgorzata , Franz Jan
Published: January 2023

In this paper, we show the influence of the chemical structure of four different conformers on the secondary electron emission and backscattering of an electron beam from a gel of methacrylic acid. The conformers have different permanent dipole moments, which determines the cross sections for elastic collisions with electrons. The cross sections are used in Monte Carlo simulations of an electron beam, which enters the gel of methacrylic acid. The secondary electron yield and the backscattering coefficient are computed as a function of the beam energy.
The Molecular Basis of Heat-Stable Enterotoxin for Vaccine Development and Cancer Cell Detection
Authors: Goto Masaya , Yoshino Shinya , Hiroshima Kyona , Kawakami Toru , Murota Kaeko , Shimamoto Shigeru , Hidaka Yuji
Published: January 2023

Heat-stable enterotoxin (STa) produced by Enterotoxigenic E. coli is responsible for causing acute diarrhea in infants in developing countries. However, the chemical synthesis of STa peptides with the native conformation and the correct intra-molecular disulfide bonds is a major hurdle for vaccine development. To address this issue, we herein report on the design and preparation of STa analogs and a convenient chemical method for obtaining STa molecules with the correct conformation. To develop an STa vaccine, we focused on a structure in a type II β-turn in the STa molecule and introduced a D-Lys residue as a conjugation site for carrier proteins. In addition, the -Glu-Leu- sequence in the STa molecule was replaced with a -Asp-Val- sequence to decrease the toxic activity of the peptide to make it more amenable for use in vaccinations. To solve several issues associated with the synthesis of STa, such as the formation of non-native disulfide isomers, the native disulfide pairings were regioselectively formed in a stepwise manner. A native form or topological isomer of the designed STa peptide, which possesses a right-handed or a left-handed spiral structure, respectively, were synthesized in high synthetic yields. The conformation of the synthetic STa peptide was also confirmed by CD and NMR spectroscopy. To further utilize the designed STa peptide, it was labeled with fluorescein for fluorescent detection, since recent studies have also focused on the use of STa for detecting cancer cells, such as Caco-2 and T84. The labeled STa peptide was able to specifically and efficiently detect 293T cells expressing the recombinant STa receptor (GC-C) protein and Caco-2 cells. The findings reported here provide an outline of the molecular basis for using STa for vaccine development and in the detection of cancer cells.
Structural and Mechanistic Basis for the Inactivation of Human Ornithine Aminotransferase by (3S,4S)-3-Amino-4-fluorocyclopentenecarboxylic Acid
Authors: Shen Sida , Butrin Arseniy , Beaupre Brett A. , Ferreira Glaucio M. , Doubleday Peter F. , Grass Daniel H. , Zhu Wei , Kelleher Neil L. , Moran Graham R. , Liu Dali , Silverman Richard B.
Published: January 2023

Ornithine aminotransferase (OAT) is overexpressed in hepatocellular carcinoma (HCC), and we previously showed that inactivation of OAT inhibits the growth of HCC. Recently, we found that (3S,4S)-3-amino-4-fluorocyclopentenecarboxylic acid (5) was a potent inactivator of γ-aminobutyric acid aminotransferase (GABA-AT), proceeding by an enamine mechanism. Here we describe our investigations into the activity and mechanism of 5 as an inactivator of human OAT. We have found that 5 exhibits 10-fold less inactivation efficiency (kinact/KI) against hOAT than GABA-AT. A comprehensive mechanistic study was carried out to understand its inactivation mechanism with hOAT. pKa and electrostatic potential calculations were performed to further support the notion that the α,β-unsaturated alkene of 5 is critical for enhancing acidity and nucleophilicity of the corresponding intermediates and ultimately responsible for the improved inactivation efficiency of 5 over the corresponding saturated analogue (4). Intact protein mass spectrometry and the crystal structure complex with hOAT provide evidence to conclude that 5 mainly inactivates hOAT through noncovalent interactions, and that, unlike with GABA-AT, covalent binding with hOAT is a minor component of the total inhibition which is unique relative to other monofluoro-substituted derivatives. Furthermore, based on the results of transient-state measurements and free energy calculations, it is suggested that the α,β-unsaturated carboxylate group of PLP-bound 5 may be directly involved in the inactivation cascade by forming an enolate intermediate. Overall, compound 5 exhibits unusual structural conversions which are catalyzed by specific residues within hOAT, ultimately leading to an enamine mechanism-based inactivation of hOAT through noncovalent interactions and covalent modification.
N, S Co-Coordinated Zinc Single-Atom Catalysts for N-Alkylation of Aromatic Amines with Alcohols: The Role of S-Doping in the Reaction
Authors: Zhang Xueping , Zhang Qiang , Reng Jiacheng , Lin Yamei , Tang Yongxing , Liu Guigao , Wang Pengcheng , Lu Guo-Ping
Published: January 2023

S-doping emerged as a promising approach to further improve the catalytic performance of carbon-based materials for organic synthesis. Herein, a facile and gram-scale strategy was developed using zeolitic imidazole frameworks (ZIFs) as a precursor for the fabrication of the ZIF-derived N, S co-doped carbon-supported zinc single-atom catalyst (CNS@Zn1-AA) via the pyrolysis of S-doped ZIF-8, which was modified by aniline, ammonia and thiourea and prepared by one-pot ball milling at room temperature. This catalyst, in which Zn is dispersed as the single atom, displays superior activity in N-alkylation via the hydrogen-borrowing strategy (120 °C, turnover frequency (TOF) up to 8.4 h−1). S-doping significantly enhanced the catalytic activity of CNS@Zn1-AA, as it increased the specific surface area and defects of this material and simultaneously increased the electron density of Zn sites in this catalyst. Furthermore, this catalyst had excellent stability and recyclability, and no obvious loss in activity after eight runs.
Graphene-TLL-Cu2ONPs Hybrid as Highly Efficient Catalyst for Degradation of Organic Compounds
Authors: Losada-Garcia Noelia , Carranza Jannier , Palomo Jose M.
Published: January 2023

In this work, Cu2O nanoparticles (NPs) were created in situ on graphene functionalized with Thermomyces lanuginosus lipase (G@TLL) where site-oriented supported TLL acted as template and binder in the presence of copper salt by tailorable synthesis under mild conditions, producing a heterogeneous catalyst. Cu2O NPs were confirmed by XRD and XPS. The TEM microscopy showed that the nanoparticles were homogeneously distributed over the G@TLL surface with sizes of 53 nm and 165 nm. This G@TLL-Cu2O hybrid was successfully used in the degradation of toxic organic compounds such as trichloroethylene (TCE) and Rhodamine B (RhB). In the case of TCE, the hybrid presented a high catalytic capacity, degrading 60 ppm of product in 60 min in aqueous solution and room temperature without the formation of other toxic subproducts. In addition, a TOF value of 7.5 times higher than the unsupported counterpart (TLL-Cu2O) was obtained, demonstrating the improved catalytic efficiency of the system in the solid phase. The hybrid also presented an excellent catalytic performance for the degradation of Rhodamine B (RhB) obtaining a complete degradation (48 ppm) in 50 min in aqueous solution and room temperature and with the presence of a green oxidant as H2O2.
Pulsed Four-Wave Mixing at Telecom Wavelengths in Si3N4 Waveguides Locally Covered by Graphene
Authors: Demongodin Pierre , El Dirani Houssein , Kerdilès Sébastien , Lhuillier Jérémy , Wood Thomas , Sciancalepore Corrado , Monat Christelle
Published: January 2023

Recently, the nonlinear optical response of graphene has been widely investigated, as has the integration of this 2D material onto dielectric waveguides so as to enhance the various nonlinear phenomena that underpin all-optical signal processing applications at telecom wavelengths. However, a great disparity continues to exist from these experimental reports, depending on the used conditions or the hybrid devices under test. Most importantly, hybrid graphene-based waveguides were tested under relatively low powers, and/or combined with waveguide materials that already exhibited a nonnegligible nonlinear contribution, thereby limiting the practical use of graphene for nonlinear applications. Here, we experimentally investigate the nonlinear response of Si3N4 waveguides that are locally covered by submillimeter-long graphene patches by means of pulsed degenerate four-wave mixing at telecom wavelength under 7 W peak powers. Our measurements and comparison with simulations allow us to estimate a local change of the nonlinearity sign as well as a moderate increase of the nonlinear waveguide parameter (γ∼−10 m−1W−1) provided by graphene. Our analysis also clarifies the tradeoff associated with the loss penalty and nonlinear benefit afforded by graphene patches integrated onto passive photonic circuits, thereby providing some guidelines for the design of hybrid integrated nonlinear devices, coated with graphene, or, more generally, any other 2D material.
PEG-Coated MnZn Ferrite Nanoparticles with Hierarchical Structure as MRI Contrast Agent
Authors: Cheraghali Sedigheh , Dini Ghasem , Caligiuri Isabella , Back Michele , Rizzolio Flavio
Published: January 2023

In this work, MnZn ferrite nanoparticles with hierarchical morphology were synthesized hydrothermally, and their surface characteristics were improved by the PEGylation process. In vitro MRI studies were also conducted to evaluate the ability of the synthesized nanoparticles as a contrast agent. All results were compared with those obtained for MnZn ferrite nanoparticles with normal structure. Microstructural evaluations showed that in ferrite with hierarchical morphology, the spherical particles with an average size of ~20 nm made a distinctive structure consisting of rows of nanoparticles which is a relatively big assembly like a dandelion. The smaller particle size and dandelion-like morphology led to an increase in specific surface area for the hierarchical structure (~69 m2/g) in comparison to the normal one (~30 m2/g) with an average particle size of ~40 nm. In vitro MRI, cytotoxicity and hemocompatibility assays confirmed the PEG-coated MnZn ferrite nanoparticles with hierarchical structure synthesized in the current study can be considered as an MRI contrast agent.
Elastic Strain Relaxation of Phase Boundary of α′ Nanoscale Phase Mediated via the Point Defects Loop under Normal Strain
Authors: Yan Zhengwei , Shi Shujing , Sang Peng , Li Kaiyue , Qin Qingqing , Li Yongsheng
Published: January 2023

Irradiation-induced point defects and applied stress affect the concentration distribution and morphology evolution of the nanophase in Fe–Cr based alloys; the aggregation of point defects and the nanoscale precipitates can intensify the hardness and embrittlement of the alloy. The influence of normal strain on the coevolution of point defects and the Cr-enriched α′ nanophase are studied in Fe-35 at.% Cr alloy by utilizing the multi-phase-field simulation. The clustering of point defects and the splitting of nanoscale particles are clearly presented under normal strain. The defects loop formed at the α/α′ phase interface relaxes the coherent strain between the α/α′ phases, reducing the elongation of the Cr-enriched α′ phase under the normal strains. Furthermore, the point defects enhance the concentration clustering of the α′ phase, and this is more obvious under the compressive strain at high temperature. The larger normal strain can induce the splitting of an α′ nanoparticle with the nonequilibrium concentration in the early precipitation stage. The clustering and migration of point defects provide the diffusion channels of Cr atoms to accelerate the phase separation. The interaction of point defect with the solution atom clusters under normal strain provides an atomic scale view on the microstructure evolution under external stress.
Urinary Hydration Biomarkers and Water Sources in Older Adults with Neurocognitive Disorder
Authors: Queirós Cátia , Machado Flávia Borges , Barros Duarte , Sampaio Joana , Sampaio Arnaldina , Barros Renata , Moreira Pedro , Ribeiro Óscar , Carvalho Joana , Padrão Patrícia
Published: January 2023

The risk of dehydration in older adults with neurocognitive disorder (NCD) is controversial. The purpose of this study was to assess hydration status, its determinants, and water intake sources in older adults with NCD. A sample of 30 participants (≥60 years) was included. Sociodemographic, clinical data and one 24-h urine sample were collected. Urinary osmolality, sodium, potassium, volume, and creatinine were quantified. Inadequate hydration status corresponded to urine osmolality > 500 mOsm/Kg, or a negative Free Water Reserve (FWR). Two 24-h food recalls were used to assess dietary intake and water sources. The adequacy of total water intake (TWI) was estimated according to EFSA. The contribution of food and beverages to TWI was calculated, and their associations with the urinary osmolality median were tested. Of the total number of participants, 30% were classified as having inadequate hydration status, with no differences between sexes. Regarding TWI, 68.4% of women and 77.8% of men did not reach the reference values. Water (23%), followed by soup (17%), contributed the most to TWI, while vegetables (2%) and alcoholic/other beverages (3%) contributed the least. According to the median urinary osmolality, there was no significant difference in sociodemographic/clinical characteristics. It is critical not to overlook hydration in this vulnerable population.
Joint Effect of Multiple Metals on Hyperuricemia and Their Interaction with Obesity: A Community-Based Cross-Sectional Study in China
Authors: Wu Shan , Huang Huimin , Ji Guiyuan , Li Lvrong , Xing Xiaohui , Dong Ming , Ma Anping , Li Jiajie , Wei Yuan , Zhao Dongwei , Ma Wenjun , Bai Yan , Wu Banghua , Liu Tao , Chen Qingsong
Published: January 2023

Metal exposures have been inconsistently related to the risk of hyperuricemia, and limited research has investigated the interaction between obesity and metals in hyperuricemia. To explore their associations and interaction effects, 3300 participants were enrolled from 11 districts within 1 province in China, and the blood concentrations of 13 metals were measured to assess internal exposure. Multivariable logistic regression, restricted cubic spline (RCS), Bayesian kernel machine regression (BKMR), and interaction analysis were applied in the single- and multi-metal models. In single-metal models, five metals (V, Cr, Mn, Co, and Zn) were positively associated with hyperuricemia in males, but V was negatively associated with hyperuricemia in females. Following the multi-metal logistic regression, the multivariate-adjusted odds ratios (95% confidence intervals) of hyperuricemia were 1.7 (1.18, 2.45) for Cr and 1.76 (1.26, 2.46) for Co in males, and 0.68 (0.47, 0.99) for V in females. For V and Co, RCS models revealed wavy and inverted V-shaped negative associations with female hyperuricemia risk. The BKMR models showed a significant joint effect of multiple metals on hyperuricemia when the concentrations of five metals were at or above their 55th percentile compared to their median values, and V, Cr, Mn, and Co were major contributors to the combined effect. A potential interaction between Cr and obesity and Zn and obesity in increasing the risk of hyperuricemia was observed. Our results suggest that higher levels of Cr and Co may increase male hyperuricemia risk, while higher levels of V may decrease female hyperuricemia risk. Therefore, the management of metal exposure in the environment and diet should be improved to prevent hyperuricemia.
Dietary Habit Modifications in Paediatric Patients after One Year of Treatment with the Crohn’s Disease Exclusion Diet
Authors: Martín-Masot Rafael , Herrador-López Marta , Navas-López Víctor Manuel
Published: January 2023

Gut microbiota alterations play a key role in the pathogenesis of inflammatory bowel disease (IBD), and its modification through specific diets is an emerging line of treatment that is currently being researched. The aim of this study was to assess changes in the dietary habits of patients with Crohn’s disease (CD) and their long-term adherence to dietary therapy with the Crohn’s disease exclusion diet (CDED) after one year. To analyse the modification of dietary habits and adherence to the Mediterranean diet (DM), the KIDMED questionnaire, a food consumption frequency questionnaire, was used. Twenty-four hour recalls at two timepoints, namely prior to the start of the dietary therapy and one year later, were also carried out. The processing degrees of the foods consumed by the patients were analysed at both timepoints using the NOVA classification system. Data from 24 patients (15 boys), with a mean age of 12.7 ± 2.9 years at the start of the dietary therapy, were analysed. All patients showed an improvement in their dietary pattern in the form of a reduction in the intake of ultra-processed foods (UPFs); a higher adherence to the MD; a decrease in the intake of cold meats, seafood, pasta, precooked foods, soft drinks, and pastries; an increase in the intake of eggs, legumes, dairy products, and nuts (p < 0.05); and adequate adherence, even in the long-term, to foods allowed during the different phases of the dietary regimen. Although more factors have an impact on the course of the disease in these patients, improving their dietary habits is essential.
Relative Enhancement in Gadoxetate Disodium-Enhanced Liver MRI as an Imaging Biomarker in the Diagnosis of Non-Alcoholic Fatty Liver Disease in Pediatric Obesity
Authors: Hojreh Azadeh , Lischka Julia , Tamandl Dietmar , Ramazanova Dariga , Mulabdic Amra , Greber-Platzer Susanne , Ba-Ssalamah Ahmed
Published: January 2023

Relative enhancement (RE) in gadoxetate disodium (Gd-EOB-DTPA)-enhanced MRI is a reliable, non-invasive method for the evaluation and differentiation between simple steatosis and non-alcoholic steatohepatitis in adults. This study evaluated the diagnostic accuracy of RE in Gd-EOB-DTPA-enhanced liver MRI and hepatic fat fraction (HFF) in unenhanced liver MRI and ultrasound (US) for non-alcoholic fatty liver disease (NAFLD) screening in pediatric obesity. Seventy-four liver US and MRIs from 68 pediatric patients (13.07 ± 2.95 years) with obesity (BMI > BMI-for-age + 2SD) were reviewed with regard to imaging biomarkers (liver size, volume, echogenicity, HFF, and RE in Gd-EOB-DTPA-enhanced MRIs, and spleen size), blood biomarkers, and BMI. The agreement between the steatosis grade, according to HFF in MRI and the echogenicity in US, was moderate. Alanine aminotransferase correlated better with the imaging biomarkers in MRI than with those in US. BMI correlated better with liver size and volume on MRI than in US. In patients with RE < 1, blood biomarkers correlated better with RE than those in the whole sample, with a significant association between gamma-glutamyltransferase and RE (p = 0.033). In conclusion, the relative enhancement and hepatic fat fraction can be considered as non-invasive tools for the screening and follow-up of NAFLD in pediatric obesity, superior to echogenicity on ultrasound.
Validation of the Arabic Version of Diabetes Eating Problem Survey–Revised (DEPS-R) among Adolescents with Type 1 Diabetes
Authors: Hummadi Abdulrahman , Yafei Saeed , Badedi Mohammed , Abutaleb Raed , Darraj Hussain , Alhagawy Ali Jaber , Khawaji Abdullah , Solan Yahia , Alzughbi Turki , Hakami Mohammed , Jaddoh Sattam , Daghriri Abdulrraheem , Khardali Mamdouh
Published: January 2023

Disordered eating behaviors (DEBs) in type 1 diabetes (T1D) have been studied globally in different age groups. However, there is no validated diabetes-specific questionnaire in the Arabic language for the screening of DEBs. This study aimed to translate the Diabetes Eating Problem Survey–Revised scale (DEPS-R) into the Arabic language and study its psychometric properties in adolescents with T1D. We adopted the forward–backward procedure to translate the DEPS-R questionnaire into Arabic. The validation study enrolled 258 Saudi adolescents with T1D aged 12–18 years who completed the Arabic DEPS-R questionnaire and the EAT-26. The Arabic DEPS-R showed good construct validity and reliability (Cronbach’s alpha = 0.86). The factor analysis revealed a three-factor structure of DEPS-R which explains 54.4 % of the variance. In total, 30.6% of the participants are at high risk for DEBs (DEPS-R score ≥ 20). The psychometric properties of the Arabic DEPS-R are satisfactory, consistent with the original scale and translations in other languages. These results support the validity of the Arabic DEPS-R for assessment of DEBs in the T1D Arabic population.
Influence of Maternal Metabolic Status and Diet during the Perinatal Period on the Metabolic Programming by Leptin Ingested during the Suckling Period in Rats
Authors: Castillo Pedro , Pomar Catalina Amadora , Palou Andreu , Palou Mariona , Picó Catalina
Published: January 2023

We aimed to analyze the long-term metabolic effects of leptin supplementation at physiological doses during suckling in the offspring of diet-induced obese rats, together with the potential benefits of improving maternal diet during lactation. Thus, the offspring of: dams fed standard-diet (SD) (CON-dams), dams fed western-diet (WD) before and during gestation and lactation (WD-dams), and dams fed as WD-dams but moved to SD during lactation (REV-dams) were supplemented throughout suckling with leptin or vehicle, and fed SD or WD from weaning to four months. Under SD, leptin treatment significantly improved metabolic profile and body fat accumulation, with stronger effects in the male offspring of CON-dams and REV-dams. Under WD, the offspring of WD-dams presented metabolic alterations that were not evident in the offspring of REV-dams. Moreover, leptin supplementation improved glucose homeostasis in the male offspring of REV-dams. Conversely, leptin supplementation in females born to WD-dams and fed WD from weaning resulted in impaired insulin sensitivity and increased hepatic lipid content. These results highlight the importance of a balanced maternal diet during the perinatal period, especially lactation, for the subsequent metabolic health of the offspring and for the beneficial effects of leptin supplementation during suckling, more evident in the male offspring.
Usability Testing an mHealth Program with Tailored Motivational Messages for Early Adolescents
Authors: Lin Carolyn A. , Vosburgh Kayla L. , Roy Deya , Duffy Valerie B.
Published: January 2023

Obesity among children is a rising concern throughout the world. In the U.S., rates of childhood obesity are the highest among children from diverse and economically disadvantaged households. Obesity in adolescence increases the risk of negative physical and psychological health consequences. Mobile-app-based health interventions have been found to be an effective tool to encourage children to adopt a healthier living style. A novel mobile app prototype was developed for early adolescents to communicate with and engage them interactively about healthy eating and active living. To test the app’s usability, students from a U.S. middle school, with a majority of children from low-income families, were recruited to use the app and report their feedback. The usability testing results confirmed that the app was equally well received by participants of different genders, normal weight versus overweight/obesity, and amounts of screen time. Study participants also provided overwhelming positive feedback for the embedded and tailored motivational messages that encourage healthy eating and active living. The conceptualization of the app prototype was guided by the self-determination theory, social cognitive theory, and priming theory, in addition to incorporating evidence-based obesity prevention principles. This prototype, hence, provides a valid platform for building theory-based behavioral interventions.
Anti-Inflammatory Effect of Garcinol Extracted from Garcinia dulcis via Modulating NF-κB Signaling Pathway
Authors: Chantree Pathanin , Martviset Pongsakorn , Thongsepee Nattaya , Sangpairoj Kant , Sornchuer Phornphan
Published: January 2023

Garcinia is a significant medicinal plant with many beneficial phytoconstituents, including garcinol. This study investigated the anti-inflammatory effect of garcinol isolated from Garcinia dulcis fruit in LPS-activated THP-1 and Raw 264.7 macrophages. The results demonstrated that the low concentration of garcinol did not alter cell viability. Furthermore, co-incubation of garcinol with LPS inhibited the production of pro-inflammatory cytokines, including TNF-α, IL-8, IL-6, IL-1β, and pro-inflammatory mediators, including iNOS and COX-2 at the mRNA and protein expression levels. Garcinol also decreased the secretion of TNF-α, IL-6, IL-1β, PGE2, and NO. Moreover, the anti-inflammatory effects involved an alteration in the NF-κB signaling pathway. Downregulation of pIKKα/β, pIκBα, and pNF-κB was observed, hence reducing the translocation of pNF-κB from the cytosol into the nucleus, which subsequently decreased the production of pro-inflammatory molecules. Therefore, garcinol isolated from Garcinia dulcis is a potential candidate as an anti-inflammatory agent for inflammation-related disease treatment.
Matcha Tea Powder’s Antidepressant-like Effect through the Activation of the Dopaminergic System in Mice Is Dependent on Social Isolation Stress
Authors: Kurauchi Yuki , Ohta Yuki , Matsuda Keigo , Sanematsu Wakana , Devkota Hari Prasad , Seki Takahiro , Katsuki Hiroshi
Published: January 2023

Matcha tea powder is believed to have various physiological benefits; however, its detailed mechanism of action has been poorly understood. Here, we investigated whether the mental state of mice, due to social isolation stress, affects the antidepressant-like effect of Matcha tea powder by using the tail suspension test. Oral administration of Matcha tea powder reduced the duration of immobility in the stress-susceptible C57BL/6J strain, but not in BALB/c strain. In C57BL/6J mice, SCH23390, a dopamine D1 receptor blocker, prevented Matcha tea powder from exerting its antidepressant-like effect. Matcha tea powder also increased the number of c-Fos-positive cells in the prefrontal cortex (PFC) region and the nucleus accumbens (NAc) region in C57BL/6J mice, but not in BALB/c mice. In contrast, Matcha tea powder did not change the number of c-Fos-positive cells in the ventral tegmental area (VTA) region. Notably, C57BL/6J mice with a shorter immobility time had a higher number of c-Fos-positive cells in the PFC, NAc, and VTA regions. However, no such correlation was observed in the stress-tolerant BALB/c mice. These results suggest that Matcha tea powder exerts an antidepressant-like effect through the activation of the dopaminergic system including the PFC-NAc-VTA circuit and that mental states are important factors affecting the physiological benefits of Matcha tea powder.
Synergistic Effect of Rhodiola rosea and Caffeine Supplementation on the Improvement of Muscle Strength and Muscular Endurance: A Pilot Study for Rats, Resistance Exercise-Untrained and -Trained Volunteers
Authors: Liu Chang , Zhao Haotian , Yan Yi , Yang Weijun , Chen Songyue , Song Ge , Li Xuehan , Gu Yujia , Yun Hezhang , Li Yi
Published: January 2023

Multi-level studies have shown that Rhodiola rosea (RHO) and Caffeine (CAF) have the potential to be nutritional supplements to enhance physical performance in resistance exercise-untrained and -trained subjects. This study examined the synergistic effects of RHO (262.7 mg/kg for rats and 2.4 g for volunteers) and CAF (19.7 mg/kg for rats and 3 mg/kg for volunteers) supplementation on improving physical performance in rats, resistance exercise-untrained volunteers and resistance exercise-trained volunteers. Rats and volunteers were randomly grouped into placebo, CAF, RHO and CAF+RHO and administered accordingly with the nutrients during the training procedure, and pre- and post-measures were collected. We found that RHO+CAF was effective in improving forelimb grip strength (13.75%), erythropoietin (23.85%), dopamine (12.65%) and oxygen consumption rate (9.29%) in the rat model. Furthermore, the current results also indicated that the combination of RHO+CAF significantly increased the bench press one-repetition maximum (1RM) (16.59%), deep squat 1RM (15.75%), maximum voluntary isometric contraction (MVIC) (14.72%) and maximum repetitions of 60% 1RM bench press (22.15%) in resistance exercise-untrained volunteers. Additionally, despite the excellent base level of the resistance exercise-trained volunteers, their deep squat 1RM and MVIC increased substantially through the synergistic effect of RHO and CAF. In conclusion, combined supplementation of RHO+CAF is more beneficial in improving the resistance exercise performance for both resistance exercise-untrained and -trained volunteers. The present results provide practical evidence that the synergies of RHO and CAF could serve as potential supplementary for individuals, especially resistance exercise-trained subjects, to ameliorate their physical performances effectively and safely.
Evidence-Based Lifestyle Guidelines and Self-Management Strategies Utilized by Women with Polycystic Ovary Syndrome
Authors: Cowan Stephanie , Grassi Angela , Monahan Couch Lynn , Jeanes Yvonne , Lim Siew , Pirotta Stephanie , Harris Jeff , McGirr Caroline , Moran Lisa
Published: January 2023

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder, affecting 13% of reproductive-aged women. While lifestyle management is the first-line treatment for improving complications, women experience challenges with implementation. This cross-sectional study aims to identify the types and sources of dietary and physical activity (PA) interventions implemented by women with PCOS and understand how they use self-management strategies to support lifestyle change. An online questionnaire was disseminated via a consumer-based PCOS website (May 2015–2016). Women (n = 1167) were aged 18–45 years and primarily born within the United States (70%). A quarter or less of women (diet 25%, PA 14%) sought lifestyle advice from health professionals (medical clinicians or dietitians) compared to over half (diet 59%, PA 67%) using alternative sources, namely from online platforms. While only 33% and 16% of women reported following formal dietary or PA guidelines, respectively, 57% had implemented a ‘special diet’ to manage their condition, many of which were inconsistent with evidence-based practice in PCOS. Participants also displayed a low level of engagement with important self-management behaviors, including goal setting and positive self-talk. These findings suggest that online information may promote inaccurate and ineffective lifestyle advice and emphasize the need to increase engagement with qualified health professionals.
EPHB4-RASA1-Mediated Negative Regulation of Ras-MAPK Signaling in the Vasculature: Implications for the Treatment of EPHB4- and RASA1-Related Vascular Anomalies in Humans
Authors: Chen Di , Van der Ent Martijn A. , Lartey Nathaniel L. , King Philip D.
Published: January 2023

Ephrin receptors constitute a large family of receptor tyrosine kinases in mammals that through interaction with cell surface-anchored ephrin ligands regulate multiple different cellular responses in numerous cell types and tissues. In the cardiovascular system, studies performed in vitro and in vivo have pointed to a critical role for Ephrin receptor B4 (EPHB4) as a regulator of blood and lymphatic vascular development and function. However, in this role, EPHB4 appears to act not as a classical growth factor receptor but instead functions to dampen the activation of the Ras-mitogen activated protein signaling (MAPK) pathway induced by other growth factor receptors in endothelial cells (EC). To inhibit the Ras-MAPK pathway, EPHB4 interacts functionally with Ras p21 protein activator 1 (RASA1) also known as p120 Ras GTPase-activating protein. Here, we review the evidence for an inhibitory role for an EPHB4–RASA1 interface in EC. We further discuss the mechanisms by which loss of EPHB4–RASA1 signaling in EC leads to blood and lymphatic vascular abnormalities in mice and the implications of these findings for an understanding of the pathogenesis of vascular anomalies in humans caused by mutations in EPHB4 and RASA1 genes. Last, we provide insights into possible means of drug therapy for EPHB4- and RASA1-related vascular anomalies.
Silk Fibroin Microneedles for Transdermal Drug Delivery: Where Do We Stand and How Far Can We Proceed?
Authors: Qi Zhenzhen , Yan Zheng , Tan Guohongfang , Jia Tianshuo , Geng Yiyu , Shao Huiyan , Kundu Subhas C. , Lu Shenzhou
Published: January 2023

Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. This review focuses on the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of silk fibroin, the types of silk fibroin microneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field. It also proposes the future research direction of silk fibroin microneedles, including increasing drug loading doses and enriching drug loading types as well as exploring silk fibroin microneedles with stimulation-responsive drug release functions. The safety and effectiveness of silk fibroin microneedles should be further verified in clinical trials at different stages.
Bio-Inspired Drug Delivery Systems: From Synthetic Polypeptide Vesicles to Outer Membrane Vesicles
Authors: Zhang Yu , Lu Yiming , Xu Yixin , Zhou Zunkang , Li Yichong , Ling Wei , Song Wenliang
Published: January 2023

Nanomedicine is a broad field that focuses on the development of nanocarriers to deliver specific drugs to targeted sites. A synthetic polypeptide is a kind of biomaterial composed of repeating amino acid units that are linked by peptide bonds. The multiplied amphiphilicity segment of the polypeptide could assemble to form polypeptide vesicles (PVs) under suitable conditions. Different from polypeptide vesicles, outer membrane vesicles (OMVs) are spherical buds of the outer membrane filled with periplasmic content, which commonly originate from Gram-negative bacteria. Owing to their biodegradability and excellent biocompatibility, both PVs and OMVs have been utilized as carriers in delivering drugs. In this review, we discuss the recent drug delivery research based on PVs and OMVs. These related topics are presented: (1) a brief introduction to the production methods for PVs and OMVs; (2) a thorough explanation of PV- and OMV-related applications in drug delivery including the vesicle design and biological assessment; (3) finally, we conclude with a discussion on perspectives and future challenges related to the drug delivery systems of PVs and OMVs.
Novel Green Crosslinked Salecan Hydrogels and Preliminary Investigation of Their Use in 3D Printing
Authors: Ianchis Raluca , Alexa Rebeca Leu , Gifu Ioana Catalina , Marin Maria Minodora , Alexandrescu Elvira , Constantinescu Roxana , Serafim Andrada , Nistor Cristina Lavinia , Petcu Cristian
Published: January 2023

Salecan, a kind of polysaccharide, is produced by the Agrobacterium ZX09 salt tolerant strain. In this study, green crosslinked citric acid-salecan hydrogels are explored as novel materials with a high potential for use in regenerative medicine. The impact of salecan and citric acid on the final crosslinked hydrogels was intensively studied and estimated in terms of the whole physicochemical properties and antimicrobial activity. FTIR spectra demonstrated the successful green crosslinking of salecan through its esterification with citric acid where the formation of strong covalent bonds collaboratively helped to stabilize the entire hydrogel systems in a wet state. Hydrogels presented a microporous morphology, good swelling capacity, pH responsiveness, great mechanical stability under stress conditions and good antibacterial activity, all related to the concentration of the biopolymers used in the synthesis step. Additionally, salecan hydrogels were preliminary investigated as printing inks. Thanks to their excellent rheological behavior, we optimized the citrate-salecan hydrogel inks and printing parameters to render 3D constructs with great printing fidelity and integrity. The novel synthesized salecan green crosslinked hydrogels enriches the family of salecan-derived hydrogels. Moreover, this work not only expands the application of salecan hydrogels in various fields, but also provides a new potential option of designing salecan-based 3D printed scaffolds for customized regenerative medicine.
Antioxidant and Anticancer Potential of the New Cu(II) Complexes Bearing Imine-Phenolate Ligands with Pendant Amine N-Donor Groups
Authors: Pinheiro Adriana Castro , Nunes Ianka Jacondino , Ferreira Wesley Vieira , Tomasini Paula Pellenz , Trindade Cristiano , Martins Carolina Cristóvão , Wilhelm Ethel Antunes , Oliboni Robson da Silva , Netz Paulo Augusto , Stieler Rafael , Casagrande Osvaldo de Lazaro , Saffi Jenifer
Published: January 2023

Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands (1a, b) and Cu(II) complexes (2a, b) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS+). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 (normal lung fibroblast). All compounds showed high cytotoxicity in the all-cell lines but showed no selectivity for tumor cell lines. Antiproliferative activity by clonogenic assay 2b showed a more significant inhibitory effect on the MCF-7 cell lines than on MRC-5. DNA damage for the 2b compound at 10 µM concentration was about three times higher in MCF-7 cells than in MRC-5 cells.
An Engineered IFNγ-Antibody Fusion Protein with Improved Tumor-Homing Properties
Authors: Di Nitto Cesare , Gilardoni Ettore , Mock Jacqueline , Nadal Lisa , Weiss Tobias , Weller Michael , Seehusen Frauke , Libbra Chiara , Puca Emanuele , Neri Dario , De Luca Roberto
Published: January 2023

Interferon-gamma (IFNγ) is one of the central cytokines produced by the innate and adaptive immune systems. IFNγ directly favors tumor growth control by enhancing the immunogenicity of tumor cells, induces IP-10 secretion facilitating (CXCR3+) immune cell infiltration, and can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that the targeted delivery of IFNγ to neoplastic lesions may be limited by the trapping of IFNγ-based products by cognate receptors found in different organs. Here we describe a novel fusion protein consisting of the L19 antibody, specific to the alternatively spliced extra-domain B of fibronectin (EDB), fused to a variant of IFNγ with reduced affinity to its cognate receptor. The product (named L19-IFNγ KRG) selectively localized to tumors in mice, showed favorable pharmacokinetic profiles in monkeys and regained biological activity upon antigen binding. The fusion protein was investigated in two murine models of cancer, both as monotherapy and in combination with therapeutic modalities which are frequently used for cancer therapy. L19-IFNγ KRG induced tumor growth retardation and increased the intratumoral concentration of T cells and NK cells in combination with anti-PD-1.
On the Possibility of Intense Unipolar THz Pulses Formation in Nonhomogeneous Nonequilibrium Nitrogen Plasma Channels
Authors: Bogatskaya Anna V. , Volkova Ekaterina A. , Popov Alexander M.
Published: January 2023

We developed a 3D, fully self-consistent model for analysis of the ultrashort THz unipolar pulse formation accompanied by its amplification in a nonequilibrium plasma channel induced in nitrogen by a femtosecond UV laser pulse. The model is based on a self-consistent numerical solution of the second-order wave equation in cylindrical geometry and the kinetic Boltzmann equation for the electron velocity distribution function (EVDF) at different points of the spatially inhomogeneous nonequilibrium plasma channel. Rapid relaxation of the electron velocity distribution function in the plasma channel results in the amplification of the leading front of the THz pulse only, while its trailing edge is not amplified or even absorbed, which gives rise to the possibility of the formation of pulses with a high degree of unipolarity. The evolution of the unipolar pulse after its transfer from the channel to open free space is analyzed in detail.