bluuebunny/crossref_metadata_2025 huggingface dataset:
High-Throughput Metabolic Soft-Spot Identification in Liver Microsomes by LC/UV/MS: Application of a Single Variable Incubation Time Approach
Authors: Zhu Yanlin , Chen Guiying , Zhang Kerong , Chen Chang , Chen Weiqing , Zhu Mingshe , Jiang Hongliang
Published: November 2022

CYP-mediated fast metabolism may lead to poor bioavailability, fast drug clearance and significant drug interaction. Thus, metabolic stability screening in human liver microsomes (HLM) followed by metabolic soft-spot identification (MSSID) is routinely conducted in drug discovery. Liver microsomal incubations of testing compounds with fixed single or multiple incubation time(s) and quantitative and qualitative analysis of metabolites using high-resolution mass spectrometry are routinely employed in MSSID assays. The major objective of this study was to develop and validate a simple, effective, and high-throughput assay for determining metabolic soft-spots of testing compounds in liver microsomes using a single variable incubation time and LC/UV/MS. Model compounds (verapamil, dextromethorphan, buspirone, mirtazapine, saquinavir, midazolam, amodiaquine) were incubated at 3 or 5 µM with HLM for a single variable incubation time between 1 and 60 min based on predetermined metabolic stability data. As a result, disappearances of the parents were around 20–40%, and only one or a few primary metabolites were generated as major metabolite(s) without notable formation of secondary metabolites. The unique metabolite profiles generated from the optimal incubation conditions enabled LC/UV to perform direct quantitative estimation for identifying major metabolites. Consequently, structural characterization by LC/MS focused on one or a few major primary metabolite(s) rather than many metabolites including secondary metabolites. Furthermore, generic data-dependent acquisition methods were utilized to enable Q-TOF and Qtrap to continuously record full MS and MS/MS spectral data of major metabolites for post-acquisition data-mining and interpretation. Results from analyzing metabolic soft-spots of the seven model compounds demonstrated that the novel MSSID assay can substantially simplify metabolic soft-spot identification and is well suited for high-throughput analysis in lead optimization.
Preparation and Application of Electrochemical Horseradish Peroxidase Sensor Based on a Black Phosphorene and Single-Walled Carbon Nanotubes Nanocomposite
Authors: Li Xiaoqing , Wang Lisi , Wang Baoli , Zhang Siyue , Jiang Meng , Fu Wanting , Sun Wei
Published: November 2022

To design a new electrochemical horseradish peroxidase (HRP) biosensor with excellent analytical performance, black phosphorene (BP) nanosheets and single-walled carbon nanotubes (SWCNTs) nanocomposites were used as the modifier, with a carbon ionic liquid electrode (CILE) as the substrate electrode. The SWCNTs-BP nanocomposite was synthesized by a simple in situ mixing procedure and modified on the CILE surface by the direct casting method. Then HRP was immobilized on the modified electrode with Nafion film. The electrocatalysis of this electrochemical HRP biosensor to various targets was further explored. Experimental results indicated that the direct electrochemistry of HRP was realized with a pair of symmetric and quasi-reversible redox peaks appeared, which was due to the presence of SWCNTs-BP on the surface of CILE, exhibiting synergistic effects with high electrical conductivity and good biocompatibility. Excellent electrocatalytic activity to trichloroacetic acid (TCA), sodium nitrite (NaNO2), and hydrogen peroxide (H2O2) were realized, with a wide linear range and a low detection limit. Different real samples, such as a medical facial peel solution, the soak water of pickled vegetables, and a 3% H2O2 disinfectant, were further analyzed, with satisfactory results, further proving the potential practical applications for the electrochemical biosensor.
Fluorine-Containing Flow Modifier for BN/PPS Composites Enabled by Low Surface Energy
Authors: Cao Bo , Huang Xiaodan , Zhang Wenxiang , Wu Peng
Published: November 2022

In this study, a fluorine-containing flow modifier (Si-DF) with low surface energy is successfully synthesized, which is applied to fabricate ideal electronic packaging materials (BN/PPS composites) with high thermal conductivity, excellent dielectric properties, processability, and toughness by conventional melt blending. Si-DPF is located at the interface between the BN fillers and the PPS matrix, which not only improves the dispersion of BN fillers but also strengthens the interaction. With the help of 5 wt% Si-DF, BN/PPS/Si-DF (70/25/5) still exhibits the high thermally conductive coefficient (3.985 W/m·K) and low dielectric constant (3.76 at 100 MHz) although BN fillers are loaded as high as 70 wt%. Moreover, the sample processes a lower stable torque value (2.5 N·m), and the area under the stress–strain curves is also increased. This work provides an efficient way to develop high-performance polymer-based composites with high thermally conductive coefficients and low dielectric constants for electronic packaging applications.
A Theoretical Study of the Halogen Bond between Heteronuclear Halogen and Benzene
Authors: Luo Jun , Dai Hongjing , Zeng Chenglu , Wu Dawang , Cao Maoqi
Published: November 2022

Halogen bonds play an important role in many fields, such as biological systems, drug design and crystal engineering. In this work, the structural characteristics of the halogen bond between heteronuclear halogen XD (ClF, BrCl, IBr, ICl, BrF and IF) and benzene were studied using density functional theory. The structures of the complexes between heteronuclear halogen and benzene have Cs symmetry. The interaction energies of the complexes between heteronuclear halogen XD (ClF, BrCl, IBr, ICl, BrF and IF) and benzene range from −27.80 to −37.18 kJ/mol, increasing with the increases in the polarity between the atoms of X and D, and are proportional to the angles of a between the Z axis and the covalent bond of heteronuclear halogen. The electron density (ρ) and corresponding Laplacian (∇2ρ) values indicate that the interaction of the heteronuclear halogen and benzene is a typical long-range weak interaction similar to a hydrogen bond. Independent gradient model analysis suggests that the van der Waals is the main interaction between the complexes of heteronuclear halogen and benzene. Symmetry-adapted perturbation theory analysis suggests that the electrostatic interaction is the dominant part in the complexes of C6H6⋯ClF, C6H6⋯ICl, C6H6⋯BrF and C6H6⋯IF, and the dispersion interaction is the main part in the complexes of C6H6⋯BrCl, C6H6⋯IBr.
Improved Activity of Herbal Medicines through Nanotechnology
Authors: Dewi Mayang Kusuma , Chaerunisaa Anis Yohana , Muhaimin Muhaimin , Joni I Made
Published: November 2022

Phytochemicals or secondary metabolites are substances produced by plants that have been shown to have many biological activities, providing a scientific basis for using herbs in traditional medicine. In addition, the use of herbs is considered to be safe and more economical compared to synthetic medicine. However, herbal medicines have disadvantages, such as having low solubility, stability, and bioavailability. Some of them can undergo physical and chemical degradation, which reduces their pharmacological activity. In recent decades, nanotechnology-based herbal drug formulations have attracted attention due to their enhanced activity and potential for overcoming the problems associated with herbal medicine. Approaches using nanotechnology-based delivery systems that are biocompatible, biodegradable, and based on lipids, polymers, or nanoemulsions can increase the solubility, stability, bioavailability, and pharmacological activity of herbals. This review article aims to provide an overview of the latest advances in the development of nanotechnology-based herbal drug formulations for increased activity, as well as a summary of the challenges these delivery systems for herbal medicines face.
Application of Peptides in Construction of Nonviral Vectors for Gene Delivery
Authors: Yang Yujie , Liu Zhen , Ma Hongchao , Cao Meiwen
Published: November 2022

Gene therapy, which aims to cure diseases by knocking out, editing, correcting or compensating abnormal genes, provides new strategies for the treatment of tumors, genetic diseases and other diseases that are closely related to human gene abnormalities. In order to deliver genes efficiently to abnormal sites in vivo to achieve therapeutic effects, a variety of gene vectors have been designed. Among them, peptide-based vectors show superior advantages because of their ease of design, perfect biocompatibility and safety. Rationally designed peptides can carry nucleic acids into cells to perform therapeutic effects by overcoming a series of biological barriers including cellular uptake, endosomal escape, nuclear entrance and so on. Moreover, peptides can also be incorporated into other delivery systems as functional segments. In this review, we referred to the biological barriers for gene delivery in vivo and discussed several kinds of peptide-based nonviral gene vectors developed for overcoming these barriers. These vectors can deliver different types of genetic materials into targeted cells/tissues individually or in combination by having specific structure–function relationships. Based on the general review of peptide-based gene delivery systems, the current challenges and future perspectives in development of peptidic nonviral vectors for clinical applications were also put forward, with the aim of providing guidance towards the rational design and development of such systems.
Design of Ni(OH)2 Nanosheets@NiMoO4 Nanofibers’ Hierarchical Structure for Asymmetric Supercapacitors
Authors: Li Junzhu , Chang Xin , Zhou Xuejiao , Zhang Mingyi
Published: November 2022

Transition−metal−based materials show great promise for energy conversion and storage due to their excellent chemical properties, low cost, and excellent natural properties. In this paper, through simple strategies such as classical electrospinning, air calcination, and the one−step hydrothermal method, a large area of Ni(OH)2 nanosheets were grown on NiMoO4 nanofibers, forming NiMoO4@Ni(OH)2 nanofibers. The one−dimensional nanostructure was distributed with loose nanosheets, and this beneficial morphology made charge−transfer and diffusion more rapid, so the newly developed material showed good capacitance and conductivity. Under the most suitable experimental conditions, the optimal electrode exhibited the highest specific capacitance (1293 F/g at 1 A/g) and considerable rate capability (56.8% at 10 A/g) under typical test conditions. Most interestingly, the corresponding asymmetrical capacitors exhibited excellent electrochemical cycle stability, maintaining 77% of the original capacitance. NiMoO4@Ni(OH)2 nanofibers were verified to be simple to prepare and to have good performances as energy−storage devices within this experiment.
Cloud Workload and Data Center Analytical Modeling and Optimization Using Deep Machine Learning
Authors: Daradkeh Tariq , Agarwal Anjali
Published: November 2022

Predicting workload demands can help to achieve elastic scaling by optimizing data center configuration, such that increasing/decreasing data center resources provides an accurate and efficient configuration. Predicting workload and optimizing data center resource configuration are two challenging tasks. In this work, we investigate workload and data center modeling to help in predicting workload and data center operation that is used as an experimental environment to evaluate optimized elastic scaling for real data center traces. Three methods of machine learning are used and compared with an analytical approach to model the workload and data center actions. Our approach is to use an analytical model as a predictor to evaluate and test the optimization solution set and find the best configuration and scaling actions before applying it to the real data center. The results show that machine learning with an analytical approach can help to find the best prediction values of workload demands and evaluate the scaling and resource capacity required to be provisioned. Machine learning is used to find the optimal configuration and to solve the elasticity scaling boundary values. Machine learning helps in optimization by reducing elastic scaling violation and configuration time and by categorizing resource configuration with respect to scaling capacity values. The results show that the configuration cost and time are minimized by the best provisioning actions.
Sustainable Nutrition for Increased Food Security Related to Romanian Consumers’ Behavior
Authors: Balan Ioana Mihaela , Gherman Emanuela Diana , Gherman Remus , Brad Ioan , Pascalau Raul , Popescu Gabriela , Trasca Teodor Ioan
Published: November 2022

Food security is a matter of global concern, as the supply of food is one of the basic needs, ensuring the survival of the species. The trend of globalization and development of the global economy has shifted the responsible, local consumption patterns towards an increased homogeneity of diets, with food products being disconnected from their source, leading to two major results: (1) increased global consumption and (2) increased uncertainty in the supply chain. To determine what is the nutritional model of Romanians, we developed a questionnaire of 32 questions and distributed it using simple random sampling method. The questionnaire was issued both in physical and digital form and received 1053 responses. The survey was conducted during 2021 and 2022, both in urban and rural areas with the aim of investigating the consumption pattern of the population. The analysis of the questionnaire data reveals overconsumption of animal products, starchy vegetables and bread and pastry products. This nutritional pattern with a high intake in animal protein, correlated with a lack of diversification, is extremely unsustainable, having a negative impact on human health and environmental health.
Reproducibility of the German and Slovakian Versions of the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN)
Authors: Cieśla Elżbieta , Suliga Edyta , Kadučáková Helena , Michel Sven , Ižová Marcela , Simočková Viera , Martin Titus , Braun Alexander , Kozieł Dorota , Głuszek Stanisław
Published: November 2022

Purpose. The aim of this study was to assess the reproducibility and reliability of the KomPAN questionnaire among two groups of university students from Germany and Slovakia. Methods. A total of 422 individuals (mean age 21.4 years, SD 4.0), including 197 from Slovakia (men 26.2%) and 225 from Germany (men 22.3%), were tested using the self-administered (SA-Q) version of the KomPAN questionnaire and then retested two weeks later. A cross-classification analysis, kappa coefficients, Cronbach’s ɑ coefficients, and a test-retest result comparison were conducted separately for each group of students to assess the reproducibility and reliability of the questionnaire. Results. The cross-classification values were higher than 46.2% among the German students and higher than 55.8% among the Slovakian students. The kappa coefficients ranged from 0.21 to 0.90 in the German students and from 0.38 to 0.94 in the Slovakian students. Cronbach’s ɑ ranged from 0.58 to 0.78. Conclusion. The questionnaire displayed a moderate to very good reproducibility, which was slightly higher in the Slovakian group than in the German group. Therefore, the questionnaire can be recommended for further analysis and comparison of the dietary habits among Germans and Slovakians on a larger scale.
Cyclosorus terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats
Authors: Songtrai Sujinda , Pratchayasakul Wasana , Arunsak Busarin , Chunchai Titikorn , Kongkaew Aphisek , Chattipakorn Nipon , Chattipakorn Siriporn , Kaewsuwan Sireewan
Published: November 2022

Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.
The Effect of Nighttime Snacking on Cognitive Function in Older Adults: Evidence from Observational and Experimental Studies
Authors: Niu Cheng-Cheng , Bao Wei-Jie , Jiang Hai-Xin , Yu Jing
Published: November 2022

Evidence shows that supplementary snacking could provide older adults with nutrients that cannot be obtained through three meals a day. However, whether and how supplementary snacking, especially nighttime snacking, affects older adults’ cognitive function remain unclear. The present study examined the effect of nighttime snacking on cognitive function for older adults. In study 1, we investigated the association between nighttime snacking and cognitive function based on data from 2618 community-dwelling older adults from the China health and nutrition survey (CHNS). In study 2, we conducted an experiment (n = 50) to explore how nighttime acute energy intake influences older adults’ performance on cognitive tasks (immediate recall, short-term delayed recall, and long-term delayed recall). Both the observational and experimental studies suggested that nighttime snacking facilitated older adults’ cognitive abilities, such as memory and mathematical ability, as indicated by subjective measures (study 1) and objective measures (studies 1 and 2). Moreover, this beneficial effect was moderated by cognitive load. These findings bridge the gap in the literature on the relationships between older adults’ nighttime snacking and cognitive function, providing insight into how to improve older adults’ dietary behaviors and cognitive function.
Associations between Sweet Taste Sensitivity and Polymorphisms (SNPs) in the TAS1R2 and TAS1R3 Genes, Gender, PROP Taster Status, and Density of Fungiform Papillae in a Genetically Homogeneous Sardinian Cohort
Authors: Melis Melania , Mastinu Mariano , Naciri Lala Chaimae , Muroni Patrizia , Tomassini Barbarossa Iole
Published: November 2022

Individual differences in sweet taste sensitivity can affect dietary preferences as well as nutritional status. Despite the lack of consensus, it is believed that sweet taste is impacted by genetic and environmental variables. Here we determined the effect of well-established factors influencing the general taste variability, such as gender and fungiform papillae density, specific genetic variants (SNPs of TAS1R2 and TAS1R3 receptors genes), and non-specific genetic factors (PROP phenotype and genotype), on the threshold and suprathreshold sweet taste sensitivity. Suprathreshold measurements showed that the sweet taste response increased in a dose-dependent manner, and this was related to PROP phenotype, gender, rs35874116 SNP in the TAS1R2 gene, and rs307355 SNP in the TAS1R3 gene. The threshold values and density of fungiform papillae exhibited a strong correlation, and both varied according to PROP phenotype. Our data confirm the role of PROP taste status in the sweet perception related to fungiform papilla density, show a higher sweet sensitivity in females who had lower BMI than males, and demonstrate for the first time the involvement of the rs35874116 SNP of TAS1R2 in the sweet taste sensitivity of normal weight subjects with body mass index (BMI) ranging from 20.2 to 24.8 kg/m2. These results may have an important impact on nutrition and health mostly in subjects with low taste ability for sweets and thus with high vulnerability to developing obesity or metabolic disease.
Curcumin-Added Whey Protein Positively Modulates Skeletal Muscle Inflammation and Oxidative Damage after Exhaustive Exercise
Authors: Dias Kelly Aparecida , da Conceição Aline Rosignoli , Pereira Stephanie Michelin Santana , Oliveira Lívya Alves , da Silva Rodrigues João Vitor , Dias Roberto Sousa , de Paula Sérgio Oliveira , Natali Antônio José , da Matta Sérgio Luis Pinto , Gonçalves Reggiani Vilela , Tako Elad , Martino Hercia Stampini Duarte , Lucia Ceres Mattos Della
Published: November 2022

(1) Background: Exhaustive exercise can induce muscle damage. The consumption of nutritional compounds with the ability to positively influence the oxidative balance and an exacerbated inflammatory process has been previously studied. However, little is known about the nutritional value of curcumin (CCM) when mixed with whey protein concentrate (WPC). This study was developed to evaluate the effect of CCM-added WPC on inflammatory and oxidative process control and histopathological consequences in muscle tissue submitted to an exhaustive swimming test (ET). (2) Methods: 48 animals were randomly allocated to six groups (n = 8). An ET was performed 4 weeks after the start of the diet and animals were euthanized 24 h post ET. (3) Results: WPC + CCM and CCM groups reduced IL-6 and increased IL-10 expression in muscle tissue. CCM reduced carbonyl protein after ET compared to standard AIN-93M ET and WPC + CCM ET diets. Higher nitric oxide concentrations were observed in animals that consumed WPC + CCM and CCM. Consumption of WPC + CCM or isolated CCM reduced areas of inflammatory infiltrate and fibrotic tissue in the muscle. (4) Conclusions: WPC + CCM and isolated CCM contribute to the reduction in inflammation and oxidative damage caused by the exhaustive swimming test.
Practical Nutrition Strategies to Support Basketball Performance during International Short-Term Tournaments: A Narrative Review
Authors: Esen Ozcan , Rozwadowski Kazimierz , Cepicka Ladislav , Gabrys Tomasz , Karayigit Raci
Published: November 2022

A short-term (e.g., 6 days) basketball tournament is a shorter version of international tournaments, and qualification in it enables participation in international tournaments such as the Olympics and World championships or preparation before major tournaments. Time for recovery between matches is shorter compared with major tournaments, resulting in an accentuated load on players, which can be repeated up to four times within the 6-day competition period. Therefore, nutritional strategies need to focus on faster and adequate recovery after each match as well as optimum fuelling and hydration before and during matches. Travelling can also create additional challenges when preparing and/or applying those nutritional strategies. There are some particular evidence-based sport foods and ergogenic aids that can improve intermittent activity and/or the execution of motor skills, which may facilitate basketball players’ recovery and performance. The present review provides practical nutritional strategies to support short-term basketball tournaments based on players’ physiological needs and current sport nutrition guidelines.
The Nutrition Literacy Assessment Instrument for Brazilians, NLit-Br: An Exploratory Cross-Cultural Validity Study
Authors: Sarkis Lívia Botelho da Silva , Teruel-Camargo Juliana , Gibbs Heather D. , Nakano Eduardo Y. , Ginani Verônica Cortez , de Aguiar Aline Silva , Chaves Camila dos Santos , Zandonadi Renata Puppin , Bastos Marcus Gomes
Published: November 2022

This study aimed to test the validity of the cross-cultural adapted Nutrition Literacy Assessment Instrument for Brazilians (NLit-Br). An observational cross-sectional study was performed in chronic disease clinics from the Brazilian Public Health System in two phases: (1) linguistic and cultural adaptation and (2) validity testing. Six registered dietitians and thirty adult patients diagnosed with at least one chronic disease participated in the study using the nutrition literacy assessment instrument (NLit-Br) and the short assessment of health literacy for Portuguese-speaking adults (SAHLPA-18). Sample descriptive variables: age, sex, race, income, education, and occupation. To adapt the instrument to the Brazilian Portuguese and Brazilian culture, we tested cognitive interviewing and the Scale Content Validity Index (S-CVI) with a group of dietitians and patients. To test the tool’s validity, health literacy (SAHLPA-18) was used as a construct that presents similarities and differences with nutrition literacy (NLit-Br). The correlation of NLit-Br and the SAHLPA-18 was tested (Spearman’s Rho). Internal consistency was measured by Kuder–Richardson Formula 20 (KR-20). The NLit-Br content validity (S-CVI = 0.85) and internal consistency (KR-20 = 0.868) were confirmed. Additionally, NLit-Br presented a significant and robust correlation with SAHLPA-18 (r = 0.665, p < 0.001). Therefore, the NLit-Br was considered a linguistic, cultural, and valid instrument to measure Brazilian’s nutrition literacy.
Association of Zinc with Anemia
Authors: Jeng Sen-Shyong , Chen Yen-Hua
Published: November 2022

Zinc is an essential trace element, and anemia is the most common blood disorder. The association of zinc with anemia may be divided into three major forms: (1) zinc deficiency contributing to anemia, (2) excess intake of zinc leading to anemia, and (3) anemia leading to abnormal blood–zinc levels in the body. In most cases, zinc deficiency coexists with iron deficiency, especially in pregnant women and preschool-age children. To a lesser extent, zinc deficiency may cooperate with other factors to lead to anemia. It seems that zinc deficiency alone does not result in anemia and that it may need to cooperate with other factors to lead to anemia. Excess intake of zinc is rare. However, excess intake of zinc interferes with the uptake of copper and results in copper deficiency that leads to anemia. Animal model studies indicate that in anemia, zinc is redistributed from plasma and bones to the bone marrow to produce new red blood cells. Inadequate zinc status (zinc deficiency or excess) could have effects on anemia; at the same time, anemia could render abnormal zinc status in the body. In handling anemia, zinc status needs to be observed carefully, and supplementation with zinc may have preventive and curative effects.
Schools’ Participation in the Community Eligibility Provision Affects Students’ Receipt of Emergency Benefits during the COVID-19 Pandemic
Authors: Acciai Francesco , Ohri-Vachaspati Punam , Yedidia Michael J.
Published: November 2022

Pandemic Electronic Benefits Transfer (P-EBT) benefits were intended for families of school children who lost access to free or reduced-price school meals (FRPMs) during the COVID-19 pandemic-related school closures. In high-poverty communities, all students from schools participating in the Community Eligibility Provision (CEP) were automatically eligible for P-EBT benefits; in non-CEP schools, only students already participating in FRPMs—for which their parents submitted an individual application—were eligible for P-EBT benefits. Using publicly available data from 105 K-12 public schools located in 4 sizeable low-income New Jersey (NJ) cities, this study investigated the association between school CEP participation status and the reach of P-EBT benefits for eligible students. A generalized linear model with a logit link, a binomial family, and robust standard errors was used. Across all levels of FRPM eligibility based on students’ household income, as expected, almost all students from CEP schools received P-EBT benefits; significantly fewer received P-EBT benefits if they attended non-CEP schools, even when they were eligible for FRPMs. Our findings show that without changes to the qualification process for CEP, large numbers of eligible children will not receive the intended health benefits of federal meals programs or similar emergency relief initiatives. Expanding CEP eligibility and simplifying the process through which schools qualify would likely improve the uptake of federal meals programs and emergency interventions, and more effectively achieve their intent.
Appearance and Performance-Enhancing Drugs and Supplements, Eating Disorders Symptoms, Drive for Muscularity, and Sexual Orientation in a Sample of Young Men
Authors: Ghaderi Ata , Welch Elisabeth
Published: November 2022

In an anonymous online study (N = 824), we investigated the frequency of use of appearance and performance-enhancing drugs and supplements (APEDS) in a sample of young men (15–30 years) in Sweden, along with their self-reported eating disorder (ED) symptoms, drive for muscularity and sexual orientation. A total of 129 participants (16.1%) reported regular use of supplements (at least once a week), including one individual using anabolic steroids (0.1%), while a lifetime use of APEDS was reported by 32.3%. The overlap between those using protein supplements and creatine was large (83.6%). Some symptoms of ED (e.g., dietary restraint, objective binge eating, self-induced vomiting, and excessive exercise) significantly predicted the use of APEDS. In addition, the use of APEDS was significantly predicted by the drive for muscularity. The prediction was stronger for the behavioral component of drive for muscularity (Exponential B = 8.50, B = 2.14, SE = 0.16, p < 0.001, Negelkerke R2 = 0.517) than for its attitudinal component (Exponential B = 1.52, B = 0.42, SE = 0.06, p < 0.001, Negelkerke R2 = 0.088). A significantly larger proportion of those identifying as heterosexual reported using APEDS (34.4%) compared to those identifying themselves as homosexual (25.0%), bisexual (19.2%) or other (23.7%). Overall, our results suggest that the use of APEDS might be more related to the drive for muscularity and sexual orientation than symptoms of ED.
Ultrafast Phonon Decay in Complex Oxides
Authors: Neupane Chandra P. , Sylvester Jeremy , Mudiyanselage Dinusha M. S. R. , Singhapurage Helani A. S. , Ganikhanov Feruz
Published: November 2022

The decay of multiple Raman active vibrations has been directly traced, in time, in technologically important wide bandgap semiconduction oxides such as BaSnO3 (BSO), STiO3 (STO), and KTiOPO4 (KTP) crystal, which have important applications in laser frequency conversion. A time-domain coherent Raman technique, with excellent time (~120 fs) and spectral resolutions, has been applied to measure the ultrafast decay rates of optical phonons with 350–1500 cm−1 frequencies. Phonon decay mechanisms via phonon energy loss due to second- and third-order parametric processes have been discussed. The correspondingly high equivalent spectral resolution allowed for the determination of the phonon line bandwidths to be within 7.2–8.3 cm−1 (BSO), 8.5–9.7 cm−1 (STO), and 6.2–18.6 cm−1 (KTP).
Protection against Lipopolysaccharide-Induced Endotoxemia by Terrein Is Mediated by Blocking Interleukin-1β and Interleukin-6 Production
Authors: Yoon Yeo Dae , Lee Myeong Youl , Choi Byeong Jo , Lee Chang Woo , Lee Hyunju , Kwon Joo-Hee , Yang Jeong-Wook , Kang Jong Soon
Published: November 2022

Terrein is a fungal metabolite and has been known to exert anti-melanogenesis, anti-cancer, and anti-bacterial activities. However, its role in endotoxemia has never been investigated until now. In the present study, we examined the effect of terrein on lipopolysaccharide (LPS)-induced endotoxemia in mice and characterized the potential mechanisms of action. Treatment with terrein increased the survival of mice and decreased the production of inflammatory cytokines, including interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an LPS-induced endotoxemia model. In addition, terrein suppressed the LPS-induced production of IL-1β and IL-6 in RAW 264.7 cells, a murine macrophage-like cell line, and the mRNA expression of IL-1β and IL-6 was also inhibited by terrein in LPS-stimulated RAW 264.7 cells. Further study demonstrated that terrein blocked LPS-induced phosphorylation of p65 subunit of nuclear factor (NF)/κB and the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) was also suppressed by terrein treatment. Collectively, these results suggest that terrein exerts a protective effect again LPS-induced endotoxemia in mice by blocking the production of inflammatory cytokines. Our results also suggest that the anti-inflammatory effect of terrein might be mediated, at least in part, by blocking the activation of NF-κB, JNK, and p38 MAPK signaling pathways.
Mechanism and Prospect of Gastrodin in Osteoporosis, Bone Regeneration, and Osseointegration
Authors: Li Yi , Li Fenglan
Published: November 2022

Gastrodin, a traditional Chinese medicine ingredient, is widely used to treat vascular and neurological diseases. However, recently, an increasing number of studies have shown that gastrodin has anti-osteoporosis effects, and its mechanisms of action include its antioxidant effect, anti-inflammatory effect, and anti-apoptotic effect. In addition, gastrodin has many unique advantages in promoting bone healing in tissue engineering, such as inducing high hydrophilicity in the material surface, its anti-inflammatory effect, and pro-vascular regeneration. Therefore, this paper summarized the effects and mechanisms of gastrodin on osteoporosis and bone regeneration in the current research. Here we propose an assumption that the use of gastrodin in the surface loading of oral implants may greatly promote the osseointegration of implants and increase the success rate of implants. In addition, we speculated on the potential mechanisms of gastrodin against osteoporosis, by affecting actin filament polymerization, renin–angiotensin system (RAS) and ferroptosis, and proposed that the potential combination of gastrodin with Mg2+, angiotensin type 2 receptor blockers or artemisinin may greatly inhibit osteoporosis. The purpose of this review is to provide a reference for more in-depth research and application of gastrodin in the treatment of osteoporosis and implant osseointegration in the future.
Optimization of Formulation Parameters in Preparation of Fructus ligustri lucidi Dropping Pills by Solid Dispersion Using 23 Full Experimental Design
Authors: Wu Kai-Rong , Chuo Wen-Ho , Huang Yuh-Tyng
Published: November 2022

Oleanolic acid (OA) is an active ingredient of the traditional Chinese medicine (TCM) Fructus ligustri lucidi (FLL). Its clinical use is restricted because it is water-insoluble and has limited dosage forms of administration at present. Hence, the FFL dropping pills were prepared by the hot-melt method of solid dispersion technology. A 23 factorial design was used to examine the effects of the materials used to prepare the dropping pills (e.g., different ratios of PEG4000 and PEG6000, FLL extract loading, and percentage of Tween 80) on parameters such as dropping pill roundness, weight variation, and disintegration time. Moreover, 23 full factorial design was utilized to search for the optimal formulation for dissolution experiments. The results showed that the percentage of Tween 80 demonstrated significant effects on dropping pill roundness, weight variation, and disintegration time; FLL extract loading affected roundness and weight variation; and different ratios of PEG4000 and PEG6000 only affected disintegration time. The optimal formulation of the dropping pills released 70% of the drug after 30 min of dissolution release, which was faster than commercially available FLL Chinese medicines. Furthermore, the amount released was higher than that of commercially available formulations. In this study, a solid dispersion technique was used to successfully produce FLL dropping pills. In addition to improving the water insolubility of FLL and increasing the dissolution release percentage of the drug, we increased the application value of FLL and reduced the issues of traditional administration dosage forms.
Nanomedicines Bearing an Alkylating Cytostatic Drug from the Group of 1,3,5-Triazine Derivatives: Development and Characterization
Authors: Sinitsyna Ekaterina , Bagaeva Irina , Gandalipov Erik , Fedotova Evgenia , Korzhikov-Vlakh Viktor , Tennikova Tatiana , Korzhikova-Vlakh Evgenia
Published: November 2022

Cancer is still one of the major diseases worldwide. The discovery of new drugs and the improvement of existing ones is one of the areas of priority in the fight against cancer. Dioxadet ([5-[[4,6-bis(aziridin-1-yl)-1,3,5-triazin-2-yl]amino]-2,2-dimethyl-1,3-dioxan-5-yl]methanol) represents one of the promising 1,3,5-triazine derivatives and has cytostatic activity towards ovarian cancer. In this study, we first report the development of dioxadet-bearing nanomedicines based on block-copolymers of poly(ethylene glycol) monomethyl ether (mPEG) and poly(D,L-lactic acid) (PLA)/poly(ε-caprolactone) (PCL) and then conduct an investigation into their characteristics and properties. The preparation of narrow-sized nanoparticles with a hydrodynamic diameter of 100–120 nm was optimized using a nanoprecipitation approach. Thoughtful optimization of the preparation of nanomedicines was carried out through adjustments to the polymer’s molecular weight, the pH of the aqueous medium used for nanoprecipitation, the initial drug amount in respect to the polymer, and polymer concentration in the organic phase. Under optimized conditions, spherical-shaped nanomedicines with a hydrodynamic diameter of up to 230 nm (PDI < 0.2) containing up to 592 ± 22 μg of dioxadet per mg of polymer nanoparticles were prepared. Study of the drug’s release in a model medium revealed the release up to 64% and 46% of the drug after 8 days for mPEG-b-PLA and mPEG-b-PCL, respectively. Deep analysis of the release mechanisms was carried out with the use of a number of mathematical models. The developed nanoparticles were non-toxic towards both normal (CHO-K1) and cancer (A2780 and SK-OV-3) ovarian cells. A cell cycle study revealed lesser toxicity of nanomedicines towards normal cells and increased toxicity towards cancer cells. The IC50 values determined for dioxadet nanoformulations were in the range of 0.47–4.98 μg/mL for cancer cells, which is close to the free drug’s efficacy (2.60–4.14 μg/mL). The highest cytotoxic effect was found for dioxadet loaded to mPEG-b-PCL nanoparticles.
Machine-Learning Exploration of Exposure-Effect Relationships of Cisplatin in Head and Neck Cancer Patients
Authors: Cauvin Céleste , Bourguignon Laurent , Carriat Laure , Mence Abel , Ghipponi Pauline , Salas Sébastien , Ciccolini Joseph
Published: November 2022

Background: Cisplatin is a pivotal drug in the treatment of head and neck cancer, and personalized dosage should help the preservation of an optimal toxicity–efficacy ratio. Methods: We analyzed the exposure-effect relationships of 80 adult patients with head and neck cancers and treated with standard Cisplatin-based regimen administered as three-hour infusion. Individual pharmacokinetics (PK) parameters of Cisplatin were identified using a Bayesian approach. Nephrotoxicity and ototoxicity were considered as typical Cisplatin-related toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) standards. Efficacy was evaluated based upon Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Up to nine different machine-learning algorithms were tested to decipher the exposure-effect relationships with Cisplatin. Results: The generalized linear model was the best algorithm with an accuracy of 0.71, a recall of 0.55 and a precision of 0.75. Among the various metrics for exposure (i.e., maximal concentration (Cmax), area-under-the-curve (AUC), trough levels), Cmax, comprising a range between 2.4 and 4.1 µg/mL, was the best one to be considered. When comparing a consequent, model-informed dosage with the standard dosage in 20 new patients, our strategy would have led to a reduced dosage in patients who would eventually prove to have severe toxicities while increasing dosage in patients with progressive disease. Conclusion: Determining a target Cmax could pave the way for PK-guided precision dosage with Cisplatin given as three-hour infusion.
Dual-Modality Molecular Imaging of Tumor via Quantum Dots-Liposome–Microbubble Complexes
Authors: Wang Jieqiong , Wang Yuanyuan , Jia Jie , Liu Chenxing , Ni Dong , Sun Litao , Guo Zhijie
Published: November 2022

Molecular imaging has demonstrated promise for evaluating the expression levels of biomarkers for the early prediction of tumor progression and metastasis. However, most of the commonly used molecular imaging modalities are relatively single and have difficulties imaging complex biological processes. Here, we fabricated αvβ3-integrin-targeted quantum-dots-loaded liposome–microbubble (iRGD-QDLM) complexes that combined ultrasound imaging with optical imaging. The resulting iRGD-QDLM has excellent binding capability to 4T1 breast cancer cells. Ultrasound molecular imaging of 4T1 tumors demonstrated that significantly enhanced ultrasound molecular signals could be observed in comparison with non-targeted QDLM. Importantly, our study also suggested that iRGD-QDL on the surface of microbubbles could be delivered into a tumor by ultrasound-mediated microbubble destruction and adhered to αvβ3 integrin on breast cancer cells, achieving transvascular fluorescent imaging. Our study provides a novel approach to dual-modality molecular imaging of αvβ3 integrin in the tumor tissue.
Pheophorbide A–Mediated Photodynamic Therapy Potentiates Checkpoint Blockade Therapy of Tumor with Low PD–L1 Expression
Authors: Tong Qinli , Xu Jiaojiao , Wu Aihua , Zhang Chen , Yang Afeng , Zhang Sihang , Lin Hongzheng , Lu Wei
Published: November 2022

Although the immune checkpoint blockade (ICB) has made a great success in cancer immunotherapy, the overall response rate to the ICB, such as anti–programmed death ligand 1 (PD–L1) therapy, remains only at 20–30%. One major reason is the low expression level of the immune checkpoint in a certain type of tumor cells and its insufficient activation of the host immune system. Herein, we reported a cyclic RGD (cRGD)–modified liposomal delivery system loading the anti–PD–L1 antibody and the photosensitizer pheophorbide A (Pa), allowing a targeting of the low PD–L1 expressing 4T1 mouse breast cancer cells through the recognition of an overexpression of αvβ3 integrin on the tumor cells. The Pa–mediated photodynamic therapy (PDT) elevated the expression of PD–L1 on the tumor cells. PDT, in combination with the anti–PD–L1 therapy, promoted the activation and maturation of dendritic cells as well as the infiltration of cytotoxic T lymphocytes, resulting in the augmented antitumor immune response for the enhanced therapeutic effect. These results demonstrated the combined therapeutic effects of PDT and ICB on the tumor with low PD–L1 levels. Our study suggested that an increase in the PD–L1 expression in tumor cells by PDT would be a promising adjuvant treatment to overcome the ICB irresponsiveness.
Plug and Pop: A 3D-Printed, Modular Platform for Drug Delivery Using Clinical Ultrasound and Microbubbles
Authors: Joshi Kushal , Sanwal Rajiv , Thu Kelsie L. , Tsai Scott S. H. , Lee Warren L.
Published: November 2022

Targeted drug and gene delivery using ultrasound and microbubbles (USMB) has the potential to treat several diseases. In vitro investigation of USMB-mediated delivery is of prime importance prior to in vivo studies because it is cost-efficient and allows for the rapid optimization of experimental parameters. Most in vitro USMB studies are carried out with non-clinical, research-grade ultrasound systems, which are not approved for clinical use and are difficult to replicate by other labs. A standardized, low-cost, and easy-to-use in vitro experimental setup using a clinical ultrasound system would facilitate the eventual translation of the technology to the bedside. In this paper, we report a modular 3D-printed experimental setup using a clinical ultrasound transducer that can be used to study USMB-mediated drug delivery. We demonstrate its utility for optimizing various cargo delivery parameters in the HEK293 cell line, as well as for the CMT167 lung carcinoma cell line, using dextran as a model drug. We found that the proportion of dextran-positive cells increases with increasing mechanical index and ultrasound treatment time and decreases with increasing pulse interval (PI). We also observed that dextran delivery is most efficient for a narrow range of microbubble concentrations.
Wound Healing Efficacy of Rosuvastatin Transethosomal Gel, I Optimal Optimization, Histological and In Vivo Evaluation
Authors: Zaki Randa Mohammed , Seshadri Vidya Devanathadesikan , Mutayran Alanoud S. , Elsawaf Lara A. , Hamad Abubaker M. , Almurshedi Alanood S. , Yusif Rehab Mohammad , Said Mayada
Published: November 2022

This study aimed to make a formulation and statistical optimization of transethosomal formulations of rosuvastatin (ROS) to enhance its topical wound healing efficiency. Design-Expert® software was used to employ I optimal design. The formulation variables in the study were surfactant concentration (%w/v), ethanol concentration (%w/v) and surfactant type (span 60 or tween 80), while the dependent responses were entrapment efficiency percent (EE%), vesicle size (VS) and zeta potential (ZP). The numerical optimization process employed by the design expert software resulted in an optimum formula composed of 0.819439 (%w/v) span 60, 40 (%w/v) ethanol and 100 mg lecithin with a desirability of 0.745. It showed a predicted EE% value of 66.5517 vs. 277.703 nm and a ZP of −33. When it was prepared and validated, it showed less than a 5% deviation from the predicted values. The optimum formula was subjected to further characterizations, such as DSC, XRD, TEM, in vitro release, the effect of aging and wound healing efficiency. The DSC thermogram made a confirmation of the compatibility of ROS with the ingredients used in the formulation. XRD showed the encapsulation of ROS in the transethosomal vesicles. The TEM image pointed out the spherical nature of the nanovesicles with the absence of aggregation. Additionally, the optimum formula revealed an enhancement of drug release in comparison with the drug suspension. It also showed good stability for one month. Furthermore, it revealed good wound healing efficiency when compared with the standard silver sulphadiazine (1% w/w) ointment or the drug-loaded gel, which could be related to the enhanced penetration of the nanosized vesicles of TESMs into the skin, which enhances the wound healing process. So, it could be regarded as a promising carrier of ROS for the treatment of chronic wounds.