bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Investigation of Transonic Flow-Induced Spontaneous Condensation in Micro-Ejector Nozzles
Authors: Han Yu , Wang Xiaodong , Wang Wei , Lee Yuan Xien , Li Ao
Published: June 2023

Micro-cooling systems are compact refrigeration systems widely applicable in microchemical analysis, biomedicine, and microelectromechanical systems (MEMS). These systems rely on the use of micro-ejectors to achieve precise, fast, and reliable flow and temperature control. However, the efficiency of micro-cooling systems is hindered by spontaneous condensation occurring downstream of the nozzle throat and within the nozzle itself, impacting the performance of the micro-ejector. A micro-scale ejector mathematical model describing wet steam flow was simulated to investigate the steam condensation phenomenon and its influence on flow, incorporating equations for liquid phase mass fraction and droplet number density transfer. The simulation results of wet vapor flow and ideal gas flow were compared and analyzed. The findings revealed that the pressure at the micro-nozzle outlet exceeded predictions based on the ideal gas assumption, while the velocity fell below it. These discrepancies indicated that condensation of the working fluid reduces the pumping capacity and the efficiency of the micro-cooling system. Furthermore, simulations explored the impact of inlet pressure and temperature conditions on spontaneous condensation within the nozzle. The results demonstrated that the properties of the working fluid directly influence transonic flow condensation, underscoring the importance of selecting appropriate working fluid parameters for nozzle design to ensure nozzle stability and optimal micro-ejector operation.
F2 Laser-Induced Micro-Reticulated Structural Changes of Amorphous Carbon Thin Films
Authors: Okoshi Masayuki
Published: June 2023

Micro/nanoprocessing of materials using lasers is currently an active research topic. In that research, the choice of the laser to be used is critical, but the F2 laser, which has the shortest wavelength (157 nm) among commercially available lasers, has few research compared to its potential. In this paper, we discovered a new photochemical processing by using an F2 laser to irradiate an amorphous carbon thin film. The short wavelength and high photon energy of the F2 laser can photoexcite the surface of the thin film at high density and generate active oxygen atoms O(1D) by photodecomposition of atmospheric oxygen molecules. As a result, the optical change of the amorphous carbon thin film was induced without thickness reduction, and a micron-sized network-like, reticulated structural change was formed in the thin film surface after one month at the latest. The formed micron-sized reticulated structure was relatively swollen, and a graphitization occurred in the structure, observed by Raman spectroscopy. However, the structure was not observed when the laser irradiated area became smaller. This work has made it possible to form a micron-sized reticulated structure including carbon nanocrystals in an amorphous carbon, which is expected to further expand the applications of carbon materials.
Petrogenesis and Geodynamic Significance of the Early Triassic Nanpo Adakitic Pluton of the Luang Prabang-Loei Tectonic Belt (Northwestern Laos) in the East Tethys Domain: Constraints from Zircon U-Pb-Hf Isotope Analyses and Whole-Rock Geochemistry
Authors: Li Hui , Gan Jie , He Zhengwei , Gan Yu , Wang Bin , Li Yong , Jiang Wei
Published: June 2023

Adakites are magmatic rocks with specific geochemical characteristics and specific dynamics that provide important clues to understanding the magmatic-tectonic evolution of orogenic belts. We studied the Early Triassic Nanpo adakitic pluton of the Luang Prabang-Loei tectonic belt in the Eastern Tethys domain (Laos Sarakan) using detailed petrological, zircon U-Pb chronological, whole-rock geochemical, and zircon Lu-Hf isotope studies to constrain their petrogenesis. The rocks are predominantly diorites and granodiorites with Early Triassic zircon U-Pb emplacement ages ranging from 247.9 ± 1.0 to 249.0 ± 2.4 Ma. Moderate SiO2 (56.26–65.95 wt%) and Na2O (3.24–5.00 wt%) contents, with Na2O/K2O values between 1.76 and 2.51 and A/CNK values between 0.81 and 0.94, indicate that the rocks belong to the metaluminous calc-alkaline rock series. The high Sr content (590–918 ppm), low Y (6.30–11.89 ppm) and Yb (1.99–3.44 ppm) contents, intermediate Mg# (42–50) values, and high Sr/Y and (La/Yb) N ratios (Sr/Y = 24–41, (La/Yb) N = 6.84–13.8) are typical for adakites. Zircon Hf isotope analysis shows a significant variation in the εHf(t) values (6.7–12.0), with a mean value of 9.4 and a TDM2 of 512–845 Ma. Geochemical evidence indicates that the Nanpo adakitic rock was formed by the partial melting of the thickened lower crust in the plate-breaking environment and has an important contribution to the underplated mantle-derived magma. We propose that the Early Triassic adakites in the Luang Prabang-Loei tectonic belt formed during the transition from subduction to a continental collision, and the mixing of crust- and mantle-derived magmas is the main mechanism for the growth of continental crust in the Paleo-Tethys orogenic belt of southeastern Asia.
A Case Study of Incorporating Variable Recovery and Specific Energy in Long-Term Open Pit Mining
Authors: Mata Jônatas Franco Campos da , Nader Alizeibek Saleimen , Mazzinghy Douglas Batista
Published: June 2023

Integrated Optimization can find optimized solutions for a project to define open pit and mine scheduling with greater reliability. This work aims to demonstrate how the insertion of geometallurgical variables can significantly change the financial return of a project. Two geometallurgical variables are considered in mine planning simulations. Specific energy corresponds to the energy consumed in the comminution of the ore, and process recovery measures the percentage of metal incorporated into the product. Three scenarios were developed considering an iron ore deposit. In the Base Case (BC) scenario, the recovery was fixed, and the specific energy of comminution was not considered. GeoMet1 considers the variable recovery varying for each block. GeoMet2 considered both recovery and specific energy as variables varying for each block. GeoMet1 and GeoMet2 presented Net Present Value (NPV), respectively, as 3.68% and 13.57% lower than the BC. This overestimation of the BC results can be viewed as an optimistic case of mine planning that is very common in the mining industry. These results show that the use of specific energy and recovery variables is fundamental to obtaining more reliable mine planning.
Social Cohesion in Interactive Digital Heritage Experiences
Authors: Pescarin Sofia , Bonanno Vanessa , Marasco Alessandra
Published: June 2023

Presently, social cohesion (SC) is a priority at different levels. Cultural heritage is an ideal context to promote SC through interactive digital technologies designed to engage groups of visitors. The purpose of the present study is to identify how to design digital heritage applications for SC and how to measure it. The results are based on the design of a cultural probe kit used to identify the design elements on top of which a collaborative and hybrid prototype, the Brancacci POV, was developed. Here, we analysed the results of this prototype, which included 107 visitors with respective groups of 5 participants and guided by an expert. From this analysis, the possibility of strengthening SC when collaborative tasks are included emerged. Additionally, it appeared to be possible to shorten the distance between citizens and cultural institutions if “mediated dialogue” approaches were adopted and if focus, motivation, trust and “in-group” perception of inclusion emerge when digital heritage experiences were set in intimate and quiet environments.
The Chronic Effect of Stair Climbing–Descending Exercises after Meals on Glycemic Control in Individuals with Type 2 Diabetes: A Randomized Controlled Trial
Authors: Honda Hiroto , Fukutomi Hiromi , Igaki Makoto , Tanaka Shinichiro , Takaishi Tetsuo , Hayashi Tatsuya
Published: June 2023

This study aimed to examine the chronic effect of a stair climbing–descending exercise (ST-EX) program on glycemic control in individuals with type 2 diabetes (T2D). Sixteen T2D participants were randomly divided into two groups and followed up over 12 weeks: they either performed regular ST-EX after meals at home (n = 8) or maintained their daily routine (CON; no training) (n = 8). The participants in the ST-EX group were instructed to perform a minimum of 12 sessions/week of ST-EX for more than three days/week. One session of ST-EX consisted of two repetitions of 3 min bouts of climbing to the second floor, followed by walking down to the first floor. Fourteen participants completed the study (seven for each group). The decrease in glycoalbumin levels was significantly greater in the ST-EX group (mean value: −1.0%) than in the CON group (+0.4%). Moreover, the knee extension force increased greatly in the ST-EX group (+0.2 Nm/kg) compared with that in the CON group (−0.1 Nm/kg), with no significant change in the skeletal muscle mass. Performing regular ST-EX after meals may be an effective strategy to improve glycemic control and lower-extremity muscle strength in individuals with T2D.
Elimination of Chirality in Three-Dimensionally Confined Open-Access Microcavities
Authors: Li Yiming , Li Yuan , Luo Xiaoxuan , Guo Chaowei , Qin Yuanbin , Fu Hongbing , Zhang Yanpeng , Yun Feng , Liao Qing , Li Feng
Published: June 2023

The emergent optical activity (OA) caused by anisotropic light emitter in microcavities is an important physical mechanism discovered recently, which leads to Rashba–Dresselhaus photonic spin-orbit (SO) coupling. In this study, we report a sharp contrast of the roles of the emergent OA in free and confined cavity photons, by observing the optical chirality in a planar–planar microcavity and its elimination in a concave–planar microcavity, evidenced by polarization-resolved white-light spectroscopy, which agrees well with the theoretical predictions based on the degenerate perturbation theory. Moreover, we theoretically predict that a slight phase gradient in real space can partially restore the effect of the emergent OA in confined cavity photons. The results are significant additions to the field of cavity spinoptronics and provide a novel method for manipulating photonic SO coupling in confined optical systems.
Butyrate Protects Barrier Integrity and Suppresses Immune Activation in a Caco-2/PBMC Co-Culture Model While HDAC Inhibition Mimics Butyrate in Restoring Cytokine-Induced Barrier Disruption
Authors: Korsten Sandra G. P. J. , Vromans Herman , Garssen Johan , Willemsen Linette E. M.
Published: June 2023

Low-grade inflammation and barrier disruption are increasingly acknowledged for their association with non-communicable diseases (NCDs). Short chain fatty acids (SCFAs), especially butyrate, could be a potential treatment because of their combined anti-inflammatory and barrier- protective capacities, but more insight into their mechanism of action is needed. In the present study, non-activated, lipopolysaccharide-activated and αCD3/CD28-activated peripheral blood mononuclear cells (PBMCs) with and without intestinal epithelial cells (IEC) Caco-2 were used to study the effect of butyrate on barrier function, cytokine release and immune cell phenotype. A Caco-2 model was used to compare the capacities of butyrate, propionate and acetate and study their mechanism of action, while investigating the contribution of lipoxygenase (LOX), cyclooxygenase (COX) and histone deacetylase (HDAC) inhibition. Butyrate protected against inflammatory-induced barrier disruption while modulating inflammatory cytokine release by activated PBMCs (interleukin-1 beta↑, tumor necrosis factor alpha↓, interleukin-17a↓, interferon gamma↓, interleukin-10↓) and immune cell phenotype (regulatory T-cells↓, T helper 17 cells↓, T helper 1 cells↓) in the PBMC/Caco-2 co-culture model. Similar suppression of immune activation was shown in absence of IEC. Butyrate, propionate and acetate reduced inflammatory cytokine-induced IEC activation and, in particular, butyrate was capable of fully protecting against cytokine-induced epithelial permeability for a prolonged period. Different HDAC inhibitors could mimic this barrier-protective effect, showing HDAC might be involved in the mechanism of action of butyrate, whereas LOX and COX did not show involvement. These results show the importance of sufficient butyrate levels to maintain intestinal homeostasis.
Forty Years after Poverty Reduction in China: The Role of Women’s Empowerment in Enhancing Food Security and Diet Diversity
Authors: Huang Yanfang , Nie Fengying , Jia Xiangping
Published: June 2023

This study analyzed the role of women’s empowerment in diversifying the diet of households through their own production. Developed from empowerment and food security theories, this study constructed measures from the household dietary diversity score (HDDS) and Women’s Empowerment Index (WEI). The study focused on poverty-stricken regions in China and conducted a thematic questionnaire-based household survey on gender and food consumption in 2021. Based on micro-level evidence from 1199 rural households, this research found a low score of women’s empowerment and an average WEI of 0.689; the status of diet diversity, measured by the HDDS, varied by income and social class; and the average rate was low. Agricultural production diversity and women’s empowerment are positively associated with diet diversity. There is strong evidence that women’s employment mitigates the side effects of decreasing production diversity on households’ diet security. As a result, women’s empowerment can potentially mitigate the adverse consequences of low agricultural diversification in household diet quality in less developed areas. This study provides evidence for repurposing food and agricultural policies toward healthy diets and gender-responsive agrifood systems.
Survey of Dietary Habits and Physical Activity in Japanese Patients with Non-Obese Non-Alcoholic Fatty Liver Disease
Authors: Yabe Yoshito , Chihara Kanako , Oshida Natsumi , Kamimaki Takashi , Hasegawa Naoyuki , Isobe Tomonori , Shoda Junichi
Published: June 2023

The incidence of non-obese non-alcoholic fatty liver disease (NAFLD), characterized by the presence of a fatty liver in individuals with a normal body mass index, is on the rise globally. Effective management strategies, including lifestyle interventions such as diet and exercise therapy, are urgently needed to address this growing public health concern. The aim of this study was to investigate the association between non-obese NAFLD, dietary habits, and physical activity levels. By elucidating these relationships, this research may contribute to the development of evidence-based recommendations for the management of non-obese NAFLD. The study had a single-center retrospective cross-sectional design and compared clinical data and dietary and physical activity habits between patients with and without non-obese NAFLD. Logistic regression analysis was utilized to investigate the relationship between food intake frequency and the development of NAFLD. Among the 455 patients who visited the clinic during the study period, 169 were selected for analysis, including 74 with non-obese NAFLD and 95 without NAFLD. The non-obese NAFLD group showed a less-frequent consumption of fish and fish products as well as olive oil and canola/rapeseed oil, while they showed more frequent consumption of pastries and cake, snack foods and fried sweets, candy and caramels, salty foods, and pickles compared to the non-NAFLD group. Logistic regression analysis revealed that NAFLD was significantly associated with the consumption of fish, fish products, and pickles at least four times a week. The physical activity level was lower and the exercise frequency was lower in patients with non-obese NAFLD compared to those without NAFLD. The results of this study suggest that a low consumption of fish and fish products and high consumption of pickles may be associated with a higher risk of non-obese NAFLD. Moreover, dietary habits and physical activity status should be taken into consideration for the management of patients with non-obese NAFLD. It is important to develop effective management strategies, such as dietary and exercise interventions, to prevent and treat NAFLD in this patient population.
The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Xu Ruhan , Liu Shenhao , Zhong Zhiqi , Guo Yifei , Xia Tianqi , Chen Yanyan , Ding Lingling
Published: June 2023

Maternal folate has been shown to relate to the risk of gestational diabetes mellitus (GDM). However, the existing studies have yielded inconsistent conclusions. The purpose of this study was to systematically review the association between maternal folate status and the risk of GDM. Observational studies up to 31 October 2022 were included. Study characteristics, the means and standard deviations (SDs) of folate levels (serum/red blood cell (RBC)), the odds ratios (ORs) with 95% confidence intervals (CIs) and the time for folate measurement were extracted. Compared with the non-GDM group, serum and RBC folate levels in women with GDM were significantly higher. Our subgroup analysis demonstrated that serum folate levels in the GDM group were significantly higher than in the non-GDM group only in the second trimester. RBC folate levels in the GDM group were significantly higher than in the non-GDM group in the first and second trimesters. Taking serum/RBC folate levels as continuous variables, the adjusted odds ratios of GDM risk showed that increased serum folate concentration rather than RBC folate elevated the risk of GDM. In the descriptive analysis, five studies reported high serum folate levels increased GDM risk, whereas the other five showed no association between serum folate levels and GDM risk. Moreover, the rest three studies pointed out high RBC folate levels increased GDM risk. Altogether we found that the risk of GDM is associated with high serum/plasma and RBC folate levels. Future studies should determine the recommended folic acid cutoff balancing the risk for GDM and fetal malformations.
Exposure to Phosphates and Nitrites through Meat Products: Estimation of the Potential Risk to Pregnant Women
Authors: Vranić Danijela , Milešević Jelena , Trbović Dejana , Gurinović Mirjana , Korićanac Vladimir , Zeković Milica , Petrović Zoran , Ranković Slavica , Milićević Dragan
Published: June 2023

Diet during pregnancy is one of the most important nutritional challenges associated with some risks for the mother and the fetus. For the first time, the study aims to estimate long-term (2018–2022) exposure to nitrate and phosphates in Serbian pregnant women, based on individual consumption data and accurate values measured in frequently consumed meat products. For this purpose, seven types of meat products, consisting of 3047 and 1943 samples, were collected from retail markets across Serbia, to analyze nitrites and phosphorus content, respectively. These data were combined with meat product consumption data from the Serbian National Food Consumption Survey to assess dietary intake of nitrites and phosphate. The results were compared with the acceptable daily intake (ADI) proposed by the European Food Safety Authority. The average dietary exposure (EDI) to phosphorus ranged from 0.733 mg/kg bw/day (liver sausage and pate) to 2.441 mg/kg bw/day (finely minced cooked sausages). Considering nitrite intake, the major sources were bacon (0.030 mg/kg bw/day) and coarsely minced cooked sausages (0.0189 mg/kg bw/day). In our study, average nitrite and phosphorus exposure in the Serbian pregnant women population are far below the EFSA recommendations (ADI 0.07 mg/kg bw/day and 40 mg/kg bw/day, respectively).
Full Breastfeeding and Allergic Diseases—Long-Term Protection or Rebound Effects?
Authors: Libuda Lars , Filipiak-Pittroff Birgit , Standl Marie , Schikowski Tamara , von Berg Andrea , Koletzko Sibylle , Bauer Carl-Peter , Heinrich Joachim , Berdel Dietrich , Gappa Monika
Published: June 2023

A previous follow-up of the GINIplus study showed that breastfeeding could protect against early eczema. However, effects diminished in adolescence, possibly indicating a “rebound effect” in breastfed children after initial protection. We evaluated the role of early eczema until three years of age on allergies until young adulthood and assessed whether early eczema modifies the association between breastfeeding and allergies. Data from GINIplus until 20-years of age (N = 4058) were considered. Information on atopic eczema, asthma, and rhinitis was based on reported physician’s diagnoses. Adjusted Odds Ratios (aOR) were modelled by using generalized estimating equations. Early eczema was associated with eczema (aORs = 3.2–14.4), asthma (aORs = 2.2–2.7), and rhinitis (aORs = 1.2–2.7) until young adulthood. For eczema, this association decreased with age (p-for-interaction = 0.002–0.006). Longitudinal models did not show associations between breastfeeding and the respective allergies from 5 to 20 years of age. Moreover, early eczema generally did not modify the association between milk feeding and allergies except for rhinitis in participants without family history of atopy. Early eczema strongly predicts allergies until young adulthood. While preventive effects of full breastfeeding on eczema in infants with family history of atopy does not persist until young adulthood, the hypothesis of a rebound effect after initial protection cannot be confirmed.
Study of the Total Phenolic Content, Total Antioxidant Activity and In Vitro Digestibility of Novel Wheat Crackers Enriched with Cereal, Legume and Agricultural By-Product Flours
Authors: Chatziharalambous Despina , Kaloteraki Chrysoula , Potsaki Panagiota , Papagianni Olga , Giannoutsos Konstantinos , Koukoumaki Danai I. , Sarris Dimitris , Gkatzionis Konstantinos , Koutelidakis Antonios E.
Published: June 2023

Wheat-flour crackers represent a staple snack option, although they lack nutritional value. Agricultural by-products such as olive and grape seeds, cereals such as barley and legumes such as lupine and chickpea are rich in bioactive compounds; therefore, flours obtained from those could represent a better option for bakery products fortification. The purpose of the present study was the investigation of total phenolic content and antioxidant activity before and after the baking of wheat crackers enriched with 10–30% olive seed, 10–30% grape seed, 10–40% lupine, 10–30% barley and 20–60% and 80% chickpea flours and the evaluation of the predicted bioavailability after in vitro digestion of crackers demonstrating the highest values. Crackers and doughs were processed and analyzed using Folin–Ciocâlteu and ferric reducing antioxidant power (FRAP) assays, respectively. Crackers with the highest properties were subjected to in vitro gastrointestinal digestion. Baking resulted in an increase in total phenolics and antioxidant activity in the majority of crackers. Olive and grape seed flour crackers demonstrated the highest antioxidant properties. Following in vitro digestion, 30% olive seed flour crackers retained the majority of polyphenols and antioxidant activity. Crackers enriched with 30% olive seed flour could represent a healthy functional bakery snack regarding their increased antioxidant properties.
Design and Beam Dynamic Studies of an Injector for a Compact THz Coherent Radiation Source
Authors: Jummunt Siriwan , Promdee Wanisa , Chanwattana Thakonwat , Junthong Nawin , Chunjarean Somjai , Klinkhieo Supat
Published: June 2023

An intense narrow-band terahertz (THz) radiation source has been designed to generate a broad tuning range of radiation frequencies between 0.5 THz and 5.0 THz. The THz radiation is produced when a short-bunch electron beam propagates through an undulator. To achieve high-power peak radiation, the source requires high-brightness electron beams with low beam emittance and short bunch length. A proposed design for the photocathode RF gun used as the electron source is presented. The gun with high mode separation and high Q-factor can be achieved for producing a good beam quality. The beam dynamics of the injector have been preliminarily optimized using the software ASTRA and Elegant, investigating the impact of laser pulse shape on electron beam quality. The results of the beam dynamics studies are comprehensively discussed in this paper.
Thymoquinone Enhances Apoptosis of K562 Chronic Myeloid Leukemia Cells through Hypomethylation of SHP-1 and Inhibition of JAK/STAT Signaling Pathway
Authors: Al-Rawashde Futoon Abedrabbu , Al-Sanabra Ola M. , Alqaraleh Moath , Jaradat Ahmad Q. , Al-Wajeeh Abdullah Saleh , Johan Muhammad Farid , Wan Taib Wan Rohani , Ismail Imilia , Al-Jamal Hamid Ali Nagi
Published: June 2023

The epigenetic silencing of tumor suppressor genes (TSGs) is critical in the development of chronic myeloid leukemia (CML). SHP-1 functions as a TSG and negatively regulates JAK/STAT signaling. Enhancement of SHP-1 expression by demethylation provides molecular targets for the treatment of various cancers. Thymoquinone (TQ), a constituent of Nigella sativa seeds, has shown anti-cancer activities in various cancers. However, TQs effect on methylation is not fully clear. Therefore, the aim of this study is to assess TQs ability to enhance the expression of SHP-1 through modifying DNA methylation in K562 CML cells. The activities of TQ on cell cycle progression and apoptosis were evaluated using a fluorometric-red cell cycle assay and Annexin V-FITC/PI, respectively. The methylation status of SHP-1 was studied by pyrosequencing analysis. The expression of SHP-1, TET2, WT1, DNMT1, DNMT3A, and DNMT3B was determined using RT-qPCR. The protein phosphorylation of STAT3, STAT5, and JAK2 was assessed using Jess Western analysis. TQ significantly downregulated the DNMT1 gene, DNMT3A gene, and DNMT3B gene and upregulated the WT1 gene and TET2 gene. This led to hypomethylation and restoration of SHP-1 expression, resulting in inhibition of JAK/STAT signaling, induction of apoptosis, and cell cycle arrest. The observed findings imply that TQ promotes apoptosis and cell cycle arrest in CML cells by inhibiting JAK/STAT signaling via restoration of the expression of JAK/STAT-negative regulator genes.
Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid–Polymer Hybrid Nanocarriers
Authors: Abo El-Enin Hadel A. , Tulbah Alaa S. , Darwish Hany W. , Salama Rania , Naguib Ibrahim A. , Yassin Heba A. , Abdel-Bar Hend Mohamed
Published: June 2023

The feasibility of using lipid–polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood–brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals’ hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.
Pharmacogenetic Testing for the Pediatric Gastroenterologist: Actionable Drug–Gene Pairs to Know
Authors: Sandritter Tracy , Chevalier Rachel , Abt Rebecca , Shakhnovich Valentina
Published: June 2023

Gastroenterologists represent some of the earlier adopters of precision medicine through pharmacogenetic testing by embracing upfront genotyping for thiopurine S-methyltransferase nucleotide diphosphatase (TPMT) before prescribing 6-mercaptopurine or azathioprine for the treatment of inflammatory bowel disease. Over the last two decades, pharmacogenetic testing has become more readily available for other genes relevant to drug dose individualization. Common medications prescribed by gastroenterologists for conditions other than inflammatory bowel disease now have actionable guidelines, which can improve medication efficacy and safety; however, a clear understanding of how to interpret the results remains a challenge for many clinicians, precluding wide implementation of genotype-guided dosing for drugs other than 6-mercaptopurine and azathioprine. Our goal is to provide a practical tutorial on the currently available pharmacogenetic testing options and a results interpretation for drug–gene pairs important to medications commonly used in pediatric gastroenterology. We focus on evidence-based clinical guidelines published by the Clinical Pharmacogenetics Implementation Consortium (CPIC®) to highlight relevant drug–gene pairs, including proton pump inhibitors and selective serotonin reuptake inhibitors and cytochrome P450 (CYP) 2C19, ondansetron and CYP2D6, 6-mercaptopurine and TMPT and Nudix hydrolase 15 (NUDT15), and budesonide and tacrolimus and CYP3A5.
Green Routes for Bio-Fabrication in Biomedical and Pharmaceutical Applications
Authors: Serri Carla , Cruz-Maya Iriczalli , Bonadies Irene , Rassu Giovanna , Giunchedi Paolo , Gavini Elisabetta , Guarino Vincenzo
Published: June 2023

In the last decade, significant advances in nanotechnologies, rising from increasing knowledge and refining of technical practices in green chemistry and bioengineering, enabled the design of innovative devices suitable for different biomedical applications. In particular, novel bio-sustainable methodologies are developing to fabricate drug delivery systems able to sagely mix properties of materials (i.e., biocompatibility, biodegradability) and bioactive molecules (i.e., bioavailability, selectivity, chemical stability), as a function of the current demands for the health market. The present work aims to provide an overview of recent developments in the bio-fabrication methods for designing innovative green platforms, emphasizing the relevant impact on current and future biomedical and pharmaceutical applications.
Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases
Authors: Mostafa Mahmoud , Al Fatease Adel , Alany Raid G. , Abdelkader Hamdy
Published: June 2023

Chronic ocular diseases can seriously impact the eyes and could potentially result in blindness or serious vision loss. According to the most recent data from the WHO, there are more than 2 billion visually impaired people in the world. Therefore, it is pivotal to develop more sophisticated, long-acting drug delivery systems/devices to treat chronic eye conditions. This review covers several drug delivery nanocarriers that can control chronic eye disorders non-invasively. However, most of the developed nanocarriers are still in preclinical or clinical stages. Long-acting drug delivery systems, such as inserts and implants, constitute the majority of the clinically used methods for the treatment of chronic eye diseases due to their steady state release, persistent therapeutic activity, and ability to bypass most ocular barriers. However, implants are considered invasive drug delivery technologies, especially those that are nonbiodegradable. Furthermore, in vitro characterization approaches, although useful, are limited in mimicking or truly representing the in vivo environment. This review focuses on long-acting drug delivery systems (LADDS), particularly implantable drug delivery systems (IDDS), their formulation, methods of characterization, and clinical application for the treatment of eye diseases.
Modified Sulfanilamide Release from Intelligent Poly(N-isopropylacrylamide) Hydrogels
Authors: Dinić Ana , Nikolić Vesna , Nikolić Ljubiša , Ilić-Stojanović Snežana , Najman Stevo , Urošević Maja , Gajić Ivana
Published: June 2023

The aim of this study was to examine homopolymeric poly(N-isopropylacrylamide), p(NIPAM), hydrogels cross-linked with ethylene glycol dimethacrylate as carriers for sulfanilamide. Using FTIR, XRD and SEM methods, structural characterization of synthesized hydrogels before and after sulfanilamide incorporation was performed. The residual reactants content was analyzed using the HPLC method. The swelling behavior of p(NIPAM) hydrogels of different crosslinking degrees was monitored in relation to the temperature and pH values of the surrounding medium. The effect of temperature, pH, and crosslinker content on the sulfanilamide release from hydrogels was also examined. The results of the FTIR, XRD, and SEM analysis showed that sulfanilamide is incorporated into the p(NIPAM) hydrogels. The swelling of p(NIPAM) hydrogels depended on the temperature and crosslinker content while pH had no significant effect. The sulfanilamide loading efficiency increased with increasing hydrogel crosslinking degree, ranging from 87.36% to 95.29%. The sulfanilamide release from hydrogels was consistent with the swelling results—the increase of crosslinker content reduced the amount of released sulfanilamide. After 24 h, 73.3–93.5% of incorporated sulfanilamide was released from the hydrogels. Considering the thermosensitivity of hydrogels, volume phase transition temperature close to the physiological temperature, and the satisfactory results achieved for sulfanilamide incorporation and release, it can be concluded that p(NIPAM) based hydrogels are promising carriers for sulfanilamide.
Toward a New Generation of Bio-Scaffolds for Neural Tissue Engineering: Challenges and Perspectives
Authors: Villanueva-Flores Francisca , Garcia-Atutxa Igor , Santos Arturo , Armendariz-Borunda Juan
Published: June 2023

Neural tissue engineering presents a compelling technological breakthrough in restoring brain function, holding immense promise. However, the quest to develop implantable scaffolds for neural culture that fulfill all necessary criteria poses a remarkable challenge for material science. These materials must possess a host of desirable characteristics, including support for cellular survival, proliferation, and neuronal migration and the minimization of inflammatory responses. Moreover, they should facilitate electrochemical cell communication, display mechanical properties akin to the brain, emulate the intricate architecture of the extracellular matrix, and ideally allow the controlled release of substances. This comprehensive review delves into the primary requisites, limitations, and prospective avenues for scaffold design in brain tissue engineering. By offering a panoramic overview, our work aims to serve as an essential resource, guiding the creation of materials endowed with bio-mimetic properties, ultimately revolutionizing the treatment of neurological disorders by developing brain-implantable scaffolds.
Novel Fluorescent Benzimidazole-Hydrazone-Loaded Micellar Carriers for Controlled Release: Impact on Cell Toxicity, Nuclear and Microtubule Alterations in Breast Cancer Cells
Authors: Bryaskova Rayna , Georgiev Nikolai , Philipova Nikoleta , Bakov Ventsislav , Anichina Kameliya , Argirova Maria , Apostolova Sonia , Georgieva Irina , Tzoneva Rumiana
Published: June 2023

Fluorescent micellar carriers with controlled release of a novel anticancer drug were developed to enable intracellular imaging and cancer treatment simultaneously. The nanosized fluorescent micellar systems were embedded with a novel anticancer drug via the self-assembling behavior of well-defined block copolymers based on amphiphilic poly(acrylic acid)-block-poly(n-butyl acrylate) (PAA-b-PnBA) copolymer obtained by Atom Transfer Radical Polymerization (ATRP) and hydrophobic anticancer benzimidazole-hydrazone drug (BzH). Through this method, well-defined nanosized fluorescent micelles were obtained consisting of a hydrophilic PAA shell and a hydrophobic PnBA core embedded with the BzH drug due to the hydrophobic interactions, thus reaching very high encapsulation efficiency. The size, morphology, and fluorescent properties of blank and drug-loaded micelles were investigated using dynamic light scattering (DLS), transmission electron microscopy (TEM), and fluorescent spectroscopy, respectively. Additionally, after 72 h of incubation, drug-loaded micelles released 3.25 μM of BzH, which was spectrophotometrically determined. The BzH drug-loaded micelles were found to exhibit enhanced antiproliferative and cytotoxic effects on MDA-MB-231 cells, with long-lasting effects on microtubule organization, with apoptotic alterations and preferential localization in the perinuclear space of cancer cells. In contrast, the antitumor effect of BzH alone or incorporated in micelles on non-cancerous cells MCF-10A was relatively weak.
In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives
Authors: Abu Lila Amr Selim , Amran Mohammed , Tantawy Mohamed A. , Moglad Ehssan H. , Gad Shadeed , Alotaibi Hadil Faris , Obaidullah Ahmad J. , Khafagy El-Sayed
Published: June 2023

This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC50 value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.
Pt and Pd Nanoparticle Crystallization in the Sol-Gel-Derived Thin SiO2 Films
Authors: Gubanova Nadezhda , Matveev Vasilii , Grebenshchikova Elena , Kirilenko Demid , Sazonova Yana , Shilova Olga
Published: June 2023

The crystallization and distribution the features of Pt, Pd and Pt/Pd nanoparticles in spin-on glass SiO2 films were studied within a wide range of the dopant concentrations in silica sol (from 10 to 80 mol.% Pt, Pd or Pt/Pd per 100 mol.% Si). The grazing incidence X-ray diffraction (GIXRD) characterization revealed that the formation of 4–8 nm sized crystalline Pt, Pd and Pt/Pd nanoparticles in SiO2 films began at the dopant concentrations of at least 10 mol.% Pt and/or Pd per 100 mol.% Si. The nanoparticles obtained from sols with the lower Pt, Pd or Pt/Pd concentrations were characterized by an amorphous structure. The dopants distribution over the film thickness (~21–47 nm) was studied using X-ray reflectometry. The effect of the dopant concentration, spin-coating modes and heat treatment temperature on the film thickness was characterized. When only one of the dopants (Pt or Pd) was introduced into the silica sol, the resulting nanoparticles were preferentially localized close to the film surface. When dopants were used together, the Pt/Pd nanoparticles were distributed more evenly.
Ecology, Biology, Environmental Impacts, and Management of an Agro-Environmental Weed Ageratum conyzoides
Authors: Kaur Amarpreet , Kaur Shalinder , Singh Harminder Pal , Datta Avishek , Chauhan Bhagirath Singh , Ullah Hayat , Kohli Ravinder Kumar , Batish Daizy Rani
Published: June 2023

Ageratum conyzoides L. (Billy goat weed; Asteraceae) is an annual herbaceous plant of American origin with a pantropical distribution. The plant has unique biological attributes and a raft of miscellaneous chemical compounds that render it a pharmacologically important herb. Despite its high medicinal value, the constant spread of the weed is noticeable and alarming. In many countries, the weed has severely invaded the natural, urban, and agroecosystems, thus presenting management challenges to natural resource professionals and farmers. Its interference with agricultural crops, grassland forbs, forest ground flora, and its ability to replace native plant species are of serious concern. Therefore, it is pertinent to monitor its continuous spread, its entry into new geographic regions, the extent of its impact, and the associated evolutionary changes. While management strategies should be improvised to control its spread and reduce its adverse impacts, the possible utilization of this noxious weed for pharmacological and agronomic purposes should also be explored. The objective of this review is to provide a detailed account of the global distribution, biological activities, ecological and environmental impacts, and strategies for the management of the agro-environmental weed A. conyzoides.
Alleviation of Shade Stress in Chinese Yew (Taxus chinensis) Seedlings with 5-Aminolevulinic Acid (ALA)
Authors: Wu Liuliu , Song Linlin , Cao Lifan , Meng Li
Published: June 2023

5-aminolevulinic acid (ALA) is a novel regulator that can promote plant growth, nitrogen uptake, and abiotic stress tolerance. Its underlying mechanisms, however, have not been fully investigated. In this study, the effects of ALA on morphology, photosynthesis, antioxidant systems, and secondary metabolites in two cultivars of 5-year-old Chinese yew (Taxus chinensis) seedlings, ‘Taihang’ and ‘Fujian’, were examined under shade stress (30% light for 30 days) using different doses of ALA (0, 30, and 60 mg/L). The findings from our study show that shade stress significantly reduced plant height, stem thickness, and crown width and increased malondialdehyde (MDA) levels. However, the application of 30 mg/L ALA effectively mitigated these effects, which further induced the activity of antioxidant enzymes under shade stress, resulting in the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) being increased by 10%, 16.4%, and 42.1%, and 19.8%, 20.1%, and 42% in ‘Taihang’ and ‘Fujian’, respectively. It also promoted their role in the absorption, conversion, and efficient use of light energy. Additionally, the use of 30 mg/L ALA caused a significant increase in the concentration of secondary metabolites, including polysaccharide (PC), carotenoid (CR), and flavonoids (FA), with increases of up to 46.1%, 13.4%, and 35.6% and 33.5%, 7.5%, and 57.5% in both yew cultivars, respectively, contributing to nutrient uptake. With ALA treatment, the yew seedlings showed higher chlorophyll (total chlorophyll, chlorophyll a and b) levels and photosynthesis rates than the seedlings that received the shade treatment alone. To conclude, the application of 30 mg/L ALA alleviated shade stress in yew seedlings by maintaining redox balance, protecting the photorespiratory system, and increasing organic metabolites, thus increasing the number of new branches and shoots and significantly promoting the growth of the seedlings. Spraying with ALA may be a sustainable strategy to improve the shade-resistant defense system of yew. As these findings increase our understanding of this shade stress response, they may have considerable implications for the domestication and cultivation of yew.
Determination of Caffeoylquinic Acids Content by UHPLC in Scolymus hispanicus Extracts Obtained through Ultrasound-Assisted Extraction
Authors: Ruano-González Antonio , Pinto Ana A. , Chinchilla Nuria , Palma Miguel , Barbero Gerardo F. , Carrera Ceferino , Vázquez-Espinosa Mercedes
Published: June 2023

Scolymus hispanicus L., also known as golden thistle, Spanish oyster thistle or, more commonly, as tagarnina is a plant that belongs to the Asteraceae family. It is collected from the wild for human consumption in Mediterranean countries. It is a relevant ingredient in Andalusian culinary culture, where the midribs of young plants are harvested for consumption. Scolymus hispanicus L. contains a wide variety of phenolic compounds such as caffeoylquinic acids (CQAs), among others. In the present work, the major phenolic compounds present in tagarnina have been identified, with 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-diCQA) being the main ones. A method based on ultrasound-assisted extraction (UAE) has been developed for the extraction of these compounds, with the percentage of methanol, sample-to-solvent ratio and the pH being the most influential factors. The developed method has been validated and employed to determine the concentration of 5-CQA and 3,5-diCQA in the midribs of Scolymus hispanicus, collected in six different places in the south of Spain. The antioxidant activity of the samples has also been determined, and a direct correlation with their caffeoylquinic compounds content has been established, showing an antioxidant effect.
Unraveling the Determinants of Platform Economy Adoption in Developing Countries: An Extended Application of the UTAUT2 Model with a Privacy Calculus Perspective
Authors: Dahmani Mounir , Ben Youssef Adel
Published: June 2023

The platform economy has emerged as a transformative force in various industries, reshaping consumer behavior and the way businesses operate in the digital age. Understanding the factors that influence the adoption of these platforms is essential for their continued development and widespread use. This study examines the determinants of economic platform adoption in Tunisia by extending the widely used unified theory of acceptance and use of technology 2 (UTAUT2) model with a privacy calculus model. By applying the partial least squares structural equation modeling (PLS-SEM) technique, the research provides significant insight. The results highlight the critical influence of factors such as performance expectancy, habit formation, trust in technology, perceived risk, privacy concerns, and price value on users’ behavioral intentions and actual usage of the platforms. These findings provide a deeper understanding of the dynamics surrounding the adoption of the platform economy in developing countries and offer valuable insight for stakeholders. By leveraging this knowledge, stakeholders can foster an inclusive digital ecosystem, drive economic growth, and create an environment conducive to the widespread adoption and use of the platform economy in developing countries.