bluuebunny/crossref_metadata_2025 huggingface dataset:
A Deployable and Cost-Effective Kirigami Antenna for Sub-6 GHz MIMO Applications
Authors: Kiani Saad Hassan , Marey Mohamed , Rafique Umair , Shah Syed Imran Hussain , Bashir Muhammad Adil , Mostafa Hala , Wong Sai-Wai , Parchin Naser Ojaroudi
Published: October 2022

In this work, a low-cost, deployable, integratable, and easy-to-fabricate multiple-input multiple-output (MIMO) Kirigami antenna is proposed for sub-6 GHz applications. The proposed MIMO antenna is inspired by Kirigami art, which consists of four radiating and parasitic elements. The radiating and parasitic elements are composed of a rectangular stub. These elements are placed in such a way that they can provide polarization diversity. The proposed MIMO antenna is designed and fabricated using a soft printed board material called flexible copper-clad laminate (FCCL). It is observed from the results that the proposed MIMO antenna resonates in the 2.5 GHz frequency band, with a 10 dB reflection coefficient bandwidth of 860 MHz ranging from 2.19 to 3.05 GHz. It is worthwhile to mention that the isolation between adjacent radiating elements is higher than 15 dB. In addition, the peak realized gain of the MIMO antenna is around 11 dBi, and the total efficiency is more than 90% within the band of interest. Moreover, the envelope correlation coefficient (ECC) is noted to be less than 0.003, and the channel capacity is ≥17 bps/Hz. To verify the simulated results, a prototype was fabricated, and excellent agreement between the measured and computed results was observed. By observing the performance attributes of the proposed design, it can be said that there are many applications in which this antenna can be adopted. Because of its low profile, it can be used in 5G small-cell mobile MIMO base stations, autonomous light mobility vehicles, and other applications.
Molecular Profiles of Multiple Antimalarial Drug Resistance Markers in Plasmodium falciparum and Plasmodium vivax in the Mandalay Region, Myanmar
Authors: Lê Hương Giang , Naw Haung , Kang Jung-Mi , Võ Tuấn Cường , Myint Moe Kyaw , Htun Zaw Than , Lee Jinyoung , Yoo Won Gi , Kim Tong-Soo , Shin Ho-Joon , Na Byoung-Kuk
Published: October 2022

Emergence and spreading of antimalarial drug resistant malaria parasites are great hurdles to combating malaria. Although approaches to investigate antimalarial drug resistance status in Myanmar malaria parasites have been made, more expanded studies are necessary to understand the nationwide aspect of antimalarial drug resistance. In the present study, molecular epidemiological analysis for antimalarial drug resistance genes in Plasmodium falciparum and P. vivax from the Mandalay region of Myanmar was performed. Blood samples were collected from patients infected with P. falciparum and P. vivax in four townships around the Mandalay region, Myanmar in 2015. Partial regions flanking major mutations in 11 antimalarial drug resistance genes, including seven genes (pfdhfr, pfdhps, pfmdr-1, pfcrt, pfk13, pfubp-1, and pfcytb) of P. falciparum and four genes (pvdhfr, pvdhps, pvmdr-1, and pvk12) of P. vivax were amplified, sequenced, and overall mutation patterns in these genes were analyzed. Substantial levels of mutations conferring antimalarial drug resistance were detected in both P. falciparum and P. vivax isolated in Mandalay region of Myanmar. Mutations associated with sulfadoxine-pyrimethamine resistance were found in pfdhfr, pfdhps, pvdhfr, and pvdhps of Myanmar P. falciparum and P. vivax with very high frequencies up to 90%. High or moderate levels of mutations were detected in genes such as pfmdr-1, pfcrt, and pvmdr-1 associated with chloroquine resistance. Meanwhile, low frequency mutations or none were found in pfk13, pfubp-1, pfcytb, and pvk12 of the parasites. Overall molecular profiles for antimalarial drug resistance genes in malaria parasites in the Mandalay region suggest that parasite populations in the region have substantial levels of mutations conferring antimalarial drug resistance. Continuous monitoring of mutations linked with antimalarial drug resistance is necessary to provide useful information for policymakers to plan for proper antimalarial drug regimens to control and eliminate malaria in the country.
Growth Performance and Recovery of Nosocomial Aspergillus spp. in Blood Culture Bottles
Authors: Pasqua Salvatore , Monaco Francesco , Cardinale Francesca , Bonelli Simone , Conaldi Pier Giulio , D’Apolito Danilo
Published: October 2022

Theoretically, Aspergillus spp. grow in culture media, but frequently, blood cultures of patients with invasive Aspergillosis are negative, even if until now, the reasons are not clear. This aspect underlines the lack of a good strategy for the cultivation and isolation of Aspergillus spp. In order to develop a complete analytical method to detect Aspergillus in clinical and pharmaceutical samples, we investigated the growth performance of two blood culture systems versus the pharmacopeia standard method. At <72 h, all test systems showed comparable sensitivity, about 1–2 conidia. However, the subculture analysis showed a suboptimal recovery for the methods, despite the positive growth and the visualization of the “Aspergillus balls” in the culture media. To investigate this issue, we studied three different subculture approaches: (i) the use of a sterile subculture unit, (ii) the use of a sterile subculture unit and the collection of a larger aliquot (100 µL), following vigorous agitation of the vials, and (iii) to decapsulate the bottle, withdrawing and centrifuging the sample, and aliquot the pellet onto SDA plates. Our results showed that only the third procedure recovered Aspergillus from all positive culture bottles. This work confirmed that our strategy is a valid and faster method to culture and isolate Aspergillus spp. from blood culture bottles.
Direct Hydroxylation of Benzene with Hydrogen Peroxide Using Fe Complexes Encapsulated into Mesoporous Y-Type Zeolite
Authors: Yamaguchi Syuhei , Ishida Yuito , Koga Hitomu , Yahiro Hidenori
Published: October 2022

Mesoporous Y-type zeolite (MYZ) was prepared by an acid and base treatment of commercial Y-type zeolite (YZ). The mesopore volume of MYZ was six times higher than that of YZ. [Fe(terpy)2]2+ complexes encapsulated into MYZ and YZ with different Fe contents (Fe(X)L-MYZ and Fe(X)L-YZ; X is the amount of Fe) were prepared and characterized. The oxidation of benzene with H2O2 using Fe(X)L-MYZ and Fe(X)L-YZ catalysts was carried out; phenol was selectively produced with all Fe-containing zeolite catalysts. As a result, the oxidation activity of benzene increased with increasing iron complex content in the Fe(X)L-MYZ and Fe(X)L-YZ catalysts. The oxidation activity of benzene using Fe(X)L-MYZ catalyst was higher than that using Fe(X)L-YZ. Furthermore, adding mesopores increased the catalytic activity of the iron complex as the iron complex content increased.
Migration of Microplastics and Phthalates from Face Masks to Water
Authors: Zuri Giuseppina , Oró-Nolla Bernat , Torres-Agulló Ana , Karanasiou Angeliki , Lacorte Silvia
Published: October 2022

Since the outbreak of COVID-19, face masks have been introduced in the complex strategy of infection prevention and control. Face masks consist of plastic polymers and additives such as phthalates. The aim of this study was to evaluate the migration of microplastics (MP) and phthalates from face masks to water. Four types of masks including FFP2 masks and surgical were studied. Masks were first characterized to determine the different layers and the material used for their fabrication. Then, masks were cut into 20 pieces of 0.5 cm2, including all their layers, placed in water, and the migration of MP and phthalates was evaluated according to the conditions stated in EU Regulation No 10/2011 on plastic materials and articles intended to come into contact with food. For MP, the morphological analysis (shape, dimension, particle count) was performed using a stereomicroscope, while the identification of both masks and MP released was conducted using μ-Fourier-transform infrared spectroscopy (µ-FT-IR). Migration of phthalates was assessed by ultra-high-performance liquid chromatography coupled to triple quadrupole mass spectrometer (UPLC-MS/MS). Face masks analyzed in the present study were made of atactic polypropylene (PP) as stated by the manufacturer. The μ-FT-IR confirmed that PP and polyamide (PA) were released as fragments, while both PP and polyester (PES) were released as fibers. In addition, 4 phthalates were identified at concentrations between 2.34 and 21.0 µg/mask. This study shows that the migration study can be applied to evaluate the potential release of MP and phthalates from face masks to water and could give a hint for the potential impact of their incorrect disposal on the aquatic resources.
Conformational Stability and Denaturation Processes of Proteins Investigated by Electrophoresis under Extreme Conditions
Authors: Masson Patrick , Lushchekina Sofya
Published: October 2022

The functional structure of proteins results from marginally stable folded conformations. Reversible unfolding, irreversible denaturation, and deterioration can be caused by chemical and physical agents due to changes in the physicochemical conditions of pH, ionic strength, temperature, pressure, and electric field or due to the presence of a cosolvent that perturbs the delicate balance between stabilizing and destabilizing interactions and eventually induces chemical modifications. For most proteins, denaturation is a complex process involving transient intermediates in several reversible and eventually irreversible steps. Knowledge of protein stability and denaturation processes is mandatory for the development of enzymes as industrial catalysts, biopharmaceuticals, analytical and medical bioreagents, and safe industrial food. Electrophoresis techniques operating under extreme conditions are convenient tools for analyzing unfolding transitions, trapping transient intermediates, and gaining insight into the mechanisms of denaturation processes. Moreover, quantitative analysis of electrophoretic mobility transition curves allows the estimation of the conformational stability of proteins. These approaches include polyacrylamide gel electrophoresis and capillary zone electrophoresis under cold, heat, and hydrostatic pressure and in the presence of non-ionic denaturing agents or stabilizers such as polyols and heavy water. Lastly, after exposure to extremes of physical conditions, electrophoresis under standard conditions provides information on irreversible processes, slow conformational drifts, and slow renaturation processes. The impressive developments of enzyme technology with multiple applications in fine chemistry, biopharmaceutics, and nanomedicine prompted us to revisit the potentialities of these electrophoretic approaches. This feature review is illustrated with published and unpublished results obtained by the authors on cholinesterases and paraoxonase, two physiologically and toxicologically important enzymes.
Effect of Amino Acids on Folates Accumulation in Wheat Seedlings during Germination under Red Light Radiation
Authors: Xie Chong , Wang Pei , Chang Jianwei , Wang Qiaoe , Han Yongbin , Yang Runqiang
Published: October 2022

Deficiency of folates can cause various health problems, and germination is a potential way to enrich folates in grain-based food materials. In the present study, the effects of six amino acids (phenylalanine, tyrosine, tryptophan, glutamate, γ-aminobutyric acid, and p-aminobenzoic acid) on folate accumulation during wheat germination under red light radiation were investigated, and an optimized combination of amino acids for promoting folate enrichment was established. The results showed that applying phenylalanine, tyrosine, tryptophan, glutamate, or p-aminobenzoic acid to wheat seedlings during germination can significantly increase the content of total folates through activating the synthesis of the precursors for folate synthesis (pterin and p-aminobenzoic acid) or condensation of these two moieties. Meanwhile, up-regulation of corresponding genes was observed by measuring their expressions to investigate the mechanism for promoting the accumulation of folates. The highest content of folates (ca. 417 µg/100 g DW) was observed when the germinated wheat was cultured with a mixture of 1.5 mM phenylalanine, 0.5 mM tyrosine, 0.5 mM tryptophan, 0.75 mM p-aminobenzoic acid, and 0.5 mM glutamic acid, which was 50% higher than the control seedlings. This study established a promising and practical approach to enhance the accumulation of folates in wheat seedlings.
Comment on Montoro-García et al. Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk. Nutrients 2022, 14, 298
Authors: López-Moreno Miguel
Published: October 2022

Montoro-García et al. [...]
Use of Drugs and Dietary Supplements in University Students of Sports Science: Results of a Survey-Based Cross-Sectional Study
Authors: Ficarra Giovanni , Rottura Michelangelo , Irrera Pierangela , Bitto Alessandra , Trimarchi Fabio , Di Mauro Debora
Published: October 2022

Dietary supplements are used to implement and balance common dietary habits. The general belief is that natural substances reduce the risk of chronic diseases and amplify sports performance with no harmful side effects. Since sports science students will become professionals of sport activities and may also have a role in suggesting the use of dietary supplements to athletes, the aim of this study was to evaluate if physical activity influences the use of drugs and dietary supplements. A modified version of the International Physical Activity Questionnaire—Short Form (IPAQSF) was administered to perform these evaluations. A total of 1452 students from the University of Messina, Italy, enrolled in sports science courses completed the survey; of these, 1075 (704 male and 371 female students) were physically active in moderate- or high-intensity training. Of those physically active students, 709 (440 male and 269 female) were competitive athletes, identified on the basis of their answer to a specific question also indicating the type of sport they practice. The results suggest that 5.6% of all respondents were regular consumers of pharmaceutical products, compared to just 1.0% of the cohort of competing athletes. In contrast, the consumption of natural supplements was similar (14% vs. 15%) between groups. The most frequently used supplements were vitamins, including vitamin C, vitamin B complex, and multivitamin complex, followed by minerals and amino acids or protein complex. The probability of using dietary supplements was mostly related to the male gender (OR 1.64; 95% CI: 1.17–2.30), having a job (OR 1.45; 95% CI: 1.07–1.96), and, most of all, performing physical activity (OR 3.53; 95% CI: 2.18–5.71). The only factor related to a higher use of drugs was female gender (OR 2.40; 95% CI: 1.52–3.79), and the most used class was antihistaminic, followed by FANS. These results suggest that among the specific population of sports science students, those performing physical activity are less prone to using pharmaceutical products and have healthier habits.
Impact of Fruit and Vegetable Protein vs. Milk Protein on Metabolic Control of Children with Phenylketonuria: A Randomized Crossover Controlled Trial
Authors: Pinto Alex , Daly Anne , Rocha Júlio César , Ashmore Catherine , Evans Sharon , Jackson Richard , Payne Anne , Hickson Mary , MacDonald Anita
Published: October 2022

Fruits and vegetables containing phenylalanine ≤ 75 mg/100 g (except potatoes) have little impact on blood phenylalanine in phenylketonuria (PKU). In a randomized, controlled, crossover intervention trial, we examined the effect of increasing phenylalanine intake from fruits and vegetables, containing phenylalanine 76–100 mg /100 g, compared with milk protein sources on blood phenylalanine control. This was a five-phase study (4 weeks each phase). In Phase A, patients remained on their usual diet and then were randomly allocated to start Phase B and C (an additional phenylalanine intake of 50 mg/day, then 100 mg from fruits and vegetables containing phenylalanine 76–100 mg/100 g) or Phase D and E (an additional phenylalanine intake of 50 mg/day then 100 mg/day from milk sources). There was a 7-day washout with the usual phenylalanine-restricted diet between Phase B/C and D/E. Blood phenylalanine was measured on the last 3 days of each week. If four out of six consecutive blood phenylalanine levels were >360 μmol/L in one arm, this intervention was stopped. Sixteen patients (median age 10.5 y; range 6–12 y) were recruited. At baseline, a median of 6 g/day (range: 3–25) natural protein and 60 g/day (range: 60–80) protein equivalent from protein substitute were prescribed. Median phenylalanine levels were: Phase A—240 μmol/L; Phase B—260 μmol/L; Phase C—280 μmol/L; Phase D—270 μmol/L and Phase E—280 μmol/L. All patients tolerated an extra 50 mg/day of phenylalanine from fruit and vegetables, containing phenylalanine 76–100 mg/100 g, but only 11/16 (69%) tolerated an additional 100 mg /day. With milk protein, only 8/16 (50%) tolerated an extra 50 mg/day and only 5/16 (31%) tolerated an additional 100 mg/day of phenylalanine. Tolerance was defined as maintaining consistent blood phenylalanine levels < 360 μmol/L throughout each study arm. There was a trend that vegetable protein had less impact on blood phenylalanine control than milk protein, but overall, the differences were not statistically significant (p = 0.152). This evidence supports the PKU European Guidelines cutoff that fruit and vegetables containing 76–100 mg phenylalanine/100 g should be calculated as part of the phenylalanine exchange system. Tolerance of the ‘free use’ of these fruits and vegetables depends on inter-patient variability but cannot be recommended for all patients with PKU.
A Longitudinal Study of Exposure to Manganese and Incidence of Metabolic Syndrome
Authors: Riseberg Emily , Chui Kenneth , James Katherine A. , Melamed Rachel , Alderete Tanya L. , Corlin Laura
Published: October 2022

The association between manganese (Mn) and metabolic syndrome (MetS) is unclear, and no prior study has studied this association longitudinally. The aim of this study was to assess longitudinal associations of Mn exposure with MetS and metabolic outcomes. We used data from the San Luis Valley Diabetes Study (SLVDS), a prospective cohort from rural Colorado with data collected from 1984–1998 (n = 1478). Urinary Mn was measured at baseline (range = 0.20–42.5 µg/L). We assessed the shape of the cross-sectional association between Mn and MetS accounting for effect modification by other metals at baseline using Bayesian kernel machine regression. We assessed longitudinal associations between baseline quartiles of Mn and incident MetS using Fine and Gray competing risks regression models (competing risk = mortality) and between quartiles of Mn and metabolic outcomes using linear mixed effects models. We did not observe evidence that quartiles of Mn were associated with incident MetS (p-value for trend = 0.52). Quartiles of Mn were significantly associated with lower fasting glucose (p-value for trend < 0.01). Lead was found to be a possible effect modifier of the association between Mn and incident MetS. Mn was associated with lower fasting glucose in this rural population. Our results support a possible beneficial effect of Mn on diabetic markers.
Critical Review for the Production of Antidiabetic Peptides by a Bibliometric Approach
Authors: Farias Ticiane Carvalho , de Souza Thaiza Serrano Pinheiro , Fai Ana Elizabeth Cavalcante , Koblitz Maria Gabriela Bello
Published: October 2022

The current bibliometric review evaluated recent papers that researched dietary protein sources to generate antidiabetic bioactive peptides/hydrolysates for the management of diabetes. Scopus and PubMed databases were searched to extract bibliometric data and, after a systematic four-step process was performed to select the articles, 75 papers were included in this review. The countries of origin of the authors who published the most were China (67%); Ireland (59%); and Spain (37%). The journals that published most articles on the subject were Food Chemistry (n = 12); Food & Function (n = 8); and Food Research International (n = 6). The most used keywords were ‘bioactive peptides’ (occurrence 28) and ‘antidiabetic’ (occurrence 10). The most used enzymes were Alcalase® (17%), Trypsin (17%), Pepsin, and Flavourzyme® (15% each). It was found that different sources of protein have been used to generate dipeptidyl peptidase IV (DPP-IV), α-amylase, and α-glucosidase inhibitory peptides. In addition to antidiabetic properties, some articles (n = 30) carried out studies on multifunctional bioactive peptides, and the most cited were reported to have antioxidant and antihypertensive activities (n = 19 and 17, respectively). The present review intended to offer bibliometric data on the most recent research on the production of antidiabetic peptides from dietary proteins to those interested in their obtention to act as hypoglycemic functional ingredients. The studies available in this period, compiled, are not yet enough to point out the best strategies for the production of antidiabetic peptides from food proteins and a more systematic effort in this direction is necessary to allow a future scale-up for the production of these possible functional ingredients.
A Novel Quantitative Computer-Assisted Score Can Improve Repeatability in the Estimate of Vascular Calcifications at the Abdominal Aorta
Authors: Fusaro Maria , Schileo Enrico , Crimi Gianluigi , Aghi Andrea , Bazzocchi Alberto , Barbanti Brodano Giovanni , Girolami Marco , Sella Stefania , Politi Cristina , Ferrari Serge , Gasperini Chiara , Tripepi Giovanni , Taddei Fulvia
Published: October 2022

In CKD and in the elderly, Vascular Calcifications (VC) are associated to cardiovascular events and bone fractures. VC scores at the abdominal aorta (AA) from lateral spine radiographs are widely applied (the 0–24 semiquantitative discrete visual score (SV) being the most used). We hypothesised that a novel continuum score based on quantitative computer-assisted tracking of calcifications (QC score) can improve the precision of the SV score. This study tested the repeatability and reproducibility of QC score and SV score. In forty-four patients with VC from an earlier study, five experts from four specialties evaluated the data twice using a dedicated software. Test–retest was performed on eight subjects. QC results were reported in a 0–24 scale to readily compare with SV. The QC score showed higher intra-operator repeatability: the 95% CI of Bland–Altman differences was almost halved in QC; intra-operator R2 improved from 0.67 for SV to 0.79 for QC. Inter-observer repeatability was higher for QC score in the first (Intraclass Correlation Coefficient 0.78 vs. 0.64), but not in the second evaluation (0.84 vs. 0.82), indicating a possible heavier learning artefact for SV. The Minimum Detectable Difference (MDD) was smaller for QC (2.98 vs. 4 for SV, in the 0–24 range). Both scores were insensitive to test–retest procedure. Notably, QC and SV scores were discordant: SV showed generally higher values, and an increasing trend of differences with VC severity. In summary, the new QC score improved the precision of lateral spine radiograph scores in estimating VC. We reported for the first time an estimate of MDD in VC assessment that was 25% lower for the new QC score with respect to the usual SV score. An ongoing study will determine whether this lower MDD may reduce follow-up times to check for VC progression.
Transcriptomic Analysis of the Anticancer Effects of Annatto Tocotrienol, Delta-Tocotrienol and Gamma-Tocotrienol on Chondrosarcoma Cells
Authors: Pang Kok-Lun , Foong Lian-Chee , Abd Ghafar Norzana , Soelaiman Ima Nirwana , Law Jia Xian , Leong Lek Mun , Chin Kok-Yong
Published: October 2022

Previous studies have demonstrated the anticancer activities of tocotrienol on several types of cancer, but its effects on chondrosarcoma have never been investigated. Therefore, this study aims to determine the anticancer properties of annatto tocotrienol (AnTT), γ-tocotrienol (γ-T3) and δ-tocotrienol (δ-T3) on human chondrosarcoma SW1353 cells. Firstly, the MTT assay was performed to determine the half-maximal inhibitory concentration (IC50) of tocotrienol on SW1353 cells after 24 h treatment. The mode of cell death, cell cycle analysis and microscopic observation of tocotrienol-treated SW1353 cells were then conducted according to the respective IC50 values. Subsequently, RNAs were isolated from tocotrienol-treated cells and subjected to RNA sequencing and transcriptomic analysis. Differentially expressed genes were identified and then verified with a quantitative PCR. The current study demonstrated that AnTT, γ-T3 and δ-T3 induced G1 arrest on SW1353 cells in the early phase of treatment (24 h) which progressed to apoptosis upon 48 h of treatment. Furthermore, tocotrienol-treated SW1353 cells also demonstrated large cytoplasmic vacuolation. The subsequent transcriptomic analysis revealed upregulated signalling pathways in endoplasmic reticulum stress, unfolded protein response, autophagy and transcription upon tocotrienol treatment. In addition, several cell proliferation and cancer-related pathways, such as Hippo signalling pathway and Wnt signalling pathway were also significantly downregulated upon treatment. In conclusion, AnTT, γ-T3 and δ-T3 possess promising anticancer properties against chondrosarcoma cells and further study is required to confirm their effectiveness as adjuvant therapy for chondrosarcoma.
Predicting Perceived Problems in Self-Administered 24-Hour Dietary Recalls: A Quantitative Think-Aloud Study Comparing Automated Self-Assisted 24-Hour Dietary Assessment Tool (ASA24®) and INTAKE24© in University Students
Authors: Mackenzie Katlyn M. , Kerr Deborah A. , Whitton Clare , Talati Zenobia , McCaffrey Tracy A. , Mullan Barbara A.
Published: October 2022

Demographic and psychosocial factors concerning dietary assessment error have been explored, but few studies have investigated the perceived problems experienced when completing dietary recalls. The aim of this research was to (i) compare the perceived problems encountered in two commonly used self-administered 24-hour dietary recall (24HR) programs (INTAKE24© and ASA24®) and (ii) explore whether mindful and habitual eating are associated with perceived problems during dietary recall. A randomised quantitative crossover design and think-aloud methodology were employed. Undergraduate university students (N = 55, Mage = 25.5, SD = 8.2, 75% female) completed a food habits and mindfulness questions pre-program, one 24HR (whilst thinking aloud), and a systems usability scale post-program. A week later, they completed the other 24HR (whilst thinking aloud). During a pilot, a coding frame of perceived problems was devised to quantify participants’ perceived problems. INTAKE24© generated significantly fewer perceived problems across all categories compared to ASA24® (17.2 vs. 33.1, p < 0.001). Of the participants, 68% reported a preference for INTAKE24© over ASA24®. Hierarchical multiple regression showed that habits and systems usability were significant predictors of perceived problems for INTAKE24© only. No significant predictors were found for ASA24®. The results provide insight into perceived problems people may encounter when using 24HR tools.
Reply to López-Moreno, M. Comment on “Montoro-García et al. Beneficial Impact of Pork Dry-Cured Ham Consumption on Blood Pressure and Cardiometabolic Markers in Individuals with Cardiovascular Risk. Nutrients 2022, 14, 298”
Authors: Montoro-García Silvia , Velasco-Soria Ángeles , Carazo-Díaz Carmen , Toldrá Fidel , Avellaneda Antonio , Abellán-Alemán José
Published: October 2022

We thank Dr. López-Moreno for the comment [...]
Indole-3-Carbinol Stabilizes p53 to Induce miR-34a, Which Targets LDHA to Block Aerobic Glycolysis in Liver Cancer Cells
Authors: Qi Yuehua , Zhang Chunjing , Wu Di , Zhang Yue , Zhao Yunfeng , Li Wenjuan
Published: October 2022

Certain cancer cells prefer aerobic glycolysis rather than oxidative phosphorylation for energy supply. Lactate dehydrogenase A (LDHA) catalyzes the reduction of pyruvate to lactate and regains NAD+ so that glycolysis is continued. As a pivotal enzyme to promote smooth glycolysis, LDHA plays an important role in carcinogenesis. Indole-3-carbinol (I3C) has displayed antitumor activity, but the exact mechanism remains to be identified. In this study, we treated liver cancer cells with I3C, performed colony formation and cell migration, measured the expression of glycolysis-related proteins, and predicted and validated LDHA-targeting miRNA from the databases. In addition, the mRNA and protein levels of p53, glycolysis-related genes and miRNAs that regulate glycolysis were detected after I3C and siRNA-p53 treatment alone or in combination. Next, the expression and colocalization of p53 and MDM2 in liver cancer cells were evaluated after I3C treatment, and the effect of I3C on p53 protein stability was examined. The results showed that I3C inhibited cell proliferation, migration, and the expression levels of glycolysis-related gene LDHAs. MiR-34a was predicted to target LDHA, and I3C downregulated its expression. Furthermore, the combined I3C and siRNA-p53 treatment demonstrated that I3C regulated the expression of LDHA via miR-34a in a p53-dependent manner. Finally, I3C inhibited MDM2 expression and its colocalization with p53 and stabilized p53 expression. In summary, I3C inhibited the degradation of p53 by MDM2 in liver cancer cells; stable p53 induced miR-34a, which targeted LDHA, a key enzyme for aerobic glycolysis, suggesting cancer metabolism is an important target for I3C in liver cancer cells.
Flow Patterns and Particle Residence Times in the Oral Cavity during Inhaled Drug Delivery
Authors: Vara Almirall Brenda , Inthavong Kiao , Bradshaw Kimberley , Singh Narinder , Johnson Aaron , Storey Pippa , Salati Hana
Published: October 2022

Pulmonary drug delivery aims to deliver particles deep into the lungs, bypassing the mouth–throat airway geometry. However, micron particles under high flow rates are susceptible to inertial impaction on anatomical sites that serve as a defense system to filter and prevent foreign particles from entering the lungs. The aim of this study was to understand particle aerodynamics and its possible deposition in the mouth–throat airway that inhibits pulmonary drug delivery. In this study, we present an analysis of the aerodynamics of inhaled particles inside a patient-specific mouth–throat model generated from MRI scans. Computational Fluid Dynamics with a Discrete Phase Model for tracking particles was used to characterize the airflow patterns for a constant inhalation flow rate of 30 L/min. Monodisperse particles with diameters of 7 μm to 26 μm were introduced to the domain within a 3 cm-diameter sphere in front of the oral cavity. The main outcomes of this study showed that the time taken for particle deposition to occur was 0.5 s; a narrow stream of particles (medially and superiorly) were transported by the flow field; larger particles > 20 μm deposited onto the oropharnyx, while smaller particles < 12 μm were more disperse throughout the oral cavity and navigated the curved geometry and laryngeal jet to escape through the tracheal outlet. It was concluded that at a flow rate of 30 L/min the particle diameters depositing on the larynx and trachea in this specific patient model are likely to be in the range of 7 μm to 16 μm. Particles larger than 16 μm primarily deposited on the oropharynx.
Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors
Authors: Urias Beatriz Silva , Pavan Aline Renata , Albuquerque Gabriela Ribeiro , Prokopczyk Igor Muccilo , Alves Tânia Mara Ferreira , de Melo Thais Regina Ferreira , Sartori Geraldo Rodrigues , da Silva João Hermínio Martins , Chin Chung Man , Santos Jean Leandro Dos
Published: October 2022

Histone deacetylases (HDAC) are epigenetic enzymes responsible for repressing gene expression through the deacetylation of histone lysine residues. Therefore, inhibition of HDACs has become an interesting approach for the treatment of several diseases, including cancer, hematology, neurodegenerative, immune diseases, bacterial infections, and more. Resveratrol (RVT) has pleiotropic effects, including pan-inhibition of HDAC isoforms; however, its ability to interfere with membranes requires additional optimization to eliminate nonspecific and off-target effects. Thus, to explore RVT as a scaffold, we designed a series of novel HDAC-1 and -2 inhibitors containing the 2-aminobenzamide subunit. Using molecular modeling, all compounds, except unsaturated compounds (4) and (7), exhibited a similar mode of interaction at the active sites of HDAC 1 and 2. The docking score values obtained from the study ranged from −12.780 to −10.967 Kcal/mol. All compounds were synthesized, with overall yields ranging from 33% to 67.3%. In an initial screening, compounds (4), (5), (7), and (20)–(26), showed enzymatic inhibitory effects ranging from 1 to 96% and 6 to 93% against HDAC-1 and HDAC-2, respectively. Compound (5), the most promising HDAC inhibitor in this series, was selected for IC50 assays, resulting in IC50 values of 0.44 µM and 0.37 µM against HDAC-1 and HDAC-2, respectively. In a panel of selectivity against HDACs 3–11, compound (5) presented selectivity towards Class I, mainly HDAC-1, 2, and 3. All compounds exhibited suitable physicochemical and ADMET properties as determined using in silico simulations. In conclusion, the optimization of the RVT structure allows the design of selective HDAC inhibitors, mainly targeting HDAC-1 and HDAC-2 isoforms.
Identification of Novel Cyanopyridones and Pyrido[2,3-d]Pyrimidines as Anticancer Agents with Dual VEGFR-2/HER-2 Inhibitory Action: Synthesis, Biological Evaluation and Molecular Docking Studies
Authors: Al-Warhi Tarfah , Sallam Al-Aliaa , Hemeda Loah , El Hassab Mahmoud , Aljaeed Nada , Alotaibi Ohoud , Doghish Ahmed , Noshy Mina , Eldehna Wagdy , Ibrahim Mona
Published: October 2022

In the current work, we designed and synthesized three families of non-fused and fused compounds based on cyanopyridone: derivatives of 6-amino-1,2-dihydropyridine-3,5-dicarbonitrile (5a-f) and 3,4,7,8-tetrahydro pyrimidine-6-carbonitrile (6a-b and 7a-e). The newly synthesized compounds’ structure were determined using a variety of techniques, including 1H NMR, 13C NMR, mass spectrum, infrared spectroscopy, and elemental analysis. The developed compounds were tested for the ability to inhibit the growth of breast adenocarcinoma (MCF-7) and hepatic adenocarcinoma (HepG2) cell lines using MTT assay. Some of the synthesized compounds were more effective towards the cancer cell lines than the standard treatment taxol. The best antiproliferative activities were demonstrated by non-fused cyanopyridones 5a and 5e against the MCF-7 cell line (IC50 = 1.77 and 1.39 μM, respectively) and by compounds 6b and 5a against the HepG2 cell line (IC50 = 2.68 and 2.71 μM, respectively). We further explored 5a and 5e, the two most potent compounds against the MCF-7 cell line, for their ability to inhibit VEGFR-2 and HER-2. Finally, docking and molecular dynamics simulations were performed as part of the molecular modeling investigation to elucidate the molecular binding modes of the tested compounds, allowing for a more thorough comprehension of the activity of compounds 5a and 5e.
Analysis of the Anti-Inflammatory and Anti-Osteoarthritic Potential of Flonat Fast®, a Combination of Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum), Evaluated in In Vitro Models of Inflammation Relevant to Osteoarthritis
Authors: Quarta Stefano , Santarpino Giuseppe , Carluccio Maria Annunziata , Calabriso Nadia , Scoditti Egeria , Siculella Luisa , Damiano Fabrizio , Maffia Michele , Verri Tiziano , De Caterina Raffaele , Massaro Marika
Published: October 2022

Osteoarthritis (OA) is a joint disease characterized by inflammation of the synovium, angiogenesis, cartilage degradation, and osteophyte formation. Harpagophytum Procumbens DC. ex Meisn., Boswellia Serrata Roxb., Curcuma longa L., Bromelain and Escin (Aesculus hippocastanum) are plants which extracts, together to Bromelain and Escin (Aesculus hippocastanum) are traditionally used in OA. However, their mechanistic role remains unclear. We aimed to investigate whether these bioactives alone or in combination (as in Flonat Fast®) can suppress TNF-α-induced inflammation, angiogenesis, and osteophyte formation using two cell models involved in OA: endothelial cells and monocytes. Each plant extract was evaluated for its polyphenol content, antioxidant activity, and toxicity. In endothelial cells and monocytes, expression of genes involved in OA was assessed, functional assays for inflammation and angiogenesis were performed, and impairment of reactive oxygen species production (ROS) was evaluated. Exposure of cells to the bioactives alone and in combination before cytokine stimulation resulted in differential counterregulation of several gene and protein expressions, including those for cyclooxygenases-2, metalloproteinase-9, transforming growth factor β1, and bone morphogenic protein-2. We demonstrated that these bioactives modulated monocyte adhesion to endothelial cells as well as cell migration and endothelial angiogenesis. Consistent with radical scavenging activity in the cell-free system, the bioactives curbed TNF-α-stimulated intracellular ROS production. We confirmed the potential anti-inflammatory and antiangiogenic effects of the combination of Harpagophytum procumbens, Boswellia, Curcuma, Bromelain, and Escin and provided new mechanistic evidence for their use in OA. However, further clinical studies are needed to evaluate the true clinical utility of these bioactives as supportive, preventive, and therapeutic agents.
Structure-Guide Design and Optimization of Potential Druglikeness Inhibitors for TGFβRI with the Pyrrolopyrimidine Scaffold
Authors: Meng Dan , Xie Jiali , Li Yihao , Li Ruoyu , Zhou Hui , Deng Ping
Published: October 2022

Among all types of TGFβ signal blockers, small molecule kinase inhibitors (SMKIs) have attracted wide attention due to their economical production, obvious stability, and ease of oral administration. Nevertheless, SMKIs of TGFβRItypically have low druggability so there are none on the market. In this study, structure-based drug design (SBDD) was performed focusing on the pyrrolopyrimidin scaffold of BMS22 to find TGFβRIinhibitors with excellent medical potential. The binding mode, druggability, and target affinity were assessed by molecular docking, ADMET predictions, and molecular dynamics (MD) simulations for the designed TGFβRIinhibitors. Finally, the highly druggable compound W8 was discovered and then synthesized, which inhibited TGFβRIwith an IC50 value of about 10 μM. In addition, the binding free energies (ΔGbind) of W8 (−42.330 ± 3.341 kcal/mol) and BMS22 (−30.560 ± 6.076 kcal/mol) indicate that the high binding affinity is not necessarily accompanied by high inhibitory activity. Last but not least, the per-residue interaction analysis revealed that the contribution energy of ASP351 to binding was the most significant difference between BMS22 and W8, −2.195 kcal/mol and 1.707 kcal/mol, respectively. As a result, increasing the affinity between SMKIs and ASP351 of TGFβRImay effectively improve the inhibitory activity. The insights gained from this study could help with structure-guided optimization in searching for better SMKIs of TGFβRI.
Functionalized Silver and Gold Nanomaterials with Diagnostic and Therapeutic Applications
Authors: Rabiee Navid , Ahmadi Sepideh , Iravani Siavash , Varma Rajender S.
Published: October 2022

The functionalization of nanomaterials with suitable capping ligands or bioactive agents is an interesting strategy in designing nanosystems with suitable applicability and biocompatibility; the physicochemical and biological properties of these nanomaterials can be highly improved for biomedical applications. In this context, numerous explorations have been conducted in the functionalization of silver (Ag) and gold (Au) nanomaterials using suitable functional groups or agents to design nanosystems with unique physicochemical properties such as excellent biosensing capabilities, biocompatibility, targeting features, and multifunctionality for biomedical purposes. Future studies should be undertaken for designing novel functionalization tactics to improve the properties of Au- and Ag-based nanosystems and reduce their toxicity. The possible release of cytotoxic radicals or ions, the internalization of nanomaterials, the alteration of cellular signaling pathways, the translocation of these nanomaterials across the cell membranes into mitochondria, DNA damages, and the damage of cell membranes are the main causes of their toxicity, which ought to be comprehensively explored. In this study, recent advancements in diagnostic and therapeutic applications of functionalized Au and Ag nanomaterials are deliberated, focusing on important challenges and future directions.
Comparative Estimation of the Cytotoxic Activity of Different Parts of Cynara scolymus L.: Crude Extracts versus Green Synthesized Silver Nanoparticles with Apoptotic Investigation
Authors: Khedr Amgad I. M. , Farrag Abdelaziz F. S. , Nasr Ali M. , Swidan Shady A. , Nafie Mohamed S. , Abdel-Kader Maged S. , Goda Marwa S. , Badr Jihan M. , Abdelhameed Reda F. A.
Published: October 2022

Different parts of Cynara scolymus L. and their green synthesized eco-friendly silver nanoparticles (AgNPs) were screened for their cytotoxicity and apoptotic activity. Results showed that flower extract AgNPs exhibited more potent cytotoxicity compared to the normal form against PC-3 and A549 cell lines with IC50 values of 2.47 μg/mL and 1.35 μg/mL, respectively. The results were compared to doxorubicin (IC50 = 5.13 and 6.19 μg/mL, respectively). For apoptosis-induction, AgNPs prepared from the flower extract induced cell death by apoptosis by 41.34-fold change and induced necrotic cell death by 10.2-fold. Additionally, they induced total prostate apoptotic cell death by a 16.18-fold change, and it slightly induced necrotic cell death by 2.7-fold. Hence, green synthesized flower extract AgNPs exhibited cytotoxicity in A549 and PC-3 through apoptosis-induction in both cells. Consequently, synthesized AgNPs were further tested for apoptosis and increased gene and protein expression of pro-apoptotic markers while decreasing expression of anti-apoptotic genes. As a result, this formula may serve as a promising source for anti-cancer candidates. Finally, liquid chromatography combined with electrospray mass spectrometry (LC-ESI-MS) analysis was assessed to identify the common bioactive metabolites in crude extracts of stem, flower, and bract.
Design and Characteristics of Diamond-Assisted Ring-Core Fiber for Space Division Multiplexing
Authors: Song Yujing , Zheng Jingjing , Pei Li , Huang Jing , Ning Tigang , Li Jing , Wang Jianshuai , Bai Bing
Published: October 2022

In this paper, a novel diamond-assisted ring-core fiber (DRF) is proposed. With the introduction of a low-refractive-index diamond-shaped region located in the center of the core, the proposed fiber effectively eliminates spatial degeneracy of the LPmn mode groups and maintains a low level of birefringence. Under the fiber structure parameters proposed in this paper, the effective refractive index difference (Δneff) between the spatial modes supported by the fiber in the entire C-band is greater than 2.25 × 10−4, and the Δneff between adjacent modes falls within the scope of (2.11~9.41) × 10−4. The degree of degenerate separation between the two polarization modes of all modes is very low, which is 2~3 orders of magnitude lower than that of the spatial mode. By discussing the mode characteristics of DRF and several other center-assisted ring-core fibers, the method that can be used to manipulate the spatial mode degenerate separation with structural symmetry is obtained, which can be applied to provide guidance for similar fiber designs. The proposed fiber structure is a promising candidate in space division multiplexing systems.
Optimization of Polystyrene Biodegradation by Bacillus cereus and Pseudomonas alcaligenes Using Full Factorial Design
Authors: Miloloža Martina , Ukić Šime , Cvetnić Matija , Bolanča Tomislav , Kučić Grgić Dajana
Published: October 2022

Microplastics (MP) are a global environmental problem because they persist in the environment for long periods of time and negatively impact aquatic organisms. Possible solutions for removing MP from the environment include biological processes such as bioremediation, which uses microorganisms to remove contaminants. This study investigated the biodegradation of polystyrene (PS) by two bacteria, Bacillus cereus and Pseudomonas alcaligenes, isolated from environmental samples in which MPs particles were present. First, determining significant factors affecting the biodegradation of MP-PS was conducted using the Taguchi design. Then, according to preliminary experiments, the optimal conditions for biodegradation were determined by a full factorial design (main experiments). The RSM methodology was applied, and statistical analysis of the obtained models was performed to analyze the influence of the studied factors. The most important factors for MP-PS biodegradation by Bacillus cereus were agitation speed, concentration, and size of PS, while agitation speed, size of PS, and optical density influenced the process by Pseudomonas alcaligenes. However, the optimal conditions for biodegradation of MP-PS by Bacillus cereus were achieved at γMP = 66.20, MP size = 413.29, and agitation speed = 100.45. The best conditions for MP-PS biodegradation by Pseudomonas alcaligenes were 161.08, 334.73, and 0.35, as agitation speed, MP size, and OD, respectively. In order to get a better insight into the process, the following analyzes were carried out. Changes in CFU, TOC, and TIC concentrations were observed during the biodegradation process. The increase in TOC values was explained by the detection of released additives from PS particles by LC-MS analysis. At the end of the process, the toxicity of the filtrate was determined, and the surface area of the particles was characterized by FTIR-ATR spectroscopy. Ecotoxicity results showed that the filtrate was toxic, indicating the presence of decomposition by-products. In both FTIR spectra, a characteristic weak peak at 1715 cm−1 was detected, indicating the formation of carbonyl groups (−C=O), confirming that a biodegradation process had taken place.