bluuebunny/crossref_metadata_2025 huggingface dataset:
New Adamantane-Containing Edaravone Conjugates as Potential Neuroprotective Agents for ALS Treatments
Authors: Lapshina Maria A. , Shevtsova Elena F. , Grigoriev Vladimir V. , Aksinenko Aleksey Yu. , Ustyugov Aleksey A. , Steinberg Daniil A. , Maleev Grigoriy V. , Dubrovskaya Elena S. , Goreva Tatiana V. , Epishina Tatiana A. , Zamoyski Vladimir L. , Makhaeva Galina F. , Fisenko Vladimir P. , Veselov Ivan M. , Vinogradova Daria V. , Bachurin Sergey O.
Published: November 2023

Currently, there are no effective drugs for the treatment of amyotrophic lateral sclerosis (ALS). Only two drugs—edaravone and riluzole—have been approved, but they have very limited efficacy. The aim of this work was to modify the structural core of the Edaravone—phenylpyrazolone moiety and combine it with aminoadamantane pharmacophore in order to expand the spectrum of its action to a number of processes involved in the pathogenesis of ALS. New conjugates of edaravone derivatives with 1-aminoadamantanes combined with alkylene or hydroxypropylene spacers were synthesized, and their biological activity was investigated. Compounds were found that could inhibit lipid peroxidation and calcium-related mitochondrial permeability, block fast sodium currents of CNS neurons, and reduce aggregation of the mutated form of the FUS-protein typical to ALS. So, the proposed modification of the edaravone molecule has allowed the obtaining of new original structures that combine some prospective therapeutic mechanisms against key chains of the pathogenesis of ALS. The identified lead compounds can be used for further optimization and development of new promising drugs on this basis for the treatment of ALS.
Comparison of Light-Sheet Fluorescence Microscopy and Fast-Confocal Microscopy for Three-Dimensional Imaging of Cleared Mouse Brain
Authors: Ryu Youngjae , Kim Yoonju , Park Sang-Joon , Kim Sung Rae , Kim Hyung-Jun , Ha Chang Man
Published: November 2023

Whole-brain imaging is important for understanding brain functions through deciphering tissue structures, neuronal circuits, and single-neuron tracing. Thus, many clearing methods have been developed to acquire whole-brain images or images of three-dimensional thick tissues. However, there are several limitations to imaging whole-brain volumes, including long image acquisition times, large volumes of data, and a long post-image process. Based on these limitations, many researchers are unsure about which light microscopy is most suitable for imaging thick tissues. Here, we compared fast-confocal microscopy with light-sheet fluorescence microscopy for whole-brain three-dimensional imaging, which can acquire images the fastest. To compare the two types of microscopies for large-volume imaging, we performed tissue clearing of a whole mouse brain, and changed the sample chamber and low- magnification objective lens and modified the sample holder of a light-sheet fluorescence microscope. We found out that light-sheet fluorescence microscopy using a 2.5× objective lens possesses several advantages, including saving time, large-volume image acquisitions, and high Z-resolution, over fast-confocal microscopy, which uses a 4× objective lens. Therefore, we suggest that light-sheet fluorescence microscopy is suitable for whole mouse brain imaging and for obtaining high-resolution three-dimensional images.
Lattice Thermal Conductivity of Mg3(Bi,Sb)2 Nanocomposites: A First-Principles Study
Authors: Peng Qing , Yuan Xiaoze , Zhao Shuai , Chen Xiao-Jia
Published: November 2023

Mg3(BixSb1−x)2 (0 ≤ x ≤ 1) nanocomposites are a highly appealing class of thermoelectric materials that hold great potential for solid-state cooling applications. Tuning of the lattice thermal conductivity is crucial for improving the thermoelectric properties of these materials. Hereby, we investigated the lattice thermal conductivity of Mg3(BixSb1−x)2 nanocomposites with varying Bi content (x = 0.0, 0.25, 0.5, 0.75, and 1.0) using first-principles calculations. This study reveals that the lattice thermal conductivity follows a classical inverse temperature-dependent relationship. There is a significant decrease in the lattice thermal conductivity when the Bi content increases from 0 to 0.25 or decreases from 1.0 to 0.75 at 300 K. In contrast, when the Bi content increases from 0.25 to 0.75, the lattice thermal conductivity experiences a gradual decrease and reaches a plateau. For the nanohybrids (x = 0.25, 0.5, and 0.75), the distribution patterns of the phonon group velocity and phonon lifetime are similar, with consistent distribution intervals. Consequently, the change in lattice thermal conductivity is not pronounced. However, the phonon group speed and phonon lifetime are generally lower compared to those of the pristine components with x = 0 and x = 1.0. Our results suggest that the lattice thermal conductivity is sensitive to impurities but not to concentrations. This research provides valuable theoretical insights for adjusting the lattice thermal conductivity of Mg3(BixSb1−x)2 nanocomposites.
Poor Nutritional Status during Recovery from Acute Myocardial Infarction in Patients without an Early Nutritional Intervention Predicts a Poor Prognosis: A Single-Center Retrospective Study
Authors: Abe Hiroshi , Miyazaki Tetsuro , Tomaru Masato , Nobushima Yuka , Ajima Tomohi , Hirabayashi Koji , Ishiwata Sayaki , Kakihara Midori , Maki Masaaki , Shimai Ryosuke , Aikawa Tadao , Isogai Hiroyuki , Ozaki Dai , Yasuda Yuki , Odagiri Fuminori , Takamura Kazuhisa , Hiki Makoto , Iwata Hiroshi , Yokoyama Ken , Tokano Takashi , Minamino Tohru
Published: November 2023

Whether malnutrition during the early phase of recovery from acute myocardial infarction (AMI) could be a predictor of mortality or morbidity has not been ascertained. We examined 289 AMI patients. All-cause mortality and composite endpoints (all-cause mortality, nonfatal stroke, nonfatal acute coronary syndrome, and hospitalization for acute decompensated heart failure) during the follow-up duration (median 39 months) were evaluated. There were 108 (37.8%) malnourished patients with GNRIs of less than 98 on arrival; however, malnourished patients significantly decreased to 91 (31.4%) during the convalescence period (p < 0.01). The incidence rates of mortality and primary composite endpoints were significantly higher in the malnourished group than in the well-nourished group both on arrival and during the convalescence period (All p < 0.05). Nutrition guidance significantly improved GNRI in a group of patients who were undernourished (94.7 vs. 91.0, p < 0.01). Malnourished patients on admission who received nutritional guidance showed similar all-cause mortality with well-nourished patients, whereas malnourished patients without receiving nutritional guidance demonstrated significantly worse compared to the others (p = 0.03). The assessment of GNRI during the convalescence period is a useful risk predictor for patients with AMI. Nutritional guidance may improve the prognoses of patients with poor nutritional status.
Blood Selenium Concentrations Are Inversely Associated with the Risk of Undernutrition in Older Adults
Authors: García-Esquinas Esther , Carballo-Casla Adrián , Ortolá Rosario , Sotos-Prieto Mercedes , Olmedo Pablo , Gil Fernando , Plans-Beriso Elena , Fernández-Navarro Pablo , Pastor-Barriuso Roberto , Rodríguez-Artalejo Fernando
Published: November 2023

Background: Selenium is an essential trace element with an antioxidant and anti-inflammatory capacity that has been associated in experimental studies with beneficial effects on appetite control, the regulation of the gut microbiota, and control of the anabolic–catabolic balance. The main aim of the present study was to evaluate the association between circulating selenium concentrations and the risk of developing undernutrition in older adults. Methods: This was a cohort study with 1398 well-nourished community-dwelling individuals aged ≥ 65 years residing in Spain in 2017, who were followed for a mean of 2.3 years. Whole blood selenium was measured at baseline using inductively coupled plasma-mass spectrometry. Undernutrition was assessed at baseline and at follow-up, and defined as having at least one of the three GLIM phenotypic criteria (involuntary weight loss, a low body mass index, and a reduced muscle mass) and at least one of the two etiologic criteria (reduced food consumption or nutrient assimilation and inflammation/disease burden). Results: During the follow-up, 142 participants (11%) developed moderate undernutrition and 113 (8.8%) severe undernutrition. The standardized relative risks of moderate and severe undernutrition at the 75th percentile of Se levels versus the 25th were 0.90 and 0.70, respectively. In dose–response analyses, the risk of severe undernutrition decreased linearly with increasing selenium concentrations. This association was independent of protein intake or diet quality and was stronger among participants with a diagnosis of a musculoskeletal disorder. Conclusions: The results suggest that an adequate dietary selenium status is needed to prevent undernutrition in older adults. Also, this may open the door for clinical trials with selenium supplementation, at doses considered as safe, to prevent undernutrition.
Association of Dietary Changes with Risk Factors of Type 2 Diabetes among Older Adults in Sharpeville, South Africa, from 2004 to 2014
Authors: Lee Hyunjung , Moyo Gugulethu T. , Theophilus Rufus J. , Oldewage-Theron Wilna
Published: November 2023

This study aimed to evaluate the associations of dietary changes with risk factors of type 2 diabetes among older populations in Sharpeville, South Africa. A 24 h recall assessment, dietary diversity, and anthropometrics were measured. Blood samples were collected to assess fasting glucose and insulin. Regression analysis was performed using SPSS version 20. The mean BMI of the total of 103 participants was 30.63 kg/m2 at baseline and 29.66 kg/m2 at follow-up. Significantly higher BMI levels were reported in women than men both at baseline (p = 0.003) and follow-up (p = 0.009). Waist circumference significantly decreased from 96.20 cm to 93.16 cm (p = 0.046). The mean levels of HOMA-B significantly increased from 88.99 to 111.19 (p = 0.021). BMI was positively associated with intakes of total energy (p = 0.22), polyunsaturated fatty acids (p = 0.050), and cholesterol (p = 0.006). Waist circumference was strongly associated with total energy (p = 0.048), polyunsaturated fatty acids (p = 0.037), trans fatty acids (p = 0.039), and cholesterol (p = 0.000). HOMA-IR and HOMA-B were associated with intakes of fat (HOMA-IR: p = 0.013; HOMA-B: p = 0.040) and monounsaturated fatty acids (HOMA-IR: p = 0.003; HOMA-B: p = 0.040).
Vitamin D Status in Bipolar Disorder
Authors: Späth Zita , Tmava-Berisha Adelina , Fellendorf Frederike T. , Stross Tatjana , Maget Alexander , Platzer Martina , Bengesser Susanne A. , Häussl Alfred , Zwigl Ina , Birner Armin , Queissner Robert , Stix Katharina , Wels Linda , Lenger Melanie , Dalkner Nina , Zelzer Sieglinde , Herrmann Markus , Reininghaus Eva Z.
Published: November 2023

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D, and its principal catabolite 24,25(OH)2D, were measured simultaneously with a validated liquid chromatography–tandem mass spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR = 100×(24,25(OH)2D/25(OH)D). The psychometric assessment comprised: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = −0.154, p = 0.040), as well as the Young Mania Rating Scale and the VMR (r = −0.238, p = 0.015). Based on the small effect size and the predominantly euthymic sample, further exploration in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers and an assessment in different phases of the disease may provide additional insights.
Post-Exercise Rehydration in Athletes: Effects of Sodium and Carbohydrate in Commercial Hydration Beverages
Authors: Ly Nhu Q. , Hamstra-Wright Karrie L. , Horswill Craig A.
Published: November 2023

The effects of varying sodium (Na) and carbohydrate (CHO) in oral rehydration solutions (ORS) and sports drinks (SD) for rehydration following exercise are unclear. We compared an ORS and SD for the percent of fluid retained (%FR) following exercise-induced dehydration and hypothesized a more complete rehydration for the ORS (45 mmol Na/L and 2.5% CHO) and that the %FR for the ORS and SD (18 mmol Na/L and 6% CHO) would exceed the water placebo (W). A placebo-controlled, randomized, double-blind clinical trial was conducted. To induce 2.6% body mass loss (BML, p > 0.05 between treatments), 26 athletes performed three 90 min interval training sessions without drinking fluids. Post-exercise, participants replaced 100% of BML and were observed for 3.5 h for the %FR. Mean ± SD for the %FR at 3.5 h was 58.1 ± 12.6% (W), 73.9 ± 10.9% (SD), and 76.9 ± 8.0% (ORS). The %FR for the ORS and SD were similar and greater than the W (p < 0.05 ANOVA and Tukey HSD). Two-way ANOVA revealed a significant interaction with the ORS having greater suppression of urine production in the first 60 min vs. W (SD did not differ from W). By 3.5 h, the ORS and SD promoted greater rehydration than did W, but the pattern of rehydration early in recovery favored the ORS.
The Remaining Challenge to Diagnose and Manage Cow’s Milk Allergy: An Opinion Paper to Daily Clinical Practice
Authors: Vandenplas Yvan , Meyer Rosan , Nowak-Wegrzyn Anna , Salvatore Silvia , Venter Carina , Vieira Mario C.
Published: November 2023

Guidelines and recommendations for the diagnosis and management of cow’s milk allergy (CMA) in childhood are based on scientific review of the available evidence. While this approach is the most rigorous, guidelines may not fully address all scenarios encountered by clinicians. Many symptoms of CMA overlap with other common childhood illnesses and are subjectively reported by the caregivers of the infant, as is the interpretation of the dietary interventions. Additionally, many healthcare professionals and caregivers do not follow the recommendations to perform an oral food challenge or reintroduction of cow’s milk after a diagnostic elimination diet because (1) the infant is doing well and (2) the carer’s fear of symptoms relapsing with this procedure. As a result, CMA in infants may be either under-diagnosed leading to reduced quality of life for families or over-diagnosed, resulting in unnecessary long-term elimination diets and increasing the risk for nutritional deficiencies. This paper discusses some of these controversial topics, focusing on misdiagnosis and mismanagement in clinical practice. The lack of objective diagnostic criteria can hamper the diagnosis and management of CMA in daily practice.
Influence of Lactose Supplementation on Regulation of Streptococcus thermophilus on Gut Microbiota
Authors: Yu Peng , Pan Yuqi , Pei Zhiwen , Guo Min , Yang Bo , Lee Yuan-Kun , Liu Xiaoming , Zhao Jianxin , Zhang Hao , Chen Wei
Published: November 2023

It has been found that Streptococcus thermophilus (S. thermophilus) influenced the gut microbiota and host metabolism with strain specificity in C57BL/6J mice in the previous study, though it remains unclear whether lactose as a dietary factor associated with dairy consumption is involved as the mediator in the interaction. In the present study, integrated analysis of 16S rRNA gene sequencing and untargeted metabolomics by liquid chromatography–mass spectrometry of fecal samples in C57BL/6J mice was applied to evaluate the effect of lactose on the regulation of gut microbiota by two S. thermophilus strains (4M6 and DYNDL13-4). The results showed that the influence of lactose supplementation on gut microbiota induced by S. thermophilus ingestion was strain-specific. Although two S. thermophilus strains ingestion introduced similar perturbations in the fecal microbiota and gut microbial metabolism, the regulation of DYNDL13-4 on the gut microbiota and metabolism was more affected by lactose than 4M6. More specifically, lactose and 4M6 supplementation mainly enriched pathways of d-glutamine and d-glutamate metabolism, alanine, aspartate, and glutamate metabolism, and tryptophan and phenylalanine metabolism in the gut, whereas 4M6 only enriched tryptophan and phenylalanine metabolism. DYNDL13-4-L (DYNDL13-4 with lactose) had significant effects on sulfur, taurine, and hypotaurine metabolism in the gut and on phenylalanine, tyrosine, tryptophan biosynthesis, and linoleic acid metabolism in serum relative to the DYNDL13-4. Our study demonstrated the strain-specific effect of lactose and S. thermophilus supplementation on gut microbiota and host metabolism. However, considering the complexity of the gut microbiota, further research is necessary to provide insights to facilitate the design of personalized fermented milk products as a dietary therapeutic strategy for improving host health.
Gut Microbiota According to the Metabolome
Authors: Scarpellini Emidio , Rinninella Emanuele
Published: November 2023

The human gut microbiota is an ecosystem harboring trillions of microorganisms, encompassing bacteria, viruses, archaea, fungi, and protozoa [...]
Instruments to Evaluate Food Neophobia in Children: An Integrative Review with a Systematic Approach
Authors: Firme Julyana Nogueira , de Almeida Priscila Claudino , dos Santos Emanuele Batistela , Zandonadi Renata Puppin , Raposo António , Botelho Raquel Braz Assunção
Published: November 2023

Food neophobia (FN), a frequent disorder in childhood, profoundly impacts the quality of a diet, restricting the intake of nutrients to maintain proper nutrition. Therefore, using the appropriate tools to assess FN in children to promote healthy eating habits is essential. The study aimed to develop an integrative review with a systematic approach to identify the instruments to measure FN in children and analyze their differences. The included studies (n = 17) were more concentrated in Europe, demonstrating the possible lack of dissemination of the topic at a global level. Among the 18 tools, 6 were represented by adaptations of the Food Neophobia Scale (FNS) and the Children’s Food Neophobia Scale (CFNS), and one was the CFNS itself, demonstrating the relevance of these pioneering tools. The need to meet mainly cultural and cognitive criteria led to the creation of other instruments (n = 11). A diversity of approaches concerning the respondents, age range, items, scales, and validation methods was revealed. Modifications to the tools in some nations highlighted their adaptability and effectiveness in addressing regional variations. The instruments can contribute to additional research to help us better understand the prevalence of FN in children, resulting in their health and well-being.
Redefining Nutritional Requirements in End-Stage Liver Disease: Towards a Personalized Approach
Authors: Chapman Brooke , Wong Darren , Whitcher Bethany , Sinclair Marie , Gow Paul , Majumdar Avik , Testro Adam
Published: November 2023

Malnutrition is ubiquitous in cirrhotic patients presenting for liver transplant (LT). Providing an appropriate energy prescription is fundamental to effective nutrition therapy. We aimed to compare measured energy expenditure (mEE) with predicted energy expenditure (pEE) in patients awaiting LT and determine clinical factors associated with mEE. In this prospective observational study, energy expenditure was measured by indirect calorimetry in 110 adult patients referred for LT and predicted by commonly utilized equations (Harris–Benedict, Schofield, and EASL guidelines). Nutritional status, anthropometry, muscle function, biochemical and clinical data were also collected. The median model for end-stage liver disease (MELD) was 19 (IQR 13, 25), and the majority were Child–Pugh B (51%) or C (37%). Malnutrition was evident in 85%. Median mEE by calorimetry was 1756 (1531, 2104) kcal/d and significantly higher than pEE as per Harris–Benedict 1480 (1322, 1722) kcal/d and Schofield 1474 (1349, 1723) kcal/d (both p < 0.001), but lower than EASL guidelines (35 kcal/kg) when an activity factor was applied to mEE; 2283 (1990, 2735) kcal/d versus 2590 (2178, 3010) kcal/d (p < 0.001). Hypermetabolism (mEE:pEE > 1.2) was evident in 48% of the cohort. Multivariate analysis found MELD, Child–Pugh class, diuretic use, and severe malnutrition to be independent predictors of hypermetabolism. A new liver-specific predictive model has been developed, showing superior agreement with mEE than common predictive equations. In conclusion, there is a poor correlation between mEE and pEE in patients awaiting LTs, and hypermetabolism is common. Relying on historical predictive equations in this patient population may result in significant under or over-feeding. A tailored energy prescription based on indirect calorimetry or a liver-specific predictive model is recommended for LT candidates.
How COVID-19 Pandemic Restrictions Affected Kuwaiti College Students’ Anthropometry, Lifestyle Behaviors, and Dietary Habits
Authors: Al-Haifi Ahmad R. , Bumaryoum Nayef Y. , Al-Awadhi Balqees A. , Alammar Fahad A. , Alkhalaf Bader N. , Al-Hazzaa Hazzaa M.
Published: November 2023

The COVID-19 pandemic and the measures implemented to control it have led to widespread lifestyle changes globally. While previous studies have explored these effects across different age groups, this research focuses uniquely on college students in Kuwait. A cross-sectional study (N = 1259) was conducted among college students using a validated online questionnaire covering various aspects, including demographics, academic performance, self-reported body weight and height, sleep duration, dietary habits, and physical activity. There were equal proportions of individuals reporting decreased, increased, or no change in body weight, BMI, and dietary habits due to COVID-19, with no significant gender differences observed. A higher decrease (44.3%) than increase (29.2%) occurred due to COVID-19 in the proportion of college students engaging in physical activity. Significant differences were found in the students’ responses to most of the eating behavior questions, concerning the changes attributable to the COVID-19 pandemic restrictions. Multivariable analysis showed significant interaction effects for gender by losing above 9 kg during the last 6 months in age (p = 0.037), total physical activity in METs-min/week (p = 0.048), and cake/donuts intake (p = 0.006). Logistic regression analysis, adjusted for age, revealed that a decrease in BMI was associated with an increase in daily vegetable intake (aOR = 1.531, p = 0.031), whereas increases in BMI were associated with an increased intake of sugar-sweetened drinks equal to or above 4 days/week (aOR = 1.551, p = 0.032) and increased chocolates/candy intake equal to or above 4 days/week (aOR = 1.792, p = 0.037). It was concluded that, in response to a major epidemic, such as COVID-19, college students, as a population, are susceptible to significant changes in lifestyle and eating behaviors that can impact their health and well-being. Future risks for college students’ health can be reduced through appropriate lifestyle interventions.
Sarcocystis Species (Apicomplexa, Eucoccidiorida) Parasitizing Snakes
Authors: Bezerra Taynar Lima , Soares Rodrigo Martins , Gondim Luís Fernando Pita
Published: November 2023

The genus Sarcocystis has approximately 200 species that are able to infect homeothermic and poikilothermic animals. So far, 23 Sarcocystis spp. have snakes as definitive hosts (DHs) and mammals and/or reptiles as intermediate hosts (IHs). Some of these species cause disease or even death in their IH. At least two Sarcocystis spp. from snakes have relevance in public health. Sarcocystis nesbitti causes serious myopathy in humans, and S. singaporensis is lethal for rats and was successfully tested in the biological control of these rodents. Molecular identification was not reported for half of Sarcocystis spp. shed by snakes. For some snake species, their role as DHs for Sarcocystis spp. is totally unknown, including certain snakes which are bred as companion animals. The aim of this review is to discuss the role of snakes as DHs or IHs of Sarcocystis spp. and the future directions for the identification of the parasites and the elucidation of their life cycles.
Low Genetic Diversity of the Only Clade of the Tick Rhipicephalus microplus in the Neotropics
Authors: Díaz-Sánchez Sandra , Hernández-Triana Luis , Labruna Marcelo , Merino Octavio , Mosqueda Juan , Nava Santiago , Szabó Matias , Tarragona Evelina , Venzal José , de la Fuente José , Estrada-Peña Agustín
Published: November 2023

This study addresses the variability of the mitochondrial cytochrome oxidase subunit I (COI) and 16S rDNA (16S), and nuclear internal transcriber spacer ITS2 (ITS2) genes in a set of field-collected samples of the cattle tick, Rhipicephalus microplus (Canestrini, 1888), and in geo-referenced sequences obtained from GenBank. Since the tick is currently considered to be a complex of cryptic taxa in several regions of the world, the main aims of the study are (i) to provide evidence of the clades of the tick present in the Neotropics, (ii) to explore if there is an effect of climate traits on the divergence rates of the target genes, and (iii) to check for a relationship between geographical and genetic distance among populations (the closest, the most similar, meaning for slow spread). We included published sequences of Rhipicephalus annulatus (Nearctic, Afrotropical, and Mediterranean) and R. microplus (Afrotropical, Indomalayan) to fully characterize the Neotropical populations (total: 74 16S, 44 COI, and 49 ITS2 sequences included in the analysis). Only the clade A of R. microplus spread in the Nearctic–Neotropics. Both the K and Lambda’s statistics, two measures of phylogenetic signal, support low divergence rates of the tested genes in populations of R. microplus in the Neotropics. These tests demonstrate that genetic diversity of the continental populations does not correlate either with the geographic distance among samples or with environmental variables. The low variability of these genes may be due to a combination of factors like (i) the recent introduction of the tick in the Neotropics, (ii) a large, effective, and fast exchange of populations, and (iii) a low effect of climate on the evolution rates of the target genes. These results have implications for the ecological studies and control of cattle tick infestations.
Design, Synthesis, In Vitro, and In Silico Studies of New N5-Substituted-pyrazolo[3,4-d]pyrimidinone Derivatives as Anticancer CDK2 Inhibitors
Authors: Zaki Waheed A. , El-Sayed Selwan M. , Alswah Mohamed , El-Morsy Ahmed , Bayoumi Ashraf H. , Mayhoub Abrahman S. , Moustafa Walaa H. , Awaji Aeshah A. , Roh Eun Joo , Hassan Ahmed H.E. , Mahmoud Kazem
Published: November 2023

CDK2 is a key player in cell cycle processes. It has a crucial role in the progression of various cancers. Hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are two common cancers that affect humans worldwide. The available therapeutic options suffer from many drawbacks including high toxicity and decreased specificity. Therefore, there is a need for more effective and safer therapeutic agents. A series of new pyrazolo[3,4-d]pyrimidine analogs was designed, synthesized, and evaluated as anticancer agents against the CRC and HCC cells, HCT116, and HepG2, respectively. Pyrazolo[3,4-d]pyrimidinone derivatives bearing N5-2-(4-halophenyl) acetamide substituents were identified as the most potent amongst evaluated compounds. Further evaluation of CDK2 kinase inhibition of two potential cytotoxic compounds 4a and 4b confirmed their CDK2 inhibitory activity. Compound 4a was more potent than the reference roscovitine regarding the CDK2 inhibitory activity (IC50 values: 0.21 and 0.25 µM, respectively). In silico molecular docking provided insights into the molecular interactions of compounds 4a and 4b with important amino acids within the ATP-binding site of CDK2 (Ile10, Leu83, and Leu134). Overall, compounds 4a and 4b were identified as interesting CDK2 inhibitors eliciting antiproliferative activity against the CRC and HCC cells, HCT116 and HepG2, respectively, for future further investigations and development.
Design, Synthesis, and Repurposing of Rosmarinic Acid-β-Amino-α-Ketoamide Hybrids as Antileishmanial Agents
Authors: Hassan Ahmed H.E. , Bayoumi Waleed A. , El-Sayed Selwan M. , Phan Trong-Nhat , Oh Taegeun , Ham Gyeongpyo , Mahmoud Kazem , No Joo Hwan , Lee Yong Sup
Published: November 2023

A series of rosmarinic acid-β-amino-α-ketoamide hybrids were synthesized and rationally repurposed towards the identification of new antileishmanial hit compounds. Two hybrids, 2g and 2h, showed promising activity (IC50 values of 9.5 and 8.8 μM against Leishmania donovani promastigotes, respectively). Their activities were comparable to erufosine. In addition, cytotoxicity evaluation employing human THP-1 cells revealed that the two hybrids 2g and 2h possess no cytotoxic effects up to 100 µM, while erufosine possessed cytotoxicity with CC50 value of 19.4 µM. In silico docking provided insights into structure–activity relationship emphasizing the importance of the aliphatic chain at the α-carbon of the cinnamoyl carbonyl group establishing favorable binding interactions with LdCALP and LARG in both hybrids 2g and 2h. In light of these findings, hybrids 2g and 2h are suggested as potential safe antileishmanial hit compounds for further development of anti-leishmanial agents.
Targeting Glucose Metabolism in Cancer Cells as an Approach to Overcoming Drug Resistance
Authors: Cunha Andrea , Silva Patrícia M. A. , Sarmento Bruno , Queirós Odília
Published: November 2023

The “Warburg effect” consists of a metabolic shift in energy production from oxidative phosphorylation to glycolysis. The continuous activation of glycolysis in cancer cells causes rapid energy production and an increase in lactate, leading to the acidification of the tumour microenvironment, chemo- and radioresistance, as well as poor patient survival. Nevertheless, the mitochondrial metabolism can be also involved in aggressive cancer characteristics. The metabolic differences between cancer and normal tissues can be considered the Achilles heel of cancer, offering a strategy for new therapies. One of the main causes of treatment resistance consists of the increased expression of efflux pumps, and multidrug resistance (MDR) proteins, which are able to export chemotherapeutics out of the cell. Cells expressing MDR proteins require ATP to mediate the efflux of their drug substrates. Thus, inhibition of the main energy-producing pathways in cancer cells, not only induces cancer cell death per se, but also overcomes multidrug resistance. Given that most anticancer drugs do not have the ability to distinguish normal cells from cancer cells, a number of drug delivery systems have been developed. These nanodrug delivery systems provide flexible and effective methods to overcome MDR by facilitating cellular uptake, increasing drug accumulation, reducing drug efflux, improving targeted drug delivery, co-administering synergistic agents, and increasing the half-life of drugs in circulation.
Field-Induced Agglomerations of Polyethylene-Glycol-Functionalized Nanoclusters: Rheological Behaviour and Optical Microscopy
Authors: Bernad Sandor I. , Socoliuc Vlad , Craciunescu Izabell , Turcu Rodica , Bernad Elena S.
Published: November 2023

This research aims to investigate the agglomeration processes of magnetoresponsive functionalized nanocluster suspensions in a magnetic field, as well as how these structures impact the behaviour of these suspensions in biomedical applications. The synthesis, shape, colloidal stability, and magnetic characteristics of PEG-functionalized nanoclusters are described in this paper. Experiments using TEM, XPS, dynamic light scattering (DLS), VSM, and optical microscopy were performed to study chain-like agglomeration production and its influence on colloidal behaviour in physiologically relevant suspensions. The applied magnetic field aligns the magnetic moments of the nanoclusters. It provides an attraction between neighbouring particles, resulting in the formation of chains, linear aggregates, or agglomerates of clusters aligned along the applied field direction. Optical microscopy has been used to observe the creation of these aligned linear formations. The design of chain-like structures can cause considerable changes in the characteristics of ferrofluids, ranging from rheological differences to colloidal stability changes.
Combination of Nanodelivery Systems and Constituents Derived from Novel Foods: A Comprehensive Review
Authors: Truzzi Eleonora , Bertelli Davide , Bilia Anna Rita , Vanti Giulia , Maretti Eleonora , Leo Eliana
Published: November 2023

Novel Food is a new category of food, regulated by the European Union Directive No. 2015/2283. This latter norm defines a food as “Novel” if it was not used “for human consumption to a significant degree within the Union before the date of entry into force of that regulation, namely 15 May 1997”. Recently, Novel Foods have received increased interest from researchers worldwide. In this sense, the key areas of interest are the discovery of new benefits for human health and the exploitation of these novel sources of materials in new fields of application. An emerging area in the pharmaceutical and medicinal fields is nanotechnology, which deals with the development of new delivery systems at a nanometric scale. In this context, this review aims to summarize the recent advances on the design and characterization of nanodelivery systems based on materials belonging to the Novel Food list, as well as on nanoceutical products formulated for delivering compounds derived from Novel Foods. Additionally, the safety hazard of using nanoparticles in food products, i.e., food supplements, has been discussed in view of the current European regulation, which considers nanomaterials as Novel Foods.
Comparison of Sonodynamic Treatment Set-Ups for Cancer Cells with Organic Sonosensitizers and Nanosonosensitizers
Authors: Radivoievych Aleksandar , Prylutska Svitlana , Zolk Oliver , Ritter Uwe , Frohme Marcus , Grebinyk Anna
Published: November 2023

Cancer sonodynamic therapy (SDT) is the therapeutic strategy of a high-frequency ultrasound (US) combined with a special sonosensitizer that becomes cytotoxic upon US exposure. The growing number of newly discovered sonosensitizers and custom US in vitro treatment solutions push the SDT field into a need for systemic studies and reproducible in vitro experimental set-ups. In the current research, we aimed to compare two of the most used and suitable SDT in vitro set-ups—“sealed well” and “transducer in well”—in one systematic study. We assessed US pressure, intensity, and temperature distribution in wells under US irradiation. Treatment efficacy was evaluated for both set-ups towards cancer cell lines of different origins, treated with two promising sonosensitizer candidates—carbon nanoparticle C60 fullerene (C60) and herbal alkaloid berberine. C60 was found to exhibit higher sonotoxicity toward cancer cells than berberine. The higher efficacy of sonodynamic treatment with a “transducer in well” set-up than a “sealed well” set-up underlined its promising application for SDT in vitro studies. The “transducer in well” set-up is recommended for in vitro US treatment investigations based on its US-field homogeneity and pronounced cellular effects. Moreover, SDT with C60 and berberine could be exploited as a promising combinative approach for cancer treatment.
The Trends and Future Prospective of In Silico Models from the Viewpoint of ADME Evaluation in Drug Discovery
Authors: Komura Hiroshi , Watanabe Reiko , Mizuguchi Kenji
Published: November 2023

Drug discovery and development are aimed at identifying new chemical molecular entities (NCEs) with desirable pharmacokinetic profiles for high therapeutic efficacy. The plasma concentrations of NCEs are a biomarker of their efficacy and are governed by pharmacokinetic processes such as absorption, distribution, metabolism, and excretion (ADME). Poor ADME properties of NCEs are a major cause of attrition in drug development. ADME screening is used to identify and optimize lead compounds in the drug discovery process. Computational models predicting ADME properties have been developed with evolving model-building technologies from a simplified relationship between ADME endpoints and physicochemical properties to machine learning, including support vector machines, random forests, and convolution neural networks. Recently, in the field of in silico ADME research, there has been a shift toward evaluating the in vivo parameters or plasma concentrations of NCEs instead of using predictive results to guide chemical structure design. Another research hotspot is the establishment of a computational prediction platform to strengthen academic drug discovery. Bioinformatics projects have produced a series of in silico ADME models using free software and open-access databases. In this review, we introduce prediction models for various ADME parameters and discuss the currently available academic drug discovery platforms.
Advances in Polymeric Micelles: Responsive and Targeting Approaches for Cancer Immunotherapy in the Tumor Microenvironment
Authors: Cheng Lichun , Yu Jiankun , Hao Tangna , Wang Wenshuo , Wei Minjie , Li Guiru
Published: November 2023

In recent years, to treat a diverse array of cancer forms, considerable advancements have been achieved in the field of cancer immunotherapies. However, these therapies encounter multiple challenges in clinical practice, such as high immune-mediated toxicity, insufficient accumulation in cancer tissues, and undesired off-target reactions. To tackle these limitations and enhance bioavailability, polymer micelles present potential solutions by enabling precise drug delivery to the target site, thus amplifying the effectiveness of immunotherapy. This review article offers an extensive survey of recent progress in cancer immunotherapy strategies utilizing micelles. These strategies include responsive and remodeling approaches to the tumor microenvironment (TME), modulation of immunosuppressive cells within the TME, enhancement of immune checkpoint inhibitors, utilization of cancer vaccine platforms, modulation of antigen presentation, manipulation of engineered T cells, and targeting other components of the TME. Subsequently, we delve into the present state and constraints linked to the clinical utilization of polymeric micelles. Collectively, polymer micelles demonstrate excellent prospects in tumor immunotherapy by effectively addressing the challenges associated with conventional cancer immunotherapies.
Descriptive Report of a Pharmacist-Directed Preconception Care Outreach Program in a Rural Maternity Care Desert
Authors: DiPietro Mager Natalie
Published: November 2023

Preconception care is the prevention and management of biomedical, behavioral, and social risk factors to improve pregnancy outcomes and overall health for reproductive-age patients. A community-based pharmacist-directed preconception care outreach program was developed for women ages 18–45 years living in a rural maternity care desert to help them identify potential health risks and provide them with the needed education, counseling, or referrals to address these risks. Supervised student pharmacists, pharmacy practice residents, and pharmacy faculty from a local University collaborated to provide this program at four community events in conjunction with a mobile health clinic. A summative evaluation was performed after the events concluded, modeled after the RE-AIM framework. One hundred and forty-one women were served by the outreach program. Nearly 98% reported at least one preconception health risk, and 45% reported a barrier preventing them from being able to have an appointment with a physician in the last year. The outreach program was feasible to implement and can be adapted to different settings. Pharmacist-directed outreach programs in rural communities may benefit patients who are not receiving or do not have access to such care in traditional healthcare settings.
What Attentional Moral Perception Cannot Do but Emotions Can
Authors: Hutton James
Published: November 2023

Jonna Vance and Preston Werner argue that humans’ mechanisms of perceptual attention tend to be sensitive to morally relevant properties. They dub this tendency “Attentional Moral Perception” (AMP) and argue that it can play all the explanatory roles that some theorists have hoped moral perception can play. In this article, I argue that, although AMP can indeed play some important explanatory roles, there are certain crucial things that AMP cannot do. Firstly, many theorists appeal to moral perception to explain how moral knowledge is possible. I argue that AMP cannot put an agent in a position to acquire moral knowledge unless it is supplemented with some other capacity for becoming aware of moral properties. Secondly, theorists appeal to moral perception to explain “moral conversions”, i.e., cases in which an experience leads an agent to form a moral belief that conflicts with her pre-existing moral beliefs. I argue that AMP cannot explain this either. Due to these shortcomings, theorists should turn to emotions for a powerful and psychologically realistic account of virtuous agents’ sensitivity to the moral landscape.
Dynamics of Electrically Pumped Semiconductor Nano-Laser Arrays
Authors: Fan Yuanlong , Shore K. Alan , Shao Xiaopeng
Published: November 2023

Semiconductor nano-lasers have been actively investigated both theoretically and experimentally with to the aim of providing a highly compact laser amenable to photonic integration. Such devices are naturally suited for assembly in close-packed one- and two-dimensional arrays. In such arrangements, optical coupling between elements of the array opens opportunities to generate a range of dynamical behaviours. In this paper, we present the first theoretical treatment of the dynamics of electrically pumped nano-laser arrays. Two specific forms of such arrays are analysed in detail: a three-element linear array, and triangular arrays. The former is the basis for extensive one-dimensional arrays, whilst the latter is a building block of many possible geometric configurations of two-dimensional nanolaser arrays. Using these prototypical configurations enables the identification of novel dynamical behaviours, which may be accessed using nano-laser arrays. A distinguishing physical feature of nano-lasers is the enhancement of the spontaneous emission rate via the so-called Purcell effect. Allowing for a range of Purcell enhancement factors, the analysis focusses on the effects of experimentally controllable parameters such as the laser drive current. It is shown that the Purcell enhancement factor is critical to the availability of a range of dynamical behaviours which arise simply due to inter-element optical coupling. Two-dimensional portraits of the regimes of differing dynamics offer a convenient means for determining the dynamics which may be accessed by varying the laser drive current.
Multi-Frequency Doppler Velocimetry Based on a Mode-Locked Distributed Bragg Reflector Laser
Authors: Song Hao , Lu Dan , Zhang Zhihao , Guo Fei , Zhou Daibing , Zhao Lingjuan
Published: November 2023

A differential multi-frequency laser Doppler velocimetry is demonstrated, utilizing the synchronized multimode of a mode-locked distributed Bragg reflector laser. This scheme enables the simultaneous detection of multiple Doppler frequency shifts. Multiple differential Doppler shifts of 0.6 Hz, 1.3 Hz, and 1.9 Hz are obtained, with an average speed of 3.677 mm/s and a standard deviation of 0.122 mm/s, demonstrating a cross-referenced velocity measurement capability. The measurement results are also compared with the dual-frequency laser Doppler velocimetry scheme using electro-optical modulation.
Fire Performance of Cotton Fabrics Coated with 10-(2,5-Dihydroxyphenyl)-9,10-dihydro-9-xa-10-phosphaphenanthrene-10-oxide (DOPO-HQ) Zr-Based Metal-Organic Frameworks
Authors: Wu Qiuyue , Lis Manuel José , Hinestroza Juan P.
Published: November 2023

We investigated the performance of cotton fabrics coated with DOPO-HQ and Zr-based Metal–organic Frameworks when exposed to fire. The chemical structure of the cotton fabrics before and after the coating was characterized using FTIR spectroscopy, and the surface morphology of cotton and their combustion residues was probed via scanning electron microscopy. In our experiments, we used flammability tests and thermogravimetric methods to understand the burning behavior of the coated fibers, as well as their thermal stability. The cotton fabrics coated with DOPO-HQ and Zr MOFs exhibited shorter combustion times, had better thermal degradation properties, promoted the creation of heat-insulating layers, and exhibited improved smoke suppression behavior.
The Bran and Grain Grinding Level Affect the Tensile Characteristics of Bioplastics Derived from Wholegrain Wheat Flours
Authors: Dominici Franco , Puglia Debora , Luzi Francesca , Governatori Catia , Tosti Giacomo , Benincasa Paolo
Published: November 2023

The mechanical performance of thermoplastic bulk samples obtained by plasticizing wheat flours differing in grain hardness, alveographic parameters, absence or presence of bran, and grinding level was assessed. Grains of four bread wheat (Triticum aestivum L.) cultivars (Altamira, Aubusson, Blasco, and Bologna) were milled with the aim of producing single-cultivar refined flour (R), or wholegrain flour with fine (F) or coarse (C) grinding. The flours were plasticized, injection molded and tested for tensile properties. The results confirmed that the presence of bran increased the strength (σ) and reduced the elongation at break (ε) of thermoplastics obtained from the flours of each cultivar. The grinding level had an effect, since σ was higher and ε was lower in F than in C samples. SEM analysis of samples revealed that the bran and its texture affected the exposure of starch granules to plasticizer. Composting experiments also revealed that the formulations are able to disintegrate within 21 days with a mass loss rate higher in plastics from F than C flours, while germination tests carried out with cress seeds indicated that it takes two months before the compost loses its phytotoxic effects. Overall, the refining and bran particle size of wheat flours, besides their gluten composition and baking properties, represent novel choice factors to be considered when tailoring the manufacturing of plastic materials for selected requirements and uses.