bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic Fingerprinting of Muscat of Alexandria Grape Musts during Industrial Alcoholic Fermentation Using HS-SPME and Liquid Injection with TMS Derivatization GC-MS Methods
Authors: Marinaki Maria , Mouskeftara Thomai , Arapitsas Panagiotis , Zinoviadou Kyriaki G. , Theodoridis Georgios
Published: June 2023

Muscat of Alexandria is one of the most aromatic grape cultivars, with a characteristic floral and fruity aroma, producing popular appellation of origin wines. The winemaking process is a critical factor contributing to the quality of the final product, so the aim of this work was to study metabolomic changes during the fermentation of grape musts at the industrial level from 11 tanks, 2 vintages, and 3 wineries of Limnos Island. A Headspace Solid-Phase Microextraction (HS-SPME) and a liquid injection with Trimethylsilyl (TMS) derivatization Gas Chromatography-Mass Spectrometry (GC-MS) methods were applied for the profiling of the main volatile and non-volatile polar metabolites originating from grapes or produced during winemaking, resulting in the identification of 109 and 69 metabolites, respectively. Multivariate statistical analysis models revealed the differentiation between the four examined time points during fermentation, and the most statistically significant metabolites were investigated by biomarker assessment, while their trends were presented with boxplots. Whilst the majority of compounds (ethyl esters, alcohols, acids, aldehydes, sugar alcohols) showed an upward trend, fermentable sugars, amino acids, and C6-compounds were decreased. Terpenes presented stable behavior, with the exception of terpenols, which were increased at the beginning and were then decreased after the 5th day of fermentation.
Novel Oleanolic Acid-Phtalimidines Tethered 1,2,3 Triazole Hybrids as Promising Antibacterial Agents: Design, Synthesis, In Vitro Experiments and In Silico Docking Studies
Authors: Lahmadi Ghofrane , Horchani Mabrouk , Dbeibia Amal , Mahdhi Abdelkarim , Romdhane Anis , Lawson Ata Martin , Daïch Adam , Harrath Abdel Halim , Ben Jannet Hichem , Othman Mohamed
Published: June 2023

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3β-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a–u bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide 4 previously prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues, 18a–u, were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes, and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained, notably against L. monocytogenes. Compounds 18d, 18g, and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. A molecular docking study was performed to explore the binding mode of the most active derivatives into the active site of the ABC substrate-binding protein Lmo0181 from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.
Identification of Sesamin from Sesamum indicum as a Potent Antifungal Agent Using an Integrated in Silico and Biological Screening Platform
Authors: Wadhwa Khushbu , Kaur Hardeep , Kapoor Neha , Brogi Simone
Published: June 2023

Due to the limited availability of antifungal drugs, their relevant side effects and considering the insurgence of drug-resistant strains, novel antifungal agents are urgently needed. To identify such agents, we have developed an integrated computational and biological screening platform. We have considered a promising drug target in antifungal drug discovery (exo-1,3-β-glucanase) and a phytochemical library composed of bioactive natural products was used. These products were computationally screened against the selected target using molecular docking and molecular dynamics techniques along with the evaluation of drug-like profile. We selected sesamin as the most promising phytochemical endowed with a potential antifungal profile and satisfactory drug-like properties. Sesamin was submitted to a preliminary biological evaluation to test its capability to inhibit the growth of several Candida species by calculating the MIC/MFC and conducting synergistic experiments with the marketed drug fluconazole. Following the screening protocol, we identified sesamin as a potential exo-1,3-β-glucanase inhibitor, with relevant potency in inhibiting the growth of Candida species in a dose-dependent manner (MIC and MFC of 16 and 32 µg/mL, respectively). Furthermore, the combination of sesamin with fluconazole highlighted relevant synergistic effects. The described screening protocol revealed the natural product sesamin as a potential novel antifungal agent, showing an interesting predicted pharmacological profile, paving the way to the development of innovative therapeutics against fungal infections. Notably, our screening protocol can be helpful in antifungal drug discovery.
Effect of Acetylation of Two Cellulose Nanocrystal Polymorphs on Processibility and Physical Properties of Polylactide/Cellulose Nanocrystal Composite Film
Authors: Chen Tong , Li Jun , Xu Jun , Gao Yi , Zhu Shiyun , Wang Bin , Ying Guangdong
Published: June 2023

Polylactide (PLA) has become a popular alternative for petroleum-based plastics to reduce environmental pollution. The broader application of PLA is hampered by its brittle nature and incompatibility with the reinforcement phase. The aim of our work was to improve the ductility and compatibility of PLA composite film and investigate the mechanism by which nanocellulose enhances PLA polymer. Here, we present a robust PLA/nanocellulose hybrid film. Two different allomorphic cellulose nanocrystals (CNC-I and CNC-III) and their acetylated products (ACNC-I and ACNC-III) were used to realize better compatibility and mechanical performance in a hydrophobic PLA matrix. The tensile stress of the composite films with 3% ACNC-I and ACNC-III increased by 41.55% and 27.22% compared to pure PLA film, respectively. Compared to the CNC-I or CNC-III enhanced PLA composite films, the tensile stress of the films increased by 45.05% with 1% ACNC-I and 56.15% with 1% ACNC-III. In addition, PLA composite films with ACNCs showed better ductility and compatibility because the composite fracture gradually transitioned to a ductile fracture during the stretching process. As a result, ACNC-I and ACNC-III were found to be excellent reinforcing agents for the enhancement of the properties of polylactide composite film, and the replacement some petrochemical plastics with PLA composites would be very promising in actual life.
Brazil Nut (Bertholletia excelsa) Beverage Processed by High-Pressure Homogenization: Changes in Main Components and Antioxidant Capacity during Cold Storage
Authors: Vasquez-Rojas Wilson Valerio , Martín Diana , Fornari Tiziana , Cano M. Pilar
Published: June 2023

High-pressure homogenization (HPH) is an emerging technology for obtaining physical and microbial stability of plant-based milks, but there is little information on the effects of this technology on the phytochemical components of the processed plant food beverage and during its cold storage. The effect of three selected HPH treatments (180 MPa/25 °C, 150 MPa/55 °C, and 50 MPa/75 °C) and pasteurization (PAS) (63 °C, 20 min) on minor lipid constituents, total proteins, phenolic compounds, antioxidant capacity, and essential minerals of Brazil nut beverage (BNB) were studied. Additionally, the study of the possible changes in these constituents was carried out during cold storage at 5 °C for 21 days. The fatty acid profile (dominated by oleic acid and linoleic acid), free fatty acid content, protein, and essential minerals (notable source of Se and Cu) of the processed BNB remained almost stable to treatments (HPH and PAS). Specifically, reductions in squalene (22.7 to 26.4%) and γ-γ-tocopherol (28.4 to 36%) were observed in beverages processed via both non-thermal HPH and thermal PAS, but β-sitosterol remained unchanged. Total phenolics were reduced (24 to 30%) after both treatments, a factor that influenced the observed antioxidant capacity. The studied individual phenolics in BNB were gallic acid, catechin, epicatechin, catechin gallate, and ellagic acid, being the most abundant compounds. During cold storage (5 °C) up to 21 days, changes in the content of phytochemicals, minerals, and total proteins were not noticeable for any treated beverages, and no lipolysis processes were promoted. Therefore, after the application of HPH processing, Brazil nut beverage (BNB) maintained almost unaltered levels of bioactive compounds, essential minerals, total protein, and oxidative stability, remarkable characteristics for its potential development as a functional food.
Modulating the Oxygen Reduction Reaction Performance via Precisely Tuned Reactive Sites in Porphyrin-Based Covalent Organic Frameworks
Authors: Liang Xiaoqing , Zhao Zhi , Shi Ruili , Yang Liting , Zhao Bin , Qiao Huijie , Zhai Lipeng
Published: June 2023

Covalent organic frameworks (COFs) have emerged as promising electrocatalysts due to their controllable architectures, highly exposed molecular active sites, and ordered structures. In this study, a series of porphyrin-based COFs (TAPP-x-COF) with various transition metals (Co, Ni, Fe) were synthesized via a facile post-metallization strategy under solvothermal synthesis. The resulting porphyrin-based COFs showed oxygen reduction reaction (ORR) activity with a trend in Co > Fe > Ni. Among them, TAPP-Co-COF exhibited the best ORR activity (E1/2 = 0.66 V and jL = 4.82 mA cm−2) in alkaline media, which is comparable to those of Pt/C under the same conditions. Furthermore, TAPP-Co-COF was employed as a cathode in a Zn-air battery, demonstrating a high power density of 103.73 mW cm–2 and robust cycling stability. This work presents a simple method for using COFs as a smart platform to fabricate efficient electrocatalysts.
An Overview of the Use of Nanoparticles in Vaccine Development
Authors: Lozano Daniel , Larraga Vicente , Vallet-Regí María , Manzano Miguel
Published: June 2023

Vaccines represent one of the most significant advancements in public health since they prevented morbidity and mortality in millions of people every year. Conventionally, vaccine technology focused on either live attenuated or inactivated vaccines. However, the application of nanotechnology to vaccine development revolutionized the field. Nanoparticles emerged in both academia and the pharmaceutical industry as promising vectors to develop future vaccines. Regardless of the striking development of nanoparticles vaccines research and the variety of conceptually and structurally different formulations proposed, only a few of them advanced to clinical investigation and usage in the clinic so far. This review covered some of the most important developments of nanotechnology applied to vaccine technologies in the last few years, focusing on the successful race for the preparation of lipid nanoparticles employed in the successful anti-SARS-CoV-2 vaccines.
Anti-Stokes Photoluminescence in Halide Perovskite Nanocrystals: From Understanding the Mechanism towards Application in Fully Solid-State Optical Cooling
Authors: Pokryshkin Nikolay S. , Mantsevich Vladimir N. , Timoshenko Victor Y.
Published: June 2023

Anti-Stokes photoluminescence (ASPL) is an up-conversion phonon-assisted process of radiative recombination of photoexcited charge carriers when the ASPL photon energy is above the excitation one. This process can be very efficient in nanocrystals (NCs) of metalorganic and inorganic semiconductors with perovskite (Pe) crystal structure. In this review, we present an analysis of the basic mechanisms of ASPL and discuss its efficiency depending on the size distribution and surface passivation of Pe-NCs as well as the optical excitation energy and temperature. When the ASPL process is sufficiently efficient, it can result in an escape of most of the optical excitation together with the phonon energy from the Pe-NCs. It can be used in optical fully solid-state cooling or optical refrigeration.
Milkshake Acutely Stimulates Dopamine Release in Ventral and Dorsal Striatum in Healthy-Weight Individuals and Patients with Severe Obesity Undergoing Bariatric Surgery: A Pilot Study
Authors: Carnell Susan , Steele Kimberley E. , Thapaliya Gita , Kuwubara Hiroto , Aghababian Anahys , Papantoni Afroditi , Nandi Ayon , Brašić James R. , Moran Timothy H. , Wong Dean F.
Published: June 2023

The overconsumption of palatable energy-dense foods drives obesity, but few human studies have investigated dopamine (DA) release in response to the consumption of a palatable meal, a putative mediator of excess intake in obesity. We imaged [11C]raclopride in the brain with positron emission tomography (PET) to assess striatal dopamine (DA) receptor binding pre- and post-consumption of a highly palatable milkshake (250 mL, 420 kcal) in 11 females, 6 of whom had severe obesity, and 5 of whom had healthy-weight. Those with severe obesity underwent assessments pre- and 3 months post-vertical sleeve gastrectomy (VSG). Our results demonstrated decreased post- vs. pre-meal DA receptor binding in the ventral striatum (p = 0.032), posterior putamen (p = 0.012), and anterior caudate (p = 0.018), consistent with meal-stimulated DA release. Analysis of each group separately suggested that results in the caudate and putamen were disproportionately driven by meal-associated changes in the healthy-weight group. Baseline (pre-meal) DA receptor binding was lower in severe obesity than in the healthy-weight group. Baseline DA receptor binding and DA release did not change from pre- to post-surgery. The results of this small pilot study suggest that milkshake acutely stimulates DA release in the ventral and dorsal striatum. This phenomenon likely contributes to the overconsumption of highly palatable foods in the modern environment.
Associations between Dietary Patterns and Metabolic Syndrome: Findings of the Korean National Health and Nutrition Examination Survey
Authors: Lee Yun-Ah , Song Sang-Wook , Kim Se-Hong , Kim Ha-Na
Published: June 2023

Metabolic syndrome (MetS) is a multifactorial cluster of metabolic disorders related to cardiovascular disease and type 2 diabetes mellitus. Diet and dietary patterns are significant factors in the development and management of MetS. The associations between dietary patterns (i.e., high-carbohydrate [HCHO], high-fat [HF], and high-protein [HP] diets) and the prevalence of MetS in Koreans were examined using data from the Korean National Health and Nutrition Examination Survey, collected between 2018 and 2020. The study included data from 9069 participants (3777 men and 5292 women). The percentage of participants with MetS was significantly higher in the HCHO diet group than in the normal diet group in women. Women with HCHO diet were positively associated with elevated blood pressure and triglyceride levels based on a comparison with the normal diet group (p = 0.032 and p = 0.005, respectively). Men with an HF diet were negatively associated with elevated fasting glucose levels based on a comparison with the normal diet group (p = 0.014). Our findings showed that HCHO intake was strongly associated with a higher risk of MetS, especially elevated blood pressure and triglyceride levels in women, and an HF diet was negatively associated with elevated fasting glucose levels in men. Further prospective studies of the impact of dietary carbohydrate, fat, and protein proportions on metabolic health are needed. The optimal types and proportions of these dietary components, as well as the underlying mechanisms through which suboptimal proportions can lead to MetS, should also be investigated.
Breakfast Frequency and Sleep Quality in College Students: The Multiple Mediating Effects of Sleep Chronotypes and Depressive Symptoms
Authors: Xian Xiaobing , Wang Chunyuan , Yu Rong , Ye Mengliang
Published: June 2023

Sleep disorders, which are prominent problems among college students, may be associated with skipping breakfast. Therefore, we aimed to explore the role of sleep chronotypes and depressive symptoms as mediators in the relationship between breakfast frequency and sleep quality. A cross-sectional survey enrolling random samples of 712 college students was conducted by the Questionnaire Star online platform. Statistical description and correlation analysis were performed by SPSS 25.0, and a chain mediation test was performed by model 6 in PROCESS 3.5. The result of the article demonstrated that breakfast frequency can affect sleep quality through two mediating pathways: ① sleep chronotypes, with a mediating effect of 32%; and ② depressive symptoms, with a mediating effect of 52.4%. However, the chain mediating effects of sleep chronotypes and depressive symptoms was not significant, and neither was the direct effect of breakfast frequency on sleep quality. Breakfast frequency can indirectly affect sleep quality by adjusting sleep chronotypes and depressive symptoms. Regular breakfast can increase morning and intermediate sleep chronotypes, reduce depressive symptoms, and thus improve sleep quality.
Perceptions and Experiences of Supplemental Nutrition Assistance Program (SNAP) Participants Related to Receiving Food and Nutrition-Related Text Messages Sent Agency-Wide: Findings from Focus Groups in San Diego County, California
Authors: Felix Celeste , Strochlic Ron , Melendrez Blanca , Tang Hao , Wright Shana , Gosliner Wendi
Published: June 2023

We developed and sent a series of five monthly text messages promoting fruit and vegetable consumption to approximately 170,000 SNAP participants in San Diego County, California. The text messages, which were sent in English and Spanish, included links to a dedicated bilingual website offering additional information, including how to select, store, and prepare seasonal fruits and vegetables, health benefits of different fruits and vegetables, recipes, and tips to reduce food waste. To our knowledge, this represents the first instance of a SNAP agency providing nutrition information directly to SNAP participants. We conducted seven focus groups (four in English and three in Spanish) with a convenience sample of twenty-six text message recipients, to elicit their perceptions of this intervention, self-reported behavior changes, and recommendations for moving forward. Respondents reported overwhelmingly positive perceptions of this effort, including increased intake of fruits and vegetables, and trying new fruits and vegetables. Participants also reported improved perceptions of SNAP. Virtually all would like this effort to continue, and many would like to receive the messages more frequently than once a month. This effort represents a relatively low-cost approach that SNAP agencies can implement to provide SNAP participants with food and nutrition information that can help them to improve their diets, optimize their food dollars, and enhance their feelings of well-being related to participating in the program.
Erigeron annuus Extract Alleviates Insulin Resistance via Regulating the Expression of Mitochondrial Damage and Endoplasmic Reticulum Stress-Related Genes
Authors: Lee Hyo Kyu , Nam Youn Hee , Shin Sung Woo , Kim Min Cheol , An Jung In , Kim Na Woo , Shim Ji Heon , Srinath Sunitha , Hong Bin Na , Kwak Jong Hwan , Kang Tong Ho
Published: June 2023

Diabetes is a prevalent and debilitating metabolic disorder affecting a large population worldwide. The condition is characterized by insulin resistance and impaired function of pancreatic β-cells, leading to elevated blood glucose levels. In this study, the antidiabetic effects of Erigeron annuus extract (EAE) on zebrafish with damaged pancreatic islets caused by insulin resistance were investigated. The study utilized the zebrafish model to monitor live pancreatic islets. RNA sequencing was also conducted to determine the mechanism by which EAE exerts its antidiabetic effect. The results showed that EAE was effective in recovering reduced islets in excess insulin-induced zebrafish. The effective concentration at 50% (EC50) of EAE was determined to be 0.54 μg/mL, while the lethal concentration at 50% (LC50) was calculated as 202.5 μg/mL. RNA sequencing indicated that the mode of action of EAE is related to its ability to induce mitochondrial damage and suppress endoplasmic reticulum stress. The findings of this study demonstrate the efficacy and therapeutic potential of EAE in treating insulin resistance in zebrafish. The results suggest that EAE may offer a promising approach for the management of diabetes by reducing mitochondrial damage and suppressing endoplasmic reticulum stress. Further research is required to establish the clinical application of EAE in diabetic patients.
Effect of a Hop Extract Standardized in 8-Prenylnaringenin on Bone Health and Gut Microbiome in Postmenopausal Women with Osteopenia: A One-Year Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Lecomte Manon , Tomassi Diego , Rizzoli René , Tenon Mathieu , Berton Thierry , Harney Sinead , Fança-Berthon Pascale
Published: June 2023

Estrogen deficiency increases the risk of osteoporosis and fracture. The aim of this study was to investigate whether a hop extract standardized in 8-prenylnaringenin (8-PN), a potent phytoestrogen, could improve bone status of osteopenic women and to explore the gut microbiome roles in this effect. In this double-blind, placebo-controlled, randomized trial, 100 postmenopausal, osteopenic women were supplemented with calcium and vitamin D3 (CaD) tablets and either a hop extract (HE) standardized in 8-PN (n = 50) or a placebo (n = 50) for 48 weeks. Bone mineral density (BMD) and bone metabolism were assessed by DXA measurements and plasma bone biomarkers, respectively. Participant’s quality of life (SF-36), gut microbiome composition, and short-chain fatty acid (SCFA) levels were also investigated. In addition to the CaD supplements, 48 weeks of HE supplementation increased total body BMD (1.8 ± 0.4% vs. baseline, p < 0.0001; 1.0 ± 0.6% vs. placebo, p = 0.08), with a higher proportion of women experiencing an increase ≥1% compared to placebo (odds ratio: 2.41 ± 1.07, p < 0.05). An increase in the SF-36 physical functioning score was observed with HE versus placebo (p = 0.05). Gut microbiome α-diversity and SCFA levels did not differ between groups. However, a higher abundance of genera Turicibacter and Shigella was observed in the HE group; both genera have been previously identified as associated with total body BMD. These results suggest that an 8-PN standardized hop extract could beneficially impact bone health of postmenopausal women with osteopenia.
Impact of Pasta Intake on Body Weight and Body Composition: A Technical Review
Authors: Sanders Lisa M. , Slavin Joanne
Published: June 2023

Pasta is a staple carbohydrate across many cultures but has been implicated in overweight and obesity due to its position as a refined carbohydrate. Yet, the unique structure of pasta and its low glycemic response suggest it may contribute to a healthy body weight. The purpose of this review is to summarize the literature on the effects of pasta and dietary patterns high in pasta on body weight and body composition outcomes, and evaluate potential mechanisms by which pasta may influence body weight. A search of PubMed and CENTRAL identified 38 relevant studies examining pasta intake and body weight outcomes or potential mechanisms. Observational studies generally report no association or an inverse association of pasta intake with body weight/body composition outcomes. One clinical trial reported no difference in weight loss between a hypocaloric diet with high intake vs. low intake of pasta. Pasta may influence body weight via its low glycemic response, but evidence of effects on appetite, appetite-related hormones, and gastric emptying is limited and inconclusive. In conclusion, observational and limited clinical data suggest pasta is either inversely or not associated with overweight or obesity in healthy children and adults, and does not contribute to weight gain within the context of a healthy diet.
Impact of Intravenous Iron Substitution on Serum Phosphate Levels and Bone Turnover Markers—An Open-Label Pilot Study
Authors: Struppe Alexandra , Schanda Jakob E. , Baierl Andreas , Watzl Paul , Muschitz Christian
Published: June 2023

The association between intravenous iron substitution therapy and hypophosphatemia was previously reported in patients with iron deficiency anemia. However, the extent of hypophosphatemia is thought to depend on the type of iron supplementation. We hypothesized that the intravenous application of ferric carboxymaltose and iron sucrose leads to a different longitudinal adaptation in serum phosphate levels. In this open-label pilot study, a total of 20 patients with inflammatory bowel diseases or iron deficiency anemia were randomly assigned to one of two study groups (group 1: ferric carboxymaltose, n = 10; group 2: iron sucrose, n = 10). Serum values were controlled before iron substitution therapy, as well as 2, 4, and 12 weeks after the last drug administration. The primary objective of the study was the longitudinal evaluation of serum phosphate levels after iron substitution therapy with ferric carboxymaltose and iron sucrose. The secondary objective was the longitudinal investigation of calcium, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone, procollagen type 1 amino-terminal propeptide (P1NP), beta-CrossLaps (CTX), hemoglobin (Hb), iron, ferritin, and transferrin saturation levels. Two weeks after drug administration, phosphate levels were significantly lower (p < 0.001) in group 1 and ferritin levels were significantly higher (p < 0.001) in group 1. Phosphate levels (0.8–1.45 mmol/L) were below the therapeutic threshold and ferritin levels (10–200 ng/mL for women and 30–300 ng/mL for men) were above the therapeutic threshold in group 1. P1NP (15–59 µg/L) and CTX (<0.57 ng/mL) levels were above the therapeutic threshold in group 2. Four weeks after drug administration, significant differences were still observed between both study groups for phosphate (p = 0.043) and ferritin (p = 0.0009). All serum values except for Hb were within the therapeutic thresholds. Twelve weeks after drug administration, no differences were observed in all serum values between both study groups. Hb values were within the therapeutic threshold in both study groups. Serum 25(OH)D levels did not differ between both study groups throughout the whole study period and remained within the therapeutic threshold.
Maternal High-Fat Diet Controls Offspring Kidney Health and Disease
Authors: Liu Hsi-Yun , Lee Chen-Hao , Hsu Chien-Ning , Tain You-Lin
Published: June 2023

A balanced diet during gestation is critical for fetal development, and excessive intake of saturated fats during gestation and lactation is related to an increased risk of offspring kidney disease. Emerging evidence indicates that a maternal high-fat diet influences kidney health and disease of the offspring via so-called renal programming. This review summarizes preclinical research documenting the connection between a maternal high-fat diet during gestation and lactation and offspring kidney disease, as well as the molecular mechanisms behind renal programming, and early-life interventions to offset adverse programming processes. Animal models indicate that offspring kidney health can be improved via perinatal polyunsaturated fatty acid supplementation, gut microbiota changes, and modulation of nutrient-sensing signals. These findings reinforce the significance of a balanced maternal diet for the kidney health of offspring.
Healthy Diets from Sustainable Food Systems: Calculating the WISH Scores for Women in Rural East Africa
Authors: Keding Gudrun B. , Sarfo Jacob , Pawelzik Elke
Published: June 2023

Diets should be healthy for the benefits of both humans and the environment. The World Index for Sustainability and Health (WISH) was developed to assess both diets’ healthiness and environmental sustainability, and the index was applied in this study. Food intake quantities for single foods were calculated based on the data collected from four 24-h recalls during two seasons in 2019/2020 with women of reproductive age in two rural areas each in Kenya, Tanzania and Uganda (n = 1152). Single foods were grouped into 13 food groups, and the amount of each food group consumed was converted to an overall WISH score and four sub-scores. The food groups with a low WISH score were fruits, vegetables, dairy foods, fish, unsaturated oils and nuts, meaning that their consumption was outside the recommended range for a healthy and sustainable diet. Contrariwise, the intake of red meat and poultry was partly above the recommended intake for those women who consumed them. The overall WISH score and sub-scores showed that the consumption of “protective” food groups needed to increase in the study population, while the consumption of “limiting” food groups was sufficient or should decrease. For future application, we recommend dividing food groups that are critical for nutrition, e.g., vegetables, into sub-groups to further understand their contribution to this index.
Classification by Nurses’ Work Values and Their Characteristics: Latent Profile Analysis of Nurses Working in Japanese Hospitals
Authors: Hara Yukari , Hirayama Hideyuki , Takada Nozomu , Sugiyama Shoko , Yamada Masako , Takahashi Miki , Toshi Keita , Asakura Kyoko
Published: June 2023

This study aimed to classify nurses with similar work values into subgroups by examining their intrinsic, extrinsic, social, and prestige work values. Additionally, we clarified the characteristics of the obtained subgroups using personal attributes, work engagement, and life satisfaction. Using a cross-sectional observational study design, we randomly sampled 52 hospitals in the Tohoku region of Japan and conducted a self-administered questionnaire survey with 2600 nurses. Latent profile analysis was performed to identify the number of subgroups. Of the 1627 collected questionnaires, 1587 were regarded as valid. The latent profile analysis revealed the following five subgroups with strong statistical significance: (1) self-oriented, (2) low, (3) medium-low, (4) medium-high, and (5) high types. The means of work engagement and life satisfaction gradually increased from the (2) low- to (5) high-type subgroups. There were significant differences among the subgroups in terms of marital status, child status, and job title. The (5) high-type subgroup had many nurses with job titles, high work engagement, and high life satisfaction. The (2) low-type subgroup included many nurses who were young, had few years of experience, were married, had children, and had low levels of work engagement and life satisfaction. Preregistration: This study was not registered.
Roles of FcRn in Antigen-Presenting Cells during Autoimmunity and a Clinical Evaluation of Efgartigimod as an FcRn Blocker
Authors: Zhou Yihan , Jiang Shisong
Published: June 2023

The immune system is a complex network of multiple cells, tissues, and organs that protects the body against foreign pathogenic invaders. However, the immune system may mistakenly attack healthy cells and tissues due to the cross-reactivity of anti-pathogen immunity, leading to autoimmunity by autoreactive T cells and/or autoantibody-secreting B cells. Autoantibodies can accumulate, resulting in tissue or organ damage. The neonatal crystallizable fragment receptor (FcRn) is an important factor in immune regulation through controlling the trafficking and recycling of immunoglobulin G (IgG) molecules, the most abundant antibody in humoral immunity. In addition to its role in IgG trafficking and recycling, FcRn is also involved in antigen presentation, which is a crucial step in the activation of the adaptive immune response via directing the internalization and trafficking of antigen-bound IgG immune complexes into compartments of degradation and presentation in antigen-presenting cells. Efgartigimod, an FcRn inhibitor, has shown promise in reducing the levels of autoantibodies and alleviating the autoimmune severity of myasthenia gravis, primary immune thrombocytopenia, and pemphigus vulgaris/foliaceus. This article aims to provide an overview of the importance of FcRn in antigen-presenting cells and its potential as a therapeutic target in autoimmune diseases, using efgartigimod as an example.
Effectiveness of Pharmacokinetic-Guided Hydroxyurea Dose Individualization in Patients with Sickle Cell Anemia: A Mini-Review
Authors: dos Santos Neres Joelma Santana , Yahouédéhou Sètondji Cocou Modeste Alexandre , Goncalves Marilda Souza
Published: June 2023

Inconsistent therapeutic responses have been observed among patients with sickle cell anemia (SCA) undergoing hydroxyurea (HU) following the adoption of the standardized protocol. Moreover, this treatment regimen necessitates a prolonged period to reach the maximum tolerated dose in which beneficial therapeutic effects are observed in most SCA patients. To overcome this limitation, several studies have performed HU dose adjustments in SCA patients based on individualized pharmacokinetic profiles. The present systematic mini-review aims to select and analyze published data to present an overview of HU pharmacokinetics studies performed in SCA patients, as well as evaluate the effectiveness of the dose adjustment strategy. A systematic search was performed in the Embase, Pubmed, Scopus, Web of Science, Scielo, Google Scholar, and the Virtual Library of Health databases from December 2020 to August 2022, with a total of five studies included. Inclusion criteria consisted of studies in which the dose adjustment was performed in SCA patients based on pharmacokinetic parameters. Quality analyzes were performed using QAT, while data synthesis was performed according to the Cochrane Manual of Systematic Reviews of Interventions. Analysis of the selected studies revealed improved HU treatment effectiveness using personalized dosages in SCA patients. Moreover, several laboratory parameters were utilized as biomarkers of the HU response, and methods designed to simplify the adoption of this practice were presented. Despite the scarcity of studies on this topic, HU-personalized treatment based on individualized pharmacokinetic profiles represents a viable alternative for SCA patients who are candidates for HU therapy, especially for pediatric patients. Registration number: PROSPERO CRD42022344512.
Preclinical Bioavailability Assessment of a Poorly Water-Soluble Drug, HGR4113, Using a Stable Isotope Tracer
Authors: Ha Eun Ji , Seo Jeong In , Rehman Shaheed Ur , Park Hyung Soon , Yoo Sang-Ku , Yoo Hye Hyun
Published: June 2023

Drug solubility limits intravenous dosing for poorly water-soluble medicines, which misrepresents their bioavailability estimation. The current study explored a method using a stable isotope tracer to assess the bioavailability of drugs that are poorly water-soluble. HGR4113 and its deuterated analog, HGR4113-d7, were tested as model drugs. To determine the level of HGR4113 and HGR4113-d7 in rat plasma, a bioanalytical method using LC-MS/MS was developed. The HGR4113-d7 was intravenously administered to rats that were orally pre-administered HGR4113 at different doses; subsequently, the plasma samples were collected. HGR4113 and HGR4113-d7 were simultaneously determined in the plasma samples, and bioavailability was calculated using plasma drug concentration values. The bioavailability of HGR4113 was 53.3% ± 19.5%, 56.9% ± 14.0%, and 67.8% ± 16.7% after oral dosages of 40, 80, and 160 mg/kg, respectively. By eliminating the differences in clearance between intravenous and oral dosages at different levels, acquired data showed that the current method reduced measurement errors in bioavailability when compared to the conventional approach. The present study suggests a prominent method for evaluating the bioavailability of drugs with poor aqueous solubility in preclinical studies.
Next-Generation Adjuvants: Applying Engineering Methods to Create and Evaluate Novel Immunological Responses
Authors: Kim Jeremiah Y. , Rosenberger Matthew G. , Rutledge Nakisha S. , Esser-Kahn Aaron P.
Published: June 2023

Adjuvants are a critical component of vaccines. Adjuvants typically target receptors that activate innate immune signaling pathways. Historically, adjuvant development has been laborious and slow, but has begun to accelerate over the past decade. Current adjuvant development consists of screening for an activating molecule, formulating lead molecules with an antigen, and testing this combination in an animal model. There are very few adjuvants approved for use in vaccines, however, as new candidates often fail due to poor clinical efficacy, intolerable side effects, or formulation limitations. Here, we consider new approaches using tools from engineering to improve next-generation adjuvant discovery and development. These approaches will create new immunological outcomes that will be evaluated with novel diagnostic tools. Potential improved immunological outcomes include reduced vaccine reactogenicity, tunable adaptive responses, and enhanced adjuvant delivery. Evaluations of these outcomes can leverage computational approaches to interpret “big data” obtained from experimentation. Applying engineering concepts and solutions will provide alternative perspectives, further accelerating the field of adjuvant discovery.
3D Porous Scaffold-Based High-Throughput Platform for Cancer Drug Screening
Authors: Zhou Yang , Pereira Gillian , Tang Yuanzhang , James Matthew , Zhang Miqin
Published: June 2023

Natural polymer-based porous scaffolds have been investigated to serve as three-dimensional (3D) tumor models for drug screening owing to their structural properties with better resemblance to human tumor microenvironments than two-dimensional (2D) cell cultures. In this study, a 3D chitosan–hyaluronic acid (CHA) composite porous scaffold with tunable pore size (60, 120 and 180 µm) was produced by freeze-drying and fabricated into a 96-array platform for high-throughput screening (HTS) of cancer therapeutics. We adopted a self-designed rapid dispensing system to handle the highly viscous CHA polymer mixture and achieved a fast and cost-effective large-batch production of the 3D HTS platform. In addition, the adjustable pore size of the scaffold can accommodate cancer cells from different sources to better mimic the in vivo malignancy. Three human glioblastoma multiforme (GBM) cell lines were tested on the scaffolds to reveal the influence of pore size on cell growth kinetics, tumor spheroid morphology, gene expression and dose-dependent drug response. Our results showed that the three GBM cell lines showed different trends of drug resistance on CHA scaffolds of varying pore size, which reflects the intertumoral heterogeneity across patients in clinical practice. Our results also demonstrated the necessity to have a tunable 3D porous scaffold for adapting the heterogeneous tumor to generate the optimal HTS outcomes. It was also found that CHA scaffolds can produce a uniform cellular response (CV < 0.15) and a wide drug screening window (Z′ > 0.5) on par with commercialized tissue culture plates, and therefore, can serve as a qualified HTS platform. This CHA scaffold-based HTS platform may provide an improved alternative to traditional 2D-cell-based HTS for future cancer study and novel drug discovery.
Overcoming Resistance to Immune Checkpoint Inhibitor Therapy Using Calreticulin-Inducing Nanoparticle
Authors: Chandrasekar Sri Vidhya , Singh Akansha , Ranjan Ashish
Published: June 2023

Nanoparticles (NPs) have the ability to transform poorly immunogenic tumors into activated ‘hot’ targets. In this study, we investigated the potential of a liposome-based nanoparticle (CRT-NP) expressing calreticulin as an in-situ vaccine to restore sensitivity to anti-CTLA4 immune checkpoint inhibitor (ICI) in CT26 colon tumors. We found that a CRT-NP with a hydrodynamic diameter of approximately 300 nm and a zeta potential of approximately +20 mV induced immunogenic cell death (ICD) in CT-26 cells in a dose-dependent manner. In the mouse model of CT26 xenograft tumors, both CRT-NP and ICI monotherapy caused moderate reductions in tumor growth compared to the untreated control group. However, the combination therapy of CRT-NP and anti-CTLA4 ICI resulted in remarkable suppression of tumor growth rates (>70%) compared to untreated mice. This combination therapy also reshaped the tumor microenvironment (TME), achieving the increased infiltration of antigen-presenting cells (APCs) such as dendritic cells and M1 macrophages, as well as an abundance of T cells expressing granzyme B and a reduction in the population of CD4+ Foxp3 regulatory cells. Our findings indicate that CRT-NPs can effectively reverse immune resistance to anti-CTLA4 ICI therapy in mice, thereby improving the immunotherapeutic outcome in the mouse model.
Potent and Selective Benzothiazole-Based Antimitotics with Improved Water Solubility: Design, Synthesis, and Evaluation as Novel Anticancer Agents
Authors: Gallego-Yerga Laura , Ceña Valentín , Peláez Rafael
Published: June 2023

The design of colchicine site ligands on tubulin has proven to be a successful strategy to develop potent antiproliferative drugs against cancer cells. However, the structural requirements of the binding site endow the ligands with low aqueous solubility. In this work, the benzothiazole scaffold is used to design, synthesize, and evaluate a new family of colchicine site ligands exhibiting high water solubility. The compounds exerted antiproliferative activity against several human cancer cell lines, due to tubulin polymerization inhibition, showing high selectivity toward cancer cells in comparison with non-tumoral HEK-293 cells, as evidenced by MTT and LDH assays. The most potent derivatives, containing a pyridine moiety and ethylurea or formamide functionalities, displayed IC50 values in the nanomolar range even in the difficult-to-treat glioblastoma cells. Flow cytometry experiments on HeLa, MCF7, and U87MG cells showed that they arrest the cell cycle at the G2/M phases at an early time point (24 h), followed by apoptotic cell death 72 h after the treatment. Tubulin binding was confirmed by microtubule network disruption observed via confocal microscopy. Docking studies support favorable interaction of the synthesized ligands at the colchicine binding site. These results validate the proposed strategy to develop potent anticancer colchicine ligands with improved water solubility.
Pharmacist and Student Knowledge and Perceptions of Herbal Supplements and Natural Products
Authors: Stayduhar Jacey M. , Covvey Jordan R. , Schreiber James B. , Witt-Enderby Paula A.
Published: June 2023

We aimed to collect parallel perspectives from pharmacists and pharmacy students on their use, knowledge, attitudes, and perceptions about herbal supplements/natural products. Two cross-sectional descriptive survey questionnaires—one focusing on pharmacists and the other focusing on pharmacy students—were administered from March to June 2021 via Qualtrics. The surveys were sent out to preceptor pharmacists and pharmacy students currently enrolled at a single U.S. school of pharmacy. The questionnaires were composed of five main sections, including (1) demographics; (2) attitudes/perceptions; (3) educational experience; (4) resource availability; and (5) objective knowledge of herbal supplements/natural products. Data analysis primarily utilized descriptive statistics with relevant comparisons across domains. A total of 73 pharmacists and 92 pharmacy students participated, with response rates of 8.8% and 19.3%, respectively. A total of 59.2% of pharmacists and 50% of pharmacy students stated they personally used herbal supplements/natural products. Most respondents (>95% for both groups) considered vitamins/minerals safe, although a lower percentage agreed on this for herbal supplements/natural products (60% and 79.3% for pharmacists and pharmacy students, respectively). Patient inquiries in the pharmacy setting were most seen for vitamin D, zinc, cannabidiol, and omega-3. A total of 34.2% of pharmacists reported having training in herbal supplements/natural products as a required part of their Pharm.D. training, and 89.1% of pharmacy students desired to learn more. The median score on the objective knowledge quiz was 50% for pharmacists and 45% for pharmacy students. Ultimately, herbal supplements/natural products are recognized by pharmacists/pharmacy students as a consistent and embedded part of pharmacy practice, although there is a need to enhance knowledge and skills in this area.
Restoration of Atmospheric Turbulence-Degraded Short-Exposure Image Based on Convolution Neural Network
Authors: Cheng Jiuming , Zhu Wenyue , Li Jianyu , Xu Gang , Chen Xiaowei , Yao Cao
Published: June 2023

Ground-based remote observation systems are vulnerable to atmospheric turbulence, which can lead to image degradation. While some methods can mitigate this turbulence distortion, many have issues such as long processing times and unstable restoration effects. Furthermore, the physics of turbulence is often not fully integrated into the image reconstruction algorithms, making their theoretical foundations weak. In this paper, we propose a method for atmospheric turbulence mitigation using optical flow and convolutional neural networks (CNN). We first employ robust principal component analysis (RPCA) to extract a reference frame from the images. With the help of optical flow and the reference frame, the tilt can be effectively corrected. After correcting the tilt, the turbulence mitigation problem can be simplified as a deblurring problem. Then, we use a trained CNN to remove blur. By utilizing (i) a dataset that conforms to the turbulence physical model to ensure the restoration effect of the CNN and (ii) the efficient parallel computing of the CNN to reduce computation time, we can achieve better results compared to existing methods. Experimental results based on actual observed turbulence images demonstrate the effectiveness of our method. In the future, with further improvements to the algorithm and updates to GPU technology, we expect even better performance.
Multi-Level Logarithmic Amplification-Based Fixed Threshold Circular Polarized On-Off Keying Detection for Free-Space Optical Communications
Authors: Yu Pei-Zheng , Jing Qian-Wen , Hong Yan-Qing
Published: June 2023

This study investigates a multi-level logarithmic amplification (MLA)-based fixed threshold circular polarized on-off keying (CP-OOK) detection for free-space optical (FSO) communication links. OOK signal is polarized into a single circular polarization state by a linear polarizer (LP) and a quarter-wave plate (QWP). In the receiver terminal, firstly, circular polarization is transformed into linear polarization utilizing QWP without polarization coordinates alignment between transmitter and receiver. Then, the background noises are decreased by polarization filtering using LP. Then, CP-OOK signal intensity variation is eliminated by nonlinear gains from MLAs in the low gain nonlinearity condition. Finally, fixed threshold decision (FTD) is realized by optimizing cascaded LAs to reduce the extinction ratio distortion of the CP-OOK signal. The proposed CP-OOK transmission is analyzed under various strengths of turbulence channel and different configurations of MLAs. Simulation results demonstrated that the proposed CP-OOK signal was effectively detected by FTD with optimized MLAs.