bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads
Authors: Wang Yangduo , Chen Shicheng , Shi Wenzheng , Liu Shuji , Chen Xiaoting , Pan Nan , Wang Xiaoyan , Su Yongchang , Liu Zhiyu
Published: February 2024

Protein hydrolysates from sea cucumber (Apostichopus japonicus) gonads are rich in active materials with remarkable angiotensin-converting enzyme (ACE) inhibitory activity. Alcalase was used to hydrolyze sea cucumber gonads, and the hydrolysate was separated by the ultrafiltration membrane to produce a low-molecular-weight peptide component (less than 3 kDa) with good ACE inhibitory activity. The peptide component (less than 3 kDa) was isolated and purified using a combination method of ACE gel affinity chromatography and reverse high-performance liquid chromatography. The purified fractions were identified by liquid chromatography–tandem mass spectrometry (LC–MS/MS), and the resulting products were filtered using structure-based virtual screening (SBVS) to obtain 20 peptides. Of those, three noncompetitive inhibitory peptides (DDQIHIF with an IC50 value of 333.5 μmol·L−1, HDWWKER with an IC50 value of 583.6 μmol·L−1, and THDWWKER with an IC50 value of 1291.8 μmol·L−1) were further investigated based on their favorable pharmacochemical properties and ACE inhibitory activity. Molecular docking studies indicated that the three peptides were entirely enclosed within the ACE protein cavity, improving the overall stability of the complex through interaction forces with the ACE active site. The total free binding energies (ΔGtotal) for DDQIHIF, HDWWKER, and THDWWKER were −21.9 Kcal·mol−1, −71.6 Kcal·mol−1, and −69.1 Kcal·mol−1, respectively. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that HDWWKER could significantly decrease the systolic blood pressure (SBP) of SHRs after intravenous administration. The results showed that based on the better antihypertensive activity of the peptide in SHRs, the feasibility of targeted affinity purification and computer-aided drug discovery (CADD) for the efficient screening and preparation of ACE inhibitory peptide was verified, which provided a new idea of modern drug development method for clinical use.
Correction: Tamadon et al. Development of Metallographic Etchants for the Microstructure Evolution of A6082-T6 BFSW Welds. Metals 2017, 7, 423
Authors: Tamadon Abbas , Pons Dirk J. , Sued Kamil , Clucas Don
Published: February 2024

In the original publication [...]
Urinary Metabolomic Differentiation of Infants Fed on Human Breastmilk and Formulated Milk
Authors: Yu Ji-Woo , Song Min-Ho , Lee Ji-Ho , Song Jun-Hwan , Hahn Won-Ho , Keum Young-Soo , Kang Nam Mi
Published: February 2024

Human breastmilk is an invaluable nutritional and pharmacological resource with a highly diverse metabolite profile, which can directly affect the metabolism of infants. Application of metabolomics can discriminate the complex relationship between such nutrients and infant health. As the most common biological fluid in metabolomic study, infant urinary metabolomics may provide the physiological impacts of different nutritional resources, namely human breastmilk and formulated milk. In this study, we aimed to identify possible differences in the urine metabolome of 30 infants (1–14 days after birth) fed with breast milk (n = 15) or formulated milk (n = 15). From metabolomic analysis with gas chromatography-mass spectrometry, 163 metabolites from single mass spectrometry (GC-MS), and 383 metabolites from tandem mass spectrometry (GC-MS/MS) were confirmed in urinary samples. Various multivariate statistical analysis were performed to discriminate the differences originating from physiological/nutritional variables, including human breastmilk/formulate milk feeding, sex, and duration of feeding. Both unsupervised and supervised discriminant analyses indicated that feeding resources (human breastmilk/formulated milk) gave marginal but significant differences in urinary metabolomes, while other factors (sex, duration of feeding) did not show notable discrimination between groups. According to the biomarker analyses, several organic acid and amino acids showed statistically significant differences between different feeding resources, such as 2-hydroxyhippurate.
Reduced Pseudomonas aeruginosa Cell Size Observed on Planktonic Cultures Grown in the International Space Station
Authors: Herrera-Jordan Katherinne , Pennington Pamela , Zea Luis
Published: February 2024

Bacterial growth and behavior have been studied in microgravity in the past, but little focus has been directed to cell size despite its impact on a myriad of processes, including biofilm formation, which is impactful regarding crew health. To interrogate this characteristic, supernatant aliquots of P. aeruginosa cultured on different materials and media on board the International Space Station (ISS) as part of the Space Biofilms Project were analyzed. For that experiment, P. aeruginosa was grown in microgravity—with matching Earth controls—in modified artificial urine medium (mAUMg-high Pi) or LB Lennox supplemented with KNO3, and its formation of biofilms on six different materials was assessed. After one, two, and three days of incubation, the ISS crew terminated subsets of the experiment by fixation in paraformaldehyde, and aliquots of the supernatant were used for the planktonic cell size study presented here. The measurements were obtained post-flight through the use of phase contrast microscopy under oil immersion, a Moticam 10+ digital camera, and the FIJI image analysis program. Statistical comparisons were conducted to identify which treatments caused significant differences in cell dimensions using the Kruskal–Wallis and Dunn tests. There were statistically significant differences as a function of material present in the culture in both LBK and mAUMg-high Pi. Along with this, the data were also grouped by gravitational condition, media, and days of incubation. Comparison of planktonic cells cultured in microgravity showed reduced cell length (from 4% to 10% depending on the material) and diameter (from 1% to 10% depending on the material) with respect to their matching Earth controls, with the caveat that the cultures may have been at different points in their growth curve at a given time. In conclusion, smaller cells were observed on the cultures grown in microgravity, and cell size changed as a function of incubation time and the material upon which the culture grew. We describe these changes here and possible implications for human space travel in terms of crew health and potential applications.
Mold Odor from Wood Treated with Chlorophenols despite Mold Growth That Can Only Be Seen Using a Microscope
Authors: Lorentzen Johnny C. , Ekberg Olle , Alm Maria , Björk Folke , Harderup Lars-Erik , Johanson Gunnar
Published: February 2024

We previously reported that indoor odorous chloroanisoles (CAs) are still being emitted due to microbial methylation of hazardous chlorophenols (CPs) present in legacy wood preservatives. Meanwhile, Swedish researchers reported that this malodor, described since the early 1970s, is caused by hazardous mold. Here, we examined to what extent CP-treated wood contains mold and if mold correlates with perceived odor. We found no studies in PubMed or Web of Science addressing this question. Further, we investigated two schools built in the 1960s with odor originating from crawlspaces. No visible mold was evident in the crawlspaces or on the surfaces of treated wood samples. Using a microscope, varying amounts of mold growth were detected on the samples, all containing both CP(s) and CA(s). Some samples smelled, and the odor correlated with the amount of mold growth. We conclude that superficial microscopic mold on treated wood suffices produced the odor. Further, we argue that CPs rather than mold could explain the health effects reported in epidemiological studies that use mold odor as an indicator of hazardous exposure.
Machine Learning-Based Lithological Mapping from ASTER Remote-Sensing Imagery
Authors: Bahrami Hazhir , Esmaeili Pouya , Homayouni Saeid , Pour Amin Beiranvand , Chokmani Karem , Bahroudi Abbas
Published: February 2024

Accurately mapping lithological features is essential for geological surveys and the exploration of mineral resources. Remote-sensing images have been widely used to extract information about mineralized alteration zones due to their cost-effectiveness and potential for being widely applied. Automated methods, such as machine-learning algorithms, for lithological mapping using satellite imagery have also received attention. This study aims to map lithologies and minerals indirectly through machine-learning algorithms using advanced spaceborne thermal emission and reflection radiometer (ASTER) remote-sensing data. The capabilities of several machine-learning (ML) algorithms were evaluated for lithological mapping, including random forest (RF), support vector machine (SVM), gradient boosting (GB), extreme gradient boosting (XGB), and a deep-learning artificial neural network (ANN). These methods were applied to ASTER imagery of the Sar-Cheshmeh copper mining region of Kerman Province, in southern Iran. First, several spectral features that were extracted from ASTER bands were used as input data. Second, correlation coefficients between the original spectral bands and features were extracted. The importance of the random forest features (RF’s feature importance) was subsequently computed, and features with less importance were removed. Finally, the remained features were given to the models as input data in the second scenario. Accuracy assessments were performed for lithological classes in the study region, including Sar-Cheshmeh porphyry, quartz eye, late fine porphyry, hornblende dike, granodiorite, feldspar dike, biotite dike, andesite, and alluvium. The overall accuracy results of lithological mapping showed that ML-based algorithms without feature extraction have the highest accuracy. The overall accuracy percentages for ML-based algorithms without conducting feature extraction were 84%, 85%, 80%, 82%, and 80% for RF, SVM, GB, XGB, and ANN, respectively. The results of this study would be of great interest to geologists for lithological mapping and mineral exploration, particularly for selecting appropriate ML-based techniques to be implemented in similar regions.
Chemically Oscillating Reactions as a New Model for the Formation of Mineral Patterns in Agate Geodes and Concretions
Authors: Papineau Dominic
Published: February 2024

Agate geodes contain spheroidal patterns characterized by spectacularly coloured and circularly concentric laminations with radially aligned quartz crystals, yet the origin of these geometric patterns has remained enigmatic. Here, detailed comparisons are documented between these kinds of patterns in a selection of geodes and concretions and those produced by abiotic chemically oscillating reactions. We find strikingly comparable self-similar, fractal patterns in both natural volcanogenic geodes and sedimentary concretions as well as in these benchtop experiments. In addition, the mineralogical composition of patterns and associated organic matter point to the oxidation of organic compounds in both geodes and concretions. This process occurred during diagenetic or supergene alteration, and it is consistent with spontaneous and abiotic chemically oscillating reactions. It is concluded that the oxidation of organic acids was involved in the formation of these patterns and that these rocks indicate oxidation–reduction reactions involving organic carbon, which itself may be abiotic or biological in origin. Hence, agate geodes and concretions represent the abiotic biosignatures of possible biological origin in volcanic and sedimentary rocks.
A New Potent Inhibitor against α-Glucosidase Based on an In Vitro Enzymatic Synthesis Approach
Authors: Zhang Huanyu , Che Xiance , Jing Hongyan , Su Yaowu , Yang Wenqi , Wang Rubing , Zhang Guoqi , Meng Jie , Yuan Wei , Wang Juan , Gao Wenyuan
Published: February 2024

Inhibiting the activity of intestinal α-glucosidase is considered an effective approach for treating type II diabetes mellitus (T2DM). In this study, we employed an in vitro enzymatic synthesis approach to synthesize four derivatives of natural products (NPs) for the discovery of therapeutic drugs for T2DM. Network pharmacology analysis revealed that the betulinic acid derivative P3 exerted its effects in the treatment of T2DM through multiple targets. Neuroactive ligand–receptor interaction and the calcium signaling pathway were identified as key signaling pathways involved in the therapeutic action of compound P3 in T2DM. The results of molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations indicate that compound P3 exhibits a more stable binding interaction and lower binding energy (−41.237 kcal/mol) with α-glucosidase compared to acarbose. In addition, compound P3 demonstrates excellent characteristics in various pharmacokinetic prediction models. Therefore, P3 holds promise as a lead compound for the development of drugs for T2DM and warrants further exploration. Finally, we performed site-directed mutagenesis to achieve targeted synthesis of betulinic acid derivative. This work demonstrates a practical strategy of discovering novel anti-hyperglycemic drugs from derivatives of NPs synthesized through in vitro enzymatic synthesis technology, providing potential insights into compound P3 as a lead compound for anti-hyperglycemic drug development.
Enhanced Electrocatalytic Oxygen Reduction Reaction of TiO2 Nanotubes by Combining Surface Oxygen Vacancy Engineering and Zr Doping
Authors: Shaddad Maged N. , Arunachalam Prabhakarn , Hezam Mahmoud S. , Aladeemy Saba A. , Aljaafreh Mamduh J. , Abu Alrub Sharif , Al-Mayouf Abdullah M.
Published: February 2024

This work examines the cooperative effect between Zr doping and oxygen vacancy engineering in anodized TiO2 nanotubes (TNTs) for enhanced oxygen reduction reactions (ORRs). Zr dopant and annealing conditions significantly affected the electrocatalytic characteristics of grown TNTs. Zr doping results in Zr4+ substituted for Ti4+ species, which indirectly creates oxygen vacancy donors that enhance charge transfer kinetics and reduce carrier recombination in TNT bulk. Moreover, oxygen vacancies promote the creation of unsaturated Ti3+(Zr3+) sites at the surface, which also boosts the ORR interfacial process. Annealing at reductive atmospheres (e.g., H2, vacuum) resulted in a larger increase in oxygen vacancies, which greatly enhanced the ORR activity. In comparison to bare TNTs, Zr doping and vacuum treatment (Zr:TNT–Vac) significantly improved the conductivity and activity of ORRs in alkaline media. The finding also provides selective hydrogen peroxide production by the electrochemical reduction of oxygen.
A Waveguide Inline Binary Metasurface for Wavelength-Selective Transmission and Standing Wave Focusing
Authors: Cho Chun-Hyung , Kim Hyuntai
Published: February 2024

This study presents an innovative inline metasurface design for selective wavelength transmission and focusing. When integrated into optical fibers, it improves the stability and compatibility with techniques like wavelength division multiplexing and phase modulation. Precise parameters, determined through analytical calculations and simulations, allow for the design of multifunctional lenses within the optical fiber platform. The numerical results demonstrate unmodulated transmission for specific wavelengths, while others exhibit standing wave focusing with a 0.67 μm beam radius and a 0.31 μm depth of focus. This technology holds promise for applications in quantum experiments, sensing, and optical communication.
Resveratrol/Selenium Nanocomposite with Antioxidative and Antibacterial Properties
Authors: Tomić Nina , Stevanović Magdalena M. , Filipović Nenad , Ganić Tea , Nikolić Biljana , Gajić Ina , Ćulafić Dragana Mitić
Published: February 2024

In this work, we synthesized a new composite material comprised of previously formulated resveratrol nanobelt-like particles (ResNPs) and selenium nanoparticles (SeNPs), namely ResSeNPs. Characterization was provided by FESEM and optical microscopy, as well as by UV-Vis and FTIR spectroscopy, the last showing hydrogen bonds between ResNPs and SeNPs. DPPH, TBA, and FRAP assays showed excellent antioxidative abilities with ResNPs and SeNPs contributing mainly to lipid peroxidation inhibition and reducing/scavenging activity, respectively. The antibacterial effect against common medicinal implant colonizers pointed to notably higher activity against Staphylococcus isolates (minimal inhibitory concentrations 0.75–1.5%) compared to tested gram-negative species (Escherichia coli and Pseudomonas aeruginosa). Antibiofilm activity against S. aureus, S. epidermidis, and P. aeruginosa determined in a crystal violet assay was promising (up to 69%), but monitoring of selected biofilm-related gene expression (pelA and algD) indicated the necessity of the involvement of a larger number of genes in the analysis in order to further establish the underlying mechanism. Although biocompatibility screening showed some cytotoxicity and genotoxicity in MTT and alkaline comet assays, respectively, it is important to note that active antioxidative and antibacterial/antibiofilm concentrations were non-cytotoxic and non-genotoxic in normal MRC-5 cells. These results encourage further composite improvements and investigation in order to adapt it for specific biomedical purposes.
Bulbils of Aerial Yam Attenuate Ethanol-Induced Hepatotoxicity in HepG2 Cells through Inhibition of Oxidative Stress by Activation of the Nuclear Factor Erythroid-2-Related Factor 2 Signaling Pathway
Authors: Yang Dong Kwon , Tungalag Tsendsuren , Kang Hyung-Sub
Published: February 2024

Bulbil of yam (BY) extract contains various active compounds possessing many pharmacological properties. However, little is known about the effect and underlying mechanism of BY extract on ethanol-induced liver damage. The present study explored the beneficial potential of BY extract on ethanol-induced hepatotoxicity. To evaluate its effectiveness, ethanol-induced HepG2 liver cells were pretreated with BY extract. BY extract effectively rescued cells from ethanol treatment through inhibition of apoptotic cell death as well as inhibiting expression of mitogen-activated protein kinase (MAPK) proteins as stress inducers. BY extract increased the expression of typical antioxidants. Furthermore, BY extract significantly inhibited mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which are major ROS-inducing factors. Finally, as an underlying mechanism of the protective effects of BY extract on ethanol-induced liver damage, it activated Nrf2 protein through translocation from the cytosol to the nucleus, which in turn activated its target oxidative stress suppressor genes. Collectively, our findings demonstrate that BY extract has potential antioxidative effects in ethanol-induced liver cells and contributes to the establishment of a treatment strategy for alcohol-derived liver injuries.
Combined Influence of Eight Lifestyle Factors on Metabolic Syndrome Incidence: A Prospective Cohort Study from the MECH-HK Study
Authors: Deng Yun-Yang , Ngai Fei-Wan , Qin Jing , Yang Lin , Wong Ka-Po , Wang Harry-Haoxiang , Xie Yao-Jie
Published: February 2024

Although previous studies have shown significant associations between individual lifestyles and metabolic syndrome, limited studies have explored the combined effect of lifestyles. The purpose of this study was to investigate whether a combined lifestyle score was associated with metabolic syndrome incidence in Hong Kong Chinese women. This prospective cohort study included 1634 women (55.9 ± 8.6 years) without baseline metabolic syndrome, diabetes, myocardial infarction, or stroke. Eight lifestyle factors (smoking, physical activity, sedentary time, sleep, stress, fatigue, diet, and alcohol) were included by assigning 0 (unhealthy) or 1 point (healthy). The overall score was the sum of these points, ranging from 0 (the least healthy) to 8 points (the healthiest). Metabolic syndrome was diagnosed by the joint interim statement. During a 1.16-year follow-up, 179 (11.0%) new metabolic syndrome cases were identified. The incidences for the 0–3-point, 4-point, 5-point, and 6–8-point groups were 12.8% (79/618), 11.5% (42/366), 9.4% (29/309), and 8.5% (29/341), respectively. Compared to the lowest combined lifestyle score group, the highest group had a 47% reduced metabolic syndrome incidence, with an adjusted odds ratio and 95% confidence interval of 0.53 (0.33–0.86) (p = 0.010). These findings indicate that a higher combined lifestyle score was associated with a lower metabolic syndrome incidence in this population.
Sex-Specific Association between Sodium Intake Estimated by 24-Hour Urinary Sodium Excretion and Nonalcoholic Fatty Liver Disease: The Community-Based Prospective Cohort Study
Authors: Lee Jihye , Lee Ju-Yeon , Yang Yun-Jung
Published: February 2024

Evidence for the association between high sodium intake and the onset of nonalcoholic fatty liver disease (NAFLD) is insufficient. This study examined the sex-specific association between sodium intake and the risk of NAFLD. This study included 2582 adults (aged 40–69 years; 1011 males and 1571 females). The total sodium excreted over 24 h was estimated from spot urine specimens using Tanaka’s equation. Based on these estimates, participants were categorized into three groups according to their 24-h urinary sodium excretion levels: lowest (T1), middle (T2), and highest (T3). In addition, the participants were divided into non-NAFLD (≤36) and NAFLD (>36) groups based on the hepatic steatosis index. During the follow-up period (14 years), NAFLD was observed in 551 participants. The estimated 24-h urinary sodium excretion levels were positively associated with the incidence of NAFLD in all subjects. Upon sex stratification, females in the T2 and T3 groups exhibited adjusted hazard ratios of 1.35 and 1.51, respectively, compared with the T1 group. However, a significant relationship was not observed in males. High intake of sodium, especially among females, may be an important factor contributing to the development of NAFLD. Individuals with high sodium intake should be appropriately counselled and monitored for the risk of NAFLD.
Between Dysbiosis, Maternal Immune Activation and Autism: Is There a Common Pathway?
Authors: Suprunowicz Maria , Tomaszek Natalia , Urbaniak Agata , Zackiewicz Klaudia , Modzelewski Stefan , Waszkiewicz Napoleon
Published: February 2024

Autism spectrum disorder (ASD) is a neuropsychiatric condition characterized by impaired social interactions and repetitive stereotyped behaviors. Growing evidence highlights an important role of the gut–brain–microbiome axis in the pathogenesis of ASD. Research indicates an abnormal composition of the gut microbiome and the potential involvement of bacterial molecules in neuroinflammation and brain development disruptions. Concurrently, attention is directed towards the role of short-chain fatty acids (SCFAs) and impaired intestinal tightness. This comprehensive review emphasizes the potential impact of maternal gut microbiota changes on the development of autism in children, especially considering maternal immune activation (MIA). The following paper evaluates the impact of the birth route on the colonization of the child with bacteria in the first weeks of life. Furthermore, it explores the role of pro-inflammatory cytokines, such as IL-6 and IL-17a and mother’s obesity as potentially environmental factors of ASD. The purpose of this review is to advance our understanding of ASD pathogenesis, while also searching for the positive implications of the latest therapies, such as probiotics, prebiotics or fecal microbiota transplantation, targeting the gut microbiota and reducing inflammation. This review aims to provide valuable insights that could instruct future studies and treatments for individuals affected by ASD.
Unveiling the Immunomodulatory Potential of Phenolic Compounds in Food Allergies
Authors: Simões Rodolfo , Ribeiro Ana Catarina , Dias Ricardo , Freitas Victor , Soares Susana , Pérez-Gregorio Rosa
Published: February 2024

Food allergies are becoming ever more prevalent around the world. This pathology is characterized by the breakdown of oral tolerance to ingested food allergens, resulting in allergic reactions in subsequent exposures. Due to the possible severity of the symptoms associated with this pathology, new approaches to prevent it and reduce associated symptoms are of utmost importance. In this framework, dietary phenolic compounds appear as a tool with a not fully explored potential. Some phenolic compounds have been pointed to with the ability to modulate food allergies and possibly reduce their symptoms. These compounds can modulate food allergies through many different mechanisms, such as altering the bioaccessibility and bioavailability of potentially immunogenic peptides, by modulating the human immune system and by modulating the composition of the human microbiome that resides in the oral cavity and the gastrointestinal tract. This review deepens the state-of-the-art of the modulation of these mechanisms by phenolic compounds. While this review shows clear evidence that dietary supplementation with foods rich in phenolic compounds might constitute a new approach to the management of food allergies, it also highlights the need for further research to delve into the mechanisms of action of these compounds and decipher systematic structure/activity relationships.
A Child with Crohn’s Disease: Problems and Stress Level of Parents–Caregivers—A Cross-Sectional Study
Authors: Pasek Małgorzata , Stoietskyi Monika , Goździalska Anna , Jochymek Małgorzata
Published: February 2024

Crohn’s disease (CD) is a chronic inflammatory bowel disease. The perception of the disease, its troublesome symptoms and the highly involved treatment mean that living with CD requires not only the affected child having to learn to cope with it, but also their parents. The aim of the study was to examine the problems and levels of stress in parents–caregivers of children with CD. The study was cross-sectional and conducted using the diagnostic survey method. An original questionnaire was used to assess the socio-demographic situation and problems of caring for a child with CD, and the standardised PSS-10 questionnaire was added. The study group consisted of 60 parents who accompanied their children during hospitalization. The surveyed caregivers of children with CD found it difficult to maintain a specialised diet and deal with the need for hospitalization and the chronic use of medications. Access to the necessary knowledge about the disease posed the least difficulty in everyday life for a child with CD. The vast majority of parents (50, 83.34%) felt a high level of stress related to caring for a child with CD and, simultaneously, a lack of acceptance of the child’s disease (39, 65%). The age of the respondents did not have a statistically significant effect on the occurrence of problems related to everyday functioning. The acceptance of the child’s disease by the parents and informal caregivers of children with CD reduced their stress level. Parents could count on support from their relatives but, unfortunately, institutional support was not properly provided.
Innovative Approach to Producing Palladium-103 for Auger-Emitting Radionuclide Therapy: A Proof-of-Concept Study
Authors: Laouameria Aicha Nour , Hunyadi Mátyás , Csík Attila , Szűcs Zoltán
Published: February 2024

Auger-emitting radionuclides, exemplified by Pd-103, exhibit considerable therapeutic potential in cancer treatment due to their high cytotoxicity and localized biological impact. Despite these advantages, the separation of such radionuclides presents a complicated challenge, requiring intricate and time-intensive “wet chemistry” methods attributed to the exceptional chemical inertness of the associated metals. This study proposes an innovative solution to this separation challenge through the design and implementation of a piece of radionuclide separation equipment (RSE). The equipment employs a dry distillation approach, capitalizing on differences in partial vapor pressures between irradiated and resulting radioactive metals, with a diffusion-driven extraction method applied to separate Pd-103 radionuclides generated via the proton irradiation of Rh-103 at cyclotron. Our optimization endeavors focused on determining the optimal temperature for effective metal separation and adjusting the diffusion, evaporation, and deposition rates, as well as addressing chemical impurities. The calculations indicate 17% ± 2% separation efficiency with our RSE. Approximately 77 ± 2% and 49 ± 2% of the deposited Pd-103 were isolated on substrates of Nb foil and ZnO-covered W disc, respectively. The proposed innovative dry distillation method that has been experimentally tested offers a promising alternative to conventional separation techniques, enabling enhanced purity and cost-efficient cancer treatment strategies.
Decreased Brain Serotonin in rbfox1 Mutant Zebrafish and Partial Reversion of Behavioural Alterations by the SSRI Fluoxetine
Authors: Adel Maja R. , Antón-Galindo Ester , Gago-Garcia Edurne , Arias-Dimas Angela , Arenas Concepció , Artuch Rafael , Cormand Bru , Fernàndez-Castillo Noèlia
Published: February 2024

RBFOX1 functions as a master regulator of thousands of genes, exerting a pleiotropic effect on numerous neurodevelopmental and psychiatric disorders. A potential mechanism by which RBFOX1 may impact these disorders is through its modulation of serotonergic neurotransmission, a common target for pharmacological intervention in psychiatric conditions linked to RBFOX1. However, the precise effects of RBFOX1 on the serotonergic system remain largely unexplored. Here we show that homozygous rbfox1sa15940 zebrafish, which express a shorter, aberrant rbfox1 mRNA, have significantly reduced serotonin levels in telencephalon and diencephalon. We observed that the acute administration of fluoxetine partially reverses the associated behavioural alterations. The hyperactive phenotype and altered shoaling behaviour of the rbfox1sa15940/sa15940 zebrafish could be reversed with acute fluoxetine exposure in the Open Field and the Shoaling test, respectively. However, in the other paradigms, hyperactivity was not diminished, suggesting a distinct intrinsic motivation for locomotion in the different paradigms. Acute fluoxetine exposure did not reverse the alterations observed in the aggression and social novelty tests, suggesting the involvement of other neurological mechanisms in these behaviours. These findings underscore the importance of investigating the intricate working mechanisms of RBFOX1 in neurodevelopmental and psychiatric disorders to gain a better understanding of the associated disorders along with their pharmacological treatment.
Anti-Bacterial Activity of Green Synthesised Silver and Zinc Oxide Nanoparticles against Propionibacterium acnes
Authors: Al-Momani Hafez , Massadeh Muhannad I. , Almasri Muna , Al Balawi Dua’a , Aolymat Iman , Hamed Saja , Albiss Borhan Aldeen , Ibrahim Lugain , Balawi Hadeel Al , Al Haj Mahmoud Sameer
Published: February 2024

Propionibacterium acnes plays a critical role in the development of acne vulgaris. There has been a rise in the number of patients carrying P. acnes strains that are resistant to antibiotics. Thus, alternative anti-microbial agents are required. Zinc oxide (ZnO-NPs) and silver (Ag-NPs) nanoparticles can be used against several antibiotic-resistant bacteria. The impact of Ag-NPs and ZnO-NPs against two clinical strains of P. acnes, P1 and P2, and a reference strain, NCTC747, were investigated in this research. A chemical approach for the green synthesis of Ag-NPs and ZnO-NPs from Peganum harmala was employed. The microtiter plate method was used to examine the effects of NPs on bacterial growth, biofilm development, and biofilm eradication. A broth microdilution process was performed in order to determine minimal inhibitory (MIC) concentrations. Ag-NPs and ZnO-NPs had a spherical shape and average dimensions of 10 and 50 nm, respectively. MIC values for all P. acnes strains for Ag-NPs and ZnO-NPs were 125 µg/mL and 250 µg/mL, respectively. Ag-NP and ZnO-NP concentrations of 3.9- 62.5 µg/mL and 15–62.5 µg/mL significantly inhibited the growth and biofilm formation of all P. acnes strains, respectively. ZnO-NP concentrations of 15–62.5 μg/mL significantly inhibited the growth of NCTC747 and P2 strains. The growth of P1 was impacted by concentrations of 31.25 μg/mL and 62.5 μg/mL. Biofilm formation in the NCTC747 strain was diminished by a ZnO-NP concentration of 15 μg/mL. The clinical strains of P. acnes were only affected by ZnO-NP titres of more than 31.25 μg/mL. Established P. acne biofilm biomass was significantly reduced in all strains at a Ag-NP and ZnO-NP concentration of 62.5 µg/mL. The findings demonstrated that Ag-NPs and ZnO-NPs exert an anti-bacterial effect against P. acnes. Further research is required to determine their potential utility as a treatment option for acne.
Towards the Magic Radioactive Bullet: Improving Targeted Radionuclide Therapy by Reducing the Renal Retention of Radioligands
Authors: de Roode Kim E. , Joosten Lieke , Behe Martin
Published: February 2024

Targeted radionuclide therapy (TRT) is an emerging field and has the potential to become a major pillar in effective cancer treatment. Several pharmaceuticals are already in routine use for treating cancer, and there is still a high potential for new compounds for this application. But, a major issue for many radiolabeled low-to-moderate-molecular-weight molecules is their clearance via the kidneys and their subsequent reuptake. High renal accumulation of radioactive compounds may lead to nephrotoxicity, and therefore, the kidneys are often the dose-limiting organs in TRT with these radioligands. Over the years, different strategies have been developed aiming for reduced kidney retention and enhanced therapeutic efficacy of radioligands. In this review, we will give an overview of the efforts and achievements of the used strategies, with focus on the therapeutic potential of low-to-moderate-molecular-weight molecules. Among the strategies discussed here is coadministration of compounds that compete for binding to the endocytic receptors in the proximal tubuli. In addition, the influence of altering the molecular design of radiolabeled ligands on pharmacokinetics is discussed, which includes changes in their physicochemical properties and implementation of cleavable linkers or albumin-binding moieties. Furthermore, we discuss the influence of chelator and radionuclide choice on reabsorption of radioligands by the kidneys.
Chitosan and Anionic Solubility Enhancer Sulfobutylether-β-Cyclodextrin-Based Nanoparticles as Dexamethasone Ophthalmic Delivery System for Anti-Inflammatory Therapy
Authors: Racaniello Giuseppe Francesco , Balenzano Gennaro , Arduino Ilaria , Iacobazzi Rosa Maria , Lopalco Antonio , Lopedota Angela Assunta , Sigurdsson Hakon Hrafn , Denora Nunzio
Published: February 2024

Cataract surgery interventions are constantly increasing, particularly among adult and elderly patients. This type of surgery can lead to inflammatory states of the ocular anterior segment (AS), usually healed via postoperative treatment with dexamethasone (DEX)-containing eye drops. The application of eye drops is challenging due to the high number of daily administrations. In this study, mucoadhesive nanoparticles (NPs) were formulated to improve the residence time of DEX on the corneal mucosa, enhancing the drug’s solubility and bioavailability. The NPs were generated using an ionotropic gelation technique, exploiting the interaction between the cationic group of chitosan (CS) and the anionic group of sulfobutylether-β-cyclodextrin (SBE-β-CD). The formation of the inclusion complex and its stoichiometry were studied through phase solubility studies, Job’s plot method, and Bi-directional transport studies on MDCKII-MDR1. The obtained NPs showed good chemical and physical characteristics suitable for drug loading and subsequent testing on animal mucosa. The DEX-loaded CS/SBE-β-CD NPs exhibited a prolonged residence time on animal mucosa and demonstrated enhanced drug permeability through the corneal membrane, showing a sustained release profile. The developed NPs posed no irritation or toxicity concerns upon local administration, making them an optimal and innovative drug delivery system for inflammatory AS diseases treatment.
Oxaliplatin(IV) Prodrugs Functionalized with Gemcitabine and Capecitabine Induce Blockage of Colorectal Cancer Cell Growth—An Investigation of the Activation Mechanism and Their Nanoformulation
Authors: Marotta Carlo , Cirri Damiano , Kanavos Ioannis , Ronga Luisa , Lobinski Ryszard , Funaioli Tiziana , Giacomelli Chiara , Barresi Elisabetta , Trincavelli Maria Letizia , Marzo Tiziano , Pratesi Alessandro
Published: February 2024

The use of platinum-based anticancer drugs, such as cisplatin, oxaliplatin, and carboplatin, is a common frontline option in cancer management, but they have debilitating side effects and can lead to drug resistance. Combination therapy with other chemotherapeutic agents, such as capecitabine and gemcitabine, has been explored. One approach to overcome these limitations is the modification of traditional Pt(II) drugs to obtain new molecules with an improved pharmacological profile, such as Pt(IV) prodrugs. The design, synthesis, and characterization of two novel Pt(IV) prodrugs based on oxaliplatin bearing the anticancer drugs gemcitabine or capecitabine in the axial positions have been reported. These complexes were able to dissociate into their constituents to promote cell death and induce apoptosis and cell cycle blockade in a representative colorectal cancer cell model. Specifically, the complex bearing gemcitabine resulted in being the most active on the HCT116 colorectal cancer cell line with an IC50 value of 0.49 ± 0.04. A pilot study on the encapsulation of these complexes in biocompatible PLGA-PEG nanoparticles is also included to confirm the retention of the pharmacological properties and cellular drug uptake, opening up to the possible delivery of the studied complexes through their nanoformulation.
Imiquimod Solubility in Different Solvents: An Interpretative Approach
Authors: Sorgi Daisy , Sartori Andrea , Germani Saveria , Gentile Rosita Nicolella , Bianchera Annalisa , Bettini Ruggero
Published: February 2024

Imiquimod (IMQ) has been successfully formulated to date mainly as semi-solid lipophilic formulations for topical application. In this study, we investigated the solubility of IMQ in solvents suitable for developing innovative formulations in the form of powder obtained, for instance, by spray drying; thus, water, ethanol, methanol, acetone, acetonitrile, and dimethyl sulfoxide were tested at different temperatures. Temperature variations, stirring intensity, and the contact time between IMQ and the solvent greatly affected the evaluation of IMQ equilibrium solubility. The attainment of the solid–liquid equilibrium requires 13 days starting from solid IMQ and 2 days from a cooled-down supersaturated IMQ solution. A correlation between IMQ solubility and the solubility parameters of solvents was not found. IMQ solutions in water, ethanol, methanol, acetonitrile, and dimethyl sulfoxide were neither ideal nor regular. The Scatchard–Hildebrand equation does not apply to IMQ solutions because of association phenomena due to intermolecular hydrogen bonds and/or π-stacking, as supported by the hyperchromic effect that was very pronounced in highly polar solvents, such as water, with the increase in temperature. Finally, IMQ solubility values measured in acetone cannot be considered reliable due to the reaction with the solvent, leading to the formation of new molecules.
The Rise of Particulars: AI and the Ethics of Care
Authors: Weinberger David
Published: February 2024

Machine learning (ML) trains itself by discovering patterns of correlations that can be applied to new inputs. That is a very powerful form of generalization, but it is also very different from the sort of generalization that the west has valorized as the highest form of truth, such as universal laws in some of the sciences, or ethical principles and frameworks in moral reasoning. Machine learning’s generalizations synthesize the general and the particular in a new way, creating a multidimensional model that often retains more of the complex differentiating patterns it has uncovered in the training process than the human mind can grasp. Particulars speak louder in these models than they do in traditional generalizing frameworks. This creates an odd analogy with recent movements in moral philosophy, particularly the feminist ethics of care which rejects the application of general moral frameworks in favor of caring responses to the particular needs and interests of those affected by a moral decision. This paper suggests that our current wide-spread and justified worries about ML’s inexplicability—primarily arising from its reliance on staggeringly complex patterns of particulars—may be preparing our culture more broadly for a valorizing of particulars as at least as determinative as generalizations, and that this might help further advance the importance of particulars in ideas such as those put forward by the ethics of care.
Multispectral Narrowband Frustrated Total Internal Reflection Filter with Inclusions of Plasmonic Nanoparticles
Authors: Petrov Nikolai I.
Published: February 2024

A spatial-frequency thin-film filter with inclusions of nanoparticles operating in the visible range of the spectrum is investigated. The effect of nanoparticles embedded in the central and lateral layers of the frustrated total internal reflection filter on the spectral characteristics, considering the frequency dispersion, is investigated. It is shown that plasmonic effects cause the splitting of the filter bandwidth into a set of narrow-band spectral lines and the angular splitting of the incident beam into a set of output beams. It is demonstrated that due to the difference in the resonance conditions for s- and p-polarization waves, the spectral lines of transparency do not coincide, which indicates the possibility of using the filter as a polarizer.
Safe Farming: Ultrafine Bubble Water Reduces Insect Infestation and Improves Melon Yield and Quality
Authors: Hung Jo-Chi , Li Ning-Juan , Peng Ching-Yen , Yang Ching-Chieh , Ko Swee-Suak
Published: February 2024

Melon pest management relies on the excessive application of pesticides. Reducing pesticide spraying has become a global issue for environmental sustainability and human health. Therefore, developing a new cropping system that is sustainable and eco-friendly is important. This study found that melon seedlings irrigated with ultrafine water containing H2 and O2 (UFW) produced more root hairs, increased shoot height, and produced more flowers than the control irrigated with reverse osmosis (RO) water. Surprisingly, we also discovered that UFW irrigation significantly reduced aphid infestation in melons. Based on cryo-scanning electron microscope (cryo-SEM) observations, UFW treatment enhanced trichome development and prevented aphid infestation. To investigate whether it was H2 or O2 that helped to deter insect infestation, we prepared UF water enrichment of H2 (UF+H2) and O2 (UF+O2) separately and irrigated melons. Cryo-SEM results indicated that both UF+H2 and UF+O2 can increase the density of trichomes in melon leaves and petioles. RT-qPCR showed that UF+H2 significantly increased the gene expression level of the trichome-related gene GLABRA2 (GL2). We planted melons in a plastic greenhouse and irrigated them with ultrafine water enrichment of hydrogen (UF+H2) and oxygen (UF+O2). The SPAD value, photosynthetic parameters, root weight, fruit weight, and fruit sweetness were all better than the control without ultrafine water irrigation. UFW significantly increased trichome development, enhanced insect resistance, and improved fruit traits. This system thus provides useful water management for pest control and sustainable agricultural production.
From Primary Data to Ethnopharmacological Investigations on Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson as a Remedy against Gastric Ailments in Valmalenco (Italy)
Authors: Bottoni Martina , Martinelli Giulia , Maranta Nicole , Sabato Emanuela , Milani Fabrizia , Colombo Lorenzo , Colombo Paola Sira , Piazza Stefano , Sangiovanni Enrico , Giuliani Claudia , Bruschi Piero , Vistoli Giulio , Dell’Agli Mario , Fico Gelsomina
Published: February 2024

(1) Background: Within the framework of the European Interreg Italy–Switzerland B-ICE & Heritage project (2018–2022), this study originated from a three-year ethnobotanical survey in Valmalenco (Sondrio, Italy). Following a preliminary work published by our group, this research further explored the folk therapeutic use of Achillea erba-rotta subsp. moschata (Wulfen) I.Richardson (Asteraceae) for dyspepsia disorders, specifically its anti-inflammatory potential at a gastrointestinal level. (2) Methods: Semi-structured interviews were performed. The bitter taste was investigated through molecular docking software (PLANTS, GOLD), while the anti-inflammatory activity of the hydroethanolic extract, infusion, and decoction was evaluated based on the release of IL-8 and IL-6 after treatment with TNFα or Helicobacter pylori. The minimum inhibitory concentration and bacterial adhesion on the gastric epithelium were evaluated. (3) Results: In total, 401 respondents were interviewed. Molecular docking highlighted di-caffeoylquinic acids as the main compounds responsible for the interaction with bitter taste receptors. The moderate inhibition of IL-6 and IL-8 release was recorded, while, in the co-culture with H. pylori, stronger anti-inflammatory potential was expressed (29–45 μg/mL). The concentration-dependent inhibition of H. pylori growth was recorded (MIC = 100 μg/mL), with a significant anti-adhesive effect. (4) Conclusions: Confirming the folk tradition, the study emphasizes the species’ potentiality for dyspepsia disorders. Future studies are needed to identify the components mostly responsible for the biological effects.
Growth Enhancement and Resistance of Banana Plants to Fusarium Wilt Disease as Affected by Silicate Compounds and Application Frequency
Authors: Zakaria Md , Sakimin Siti , Ismail Mohd , Ahmad Khairulmazmi , Kasim Susilawati
Published: February 2024

The amendment of soils with silicate (Si) compounds is essential to promote growth performance and control Fusarium wilt disease in bananas. Two successive greenhouse trials were conducted at the experimental farm of the University of Putra Malaysia. The treatments were arranged in split plots using a randomized complete block design (RCBD) with four replicates to investigate the effects of Si compounds and application frequency on controlling FOC. Si compounds were used at a constant concentration of 0.1%: T0 (control), T1 (13% SiO2:20% K2O), T2 (26.6% SiO2:13.4% K2O) and T3 (36.2% SiO2:17% Na2O). There were three application frequencies by day intervals (DI): 0DI (without any application), 7DI (12× within 12 weeks after transplanting (WAT)), 15DI (6× within 12 WAT) and 30DI (3× within 12 WAT). From these findings, we observed that the photosynthesis rate started to increase from 10.6 to 19.4 µmol CO2 m−2s−1, when the total chlorophyll content started to increase from 3.85 to 7.61 mgcm−2. The transpiration rate started to increase from a value of 1.94 to 4.31 mmol H2O m−2s−1, when the stomata conductance started to increase from 0.237 to 0.958 mmol m−2s−1. The proline content started to increase from 22.89 to 55.07 µmg−1, when the relative water content started to increase from 42.92 to 83.57%.