bluuebunny/crossref_metadata_2025 huggingface dataset:
Interaction of 6-Thioguanine with Aluminum Metal–Organic Framework Assisted by Mechano-Chemistry, In Vitro Delayed Drug Release, and Time-Dependent Toxicity to Leukemia Cells
Authors: Umar Sheriff , Welch Xavier , Obichere Chihurumanya , Carter-Cooper Brandon , Samokhvalov Alexander
Published: September 2024

6-thioguanine (6-TG) is an antimetabolite drug of purine structure, approved by the FDA for the treatment of acute myeloid lesukemia, and it is of interest in treating other diseases. The interaction of drugs with matrices is of interest to achieving a delayed, sustained, and local release. The interaction of 6-TG with an aluminum metal–organic framework (Al-MOF) DUT-4 is studied using a novel experimental approach, namely, mechano-chemistry by liquid-assisted grinding (LAG). The bonding of 6-TG to the DUT-4 matrix in the composite (6-TG)(DUT-4) was studied using ATR-FTIR spectroscopy and XRD. This interaction involves amino groups and C and N atoms of the heterocyclic ring of 6-TG, as well as the carboxylate COO− and (Al)O-H groups of the matrix, indicating the formation of the complex. Next, an in vitro delayed release of 6-TG was studied from composite powder versus pure 6-TG in phosphate buffered saline (PBS) at 37 °C. Herein, an automated drug dissolution apparatus with an autosampler was utilized, and the molar concentration of the released 6-TG was determined using an HPLC–UV analysis. Pure 6-TG shows a quick (<300 min) dissolution, while the composite gives the dissolution of non-bonded 6-TG, followed by a significantly (factor 6) slower release of the bonded drug. Each step of the release follows the kinetic pseudo-first-order rate law with distinct rate constants. Then, a pharmaceutical shaped body was prepared from the composite, and it yields a significantly delayed release of 6-TG for up to 10 days; a sustained release is observed with the 6-TG concentration being within the therapeutically relevant window. Finally, the composite shows a time-dependent (up to 9 days) stronger inhibition of leukemia MV-4-11 cell colonies than 6-TG.
Enhanced Photocatalytic Paracetamol Degradation by NiCu-Modified TiO2 Nanotubes: Mechanistic Insights and Performance Evaluation
Authors: Pinna Marco , Zava Martina , Grande Tommaso , Prina Veronica , Monticelli Damiano , Roncoroni Gianluca , Rampazzi Laura , Hildebrand Helga , Altomare Marco , Schmuki Patrik , Spanu Davide , Recchia Sandro
Published: September 2024

Anodic TiO2 nanotube arrays decorated with Ni, Cu, and NiCu alloy thin films were investigated for the first time for the photocatalytic degradation of paracetamol in water solution under UV irradiation. Metallic co-catalysts were deposited on TiO2 nanotubes using magnetron sputtering. The influence of the metal layer composition and thickness on the photocatalytic activity was systematically studied. Photocatalytic experiments showed that only Cu-rich co-catalysts provide enhanced paracetamol degradation rates, whereas Ni-modified photocatalysts exhibit no improvement compared with unmodified TiO2. The best-performing material was obtained by sputtering a 20 nm thick film of 1:1 atomic ratio NiCu alloy: this material exhibits a reaction rate more than doubled compared with pristine TiO2, enabling the complete degradation of 10 mg L−1 of paracetamol in 8 h. The superior performance of NiCu-modified systems over pure Cu-based ones is ascribed to a Ni and Cu synergistic effect. Kinetic tests using selective holes and radical scavengers unveiled, unlike prior findings in the literature, that paracetamol undergoes direct oxidation at the photocatalyst surface via valence band holes. Finally, Chemical Oxygen Demand (COD) tests and High-Resolution Mass Spectrometry (HR-MS) analysis were conducted to assess the degree of mineralization and identify intermediates. In contrast with the existing literature, we demonstrated that the mechanistic pathway involves direct oxidation by valence band holes.
Enhanced Flexible Piezoelectric Nanogenerators Using Ethanol-Exfoliated g-C3N4/PVDF Composites via 3D Printing for Self-Powered Applications
Authors: Pawar Omkar Y. , Lu Baoyang , Lim Sooman
Published: September 2024

This study presents the development of flexible piezoelectric nanogenerators (PENGs) utilizing graphitic carbon nitride (g-C3N4) nanoflakes (CNNFs) and polyvinylidene fluoride (PVDF) composites fabricated via the direct ink writing (DIW) 3D printing method. A novel approach of synthesizing CNNFs using the ethanol exfoliation method was demonstrated, which significantly reduces preparation time and cost compared to traditional acid exfoliation. The CNNFs are incorporated into PVDFs at varying weight percentages (5, 7.5, 10, and 15 wt.%) to optimize the β-phase content and piezoelectric properties. Characterization techniques including XRD, FTIR, and FESEM confirm the successful synthesis and alignment of nanoflakes inside the PVDF matrix. The film with 7.5% CNNF achieves the highest performance, exhibiting a peak output voltage of approximately 6.5 V under a 45 N force. This study also explores the effects of UV light exposure. Under a UV light, the film exhibits an output voltage of 8 V, indicating the device’s durability and potential for practical applications. The fabricated device showed significant voltage outputs during various human motions, confirming its suitability for wearable self-powered IoT applications. This work highlights the efficacy of the ethanol exfoliation method and the DIW printing technique in enhancing the performance of flexible PENGs.
Novel Synthesis Route of Plasmonic CuS Quantum Dots as Efficient Co-Catalysts to TiO2/Ti for Light-Assisted Water Splitting
Authors: Chaperman Larissa , Chaguetmi Samiha , Deng Bingbing , Gam-Derrouich Sarra , Nowak Sophie , Mammeri Fayna , Ammar Souad
Published: September 2024

Self-doped CuS nanoparticles (NPs) were successfully synthesized via microwave-assisted polyol process to act as co-catalysts to TiO2 nanofiber (NF)-based photoanodes to achieve higher photocurrents on visible light-assisted water electrolysis. The strategy adopted to perform the copper cation sulfidation in polyol allowed us to overcome the challenges associated with the copper cation reactivity and particle size control. The impregnation of the CuS NPs on TiO2 NFs synthesized via hydrothermal corrosion of a metallic Ti support resulted in composites with increased visible and near-infrared light absorption compared to the pristine support. This allows an improved overall efficiency of water oxidation (and consequently hydrogen generation at the Pt counter electrode) in passive electrolyte (pH = 7) even at 0 V bias. These low-cost and easy-to-achieve composite materials represent a promising alternative to those involving highly toxic co-catalysts.
Spectral Control by Silver Nanoparticle-Based Metasurfaces for Mitigation of UV Degradation in Perovskite Solar Cells
Authors: Delgado-Rodríguez Silvia , Jaldo Serrano Eva , Elshorbagy Mahmoud H. , Alda Javier , del Pozo Gonzalo , Cuadrado Alexander
Published: September 2024

Perovskite solar cells are considered to be one of the most promising solar cell designs in terms of photovoltaic efficiency. However, their practical deployment is strongly affected by their short lifetimes, mostly caused by environmental conditions and UV degradation. In this contribution, we present a metasurface made of silver nanoparticles used as a UV filter on a perovskite solar cell. The UV-blocking layer was fabricated and morphologically and compositionally analyzed. Its optical response, in terms of optical transmission, was also experimentally measured. These results were compared with simulations made through the use of a well-proven computational electromagnetism model. After analyzing the discrepancies between the experimental and simulated results and checking those obtained from electron beam microscopy and electron dispersion spectroscopy, we could see that a residue from fabrication, sodium citrate, strongly modified the optical response of the system, generating a redshift of about 50 nm. Then, we proposed and simulated the optical behavior of core–shell nanoparticles made of silver and silica. The calculated spectral absorption at the active perovskite layer shows how the appropriate selection of the geometrical parameters of these core–shell particles is able to tune the absorption at the active layer by removing a significant portion of the UV band and reducing the absorption of the active layer from 90% to 5% at a resonance wavelength of 403 nm.
Size Effects of Copper(I) Oxide Nanospheres on Their Morphology on Copper Thin Films under Near-Infrared Femtosecond Laser Irradiation
Authors: Mizoshiri Mizue , Tran Thuan Duc , Nguyen Kien Vu Trung
Published: September 2024

The femtosecond laser direct writing of metals has gained significant attention for micro/nanostructuring. Copper (I) oxide nanospheres (NSs), a promising material for multi-photon metallization, can be reduced to copper (Cu) and sintered through near-infrared femtosecond laser pulse irradiation. In this study, we investigated the size effect of copper (I) oxide nanospheres on their morphology when coated on Cu thin films and irradiated by near-infrared femtosecond laser pulses. Three Cu2O NS inks were prepared, consisting of small (φ100 nm), large (φ200 nm), and a mixture of φ100 nm and φ200 nm NSs. A unique phenomenon was observed at low laser pulse energy: both sizes of NSs bonded as single layers when the mixed NSs were used. At higher pulse energies, the small NSs melted readily compared to the large NSs. In comparisons between the large and mixed NSs, some large NSs remained intact, suggesting that the morphology of the NSs can be controlled by varying the concentration of different-sized NSs. Considering the simulation results indicating that the electromagnetic fields between large and small NSs are nearly identical, this differential morphology is likely attributed to the differences in the heat capacity of the NSs.
Froin’s Syndrome: A Comprehensive Review of the Literature and the Addition of Two New Cases
Authors: Jacobs Lucas , Delsaut Bertil , Lamartine S. Monteiro Marta , Cambier Audrey , Alcan Ibrahim , Maillart Evelyne , Taghavi Maxime
Published: September 2024

Background. Froin’s syndrome (FS) is a rare entity with uncertain prevalence and prognosis, defined by a pathognomonic triad: cerebrospinal fluid (CSF) xanthochromia, elevated protein levels in the CSF, and hypercoagulated CSF, usually obtained through lumbar puncturing below the level of a partial or complete spinal block. Methods. We conducted a comprehensive review of the literature on FS from its first description in 1903 to December 2023, utilizing PubMed and Google Scholar, and included two new cases from our clinical practice. Results. We describe two patients who suffered from Froin’s syndrome secondary to spinal abscesses. According to our review, FS is caused by neoplasia in 33% of cases, non-malignant mechanical causes in 27%, infections in 27%, non-infectious inflammatory processes in 6%, and vascular in 6%. The most prevalent symptoms are paraplegia/paraparesis (64%), back pain (38%), altered mental state and/or confusion (23%), sciatica (17%), headaches (17%), leg sensory defects (17%), and urinary retention (14%), and are thought to be linked with the underlying causes rather than the CSF characteristics. FS holds a poor prognosis: only 22% recuperate fully after treatment, 22% die due to the cause leading to FS, and 14% retain sequelae. Conclusions. Xanthochromia and proteinorachia >500 mg/dL are not specific to any single pathological condition, but indicate defective CSF recirculation and spinal block, causing diffusive and/or inflammatory processes resulting in the hyperproteinosis and coagulation of the CSF. We reviewed the pathophysiology, etiologies, symptoms, outcomes, and workups of Froin’s syndrome according to the existing medical literature.
Morpho-Physiological and Biochemical Responses in Prosopis laevigata Seedlings to Varied Nitrogen Sources
Authors: Basave-Villalobos Erickson , Valenzuela-Núñez Luis Manuel , García-Rodríguez José Leonardo , Sarmiento-López Homero , García-Pérez José Luis , Calixto-Valencia Celi Gloria , Sigala José A.
Published: September 2024

Nitrogen (N) fertilization promotes morphofunctional attributes that enhance plant performance under stress conditions, but the amount and form supplied modify the magnitude of plant responses. We assessed several morpho-physiological and biochemical responses of Prosopis laevigata seedlings to a high supply of N, provided as either inorganic (NH4NO3) or organic (amino acids). Such N treatments were applied on four-month-old seedlings as a supplement of 90 mg N to a regular supply of 274 mg N plant−1. Nitrogen supply modified biomass allocation patterns between leaves and roots regardless of N form. Increased N input decreased photosynthetic capacity, even when plants had high internal N reserves. Organic N fertilization reduced the N use efficiency, but increased leaf and root amino acid concentrations. Proteins accumulated in stems in plants receiving inorganic N, while the organic N increased leaf proteins. High N supply promoted root starch accumulation irrespective of N form. Nitrogen supply did not directly influence plants’ regrowth capacity. Still, resprouting was correlated to initial root-to-shoot ratios and root starch, confirming the importance of roots as storage reserves of starch for recovering biomass after browsing. These findings have practical implications for designing nutritional management strategies in nurseries to improve seedling performance in afforestation efforts.
Comparative Analysis of Dietary Habits and Obesity Prediction: Body Mass Index versus Body Fat Percentage Classification Using Bioelectrical Impedance Analysis
Authors: Pescari Denisa , Mihuta Monica Simina , Bena Andreea , Stoian Dana
Published: September 2024

Background: Obesity remains a widely debated issue, often criticized for the limitations in its identification and classification. This study aims to compare two distinct systems for classifying obesity: body mass index (BMI) and body fat percentage (BFP) as assessed by bioelectrical impedance analysis (BIA). By examining these measures, the study seeks to clarify how different metrics of body composition influence the identification of obesity-related risk factors. Methods: The study enrolled 1255 adults, comprising 471 males and 784 females, with a mean age of 36 ± 12 years. Participants exhibited varying degrees of weight status, including optimal weight, overweight, and obesity. Body composition analysis was conducted using the TANITA Body Composition Analyzer BC-418 MA III device (T5896, Tokyo, Japan), evaluating the following parameters: current weight, basal metabolic rate (BMR), adipose tissue (%), muscle mass (%), and hydration status (%). Results: Age and psychological factors like cravings, fatigue, stress, and compulsive eating were significant predictors of obesity in the BMI model but not in the BFP model. Additionally, having a family history of diabetes was protective in the BMI model (OR: 0.33, 0.11–0.87) but increased risk in the BFP model (OR: 1.66, 1.01–2.76). The BMI model demonstrates exceptional predictive ability (AUC = 0.998). In contrast, the BFP model, while still performing well, exhibits a lower AUC (0.975), indicating slightly reduced discriminative power compared to the BMI model. Conclusions: BMI classification demonstrates superior predictive accuracy, specificity, and sensitivity. This suggests that BMI remains a more reliable measure for identifying obesity-related risk factors compared to the BFP model.
A Risk Correlative Model for Sleep Disorders in Chinese Older Adults Based on Blood Micronutrient Levels: A Matched Case-Control Study
Authors: Cheng Cheng , Chen Xukun , Zhang Liyang , Wang Zehao , Duan Huilian , Wu Qi , Yan Ruiting , Wang Di , Li Zhongxia , He Ruikun , Li Zhenshu , Chen Yongjie , Ma Fei , Du Yue , Li Wen , Huang Guowei
Published: September 2024

Background: The physical abilities of older adults decline with age, making them more susceptible to micronutrient deficiency, which may affect their sleep quality. Objectives: This study aimed to construct a risk correlative model for sleep disorders in Chinese older adults based on blood micronutrient levels. Methods: In this matched case-control study, we recruited 124 participants with sleep disorders and 124 matched controls from the Tianjin Elderly Nutrition and Cognition cohort in China. Micronutrient levels in whole blood were measured using the dried blood spot technique. We compared the differences in micronutrient levels between the two groups and also constructed a receiver operating characteristic (ROC) model and nomogram for sleep disorders. Results: In comparison to the control group, the sleep disorders group showed lower levels of blood vitamin A, vitamin E (VE), folate, magnesium, copper, iron, and selenium (Se) in the univariate analysis (p < 0.05). The ROC curve analysis indicated that the combination of VE + folate + Se may have an excellent diagnostic effect on sleep disorders, with an area under the curve of 0.964. This VE + folate + Se was integrated into a nomogram model to demonstrate their relationship with sleep disorders. The consistency index of the model was 0.88, suggesting that the model assessed sleep disorders well. Conclusions: The sleep disorders risk correlative model constructed by the levels of VE, folate, and Se in whole blood might show good performance in assessing the risk of sleep disorders in older adults.
Does the Composition of Breast Milk in the First Week Postpartum Differ Due to Maternal Factors or Neonatal Birth Weight and Percent Fat Body Mass?
Authors: Karcz Karolina , Gaweł Paulina , Królak-Olejnik Barbara
Published: September 2024

Background: The composition of breast milk is dependent on numerous factors. However, the precise impact of maternal health conditions on breast milk composition remains to be fully elucidated. Similarly, there is a paucity of evidence regarding the correlation between neonatal body composition and human milk. The objective of the study was to evaluate the macronutrient composition of breast milk collected during the first week postpartum from mothers with gestational diabetes and healthy mothers in terms of selected maternal and neonatal factors. Methods: n = 70 breast milk samples were analyzed for fat, protein, carbohydrate, dry matter, true protein, and energy. The results were evaluated in terms of selected maternal factors, as well as neonatal birth weight (BW) and percent fat body mass (%FBM), which was assessed with a bioimpedance method. Results: Energy of breast milk in the study group was as follows: median 55.5 kcal/dL in GDM G1, median 55.5 kcal/dL in GDM G2, and median 65.0 kcal/dL in non-GDM, which differed significantly in Kruskal–Wallis ANOVA. Neonatal %FBM, but not BW, was found to be significantly related to concentrations of protein, true protein and dry matter. Maternal gestational weight gain, history of hypothyroidism, and classification by study group were identified as factors affecting both breast milk and neonatal body composition. Conclusions: The composition of breast milk in the initial week following childbirth is predominantly determined by maternal factors. The relationship between selected macronutrients and neonatal percent fat body mass was found to be weak, yet the significance of this finding is unclear. Further research is required to ascertain the influence of maternal milk composition on early infantile nutritional programming.
Influence of Peanut Consumption on the Gut Microbiome: A Randomized Clinical Trial
Authors: Nguyen Sang Minh , Tran Thi Du Chi , Tran Thi Mo , Wang Cong , Wu Jie , Cai Qiuyin , Ye Fei , Shu Xiao-Ou
Published: September 2024

Background: Peanut consumption could impact cardiometabolic health through gut microbiota, a hypothesis that remains to be investigated. A randomized clinical trial in Vietnam evaluated whether peanut consumption alters gut microbiome communities. Methods: One hundred individuals were included and randomly assigned to the peanut intervention and control groups. A total of 51 participants were provided with and asked to consume 50 g of peanuts daily, while 49 controls maintained their usual dietary intake for 16 weeks. Stool samples were collected before and on the last day of the trial. After excluding 22 non-compliant participants and those who received antibiotic treatment, 35 participants from the intervention and 43 from the control were included in the analysis. Gut microbiota composition was measured by shotgun metagenomic sequencing. Associations of changes in gut microbial diversity with peanut intervention were evaluated via linear regression analysis. Linear mixed-effects models were used to analyze associations of composition, sub-community structure, and microbial metabolic pathways with peanut intervention. We also performed beta regression analysis to examine the impact of peanut intervention on the overall and individual stability of microbial taxa and metabolic pathways. All associations with false discovery rate (FDR)-corrected p-values of <0.1 were considered statistically significant. Results: No significant changes were found in α- and β-diversities and overall gut microbial stability after peanut intervention. However, the peanut intervention led to lower enrichment of five phyla, five classes, two orders, twenty-four metabolic pathways, and six species-level sub-communities, with a dominant representation of Bifidobacterium pseudocatenulatum, Escherichia coli D, Holdemanella biformis, Ruminococcus D bicirculans, Roseburia inulinivorans, and MGYG-HGUT-00200 (p < 0.05 and FDR < 0.1). The peanut intervention led to the short-term stability of several species, such as Faecalibacterium prausnitzii F and H, and a metabolic pathway involved in nitrate reduction V (p < 0.05; FDR < 0.1), known for their potential roles in human health, especially cardiovascular health. Conclusions: In summary, a 16-week peanut intervention led to significant changes in gut microbial composition, species-level sub-communities, and the short-term stability of several bacteria, but not overall gut microbial diversity and stability. Further research with a larger sample size and a longer intervention period is needed to confirm these findings and investigate the direct impact of gut-microbiome-mediated health effects of peanut consumption. Trial registration: The International Traditional Medicine Clinical Trial Registry (ITMCTR). Registration number: ITMCTR2024000050. Retrospectively Registered 24 April 2024.
The Relevance of Plant-Based Diets and Micronutrient Supplementation for Body Composition: Data from the VeggieNutri Cross-Sectional Study
Authors: Pinheiro Cátia , Silva Flávia , Rocha Inês , Martins Carina , Giesteira Liliana , Dias Bruna , Lucas Ana , Alexandre Ana Margarida , Ferreira Catarina , Viegas Bruna , Bracchi Isabella , Guimarães Juliana , Amaro Joana , Amaral Teresa F. , Dias Cláudia Camila , Oliveira Andreia , Ndrio Altin , Guimarães João Tiago , Leite João Costa , Negrão Rita , Keating Elisa
Published: September 2024

Objectives: This study aimed to compare the anthropometry and body composition of vegetarian and omnivorous adults living in Portugal, while exploring nutritional and health parameters underlying observed differences. Methods: 425 omnivorous (OMNI), lacto-ovo-vegetarian (LOV), or vegan (VEG) healthy adults were recruited. Anthropometry was measured, and bioelectrical impedance analysis was performed. Participants answered food frequency, sociodemographic, and lifestyle questionnaires. Serum iron, ferritin, and CRP were quantified by spectrophotometry, and serum B12 vitamin and homocysteine were quantified by chemiluminescent microparticle immunoassay. Results: Total protein intake significantly decreased with increasing strictness of vegetarian habits (median (P25; P75) in g/day: 98.6 (79.5; 123.1), 90.4 (65.9; 121.0), and 87.6 (59.8; 118.5) for OMNI, LOV and VEG, respectively; p = 0.020), and carbohydrate intake was the highest in LOV (median (P25; P75) in g/day: 231.5 (178.4; 287.9), 283.9 (227.3; 342.6), and 263.0 (222.0; 348.3) for OMNI, LOV and VEG, respectively; p = 0.001). VEG were the main users of B12 vitamin (93% in VEG vs. 17% in OMNI and 59% in LOV, p = 0.001), and LOV were the main users of iron supplements (29% in LOV vs. 14% in OMNI and 13% in VEG, p = 0.042), respectively. Blood levels of B12 vitamin correlated negatively with blood homocysteine (rs = −0.386, p < 0.001) and positively with % muscle mass (rs = 0.136, p = 0.005). Participants using iron supplements presented higher C-reactive protein (CRP) (p = 0.014) and they had lower % MM (p = 0.003). Finally, when compared to being OMNI, being LOV independently associated with: (a) having +4.8% (p = 0.002) of fat mass, which could be due to higher carbohydrate intake, and (b) having −2.2% (p = 0.043) of muscle mass. Our data suggest that the association between diet and muscle mass could be attenuated in VEG due to B12 supplementation and/or aggravated in LOV due to iron supplementation-associated inflammation.
Lentil Waste Extracts for Inflammatory Bowel Disease (IBD) Symptoms Control: Anti-Inflammatory and Spasmolytic Effects
Authors: Panaro Maria Antonietta , Budriesi Roberta , Calvello Rosa , Cianciulli Antonia , Mattioli Laura Beatrice , Corazza Ivan , Rotondo Natalie Paola , Porro Chiara , Lamonaca Antonella , Ferraro Valeria , Muraglia Marilena , Corbo Filomena , Clodoveo Maria Lisa , Monaci Linda , Cavalluzzi Maria Maddalena , Lentini Giovanni
Published: September 2024

Background/Objectives: In the contest of agro-industrial waste valorization, we focused our attention on lentil seed coats as a source of health-promoting phytochemicals possibly useful in managing inflammatory bowel diseases (IBDs), usually characterized by inflammation and altered intestinal motility. Methods: Both traditional (maceration) and innovative microwave-assisted extractions were performed using green solvents, and the anti-inflammatory and spasmolytic activities of the so-obtained extracts were determined through in vitro and ex vivo assays, respectively. Results: The extract obtained through the microwave-assisted procedure using ethyl acetate as the extraction solvent (BEVa) proved to be the most useful in inflammation and intestinal motility management. In LPS-activated Caco-2 cells, BEVa down-regulated TLR4 expression, reduced iNOS expression and the pro-inflammatory cytokine IL-1 production, and upregulated the anti-inflammatory cytokine IL-10 production, thus positively affecting cell inflammatory responses. Moreover, a significant decrease in the longitudinal and circular tones of the guinea pig ileum, with a reduction of transit speed and pain at the ileum level, together with reduced transit speed, pain, and muscular tone at the colon level, was observed with BEVa. HPLC separation combined with an Orbitrap-based high-resolution mass spectrometry (HRMS) technique indicated that 7% of all the identified metabolites were endowed with proven anti-inflammatory and antispasmodic activities, among which niacinamide, apocynin, and p-coumaric acid were the most abundant. Conclusions: Our results suggest that lentil hull extract consumption could contribute to overall intestinal health maintenance, with BEVa possibly representing a dietary supplementation and a promising approach to treating intestinal barrier dysfunction.
Identification of Key Immune and Cell Cycle Modules and Prognostic Genes for Glioma Patients through Transcriptome Analysis
Authors: Guo Kaimin , Yang Jinna , Jiang Ruonan , Ren Xiaxia , Liu Peng , Wang Wenjia , Zhou Shuiping , Wang Xiaoguang , Ma Li , Hu Yunhui
Published: September 2024

Background: Gliomas, the most prevalent type of primary brain tumor, stand out as one of the most aggressive and lethal types of human cancer. Methods & Results: To uncover potential prognostic markers, we employed the weighted correlation network analysis (WGCNA) on the Chinese Glioma Genome Atlas (CGGA) 693 dataset to reveal four modules significantly associated with glioma clinical traits, primarily involved in immune function, cell cycle regulation, and ribosome biogenesis. Using the least absolute shrinkage and selection operator (LASSO) regression algorithm, we identified 11 key genes and developed a prognostic risk score model, which exhibits precise prognostic prediction in the CGGA 325 dataset. More importantly, we also validated the model in 12 glioma patients with overall survival (OS) ranging from 4 to 132 months using mRNA sequencing and immunohistochemical analysis. The analysis of immune infiltration revealed that patients with high-risk scores exhibit a heightened immune infiltration, particularly immune suppression cells, along with increased expression of immune checkpoints. Furthermore, we explored potentially effective drugs targeting 11 key genes for gliomas using the library of integrated network-based cellular signatures (LINCS) L1000 database, identifying that in vitro, both torin-1 and clofarabine exhibit promising anti-glioma activity and inhibitory effect on the cell cycle, a significant pathway enriched in the identified glioma modules. Conclusions: In conclusion, our study provides valuable insights into molecular mechanisms and identifying potential therapeutic targets for gliomas.
Drugs Targeting Sirtuin 2 Exhibit Broad-Spectrum Anti-Infective Activity
Authors: Shenk Thomas , Kulp III John L. , Chiang Lillian W.
Published: September 2024

Direct-acting anti-infective drugs target pathogen-coded gene products and are a highly successful therapeutic paradigm. However, they generally target a single pathogen or family of pathogens, and the targeted organisms can readily evolve resistance. Host-targeted agents can overcome these limitations. One family of host-targeted, anti-infective agents modulate human sirtuin 2 (SIRT2) enzyme activity. SIRT2 is one of seven human sirtuins, a family of NAD+-dependent protein deacylases. It is the only sirtuin that is found predominantly in the cytoplasm. Multiple, structurally distinct SIRT2-targeted, small molecules have been shown to inhibit the replication of both RNA and DNA viruses, as well as intracellular bacterial pathogens, in cell culture and in animal models of disease. Biochemical and X-ray structural studies indicate that most, and probably all, of these compounds act as allosteric modulators. These compounds appear to impact the replication cycles of intracellular pathogens at multiple levels to antagonize their replication and spread. Here, we review SIRT2 modulators reported to exhibit anti-infective activity, exploring their pharmacological action as anti-infectives and identifying questions in need of additional study as this family of anti-infective agents advances to the clinic.
Discovering Photoswitchable Molecules for Drug Delivery with Large Language Models and Chemist Instruction Training
Authors: Hu Junjie , Wu Peng , Li Yulin , Li Qi , Wang Shiyi , Liu Yang , Qian Kun , Yang Guang
Published: September 2024

Background: As large language models continue to expand in size and diversity, their substantial potential and the relevance of their applications are increasingly being acknowledged. The rapid advancement of these models also holds profound implications for the long-term design of stimulus-responsive materials used in drug delivery. Methods: The large model used Hugging Face’s Transformers package with BigBird, Gemma, and GPT NeoX architectures. Pre-training used the PubChem dataset, and fine-tuning used QM7b. Chemist instruction training was based on Direct Preference Optimization. Drug Likeness, Synthetic Accessibility, and PageRank Scores were used to filter molecules. All computational chemistry simulations were performed using ORCA and Time-Dependent Density-Functional Theory. Results: To optimize large models for extensive dataset processing and comprehensive learning akin to a chemist’s intuition, the integration of deeper chemical insights is imperative. Our study initially compared the performance of BigBird, Gemma, GPT NeoX, and others, specifically focusing on the design of photoresponsive drug delivery molecules. We gathered excitation energy data through computational chemistry tools and further investigated light-driven isomerization reactions as a critical mechanism in drug delivery. Additionally, we explored the effectiveness of incorporating human feedback into reinforcement learning to imbue large models with chemical intuition, enhancing their understanding of relationships involving -N=N- groups in the photoisomerization transitions of photoresponsive molecules. Conclusions: We implemented an efficient design process based on structural knowledge and data, driven by large language model technology, to obtain a candidate dataset of specific photoswitchable molecules. However, the lack of specialized domain datasets remains a challenge for maximizing model performance.
An Antagonist Antibody That Inhibits Cancer Cell Growth In Vitro through RACK1
Authors: Kim Ji Hoe , Lee Eun Ji , Han Kyung Ho
Published: September 2024

Background/Objectives: Our research introduces a novel screening method to identify antibodies that can suppress cell proliferation and induce apoptosis. Methods: By using an autocrine signaling system with lentivirus, we developed an antibody screening method based on FACS sorting assays and cell cycle analysis to inhibit tumor growth in vitro. This approach is particularly well suited for studying tumor suppressors. Inducing the G0 phase in tumor cells with specific antibodies may arrest their growth permanently or trigger apoptosis. The cell cycle is composed of tightly regulated phases for cell growth and division, with tumorigenesis or apoptosis occurring when these regulatory mechanisms fail. Results: In our study, we identified RACK1 as a key regulator of cancer cell growth. The H9 antibody against RACK1 selected from a human antibody library effectively suppressed cell proliferation by inhibiting RACK1 function. Conclusions: These findings suggest that RACK1 plays a crucial role in tumor cell cycling and could represent a novel therapeutic target for cancer treatment. Although RACK1 is recognized as a significant target protein in various tumors, no commercial therapeutic agents currently exist. Our results suggest that the H9 antibody could be a promising candidate for the development of novel cancer therapies.
Protective Effects of Sesame Glycoproteins on Ultraviolet-Induced Skin Aging: In Vitro and In Vivo Studies
Authors: Baik Kyung Kyu , Song Woo-Yong , Song Dong Keun , Yun Jaehyeok , Jang Ji Hwan , Oh Jae Young , Lee Mi-Jin , Go Eunjandi , Lee Kyong Jin , Roh Eunmiri , Kim Jong-Eun
Published: September 2024

Background/Objectives: Ultraviolet (UV) radiation is a primary factor in skin photoaging, leading to wrinkles, reduced elasticity, and pigmentation changes due to damage to cellular DNA, proteins, and lipids. Glycoproteins from sesame cake (SPE) have potential protective effects against UV-induced skin aging. This study investigated the anti-photoaging effects of SPE on UV-induced damage in human keratinocyte HaCaT cells and SKH-1 hairless mice. Methods: SPE was evaluated for its ability to mitigate UV-induced damage in HaCaT cells by assessing MMP-1 protein and mRNA expression levels, as well as the activity of transcription factors AP-1 and NF-κB. The phosphorylation of AKT and MAPK pathways was also analyzed. In vivo, SKH-1 hairless mice were exposed to UV radiation, and the effects of SPE on wrinkle formation and skin structure were assessed by measuring wrinkle length, area, and volume. Results: SPE significantly inhibited UV-induced MMP-1 protein and mRNA expression in HaCaT cells, indicating suppression of AP-1 and NF-κB transcription factors involved in MMP-1 production. Additionally, SPE reduced UV-induced phosphorylation of AKT and MAPK pathways. In SKH-1 hairless mice, SPE treatment led to significant reductions in wrinkle length, area, and volume, preserving skin structure in UV-exposed mice. Conclusions: The findings demonstrate that SPE has protective effects against UV-induced photoaging by inhibiting key molecular pathways associated with skin aging. SPE shows promise as a natural anti-photoaging agent, providing a foundation for future skincare product development. Further studies are warranted to explore the molecular mechanisms in detail and to validate these effects through clinical trials.
A Network Pharmacology Identified Metastasis Target for Oral Squamous Cell Carcinoma Originating from Breast Cancer with a Potential Inhibitor from F. sargassaceae
Authors: Alqarni Abdullah , Hosmani Jagadish , Alassiri Saeed , Alqahtani Ali Mosfer A. , Assiri Hassan Ahmed
Published: September 2024

This study aimed to identify specific therapeutic targets for oral squamous cell carcinoma (OSCC) that metastasize from breast cancer (BC) by using network pharmacology. The Gene Expression Omnibus for OSCC and BC served as the source of gene expression datasets and their analysis. Upregulated genes and the common intersecting genes of these cancers were determined along with that of the phytochemicals of F. sargassum to predict the pharmacological targets. Further, gene enrichment analysis revealed that their metastasis signature and metastasis targets were determined via a protein interaction network. Molecular docking and pharmacokinetic screening determined the potential therapeutic phytochemicals against the targets. The interaction network of 39 genes thus identified encoding proteins revealed HIF1A as a prominent metastasis target due to its high degree of connectivity and its involvement in cancer-related pathways. Molecular docking showed a strong binding affinity of isonahocol D2, a sargassum-derived compound with HIF1A, presenting a binding energy of −7.1 kcal/mol. Further, pharmacokinetic screening showed favorable ADME properties and molecular dynamics simulations showed stable interactions between isonahocol D2 and HIF1A, with significant stability over 100 ns. This study’s results emphasized that isonahocol D2 is a promising therapeutic candidate against HIF1A in OSCC metastasized from breast cancer in translational medicine.
Off-Label Use of Dalbavancin in Enterococcus spp. Abscess and Streptococcus pneumoniae Bacteremia Secondary to Septic Arthritis: A Retrospective Case Report
Authors: Morkos Miriam Banoub , Leon Giovani , Hong Mai-Chi , Garcia Joshua Allan , Breen Martin J. , Sud Bhanu , Nguyen Lee
Published: September 2024

Dalbavancin, a semi-synthetic lipoglycopeptide with an extended half-life that allows for weekly dosing, is currently approved for the treatment of bacterial skin and soft tissue infections caused by susceptible gram-positive organisms. This case report discusses the successful treatment of septic arthritis with dalbavancin in a 38-year-old obese male. Septic arthritis, commonly caused by Staphylococcus aureus and Streptococcus species, was diagnosed in this patient following a mechanical fall that led to worsening shoulder pain. Given the patient’s morbid obesity and concerns about antibiotic penetration, dalbavancin 1500 mg IV biweekly was chosen for its extended half-life and ease of administration. This case underscores dalbavancin’s efficacy in managing septic arthritis in obese patients, offering a convenient alternative to traditional therapies that require a peripherally inserted central catheter (PICC line), frequent dosing, therapeutic monitoring, and prolonged hospital stays. Despite its higher cost, dalbavancin’s advantages include reduced need for PICC lines, additional staff and resources to monitor therapeutic drug levels, and fewer complications, which can offset some expenses. To our knowledge, this is the first documented case investigating the use of dalbavancin for enterococcal septic arthritis with a biweekly dosing regimen.
SLNs and NLCs for Skin Applications: Enhancing the Bioavailability of Natural Bioactives
Authors: Safta Diana Antonia , Bogdan Cătălina , Moldovan Mirela-Liliana
Published: September 2024

Natural bioactives are mixtures of compounds extracted from plants with physicochemical properties that are usually not favorable for penetrating the skin’s complex barrier. Nanoparticles have important advantages both in dermatology and cosmetology: improved solubility and stability of encapsulated phytocompounds, controlled and sustained skin delivery, and enhanced skin permeation, leading to an improved bioavailability. This review focuses on two generations of lipid-based nanoparticles: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). An extensive overview on the recent studies on SLNs and NLCs entrapping essential oils, oils, herbal extracts, and phytocompounds for topical applications is presented, emphasizing their composition, physicochemical characterization, efficacy, and methodologies used to evaluate them. This review also summarizes topical systems containing natural bioactives incorporated into SLNs and NLCs, commercially available products and registered patents in the field. SLNs and NLCs turn out to be effective nanocarriers for skin applications, offering significantly improved encapsulation efficiency, stability, and bioactives delivery. However, their full potential is underexplored. Future applications should study the encapsulation potential of new natural bioactives and show more specialized solutions that address specific requirements; an improved product performance and a pleasant sensory profile could lead to increased customer compliance with the product use.
A Stealthiness Evaluation of Main Chain Carboxybetaine Polymer Modified into Liposome
Authors: Najmina Mazaya , Kobayashi Shingo , Shimazui Rena , Takata Haruka , Shibata Mayuka , Ishibashi Kenta , Kamizawa Hiroshi , Kishimura Akihiro , Shiota Yoshihito , Ida Daichi , Shimizu Taro , Ishida Tatsuhiro , Katayama Yoshiki , Tanaka Masaru , Mori Takeshi
Published: September 2024

Background: Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. Objectives: In this study, we designed and synthesized a polymer employing CB in its main chain, poly(N-acetic acid-N-methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. Results: The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. Conclusions: The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation.
Harnessing Cannabis sativa Oil for Enhanced Skin Wound Healing: The Role of Reactive Oxygen Species Regulation
Authors: Israni Dipa K. , Raghani Neha R. , Soni Jhanvi , Shah Mansi , Prajapati Bhupendra G. , Chorawala Mehul R. , Mangmool Supachoke , Singh Sudarshan , Chittasupho Chuda
Published: September 2024

Cannabis sativa emerges as a noteworthy candidate for its medicinal potential, particularly in wound healing. This review article explores the efficacy of cannabis oil in reducing reactive oxygen species (ROS) during the healing of acute and chronic wounds, comparing it to the standard treatments. ROS, produced from various internal and external sources, play a crucial role in wound development by causing cell and tissue damage. Understanding the role of ROS on skin wounds is essential, as they act both as signaling molecules and contributors to oxidative damage. Cannabis oil, recognized for its antioxidant properties, may help mitigate oxidative damage by scavenging ROS and upregulating antioxidative mechanisms, potentially enhancing wound healing. This review emphasizes ongoing research and the future potential of cannabis oil in dermatological treatments, highlighted through clinical studies and patent updates. Despite its promising benefits, optimizing cannabis oil formulations for therapeutic applications remains a challenge, underscoring the need for further research to realize its medicinal capabilities in wounds.
Study on the Consumption of Non-Steroidal Anti-Inflammatory Drugs and Antibiotics by the Brazilian Adult Population: A Cohort Study
Authors: Pedrolongo Douglas Araujo , Sagioneti Fernanda Teixeira , Weckwerth Giovana Maria , Oliveira Gabriela Moraes , Santos Carlos Ferreira , Calvo Adriana Maria
Published: September 2024

Self-medication without a medical or dental prescription is an action that leads to a significant problems associated with the overuse of medication in Brazil. The inappropriate use of antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) leads to problems related to microbial agent resistance and gastrointestinal complications. The purpose of this study was to elucidate the patterns of antibiotic and NSAIDs consumption among the adult population of Brazil. The questionnaire was answered by 400 people residing in Brazil who had access to the link in the year 2023. The findings showed that approximately 89.5% of the volunteers had used NSAIDs, and 32.2% had used antibiotics whether or not these medications had been prescribed by doctors or dentists. It was noted that a large proportion of the adverse effects reported by the volunteers involved symptoms related to gastrointestinal complaints. There was a high prevalence of NSAIDs consumption in the studied population, which is consistent with the high frequency of risk of adverse reactions caused by these drugs, particularly in the gastrointestinal tract. In relation to antibiotics, it was observed that the non-prescription consumption of these medications by the population was considered high, reaching one-third of the total number of volunteers who consumed such medications.
The Time of a Missing People: Elliptically Uncovering the Workday of the “Extra” in Bruno Varela’s Papeles Secundarios (2004) and Cuerpos Complementarios (2022)
Authors: Davies Byron
Published: September 2024

This article examines some work by the Oaxaca-based Mexican experimental filmmaker and video artist Bruno Varela in order to explore the sense of Gilles Deleuze’s view that modern political cinema is characterized by a “missing” people, to which the adequate response is the people-sustaining or people-generating trance. I argue that the element missing from Deleuze’s discussion is how the typical way for a people to go “missing” under capitalism involves the obfuscation of their labor, an idea that sustains the materially grounded trance in Varela’s Papeles Secundarios (2004) and Cuerpos Complementarios (2022), drawn from the filmmaker’s experience as casting director of Iranian artist Shirin Neshat’s production of her video installation Tooba (2002) in Oaxaca. The article discusses the “baroque critique” involved in Varela’s elliptically representing the workday of the non-professional Oaxacan actors employed in Neshat’s production, understood here as a critique articulated using the detritus of that production. The result is a paradigm of trans-temporal playfulness on film that also challenges the claims to trans-temporal experience sought in Neshat’s work. Thus, the article also locates these arguments within debates about whether films can “do philosophy”, including a hypothesis about the obfuscations of labor lying behind why making-of documentaries—and their capacities to critique the philosophical pretensions of their original subjects—have not figured more centrally in those debates.