bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Metabolomics Profiling and Bioactivity Study of Lycium shawii (Awsaj) Extracts with Particular Emphasis on Potential Anti-Malarial Properties
Authors: Al-Nemi Ruba , Akkawi Mutaz , Sawalha Khalid , Kusumastuti Siska Andrina , Nuralih  , Kusumaningrum Susi , Okselni Tia , Situmorang Vania Chlarisa , Septama Abdi Wira , Jaremko Mariusz , Emwas Abdul-Hamid
Published: February 2025

Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.
Real-Time 0.89 THz Terahertz Imaging with High-Electron-Mobility Transistor Detector and Hydrogen Cyanide Laser for Non-Destructive Nut Detection
Authors: Zhang Nu , Liu Haiqing , Yan Huihui , Wang Hongbei , Xie Jiaxing , Jie Yinxian , Yao Damao
Published: February 2025

We present a method for real-time terahertz imaging that employs a hydrogen cyanide (HCN) laser as a terahertz source at 0.89 THz and an AlGaN/GaN high-electron-mobility transistor (HEMT) terahertz detector as a camera. We developed an HCN laser and constructed a transmission imaging system based on it. This combination utilizes a high-power HCN laser with a highly sensitive terahertz detector, enabling practical applications of real-time terahertz imaging. A resolution test plane was produced to determine that the system could achieve a lateral resolution of 2 mm, and real-time terahertz imaging was carried out on Siemens star, pistachios, and sunflower seeds. The results demonstrate that the hidden structures inside nuts can be observed by terahertz imaging. Through our analysis of terahertz images of both sunflower seeds and pine nuts, we successfully assessed their fullness and demonstrated the capability to distinguish between full and unfilled nuts. These findings validate the potential of this technique for future applications in nut detection. We discuss the limitations of the current setup, potential improvements, and possible applications, and we outline the introduction of aspherical lenses and terahertz transmission tomography.
Effect of Bacteria from the Genus Azospirillum on Oxidative Stress Levels in Wheat Triticum aestivum L. in the Presence of Copper, Nickel, and Lead
Authors: Gureeva Maria V. , Kirillova Marina S. , Trandina Veronika A. , Kryukova Vera A. , Eremina Anna A. , Alimova Alina A. , Grabovich Margarita Y. , Gureev Artem P.
Published: February 2025

Heavy metals (HMs) exert a negative impact on physiological processes in plants, which can adversely affect the productivity of agricultural crops. In this experiment, we assessed the potential to mitigate the toxic effects of HMs on soft wheat through the use of rhizospheric microorganisms from the genus Azospirillum. In the initial phase of the experiment, we identified the most resistant Azospirillum strains to Cu (from 1.5 to 15 mg/L), Ni (from 2 to 20 mg/L), and Pb (from 15.9 to 159.4 mg/L). Both Ni and Pb significantly inhibited bacterial growth and induced substantial oxidative stress in the majority of the studied strains. The strain A. picis B-2897T exhibited the highest resistance to all HMs. The cultivation of wheat in soil supplemented with Cu led to an increased growth rate and enhanced wheat productivity. Conversely, Ni and Pb reduced wheat productivity by 65% and 27%, respectively. This was accompanied by chlorophyll depletion and a decrease in the expression of genes NDOR and GST, which are involved in xenobiotic detoxification. Pre-inoculation of seeds with Azospirillum led to a decrease in HM concentration in the plant seedlings; in particular, A. picis B-2897T reduced the level of Ni from 0.005% to a concentration below the detectable level (i.e., below 0.001%), and Pb from 0.014% to 0.008%. The bacteria stimulated the expression of genes responsible for xenobiotic detoxification and contributed to the increased growth and productivity of wheat. Thus, Azospirillum can be utilized as a bioproduct to alleviate the toxic effects of HMs.
Streptococcus suis: A Possible Emerging Zoonotic Pathogen in Romania
Authors: Benea Serban Nicolae , Moroti Ruxandra , Deaconu Teodora , Ciont Corina , Benea Mihaela Anca , Savulescu Fiedler Ilinca
Published: February 2025

Streptococcus suis is a common germ in pig populations, with high carrier rates. Recent studies identify it as an emerging zoonotic pathogen, particularly in Southeast Asia, where raw pork is traditionally consumed. Data on Streptococcus suis infection in Europe, especially Eastern European countries like Romania, are limited. Our study reviewed data from an infectious diseases tertiary hospital in Bucharest between 2001 and 2024, including eight patients diagnosed with a Streptococcus suis invasive infection. The median age was 53.3 years, with a male-to-female ratio 3:1. Three patients had risk factors such as contact with pigs or handling fresh pork. Seven patients were initially diagnosed with meningitis and one with endocarditis. During hospitalization, an additional endocarditis case was identified among the meningitis patients. Laboratory samples indicated bacterial infection, with Streptococcus suis isolated from CSF in six cases and blood cultures in two cases. All strains tested were susceptible to beta-lactam antibiotics, but resistant to lincosamides and macrolides. There were no deaths, but half of our patients experienced severe meningitis-related sequelae, mainly hearing loss. Clinicians should be aware of Streptococcus suis as an etiologic agent of meningitis in non-endemic areas like Romania, especially in patients with risk factors (contact with pigs, pork).
Synthesis of Amorphous MnFe@SBA Composites for Efficient Adsorptive Removal of Pb(Ⅱ) and Sb(V) from Aqueous Solution
Authors: Shi Zhou , Zhu Aogui , Chen Fan , Cai Yishu , Deng Lin
Published: February 2025

The extensive release of water contaminated with lead (Pb(II)) and antimony (Sb(V)) constitutes a serious threat to the human living environment and public health, necessitating immediate attention. In this study, a novel MnFe@SBA composite was synthesized using the hydrothermal method through the in situ growth of MnFe2O4 on SBA-15. The MnFe@SBA exhibits an amorphous structure with a high specific surface area of 405.9 m2/g and pore sizes ranging from 2 to 10 nm. Adsorption experiments demonstrated that MnFe@SBA removed over 99% of Pb(II) and 80% of Sb(V) within 120 min at initial concentrations of 10 mg/L, whereas both MnFe2O4 and SBA-15 exhibited poor adsorption capacities. Additionally, the MnFe@SBA displayed excellent tolerance towards coexisting cations, including Na+, K+, Mg2+, Ca2+, Zn2+, Ni2+, and Cd2+, as well as anions such as Cl−, NO3−, CO32−, and PO43−. The adsorption behavior of Pb(II) onto MnFe@SBA was satisfactorily described by the pseudo-second-order kinetic model and the Freundlich isotherm, while the adsorption of Sb(V) was well-fitted by the pseudo-second-order kinetic model and the Langmuir isotherm. At 318 K, the maximum adsorption capacities of MnFe@SBA for Pb(II) and Sb(V) were determined to be 329.86 mg/g and 260.40 mg/g, respectively. Mechanistic studies indicated that the adsorption of Pb(II) and Sb(V) onto MnFe@SBA involved two primary steps: electrostatic attraction and complexation. In conclusion, the MnFe@SBA is anticipated to serve as an ideal candidate for efficient removal of Pb(II) and Sb(V) from contaminated water.
Dynamic Behavior of the Glassy and Supercooled Liquid States of Aceclofenac Assessed by Dielectric and Calorimetric Techniques
Authors: Viciosa M. Teresa , Moura Ramos Joaquim J. , Garcia Ana Rosa , Diogo Hermínio P.
Published: February 2025

Aceclofenac (ACF), a non-steroidal anti-inflammatory drug, was obtained in its amorphous state by cooling from melt. The glass transition was investigated using dielectric and calorimetric techniques, namely, dielectric relaxation spectroscopy (DRS), thermally stimulated depolarization currents (TSDC), and conventional and temperature-modulated differential scanning calorimetry (DSC and TM-DSC). The dynamic behavior in both the glassy and supercooled liquid states revealed multiple relaxation processes. Well below the glass transition, DRS was able to resolve two secondary relaxations, γ and β, the latter of which was also detectable by TSDC. The kinetic parameters indicated that both processes are associated with localized motions within the molecule. The main (α) relaxation was clearly observed by DRS and TSDC, and results from both techniques confirmed a non-Arrhenian temperature dependence of the relaxation times. However, the glass transition temperature (Tg) extrapolated from DRS data significantly differed from that obtained via TSDC, which in turn showed reasonable agreement with the calorimetric Tg (Tg-DSC = 9.2 °C). The values of the fragility index calculated by the three experimental techniques converged in attributing the character of a moderately fragile glass former to ACF. Above the α relaxation, TSDC showed a well-defined peak. In DRS, after “removing” the high-conductivity contribution using ε’ derivative analysis, a peak with shape parameters αHN = βHN = 1 was also detected. The origin of these peaks, found in the full supercooled liquid state, has been discussed in the context of structural and dynamic heterogeneity. This is supported by significant differences observed between the FTIR spectra of the amorphous and crystalline samples, which are likely related to aggregation differences resulting from variations in the hydrogen bonds between the two phases. Additionally, the pronounced decoupling between translational and relaxational motions, as deduced from the low value of the fractional exponent x = 0.72, derived from the fractional Debye–Stokes–Einstein (FDSE) relationship, further supports this interpretation.
Application of Fourier Transform Infrared (FTIR) Spectroscopy in Characterization of Green Synthesized Nanoparticles
Authors: Pasieczna-Patkowska Sylwia , Cichy Marcin , Flieger Jolanta
Published: February 2025

The fundamental principle of Fourier Transform Infrared (FTIR) spectroscopy is based on the vibration and rotation of atoms, and it has become a universal and widely used spectral methodology for the detection of internal molecular structures in a diverse range of fields. A considerable number of review articles pertaining to the applications of FTIR spectroscopy have been published in recent years. Nevertheless, a comprehensive summary of the application of FTIR spectroscopy in nanoparticles’ (NPs’) green synthesis has yet to be presented. In the present paper, we propose a series of case studies that demonstrate the application of FTIR spectroscopy in the analysis of metal and metal oxide NPs that have been synthesized using green synthesis processes. Furthermore, a summary is presented of the position of functional group bands in FTIR spectra that are responsible for the reduction, capping and stabilization of NPs. In this review, we explore the advantages and limitations of FTIR and propose methodologies for overcoming these challenges. We also present potential solutions for the analysis of complex FTIR spectra. The present summary is intended to serve as a compendium of information for researchers engaged in the field of green synthesis of NPs, utilizing FTIR spectroscopy as a research tool.
Does Transglutaminase Crosslinking Reduce the Antibody Recognition Capacity of β-Lactoglobulin: An Analysis from Conformational Perspective
Authors: Fang Lei , Han Xun , Zhang Yue , Hui Tianran , Ding Lingling , Dai Wenlu , Han Yujie , Zheng Maoqiang , Xing Guangliang
Published: February 2025

Food allergies are a global concern, with β-lactoglobulin (β-LG) in bovine milk being a major allergenic protein. This study investigated the effects of transglutaminase (TGase)-mediated crosslinking on the antibody recognition capacity (ARC) and structural properties of β-LG, with the aim of developing hypoallergenic dairy products. β-LG solutions were treated with TGase at varying concentrations (0, 5, 10, 15, and 20 U/g) and durations (0, 6, 18, 24, and 42 h), followed by analysis using electrophoresis, enzyme-linked immunosorbent assay (ELISA), and spectroscopy. The results demonstrated that treatment with TGase at 20 U/g significantly reduced the ARC and immunoglobulin E (IgE) binding capacity of β-LG to 90.0 ± 0.4% and 58.4 ± 1.0%, respectively, with the optimal ARC reduction observed after 6 h of treatment (86.7 ± 1.2%, p < 0.05). Although electrophoresis did not reveal significant crosslinking of β-LG, ultraviolet absorption, fluorescence intensity, and hydrophobicity all increased with prolonged crosslinking time, while sulfhydryl content fluctuated irregularly. These findings suggest that β-LG underwent varying degrees of structural modification, which led to the masking of antigenic epitopes during the early stages (0–24 h), followed by their re-exposure at the later stage (42 h). Overall, these results highlight the potential of TGase to reduce β-LG potential allergenicity, presenting a promising strategy for the development of hypoallergenic dairy products.
Life-Cycle Risk Assessment of Second-Generation Cellulose Nanomaterials
Authors: Ede James D. , Charlton-Sevcik Amanda K. , Griffin Julia , Srinivasan Padmapriya , Zhang Yueyang , Sayes Christie M. , Hsieh You-Lo , Stark Nicole , Shatkin Jo Anne
Published: February 2025

A nanomaterial life-cycle risk assessment (Nano LCRA) was conducted for second-generation functionalized cellulose nanomaterials (CNs) in five case studies, including applications in water filtration, food contact packaging (including as an additive and coating), and food additives, to identify and prioritize potential occupational, health, consumer, and environmental risks. Exposure scenarios were developed and ranked for each product life-cycle stage. A Safer-by-Design Toolbox (SbD Toolbox) representing a compendium of high-throughput physical, chemical, and toxicological new approach methodologies (NAMs) was used for a screening-level hazard assessment. Overall, risks identified for the CN-enabled products were low. Of the exposure scenarios, occupational inhalation exposures during product manufacturing and application ranked the highest. Despite differences in chemistry and morphology, the materials behaved similarly in oral, dermal, and inhalation models, supporting their grouping and read-across. The screening-level hazard assessment identified potential lung inflammation associated with CN exposure, and a review of the literature supported this funding, suggesting CNs behave as poorly soluble, low-toxicity dusts with the potential to irritate the lung. Key research gaps to reduce uncertainty include evaluating long-term, low-dose exposures typical of the workplace, as well as the potential release and toxicity of CN-containing composite particles.
Dose-Dependent Effects of Short-Chain Fatty Acids on 3T3-L1 Adipocyte Adipokine Secretion and Metabolic Function
Authors: Alzubi Ala , Glowacki Hannah X. , Burns Jessie L. , Van Kelsey , Martin Jamie L. A. , Monk Jennifer M.
Published: February 2025

Background: Short-chain fatty acids (SCFAs) produced from microbial fermentation of non-digestible carbohydrates and protein have been shown to modulate adipocyte adipokine secretion and metabolic function, which has implications for mitigating dysfunction in obese adipose tissue; however, the individual effects of different SCFAs and the optimal concentration required is unknown. The purpose of this study was to dose-dependently determine the effects of individual SCFAs on adipocyte adipokine secretion and metabolic function. Methods: We recapitulated the obese adipocyte inflammatory conditions using mature 3T3-L1 adipocytes and a physiological concentration of lipopolysaccharide (LPS) ± individual SCFAs, namely acetate, propionate, and butyrate, in a dose-dependent manner (0.25 mM, 0.5 mM, and 1 mM) for 24 h. Results: SCFAs dose-dependently affected inflammatory adipokine secretion, wherein at 1 mM, all three SCFAs reduced the secretion of leptin, IL-6 and IL-1β, but only propionate and butyrate reduced MCP-1/CCL2 and MIP-1α/CCL3 compared to control (p < 0.05). Interestingly, 1 mM acetate increased RANTES/CCL5 secretion versus control, whereas propionate and butyrate decreased RANTES/CCL5 secretion, and only 1 mM propionate reduced MCP-3/CCL7 secretion (p < 0.05). At the lower 0.5 mM concentration, both propionate and butyrate reduced IL-6 and IL-1β secretion compared to control (p < 0.05), and there was no difference in adipokine secretion between groups at the 0.25 mM SCFA concentration (p > 0.05). Intracellular protein expression in the ratio of phosphorylated–to–total STAT3 was reduced by all SCFAs at 1 mM and by propionate and butyrate at 0.5 mM versus control (p < 0.05). The ratio fo phosphorylated–to–total NFκB p65 expression was reduced by propionate and butyrate at 1 mM and by butyrate alone at 0.5 mM compared to control (p < 0.05). Basal (no insulin stimulation) and insulin-stimulated glucose uptake did not differ between control and any 1 mM SCFA treatment conditions (p > 0.05). Conclusions: Individual SCFAs exert different dose-dependent effects on LPS-stimulated adipocyte function.
Comparative Patho-Genomics of Salmonella enterica Serovar Enteritidis Reveal Potential Host-Specific Virulence Factors
Authors: Moreau Matthew R. , Edison Lekshmi K. , Ivanov Yury V. , Wijetunge Dona Saumya S. , Hewage Eranda Mangala K. Kurundu , Linder Jessica E. , Kariyawasam Subhashinie
Published: February 2025

Salmonella enterica serovar Enteritidis (S. Enteritidis) is one of the most common causes of bacterial foodborne infections worldwide. It has an extensive host range, including birds and humans, making it one of the most adaptable Salmonella serovars. This study aims to define the virulence gene profile of S. Enteritidis and identify genes critical to its host specificity. Currently, there is limited understanding of the molecular mechanisms that allow S. Enteritidis to continue as an important foodborne pathogen. To better understand the genes that may play a role in the host-specific virulence and/or fitness of S. Enteritidis, we first compiled a virulence gene profile-based genome analysis of sequenced S. Enteritidis strains isolated from shell eggs in our laboratory. This analysis was subsequently used to compare the representative genomes of Salmonella serovars with varying host ranges and S. Enteritidis genomes. The study involved a comprehensive and direct examination of the conservation of virulence and/or fitness factors, especially in a host-specific manner—an area that has not been previously explored. Key findings include the identification of 10 virulence-associated clusters of orthologous genes (COGs) specific to poultry-colonizing serovars and 12 virulence-associated COGs unique to human-colonizing serovars. Virulence/fitness-associated gene analysis identified more than 600 genes. The genome sequences of the two S. Enteritidis isolates were compared to those of the other serovars. Genome analysis revealed a core of 2817 COGs that were common to all the Salmonella serovars examined. Comparative genome analysis revealed that 10 virulence-associated COGs were specific to poultry-colonizing serovars, whereas 12 virulence-associated COGs were present in all human-colonizing serovars. Phylogenetic analyses further highlight the evolution of host specificity in S. Enteritidis. This study offers the first comprehensive analysis of genes that may be unique to and possibly essential for the colonization and/or pathogenesis of S. Enteritidis in various and specific hosts.
Putrescine Depletion in Leishmania donovani Parasites Causes Immediate Proliferation Arrest Followed by an Apoptosis-like Cell Death
Authors: Johnston Julia , Taylor Jonathan , Nahata Surbhi , Gatica-Gomez Angelica , Anderson Yvette L. , Kiger Sophia , Pham Thong , Karimi Kayhan , Lacar Jasmin-Faith , Carter Nicola S. , Roberts Sigrid C.
Published: February 2025

The polyamine pathway in Leishmania parasites has emerged as a promising target for therapeutic intervention, yet the functions of polyamines in parasites remain largely unexplored. Ornithine decarboxylase (ODC) and spermidine synthase (SPDSYN) catalyze the sequential conversion of ornithine to putrescine and spermidine. We previously found that Leishmania donovani Δodc and Δspdsyn mutants exhibit markedly reduced growth in vitro and diminished infectivity in mice, with the effect being most pronounced in putrescine-depleted Δodc mutants. Here, we report that, in polyamine-free media, ∆odc mutants arrested proliferation and replication, while ∆spdsyn mutants showed a slow growth and replication phenotype. Starved ∆odc parasites also exhibited a marked reduction in metabolism, which was not observed in the starved ∆spdsyn cells. In contrast, both mutants displayed mitochondrial membrane hyperpolarization. Hallmarks of apoptosis, specifically DNA fragmentation and membrane modifications, were observed in Δodc mutants incubated in polyamine-free media. These results show that putrescine depletion had an immediate detrimental effect on cell growth, replication, and mitochondrial metabolism and caused an apoptosis-like death phenotype. Our findings establish ODC as the most promising therapeutic target within the polyamine biosynthetic pathway for treating leishmaniasis.
Synergistic Antibacterial and Antibiofilm Effects of Clindamycin and Zinc Oxide Nanoparticles Against Pathogenic Oral Bacillus Species
Authors: Khalil Maha A. , Alzaidi Tahany M. , Alsharbaty Mohammed Hussein M. , Ali Sameh S. , Schagerl Michael , Elhariry Hesham M. , Aboshady Tamer A.
Published: February 2025

Oral bacterial pathogens, including Bacillus species, form biofilms that enhance antibiotic resistance, promote bacterial adherence, and maintain structural integrity. The ability of bacteria to form biofilms is directly linked to several oral diseases, including gingivitis, dental caries, periodontitis, periapical periodontitis, and peri-implantitis. These biofilms act as a predisposing factor for such infections. Nanoparticles, known for their strong antibacterial properties, can target specific biofilm-forming microorganisms without disturbing the normal microflora of the oral cavity. This study focuses on the biofilm-forming ability and clindamycin (CM) resistance of Bacillus species found in the oral cavity. It aims to evaluate the antibacterial and antibiofilm properties of zinc oxide nanoparticles (ZnO-NPs) against oral Bacillus species and assess the effectiveness of combining CM with ZnO-NPs in reducing antibiotic resistance. The antibacterial susceptibility of Bacillus isolates was tested using ZnO-NPs and CM, demonstrating synergistic effects that reduced the minimum inhibitory concentrations by up to 8-fold. The fractional inhibitory concentration (FIC) index indicated a significant synergistic effect in most strains, with FIC values ranging from 0.375 to 0.5. It was found that the majority of Bacillus strains exhibited significant biofilm-forming capabilities, which were reduced when treated with the ZnO-NPs and CM combination. The study also evaluated the cytotoxicity of ZnO-NPs on cancer cells (CAL27) and normal fibroblasts (HFB4). CAL27 cells showed stronger cytotoxicity, with an IC50 of 52.15 µg/mL, compared to HFB4 cells, which had an IC50 of 36.3 µg/mL. Genetic analysis revealed the presence of biofilm-associated genes such as sipW and tasA, along with antibiotic resistance genes (ermC), which correlated with the observed biofilm phenotypes. Overall, this study demonstrates the potential of combining ZnO-NPs with CM to overcome antibiotic resistance and biofilm formation in the oral bacterial pathogens, Bacillus species. These findings suggest new approaches for developing more effective dental treatments targeting oral biofilm-associated infections and antibiotic resistance.
Outbreak of Trypanosoma vivax in Dairy Cows: Hematologic, Immunological and Antioxidant Responses Before and After Treatment with Isometamidium Chloride
Authors: Fritzen Alexandro , de Vitt Maksuel Gatto , Deolindo Guilherme Luiz , Signor Mateus Henrique , Correa Nathalia Gemelli , Ribeiro Brenda Guedes , Marques Julia , das Neves Gabriella Bassi , Miletti Luiz Claudio , da Silva Aleksandro Schafer
Published: February 2025

Trypanosoma vivax infection is an emerging condition that causes damage and mortality among cattle and is transmitted by mechanical vectors or contaminated fomites. This disease has been spreading in southern Brazil, causing anemia, weight loss, diarrhea, abortion, and infertility; however, its behavior and host–parasite relationships are not yet fully understood. To clarify this issue, animals that presented clinical signs were subjected to an immunochromatographic screening test. An indirect immunofluorescence test was then performed on samples collected before treatment (the gold standard test), which showed that in the herd of 20 cows, we had 14 seropositive for T. vivax. Blood samples were collected before and after treatment to study the effects of the disease and treatment, with the cows divided into two groups: infected and uninfected. Cows were evaluated for hematologic, biochemical, and antioxidant responses, comparing them with uninfected and infected animals, as well as pre- and post-treatment (isometamidium chloride—1 mg/kg body weight [BW]). There was no difference (p > 0.05) between groups in milk production and feed intake; however, ten days after treatment, there was an increase of 1.72 kg of milk in cows diagnosed as infected with T. vivax. Seropositive cows had lower erythrocyte counts, hemoglobin concentrations, hematocrit, platelet counts, and lymphocyte and granulocyte counts. In seropositive cows, the higher total protein concentration is due to increased globulins, which the protein profile by electrophoresis showed to be related to higher levels of immunoglobulins (IgA and other heavy-chain immunoglobulins), ceruloplasmin, haptoglobin, ferritin, C-reactive protein; associated with lower transferrin levels. The activity of the enzymes aspartate aminotransferase, gamma-glutamyl transferase, cholinesterases, and creatine kinase were compared in seronegative and seropositive cows for T. vivax. Lower serum calcium levels were observed in seropositive cows. Cows diagnosed with trypanosomosis presented high levels of reactive oxygen species, lipid peroxidation, protein oxidation, nitrite/nitrate activity, superoxide dismutase, and glutathione peroxidase. The enzymes catalase and glutathione S-transferase presented lower activity in the blood of seropositive cows compared to the control on the day of diagnosis, which was no longer observed ten days after treatment. The animals exhibited hypogalactia, anemia, thrombocytopenia, leukopenia, and acute phase response accompanied by liver and muscle tissue damage and oxidative stress, demonstrating the effect of T. vivax infection in naturally infected Jersey cows.
Discovering the Potential of Cannabidiol for Cosmeceutical Development at the Cellular Level
Authors: Tassaneesuwan Natjira , Khongkow Mattaka , Jansrinual Siriyakorn , Khongkow Pasarat
Published: February 2025

Backgrounds: Cannabidiol (CBD) has been used for the development of extensive cosmeceutical commercial products. However, the safety and unclear bioactivity of CBD are still concerns and need to be examined to assess the impact of CBD on skin cells through cosmeceutical applications, particularly its impact on anti-aging and wound healing activities. Methods: In our study, the cytotoxicity of CBD was investigated on keratinocytes and fibroblasts in short-term and long-term treatments using a sulforhodamine B (SRB) assay and a clonogenic assay, respectively. Next, the antioxidant, anti-aging, and wound healing bioactivities of CBD were assessed. Then, we investigated the expression of the related genes. Results: Our results show that CBD at low concentrations (0.625–2.5 µg/mL) was not toxic to cells in the short-term treatment and significantly enhanced the growth of keratinocytes and fibroblasts under long-term exposure. Furthermore, CBD exhibited promising cellular bioactivities, including antioxidant and anti-aging activities in keratinocytes and fibroblasts, and it enhanced wound healing in skin cells. Moreover, CBD has affected the expression of skin regenerative genes in fibroblasts via TGF-β, VEGF, and NF-κB expression. In addition, CBD promoted CO1A2 expression, which is related to collagen production. Conclusions: Altogether, our findings confirm the promising potential of CBD, showing that it can be applied in various topical cosmeceutical products. However, further studies, including in vivo studies and clinical trials, should be conducted to confirm the safety and long-term effectiveness of CBD on the skin.
Formulation, Quality Control and Stability Study of Pediatric Oral Dextrose Gel
Authors: Lamy Edouard , Orneto Caroline , Ali Oumil Her Abdou , Kireche Lyna , Mathias Fanny , Bouguergour Cyrielle , Peyron Florence , Primas Nicolas , Sauzet Christophe , Piccerelle Philippe , Maillotte Anne-Marie , Brevaut-Malaty Veronique , Rathelot Pascal , Vanelle Patrice , Curti Christophe
Published: February 2025

Background/Objective: Little information is available on the stability and quality controls of compounded 40% dextrose gel required to ensure its safe use in the treatment and prevention of neonatal hypoglycemia. Whether its efficacy relies on buccal absorption also remains uncertain. This study investigates the stability, microbiological safety, rheological properties and dextrose diffusion of a compounded 40% oral dextrose gel, ensuring it can be widely compounded and stored for clinical use. Methods: A 40% dextrose gel compounded with anhydrous dextrose, carboxymethylcellulose, citric acid, sorbic acid and sterile water was subjected to quality control measures including a dextrose content assay, degradation product analysis, microbiological testing and preservative efficacy. Stability studies were conducted at refrigerated (4–8 °C) and ambient temperatures for 7 days and 3 months, respectively. Rheological properties were assessed, and dextrose permeation was measured through an artificial membrane model that mimics a biological membrane. Results: The compounded gel demonstrated stability for up to 7 days at ambient temperature and 90 days when refrigerated. The dextrose content remained within the acceptable range (90–110%) and microbiological tests confirmed compliance with safety standards. The gel exhibited the consistent rheological properties and shear-thinning behavior appropriate for oral mucosal administration. In vitro permeation studies showed no evidence of dextrose diffusion with a long lag time followed by a low steady-state permeation flux. Conclusions: This study validates the compounding process of a stable 40% oral dextrose gel formulation for neonatal hypoglycemia management, which meets quality control criteria and can be safely administered in clinical practice, offering a cost-effective and safe alternative for neonatal care.
AI-Driven Innovation in Skin Kinetics for Transdermal Drug Delivery: Overcoming Barriers and Enhancing Precision
Authors: Albayati Nubul , Talluri Sesha Rajeswari , Dholaria Nirali , Michniak-Kohn Bozena
Published: February 2025

Transdermal drug delivery systems (TDDS) offer an alternative to conventional oral and injectable drug administration by bypassing the gastrointestinal tract and liver metabolism, improving bioavailability, and minimizing systemic side effects. However, widespread adoption of TDDS is limited by challenges such as the skin’s permeability barrier, particularly the stratum corneum, and the need for optimized formulations. Factors like skin type, hydration levels, and age further complicate the development of universally effective solutions. Advances in artificial intelligence (AI) address these challenges through predictive modeling and personalized medicine approaches. Machine learning models trained on extensive molecular datasets predict skin permeability and accelerate the selection of suitable drug candidates. AI-driven algorithms optimize formulations, including penetration enhancers and advanced delivery technologies like microneedles and liposomes, while ensuring safety and efficacy. Personalized TDDS design tailors drug delivery to individual patient profiles, enhancing therapeutic precision. Innovative systems, such as sensor-integrated patches, dynamically adjust drug release based on real-time feedback, ensuring optimal outcomes. AI also streamlines the pharmaceutical process, from disease diagnosis to the prediction of drug distribution in skin layers, enabling efficient formulation development. This review highlights AI’s transformative role in TDDS, including applications of models such as Deep Neural Networks (DNN), Artificial Neural Networks (ANN), BioSIM, COMSOL, K-Nearest Neighbors (KNN), and Set Covering Machine (SVM). These technologies revolutionize TDDS for both skin and non-skin diseases, demonstrating AI’s potential to overcome existing barriers and improve patient care through innovative drug delivery solutions.
LB-100 Enhances Drugs Efficacy Through Inhibition of P-Glycoprotein Expression in Multidrug-Resistant Glioblastoma and Non-Small Cell Lung Carcinoma Cellular Models
Authors: Podolski-Renić Ana , Chigriai Margarita , Jovanović Stojanov Sofija , Grozdanić Marija , Lupšić Ema , Nikolić Igor , Dragoj Miodrag , Dinić Jelena , Pešić Milica
Published: February 2025

Background/Objectives: This study explores the potential of LB-100 (a protein phosphatase 2A—PP2A inhibitor) combined with adavosertib (a WEE1 kinase inhibitor) and doxorubicin (DOX), to overcome multidrug resistance (MDR) in cancer cells and enhance treatment efficacy. Methods: We evaluated LB-100 combinations with adavosertib and DOX in patient-derived glioblastoma and non-small cell lung carcinoma cells (NSCLCs) using a real-time cell analyzer. Effectiveness was also assessed through immunofluorescence assay, and interactions were analyzed via SynergyFinder+. We also examined P-glycoprotein (P-gp) expression and drug resistance genes’ expression in MDR glioblastoma and NSCLCs after LB-100 treatment, as well as LB-100 sensitizing effect on DOX and DOX accumulation. Results: LB-100 significantly boosts the effectiveness of adavosertib and DOX after multiple applications. It also enhances these drugs’ cytotoxicity in a single application without acting synergistically. Additionally, LB-100 reduces P-gp expression in MDR glioblastoma and NSCLCs, sensitizing them to DOX and increasing its accumulation. Conclusions: LB-100 enhances the effectiveness of drugs against MDR cancer cells, presenting a promising strategy to overcome drug resistance in glioblastoma and NSCLCs through P-gp modulation.
Modulating Polyphenol Activity with Metal Ions: Insights into Dermatological Applications
Authors: Cioanca Oana , Lungu Ionut-Iulian , Batir-Marin Denisa , Lungu Andreea , Marin George-Alexandru , Huzum Riana , Stefanache Alina , Sekeroglu Nazim , Hancianu Monica
Published: February 2025

Background: The skin represents the first barrier of defense, and its integrity is crucial for overall health. Skin wounds present a considerable risk seeing how their progression is rapid and sometimes they are caused by comorbidities like diabetes and venous diseases. Nutraceutical combinations like the ones between polyphenols and metal ions present considerable applications thanks to their increased bioavailability and their ability to modulate intrinsic molecular pathways. Methods: The research findings presented in this paper are based on a systematic review of the current literature with an emphasis on nanotechnology and regenerative medicine strategies that incorporate polyphenols and metallic nanoparticles (NPs). The key studies which described the action mechanisms, efficacy, and safety of these hybrid formulations were reviewed. Results: Nanocomposites of polyphenol and metal promote healing by activating signaling pathways such as PI3K/Akt and ERK1/2, which in turn improve fibroblast migration and proliferation. Nanoparticles of silver and copper have antibacterial, angiogenesis-promoting, inflammation-modulating capabilities. With their ability to induce apoptosis and restrict cell growth, these composites have the potential to cure skin malignancies in addition to facilitating wound healing. Conclusions: Nanocomposites of polyphenols and metals provide hope for the treatment of cancer and chronic wounds. Their antimicrobial capabilities, capacity to modulate inflammatory responses, and enhancement of fibroblast activity all point to their medicinal potential. Furthermore, these composites have the ability to decrease inflammation associated with tumors while simultaneously inducing cell death in cancer cells. Clarifying their mechanisms, guaranteeing stability, and enhancing effective delivery techniques for clinical usage should be the focus of future studies.
Operational Definitions of Polypharmacy and Their Association with All-Cause Hospitalization Risk: A Conceptual Framework Using Administrative Databases
Authors: Scotti Stefano , Scotti Lorenza , Galimberti Federica , Xie Sining , Casula Manuela , Olmastroni Elena
Published: February 2025

Polypharmacy, defined as the concurrent use of multiple medications, increases the risk of various adverse outcomes. However, the variability in definitions across the literature contributes to substantial heterogeneity. Building on the published literature, this study aimed to identify a set of operational definitions of polypharmacy applicable to administrative databases and to assess their association with all-cause hospitalization. Data from the pharmacy refill and hospitalization databases of the Local Health Unit (LHU) of Bergamo, Lombardy, were analyzed. Patients aged ≥40 with at least one reimbursed drug prescription in 2017 were included. Prescription coverage was evaluated using total defined daily doses (DDDs), and all-cause hospitalizations from January to June 2018 were considered. Definitions explored included (i) the WHO’s criterion of ≥5 medications by ATC fourth-level code; (ii) the exclusion of prescriptions usually for short-term treatments; and (iii) drugs with cumulative annual DDD ≥ 60. Approaches were assessed annually, quarterly, and monthly, and logistic regression was used to estimate odds ratios (ORs) for hospitalization risk. Among 431,620 patients, the DDD ≥ 60 definition showed the least variability (20.47–21.16%) and identified an older more complex cohort. All definitions showed a dose-dependent association with hospitalization risk. Different definitions of polypharmacy result in varying prevalence, with DDD ≥ 60 being the most consistent. A patient-centric approach is crucial to assess the appropriateness of polypharmacy.
Designing Effective Protocol-Based Pharmacotherapy Management: Assessment of the Development Processes and Outcomes in Inflammatory Bowel Disease Care Prescription Management
Authors: Sato Masatsugu , Fujita Shiho , Kimura Masahiko , Takeuchi Ken , Hamahata Yukihiro , Matsuda Yoshikazu
Published: February 2025

Prolonged working hours among physicians in Japan, alongside rising inflammatory bowel disease (IBD) cases, have heightened the need for additional support in IBD care. Protocol-based pharmacotherapy management (PBPM) has emerged as an effective approach that allows pharmacists to assist in prescription management under predefined protocols, potentially reducing physicians’ workload. However, the detailed process of formulating PBPMs remains unclear. This study developed effective PBPM protocols by reviewing past provisional prescriptions. Provisional prescriptions made by pharmacists based on verbal instructions from physicians were reviewed to develop new PBPMs at Tsujinaka Hospital, Kashiwanoha. We retrospectively analyzed the PBPM application rate during three months before and after this initiative based on the proportion of prescriptions processed under standard procedure (SP), pharmacist provisional prescribing (PPP), and PBPM (PBPM-P). A total of 1259 prescriptions were retrospectively analyzed in this study. Before the initiative, there were 586 prescriptions (oral/topical, 128; injection, 458); after the initiative, there were 673 prescriptions (oral/topical, 242; injection, 431). The pre-initiative rates for SP, PPP, and PBPM-P were 68.3%, 30.7%, and 1.0%, respectively. Post-initiative, the rates were 48.3%, 26.6%, and 25.1%, respectively. A significant decrease was observed in the proportion of SP and PPP, while PBPM-P showed a significant increase after the initiative. Specifically, the proportion of PBPM-P increased by 24.1 percentage points, reflecting its broader adoption. In terms of safety, the proportion of pharmacists’ prescription questions decreased significantly from 3.1% before to 0.3% after the initiative. Additionally, the proportion of prescription changes resulting from these questions decreased significantly, from 1.2% to 0%. The PBPM development process evaluated here could successfully form effective PBPMs, which have the potential to reduce physicians’ workload, indicating that the process detailed in this study could be applied to future protocol development.
Sagnac Interference-Based Contact-Type Fiber-Optic Vibration Sensor
Authors: Li Hongmei , Tang Longhuang , Zhang Lijie , Huang Wenjuan , Cao Rong , Huang Cheng , Hu Xiaobo , Sun Yifei , Shi Jia
Published: February 2025

The observation and evaluation of vibration signals is crucial for enhancing engineering quality and ensuring the safe operation of equipment. This paper proposes a fiber-optic vibration sensor based on the Sagnac interference principle. The polarization-maintaining fiber (PMF) is spliced between two single mode fibers (SMFs) to form the SMF-PMF-SMF (SPS) fiber structure. The Sagnac interferometer consists of an SPS fiber structure connected to a 3 dB coupler. Due to the principle of the elastic-optical effect, the interferometric spectrum of the PMF-based Sagnac interferometric structure changes when the PMF is subjected to stress, enabling vibration to be measured. The experimental results show that the relative measurement error of the fiber-optic vibration sensor for healthy and faulty bearings is less than 1.8%, which verifies the effectiveness and accuracy of the sensor. The sensor offers benefits of excellent anti-vibration fatigue characteristics, simple production, small size, light weight, and has a wide range of applications in mechanical engineering, fault detection, safety and security, and other fields.
A Conceptual Study of Rapidly Reconfigurable and Scalable Bidirectional Optical Neural Networks Leveraging a Smart Pixel Light Modulator
Authors: Ju Young-Gu
Published: February 2025

We explore the integration of smart pixel light modulators (SPLMs) into bidirectional optical neural networks (BONNs), highlighting their advantages over traditional spatial light modulators (SLMs). SPLMs enhance BONN performance by enabling faster light modulation in both directions, significantly increasing the refresh rate of neural network weights to hundreds of megahertz, thus facilitating the practical implementation of the backpropagation algorithm and two-mirror-like BONN structures. The architecture of an SPLM-based BONN (SPBONN) features bidirectional modulation, simplifying hardware with electrical fan-in and fan-out. An SPBONN with an array size of 96 × 96 can achieve high throughput, up to 4.3 × 1016 MAC/s with 10 layers. Energy assessments showed that the SPLM array, despite its higher power consumption compared to the SLM array, is manageable via effective heat dissipation. Smart pixels with programmable memory in the SPBONN provide a cost-effective solution for expanding network node size and overcoming scalability limitations without the need for additional hardware.
Effects of Hydrochar Incorporation on the Nitrogen Leaching Flux Pattern and Load in Rice Paddy Soil and Crop Production
Authors: Ma Meng , Chen Yudong , Zhang Jinjin , Liu Chang , Sun Haijun
Published: February 2025

Hydrochar (HC) incorporation affects soil nitrogen (N) transformation, which could further affect the N leaching loss. We conducted a soil lysimeter experiment to evaluate the responses in terms of N leaching and rice yield to HC applied at a low (0.5%) or high (1.5%) rate, while considering three N inputs, i.e., 240, 192, and 144 kg/ha (named N240, N192, and N144, respectively). The results showed that the rice grain yield was highest (124.3 g/pot) for N192, while being significantly reduced to the minimum yield achieved in the study (110.3 g/pot) for N144. Interestingly, for the N input 144 kg/ha, HC application increased the rice grain yield by 6.9–8.0%, which was equivalent to that of N240. NH4+-N leaching occurred mainly during the first 4 weeks of the rice season, and HC did not influence NH4+-N leaching for both the N inputs, 192 and 240 kg/ha. However, compared to N144, N144 + HC1.5% recorded a significantly higher NH4+-N leaching loss of 34.6%. This suggests that the application of a high amount of HC increases the NH4+-N leaching risk when the N input is low. HC application resulted in 10.2–45.3% more NO3−-N leaching loss when the three N inputs were applied, the effect of which was significant in regard to the applications involving a 20 and 40% N reduction, but this occurred only with the applied treatments involving 1.5% HC. Moreover, we found that organic N was the main form of leachate N (>80%). More specifically, N144 + HC recorded 7.8–8.3% lower organic N leaching than N192. Based on the effects of HC on the rice grain yield and N leaching, we recommend applications involving a 40% N reduction (N144) with a lower amount of HC (HC 0.5%) to ensure high crop production and to protect the water environment.