bluuebunny/crossref_metadata_2025 huggingface dataset:
Tandem Mass Spectrometry in Untargeted Lipidomics: A Case Study of Peripheral Blood Mononuclear Cells
Authors: Ventura Giovanni , Bianco Mariachiara , Calvano Cosima Damiana , Losito Ilario , Cataldi Tommaso R. I.
Published: November 2024

Peripheral blood mononuclear cells (PBMCs), including lymphocytes, are important components of the human immune system. These cells contain a diverse array of lipids, primarily glycerophospholipids (GPs) and sphingolipids (SPs), which play essential roles in cellular structure, signaling, and programmed cell death. This study presents a detailed analysis of GP and SP profiles in human PBMC samples using tandem mass spectrometry (MS/MS). Hydrophilic interaction liquid chromatography (HILIC) and electrospray ionization (ESI) coupled with linear ion-trap MS/MS were employed to investigate the diagnostic fragmentation patterns that aided in determining regiochemistry in complex lipid extracts. Specifically, the study explored the fragmentation patterns of various lipid species, including phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), their plasmalogen and lyso forms, phosphatidylserines (PSs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs), sphingomyelins (SMs), and dihexosylceramides (Hex2Cer). Our comprehensive analysis led to the characterization of over 200 distinct lipid species, significantly expanding our understanding of PBMC lipidome complexity. A freely available spreadsheet tool for simulating MS/MS spectra of GPs is provided, enhancing the accessibility and reproducibility of this research. This study advances our knowledge of PBMC lipidomes and establishes a robust analytical framework for future investigations in lipidomics.
Optimization of Whole-Genome Resequencing Depth for High-Throughput SNP Genotyping in Litopenaeus vannamei
Authors: Lin Pengfei , Yu Yang , Bao Zhenning , Li Fuhua
Published: November 2024

The application of whole-genome resequencing in genetic research is rapidly expanding, yet the impact of sequencing depth on data quality and variant detection remains unclear, particularly in aquaculture species. This study re-sequenced 31 Litopenaeus vannamei (L. vannamei) samples at over 28× sequencing depth using the Illumina NovaSeq system and down-sampled the data to simulate depths from 0.5× to 20×. Results showed that when the sequencing depth was below 10×, the number of SNP identifications increased sharply with the rise in depth, with single nucleotide polymorphisms (SNPs) detected at 10× accounting for approximately 69.16% of those detected at 20×. The genotyping accuracy followed a similar trend to SNP detection results, being approximately 0.90 at 6×. Further analyses showed that the main cause of genotyping errors was the misidentification of heterozygous variants as homozygous variants. Therefore, considering both the quantity and quality of SNPs, a sequencing depth of 10× is recommended for whole-genome studies and genetic mapping, while a depth of 6× is more cost-effective for population structure analysis. This study underscores the importance of selecting optimal sequencing depth to ensure reliable variant detection and high data quality, providing valuable guidance for whole-genome resequencing in shrimp and other aquatic species.
The Link Between the Gut Microbiome and Bone Metastasis
Authors: Sevcikova Aneta , Martiniakova Monika , Omelka Radoslav , Stevurkova Viola , Ciernikova Sona
Published: November 2024

The gut microbiome is essential for regulating host metabolism, defending against pathogens, and shaping the host’s immune system. Mounting evidence highlights that disruption in gut microbial communities significantly impacts cancer development and treatment. Moreover, tumor-associated microbiota, along with its metabolites and toxins, may contribute to cancer progression by promoting epithelial-to-mesenchymal transition, angiogenesis, and metastatic spread to distant organs. Bones, in particular, are common sites for metastasis due to a rich supply of growth and neovascularization factors and extensive blood flow, especially affecting patients with thyroid, prostate, breast, lung, and kidney cancers, where bone metastases severely reduce the quality of life. While the involvement of the gut microbiome in bone metastasis formation is still being explored, proposed mechanisms suggest that intestinal dysbiosis may alter the bone microenvironment via the gut-immune-bone axis, fostering a premetastatic niche and immunosuppressive milieu suitable for cancer cell colonization. Disruption in the delicate balance of bone modeling and remodeling may further create a favorable environment for metastatic growth. This review focuses on the link between beneficial or dysbiotic microbiome composition and bone homeostasis, as well as the role of the microbiome in bone metastasis development. It also provides an overview of clinical trials evaluating the impact of gut microbial community structure on bone parameters across various conditions or health-related issues. Dietary interventions and microbiota modulation via probiotics, prebiotics, and fecal microbiota transplantation help support bone health and might offer promising strategies for addressing bone-related complications in cancer.
An Immune-Independent Mode of Action of Tacrolimus in Promoting Human Extravillous Trophoblast Migration Involves Intracellular Calcium Release and F-Actin Cytoskeletal Reorganization
Authors: Albaghdadi Ahmad J. H. , Xu Wei , Kan Frederick W. K.
Published: November 2024

We have previously reported that the calcineurin inhibitor macrolide immunosuppressant Tacrolimus (TAC, FK506) can promote the migration and invasion of the human-derived extravillous trophoblast cells conducive to preventing implantation failure in immune-complicated gestations manifesting recurrent implantation failure. Although the exact mode of action of TAC in promoting implantation has yet to be elucidated, the integral association of its binding protein FKBP12 with the inositol triphosphate receptor (IP3R) regulated intracellular calcium [Ca2+]i channels in the endoplasmic reticulum (ER), suggesting that TAC can mediate its action through ER release of [Ca2+]i. Using the immortalized human-derived first-trimester extravillous trophoblast cells HTR8/SVneo, our data indicated that TAC can increase [Ca2+]I, as measured by fluorescent live-cell imaging using Fluo-4. Concomitantly, the treatment of HTR8/SVneo with TAC resulted in a major dynamic reorganization in the actin cytoskeleton, favoring a predominant distribution of cortical F-actin networks in these trophoblasts. Notably, the findings that TAC was unable to recover [Ca2+]i in the presence of the IP3R inhibitor 2-APB indicate that this receptor may play a crucial role in the mechanism of action of TAC. Taken together, our results suggest that TAC has the potential to influence trophoblast migration through downstream [Ca2+]i-mediated intracellular events and mechanisms involved in trophoblast migration, such as F-actin redistribution. Further research into the mono-therapeutic use of TAC in promoting trophoblast growth and differentiation in clinical settings of assisted reproduction is warranted.
Plant-Derived Exosome-like Nanoparticles: A Comprehensive Overview of Their Composition, Biogenesis, Isolation, and Biological Applications
Authors: Sha Ajia , Luo Yingyong , Xiao Wenqi , He Jing , Chen Xiaodie , Xiong Zhuang , Peng Lianxin , Zou Liang , Liu Bingliang , Li Qiang
Published: November 2024

Plant-derived exosome-like nanoparticles (PELNs) are a type of membranous vesicle isolated from plant tissues. They contain proteins, lipids, nucleic acids, and other components. PELNs are involved in the defensive response to pathogen attacks by exerting anti-inflammatory, antiviral, antifibrotic, and antitumor effects through the substances they contain. Most PELNs are edible and can be used as carriers for delivering specific drugs without toxicity and side effects, making them a hot topic of research. Sources of PELNs are abundantly, and they can be produced in high yields, with a low risk of developing immunogenicity in vivo. This paper summarizes the formation, isolation, and purification methods; physical properties; and composition of PELNs through a comprehensive literature search. It also analyzes the biomedical applications of PELNs, as well as future research directions. This paper provides new ideas and methods for future research on PELNs.
The Effect of Low-Frequency Magnetic Fields with Low Induction and Red LED Light on Keratinocyte Biological Activity—An In Vitro Research Model
Authors: Woźniacka Renata , Lechowska-Liszka Agnieszka , Stenka Beata , Bac Aneta , Homa Joanna , Chadzińska Magdalena , Ścisłowska-Czarnecka Anna
Published: November 2024

For several decades, there has been growing interest in the influence of low-frequency magnetic fields (LFMFs) and red LED light on the healing process. Keratinocytes are cells that play a significant role in the process of wound healing and tissue regeneration. A human keratinocyte cell line (HaCaT) was exposed to an LFMF with low induction (180–195 Hz; 60 µT, magnetostimulation), red LED light (630 nm; 300 mW, LED therapy), and their combined action (magneto-LED therapy) in in vitro culture conditions. On day 4 and 8 of the experiment, the following parameters were determined: adhesion/proliferation, adenylate kinase (AK), nitric oxide (NO), cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF-α), metalloproteinases (MMP-2, MMP-9), and collagen IV. It was shown that magnetostimulation caused an increase in keratinocyte adhesion/proliferation and IL-8 secretion and a decrease in IL-12 secretion. The LED therapy resulted in a transient increase in the secretion of NO and cytokines IL-1, IL-12, and IL-6 in keratinocytes. The use of magneto-LED therapy resulted in an increase in keratinocyte adhesion/proliferation, the secretion of cytokines IL-6 and IL-8, and NO with a simultaneous decrease in MMP-9 secretion. The results of our studies showed that the action of an LFMF with low-induction and LED light on keratinocytes can modulate the biological activity of keratinocytes towards improving the skin healing process.
Assessing the Recreational Resource Value of National Park Based on Visitor Perception—A Case of Three-River-Source National Park in China
Authors: Luo Xiao , Huang Zongcai , Wang Lingen
Published: November 2024

National parks serve as critical practical sites for advancing the concept of “harmonious coexistence between humans and nature” and hold a strategic role in establishing global ecological security barriers. Scholars and decision-makers have expressed significant interest in rigorous assessments of the recreational resource value in national parks. This paper focuses on the Three-River-Source National Park, examining the characteristics and components of its recreational resource value through the lens of human–environment relationship theory. Analysis spans dimensions of geological and geomorphological value, ecological service value, historical and cultural value, and aesthetic landscape value. By extracting visitor comments rich in vocabulary related to their perceptions, this study compares variations in resource values and the “resource value–visitor perception” synergy within Three-River-Source National Park, employing text analysis, semantic network analysis, and coordination analysis methods. The findings reveal that (1) Visitor perceptions of recreational resource value display a clear hierarchy, with aesthetic landscape value (43.6%) ranking highest, followed by geological and geomorphological value (26.7%), historical and cultural value (19.3%), and ecological service value (10.4%), showing significant variation among categories; the vocabulary across these value types exhibits a pronounced long-tail distribution. (2) The recreational resource value in the park forms a distinct core centered on prominent attractions, accompanied by patterns of vocabulary aggregation and dispersion. (3) Visitors demonstrate strong synergy in their perception of geological and aesthetic value, weaker perception regarding historical and cultural value, and a relatively narrow understanding of ecological service value. This research enhances public comprehension of the recreational resource value of national parks and provides a scientific foundation for the conservation and sustainable use of recreational resources in national parks, advancing the realization of their recreational functions.
Location Preferences and Changes in Pollution-Intensive Firms from the Yangtze River Economic Belt, China
Authors: Liu Chang , Zhou Huixin , Li Zitong , Zhou Dingyang , Tian Yingying , Jiang Guanghui
Published: November 2024

This study examined the location preferences and changes in pollution-intensive firms by analyzing the spatiotemporal distribution and drivers in the Yangtze River Economic Belt, a transitional manufacturing region in China. To analyze the distribution of firms under natural growth conditions prior to the implementation of the national “Great Protection of the Yangtze River” policy in 2016, this study utilized data on newly expanded industrial land use from 2007 to 2016. The results indicated that new pollution-intensive firms predominantly focused on water pollution, occupying over 40% of the total area annually. The new pollution-intensive firms preferred the geographic agglomeration siting strategy, mostly along the Yangtze River or in urban agglomerations, while gradually moving westward. The total area and number of new pollution-intensive firms in the Yangtze River Economic Belt showed an overall trend of “inverted U-shaped” variation during the study period, and the average size of the pollution-intensive firms gradually decreased. GeoDetector analysis revealed that geographical factors have always been significant. Local economic factors attracted new pollution-intensive firms, but later in the study period, these factors showed some inhibitory effect on the increase in pollution-intensive firms in the lower reaches. Government intervention worked less effectively but was significantly enhanced after interaction with other factors. Finally, the results suggested that local governments should build a stronger synergy between industrial land policies and environmental regulations to ensure sustainable growth and rational allocation of pollution-intensive firms.
Impact of hBN Content on the Tribological Behavior and Thermal Diffusivity of HVOF-Sprayed Cr3C2-NiCr Coatings
Authors: Eßler Julian , Woelk Dino , Utu Ion-Dragos , Marginean Gabriela
Published: November 2024

Considering the significant health risks posed by hard chrome plating during its application, thermally sprayed Cr3C2-NiCr cermet coatings represent a suitable alternative. Incorporating hexagonal boron nitride (hBN) as a dry lubricant into the feedstock powder can further enhance wear resistance and thermal conductivity, crucial for preventing premature failure caused by inadequate lubrication. In this study, the mass fraction of hBN was varied between 0 and 15 wt.% to assess its influence on the tribological performance of the coatings using pin-on-disk tests. The coating’s hardness was measured via the Vickers method, and its cracking tendency at the coating/substrate interface was evaluated. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were employed to analyze the microstructure and phase composition, while thermal diffusivity was determined using the laser flash method. The findings revealed that the inclusion of hBN, at concentrations of up to 10 wt.%, leads to an improvement in thermal diffusivity and a reduction in the coefficient of friction. However, exceeding this threshold leads to a decrease in hardness and increased crack formation tendency, highlighting the trade-off between frictional and mechanical properties.
Broaching Digital Twin to Predict Forces, Local Overloads, and Surface Topography Irregularities
Authors: Ortiz-de-Zarate Gorka , Madariaga Aitor , Soler Daniel , Arrazola Pedro J.
Published: November 2024

Broaching is a key manufacturing process that directly influences the surface integrity of critical components, impacting their functional performance in sectors such as aeronautics, automotive, and energy. Such components are subjected to severe conditions, including high thermomechanical loads, fatigue, and corrosion. For this reason, the development of predictive models is essential for determining the optimal tool design and machining conditions to ensure proper in-service performance. This study, therefore, presents a broaching digital twin based on hybrid modelling, which combines analytical, numerical, and empirical approaches to provide rapid and accurate predictions of the forces per tooth, local overloads, and surface topography irregularities. The digital twin was validated with a critical industrial case study involving fir-tree broaching of turbine discs made of forged and age-hardened Inconel 718. The accuracy of the digital twin was demonstrated by the results: the average error in force predictions was below 10%, and the model effectively identified the most critical teeth and zones prone to failure. It also predicted surface topography irregularities with an error of less than 15%. Interestingly, the relationship between surface topography irregularities and surface residual stress variations across the machined surface was observed experimentally for the first time.
Scott Blair Fractional-Type Viscoelastic Behavior of Clear Spruce Wood: Influence of Compression Wood on Power-Law Stiffness Parameters
Authors: Pichler Christian , Maderebner Roland , Dummer Alexander , Stieb Thomas , Lackner Roman
Published: November 2024

In this paper, we investigate the influence of intrinsic compositional parameters on the viscoelastic compliance by employing three-point bending creep tests on clear, i.e., defect-free, spruce samples with a dimension of 15 × 15 × 280 mm3. In addition to the regular samples, a prominent wood variation was investigated: so-called compression wood, stemming from an adaptive response of the growing tree to maintain structural stability. Tests were conducted at constant ambient conditions: isothermal at 20 degrees Celsius and at a relative humidity of 65 percent. These conditions were also employed during sample conditioning, leading to an equilibrium moisture content of the specimens of approximately 12 percent. Hence, so-called basic creep properties were investigated. Furthermore, we show that the experimentally observed compliance can be exceptionally well-modeled by a Scott Blair fractional-type element, with the latter calibrated by a mere number of two independent material parameters. This allows to render rather explicit dependencies of these parameters with respect to the dry density and the volumetric content of the compression wood. There, the quasi-instantaneous stiffness of the employed Scott Blair element is an increasing function of the dry density. While this primary dependency is also observed for compression wood, the quasi-instantaneous stiffness is significantly smaller over the investigated density range.
Theoretical Study of Quaternary nBp InGaAsSb SWIR Detectors for Room Temperature Condition
Authors: Manyk Tetiana , Rutkowski Jarosław , Kopytko Małgorzata , Kłos Krzysztof , Martyniuk Piotr
Published: November 2024

This paper presents a theoretical analysis of an nBp infrared barrier detector’s performance intended to operate at a room temperature (300 K) based on AIIIBV materials—In1-xGaxAsySb1−y quaternary compound—lattice-matched to the GaSb substrate with a p-n heterojunction ternary Al1−xGaxSb barrier. Numerical simulations were performed using a commercial Crosslight Software—package APSYS. The band structure of the nBp detector and the electric field distribution for the p-n heterojunction with and without a potential barrier were determined. The influence of the barrier-doping level on the detector parameters was analyzed. It was shown that Shockley-Read-Hall (SRH) recombination plays a decisive role in carrier transport for lifetimes shorter than 100 ns. The influence of the absorber/barrier thickness on the detector’s dark current density and photocurrent was investigated. It was shown that valence band offset does not influence the device’s performance. The quantum efficiency reaches its maximum value for an absorber’s thickness of ~3 μm. The performed simulations confirmed the possibility of the detector’s fabrication exhibiting high performance at room temperature based on quaternary compounds of AIIIBV materials for the short wavelength infrared range.
The Thermomechanical, Functional and Biocompatibility Properties of a Au–Pt–Ge Alloy for PFM Dental Restorations
Authors: Majerič Peter , Lazić Minja Miličić , Mitić Dijana , Lazić Marko , Lazić Ema Krdžović , Vastag Gyöngyi , Anžel Ivan , Lazić Vojkan , Rudolf Rebeka
Published: November 2024

A high-noble Au–Pt–Ge porcelain-fused-to-metal (PFM) dental alloy without the known adverse metallic elements and with the addition of germanium (Ge) was produced as a more cost-effective alternative to other precious alloying metals, with investigations for determining the functionality and clinical use of this alloy. The thermomechanical, biocompatibility, durability, workability and economic characteristics of the produced dental alloy were investigated. These properties were investigated with in vitro biocompatibility testing on human gingival fibroblasts (HGFs); static immersion testing for metal ion release; DSC analysis; hardness, tensile testing, density and coefficient of thermal expansion (CTE) measurements; metallographic and SEM/EDX microstructure investigations; and finally with the production of a test PFM dental bridge. The results of the thermomechanical testing showed alloy properties suitable for dental restorations and clinical use, with somewhat lower mechanical properties, making the alloy not suitable for extensive multiunit fixed restorations. The microstructure investigations showed segregations of Ge in the homogeneous alloy matrix, which reduce the alloy’s mechanical properties. The produced PFM dental bridge showed excellent workability of the alloy in a dental laboratory setting, as well as a high standard of the final dental restoration. The ion release was negligible, well below any harmful quantities, while the cell viability examination showed significantly higher viability ratings on polished alloy samples as compared to as-cast samples. The results showed that a dental substructure in direct contact with oral tissue and fluids should be highly polished. The performed investigations showed that the produced PFM dental alloy is suitable for clinical use in producing high-quality dental restorations with high biocompatibility for patients prone to metal allergies.
Evaluation of the Influence of Surface Roughness Parameters on Ultrasonic Rayleigh Waveforms
Authors: Grochalski Karol , Kowalczyk Jakub , Jósko Marian , Wieczorowski Michal
Published: November 2024

Ultrasonic nondestructive testing is widely used not only in the laboratory, but also in industry. The tests use various types of ultrasonic waves, diverse measurement techniques and different apparatus. One of the problems encountered is the high susceptibility of the surface wave to interference. Some of the interference is random in nature and can be minimized (e.g., contamination of the surface or resting a finger on the surface under study). Some of the interference is permanent in nature, such as variable surface roughness. The aim of the conducted research was to evaluate the influence of roughness on ultrasonic wave propagation. The study used samples with surface roughness Sa from 0.28 to 219 µm, and ultrasonic surface wave probes with frequencies from 1.41 to 8.02 MHz. It was observed that roughness significantly affects the attenuation of the ultrasonic wave, and the differences in signal amplification reached more than 15 dB. Similarly, the effect of the ultrasonic wave’s transit time through surfaces of different roughness was noted. It was found that the difference in the ultrasonic wave transition time was more than 50 µs. The results of the study can be helpful for the ultrasonic testing of materials with different surface conditions.
Effect of Co Addition on the Microstructure and Mechanical Properties of Sn-11Sb-6Cu Babbitt Alloy
Authors: Cheng Zhan , Wang Meng , Wang Bo , Zhang Lei , Zhu Ting , Li Ningbo , Zhou Jifa , Jia Fei
Published: November 2024

A Babbitt alloy SnSb11Cu6 with 0–2.0 wt.% Co was synthesized using the induction melting process. This study examined the effect of cobalt (Co) on the microstructure, tensile properties, compressive properties, Brinell hardness, and wear properties of SnSb11Cu6 using optical microscopy (OM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), a universal tensile testing machine, a Brinell hardness tester, and a wear testing machine. The results indicate that the optimal quantity of Co can enhance the microstructure of the Babbitt alloy and promote microstructure uniformity, with presence of Co3Sn2 in the matrix. With the increase in Co content, the tensile and compressive strength of the Babbitt alloy first increased and then decreased, and the Brinell hardness gradually increased with the increase in Co content. The presence of trace Co has a minimal effect on the dry friction coefficient of the Babbitt alloy. When the Co content exceeds 1.5 wt.%, the friction properties of the Babbitt alloy deteriorate significantly. The optimized Babbitt alloy SnSb11Cu6-1.5Co was subsequently fabricated into wires, followed by conducting cold metal transfer (CMT) surfacing experiments. The Co element can promote the growth of interfacial compounds. The microstructure at the interface of the Babbitt alloy/steel is dense, and there is element diffusion between it. The metallurgical bonding is good, and there are serrated compounds relying on the diffusion layer to extend to the direction of the additive layer with serrated compounds extending and growing from the diffusion layer to the additive layer. Overall, Babbitt alloys such as SnSb11Cu6 exhibit improved comprehensive properties when containing 1.5 wt.% Co.
Green Synthesis of Ag and Cu Nanoparticles Using E. telmateia Ehrh Extract: Coating, Characterization, and Bioactivity on PEEK Polymer Substrates
Authors: Altınsoy Şakir , Kızılbey Kadriye , İlim Hümeyra Berfin
Published: November 2024

PEEK-based implant materials have gained increasing attention as an alternative to titanium due to their biocompatibility and bone-like elasticity. However, PEEK’s surface quality and wear resistance are lower than those of metals. This study aimed to enhance the bioactivity and surface quality of PEEK by coating it with silver and copper nanoparticles synthesized via a green method using Equisetum telmateia Ehrh. extract. PEEK samples (Ø 25 mm, 3 mm thick) were coated with single and double layers using spray (airbrush-spray) and drop-coating methods. Comprehensive analyses including SEM, EDX, FT-IR, UV-Vis, surface roughness, release studies, antioxidant and cytotoxicity activity, and antibacterial tests were conducted on the coated samples. The results demonstrated that AgNPs and CuNPs coatings significantly improved the surface quality of PEEK. SEM analysis revealed particle sizes ranging from 48 to 160 nm for AgNPs and 50–135 nm for CuNPs, with superior dispersion obtained using the airbrush-spray method. Surface roughness measurements showed a reduction of 17–33% for AgNPs-coated samples and 7–15% for CuNPs-coated samples compared to uncoated PEEK, with airbrush-spray coatings providing smoother surfaces. Antioxidant activity tests indicated that AgNPs provided 35% higher antioxidant activity compared to CuNPs. Additionally, antibacterial tests revealed that AgNPs exhibited a higher zone of inhibition (up to 14 mm for S. aureus and 18 mm for E. coli) compared to CuNPs, which exhibited zones of 8 mm and 10 mm, respectively. This study concludes that green-synthesized AgNPs, in particular, enhance the bioactivity and surface properties of PEEK, making it a promising material for biomedical applications such as infection-resistant implants.
Comparison of Microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis Lipid Extracts Effects on UVA-Induced Changes in Human Skin Fibroblasts Proteome
Authors: Atalay Ekiner Sinemyiz , Gęgotek Agnieszka , Domingues Pedro , Domingues Maria Rosário , Skrzydlewska Elżbieta
Published: November 2024

Lipid extracts from the microalgae Nannochloropsis oceanica and Chlorococcum amblystomatis have great potential to prevent ultraviolet A (UVA)-induced metabolic disorders. Therefore, the aim of this study has been to analyze their cytoprotective effect, focused on maintaining intracellular redox balance and inflammation in UVA-irradiated skin fibroblasts, at the proteome level. The above lipid extracts reversed the suppression of the antioxidant response caused by UVA radiation, which was more visible in the case of C. amblystomatis. Modulations of interactions between heme oxygenase-1 and matrix metalloproteinase 1/Parkinson’s disease protein 7/transcript1-α/β, as well as thioredoxin and migration inhibitory factor/Parkinson’s disease protein 7/calnexin/ATPase p97, created key molecular signaling underlying their cytoprotective actions. Moreover, they reduced pro-inflammatory processes in the control group but they also showed the potential to regulate the cellular inflammatory response by changing inflammasome signaling associated with the changes in the caspase-1 interaction area, including heat shock proteins HSP90, HSPA8, and vimentin. Therefore, lipid extracts from N. oceanica and C. amblystomatis protect skin fibroblast metabolism from UVA-induced damage by restoring the redox balance and regulating inflammatory signaling pathways. Thus, those extracts have proven to have great potential to be used in cosmetic or cosmeceutical products to protect the skin against the effects of solar radiation. However, the possibility of their use requires the evaluation of their effects at the skin level in in vivo and clinical studies.
Zic-HILIC MS/MS Method for NADomics Provides Novel Insights into Redox Homeostasis in Escherichia coli BL21 Under Microaerobic and Anaerobic Conditions
Authors: Rane Divyata Vilas , García-Calvo Laura , Kristiansen Kåre Andre , Bruheim Per
Published: November 2024

Background: Nicotinamide adenine dinucleotide (NAD+), its precursors, and its derivatives (collectively NADome) play a crucial role in cellular processes and maintain redox homeostasis. Understanding the dynamics of these metabolic pools and redox reactions can provide valuable insights into metabolic functions, especially cellular regulation and stress response mechanisms. The accurate quantification of these metabolites is challenging due to the interconversion between the redox forms. Methods: Our laboratory previously developed a zwitterionic hydrophilic interaction liquid chromatography (zic-HILIC)–tandem mass spectrometry method for the quantification of five essential pyridine nucleotides, including NAD+ derivatives and it’s reduced forms, with 13C isotope dilution and matrix-matched calibration. In this study, we have improved the performance of the chromatographic method and expanded its scope to twelve analytes for a comprehensive view of NAD+ biosynthesis and utilization. The analytical method was validated and applied to investigate Escherichia coli BL21 under varying oxygen supplies including aerobic, microaerobic, and anaerobic conditions. Conclusions: The intracellular absolute metabolite concentrations ranged over four orders of magnitude with NAD+ as the highest abundant, while its precursors were much less abundant. The composition of the NADome at oxygen-limited conditions aligned more with that in the anaerobic conditions rather than in the aerobic phase. Overall, the NADome was quite homeostatic and E. coli rapidly, but in a minor way, adapted the metabolic activity to the challenging shift in the growth conditions and achieved redox balance. Our findings demonstrate that the zic-HILIC-MS/MS method is sensitive, accurate, robust, and high-throughput, providing valuable insights into NAD+ metabolism and the potential significance of these metabolites in various biological contexts.
Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review
Authors: Contella Lindsey , Farrell Christopher L. , Boccuto Luigi , Litwin Alain H. , Snyder Marion L.
Published: November 2024

Background/Objectives: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pathways. The metabolites of these pathways play a role in the biological reward system. Addictive substances have been shown to cause imbalances in the ratios of these metabolites. With current treatment and therapeutic options being suboptimal, identifying biochemical mechanisms that are impacted during the use of addictive substances can provide alternative options for treatment or drug discovery. Methods: A systematic literature search was conducted to identify studies evaluating the relationship between substance use disorder and tryptophan metabolism through the kynurenine pathway. A total of 32 articles meeting eligibility criteria were used to review the relationship between the kynurenine pathway, tryptophan breakdown, and addictive substances. Results: The use of addictive substances dysregulates tryptophan metabolism and kynurenine metabolite concentrations. This imbalance directly affects the dopamine reward system and is thought to promote continued substance use. Conclusions: Further studies are needed to fully evaluate the metabolites of the kynurenine pathway, along with other options for treatment to repair the metabolite imbalance. Several possible therapeutics have been identified; drugs that restore homeostasis, such as Ro 61-8048 and natural products like Tinospora cordifolia or Decaisnea insignis, are promising options for the treatment of substance use disorder.
Solubility of Sulfamerazine in Acetonitrile + Ethanol Cosolvent Mixtures: Thermodynamics and Modeling
Authors: Ortiz Claudia Patricia , Caviedes-Rubio Diego Ivan , Martinez Fleming , Delgado Daniel Ricardo
Published: November 2024

Sulfamerazine (SMR) is a drug used as an antibacterial agent in the treatment of some pathologies, such as bronchitis, prostatitis and urinary tract infections. Although this drug was developed in 1945 and, due to its toxicity, was partially displaced by penicillin, due to the current problem of bacterial resistance, compounds such as SMR have regained validity. In this context, the thermodynamic study of SMR in cosolvent mixtures of acetonitrile (MeCN) + ethanol (EtOH) at nine temperatures (278.15–318.15 K) is presented. The solubility of SMR was determined by UV–Vis spectrophotometry, following the guidelines of the shake-flask method. The solubility process was endothermic in all cases; thus, the minimum solubility was reached in pure EtOH at 278.15 K, and the maximum solubility was reached in pure MeCN at 318.15 K. Both the solution process and the mixing process were entropy-driven. On the other hand, the solubility data were modeled by using the van’t Hoff–Yalkowsky–Roseman model, obtaining an overall average relative deviation of 3.9%. In general terms, it can be concluded that the solution process of SMR in {MeCN (1) + EtOH (2)} mixtures is thermodependent, favored by the entropy of the solution and mixture; additionally, the van’t Hoff–Yalkowsky–Roseman model allows very good approximations to be obtained and is a simple model that starts from only four experimental data.
Kratom Alkaloids: A Blood–Brain Barrier Specific Membrane Permeability Assay-Guided Isolation and Cyclodextrin Complexation Study
Authors: Dohárszky András , Vági Erika Mária , Könczöl Árpád , Simon Alexandra , Várnagy Erzsébet , Muratov Miras , Steiger Kristóf István , Várnai Bianka , Béni Szabolcs , Riethmüller Eszter , Fejős Ida
Published: November 2024

Mitragynine is an “atypic opioid” analgesic with an alternative mechanism of action and a favorable side-effect profile. Our aim was to optimize the alkaloid extraction procedure from kratom leaves and to determine and isolate the most relevant compounds capable of penetrating the central nervous system. The PAMPA-BBB study revealed that mitragynine and its coalkaloids, speciociliatine, speciogynine, and paynantheine, possess excellent in vitro BBB permeability. An optimized sequence of CPC, flash chromatography, and preparative HPLC methods was used to isolate the four identified BBB+ alkaloids. To improve the bioavailability of the isolated alkaloids, their cyclodextrin (CD) complexation behavior was investigated via affinity capillary electrophoresis using almost 40 CD derivatives. The apparent alkaloid–CD complex stability constants were determined and compared, and the most relevant CDs phase-solubility studies were also performed. Both the neutral and negatively charged derivatives were able to form complexes with all four kratom alkaloids. It was found that cavity size, substituent type, and degree of substitution also influenced complex formation. The negatively charged Sugammadex, Subetadex, and the sufoalkylated-beta-CD analogs were able to form the most stable complexes, exceeding 1000 M−1. These results serve as a good basis for further solubility and stability enhancement studies of kratom alkaloids.
Liposomal Formulations of Novel BODIPY Dimers as Promising Photosensitizers for Antibacterial and Anticancer Treatment
Authors: Porolnik Weronika , Ratajczak Magdalena , Mackowiak Aleksandra , Murias Marek , Kucinska Malgorzata , Piskorz Jaroslaw
Published: November 2024

Synthesis, photochemical properties, liposomal encapsulation, and in vitro photodynamic activity studies of novel BODIPY dimer connected at meso-meso positions and its brominated and iodinated analogs were described. UV-Vis measurements indicated that the dimeric structure of obtained BODIPYs did not significantly influence the positions of the absorption maxima. Emission properties and singlet oxygen generation studies revealed a strong heavy atom effect of brominated and iodinated BODIPY dimers, manifested by fluorescence intensity reduction and increased singlet oxygen generation ability compared to analog without halogen atoms. For the in vitro photodynamic activity studies, dimers were incorporated into two different types of liposomes: positively charged DOTAP:POPC and negatively charged POPG:POPC. The photoinactivation studies revealed high activity of brominated and iodinated dimers incorporated into DOTAP:POPC liposomes on both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Anticancer studies on human breast adenocarcinoma MDA-MB-231 and human ovarian carcinoma A2780 cells revealed that DOTAP:POPC liposomes containing brominated and iodinated dimers were active even at low nanomolar concentrations. In addition, they were more active against MDA-MB-231 cells than A2780 cells, which is particularly important since the MDA-MB-231 cell line represents triple-negative breast cancer, which has limited therapeutic options.
Antioxidant Potential of Medicinal Plants in the Treatment of Scabies Infestation
Authors: Wróblewski Marcin , Wróblewska Joanna , Nuszkiewicz Jarosław , Mila-Kierzenkowska Celestyna , Woźniak Alina
Published: November 2024

Oxidative stress, characterized by an overproduction of reactive oxygen species that overwhelm the body’s physiological defense mechanisms, is a key factor in the progression of parasitic diseases in both humans and animals. Scabies, a highly contagious dermatological condition caused by the mite Sarcoptes scabiei var. hominis, affects millions globally, particularly in developing regions. The infestation leads to severe itching and skin rashes, triggered by allergic reactions to the mites, their eggs, and feces. Conventional scabies treatments typically involve the use of scabicidal agents, which, although effective, are often associated with adverse side effects and the increasing threat of resistance. In light of these limitations, there is growing interest in the use of medicinal plants as alternative therapeutic options. Medicinal plants, rich in bioactive compounds with antioxidant properties, offer a promising, safer, and potentially more effective approach to treatment. This review explores the role of oxidative stress in scabies pathogenesis and highlights how medicinal plants can mitigate this by reducing inflammation and oxidative damage, thereby alleviating symptoms and improving patient outcomes. Through their natural antioxidant potential, these plants may serve as viable alternatives or complementary therapies in the management of scabies, especially in cases where resistance to conventional treatments is emerging.
New Insights into the Development of Donepezil-Based Hybrid and Natural Molecules as Multi-Target Drug Agents for Alzheimer’s Disease Treatment
Authors: Angelova Violina T. , Stoyanov Boris P. , Simeonova Rumyana
Published: November 2024

Alzheimer’s disease (AD) involves a complex pathophysiology with multiple interconnected subpathologies, including protein aggregation, impaired neurotransmission, oxidative stress, and microglia-mediated neuroinflammation. Current treatments, which generally target a single subpathology, have failed to modify the disease’s progression, providing only temporary symptom relief. Multi-target drugs (MTDs) address several subpathologies, including impaired aggregation of pathological proteins. In this review, we cover hybrid molecules published between 2014 and 2024. We offer an overview of the strategies employed in drug design and approaches that have led to notable improvements and reduced hepatotoxicity. Our aim is to offer insights into the potential development of new Alzheimer’s disease drugs. This overview highlights the potential of multi-target drugs featuring heterocycles with N-benzylpiperidine fragments and natural compounds in improving Alzheimer’s disease treatment.
Advancements in p53-Based Anti-Tumor Gene Therapy Research
Authors: Peng Yuanwan , Bai Jinping , Li Wang , Su Zhengding , Cheng Xiyao
Published: November 2024

The p53 gene is one of the genes most closely associated with human tumors and has become a popular target for tumor drug design. Currently, p53-based gene therapy techniques have been developed, but these therapies face challenges such as immaturity, high safety hazards, limited efficacy, and low patient acceptance. However, researchers are no less enthusiastic about the treatment because of its theoretical potential to treat cancer. In this paper, the advances in p53-based gene therapy and related nucleic acid delivery technologies were reviewed and prospected in order to support further development in this field.
How Do Cyclodextrins and Dextrans Affect the Gut Microbiome? Review of Prebiotic Activity
Authors: Gościniak Anna , Lainé Emmanuelle , Cielecka-Piontek Judyta
Published: November 2024

The modulation of the gut microbiome through dietary components has garnered significant attention for its potential health benefits. Prebiotics, non-digestible food ingredients that promote the growth of beneficial gut bacteria, play a crucial role in maintaining gut health, enhancing immune function, and potentially preventing various metabolic and inflammatory disorders. This review explores the prebiotic activity of cyclodextrins and dextrans, focusing on their ability to influence gut microbiota composition and function. Both cyclodextrins and dextrans have demonstrated the capacity to promote the growth of beneficial bacterial populations, while also impacting short-chain fatty acid production, crucial for gut health.
Comparative Analysis of Thin and Thick MoTe2 Photodetectors: Implications for Next-Generation Optoelectronics
Authors: Hussain Saddam , Zhao Shaoguang , Zhang Qiman , Tao Li
Published: November 2024

Due to its outstanding optical and electronic properties, molybdenum ditelluride (MoTe2) has become a highly regarded material for next-generation optoelectronics. This study presents a comprehensive, comparative analysis of thin (8 nm) and thick (30 nm) MoTe2-based photodetectors to elucidate the impact of thickness on device performance. A few layers of MoTe2 were exfoliated on a silicon dioxide (SiO2) dielectric substrate, and electrical contacts were constructed via EBL and thermal evaporation. The thin MoTe2-based device presented a maximum photoresponsivity of 1.2 A/W and detectivity of 4.32 × 108 Jones, compared to 1.0 A/W and 3.6 × 108 Jones for the thick MoTe2 device at 520 nm. Moreover, at 1064 nm, the thick MoTe2 device outperformed the thin device with a responsivity of 8.8 A/W and specific detectivity of 3.19 × 109 Jones. Both devices demonstrated n-type behavior, with linear output curves representing decent ohmic contact amongst the MoTe2 and Au/Cr electrodes. The enhanced performance of the thin MoTe2 device at 520 nm is attributed to improved carrier dynamics resulting from effective electric field penetration. In comparison, the superior performance of the thick device at 1064 nm is due to sufficient absorption in the near-infrared range. These findings highlight the importance of thickness control in designing high-performance MoTe2-based photodetectors and position MoTe2 as a highly suitable material for next-generation optoelectronics.
Diet Quality and Dietary Intake in Breast Cancer Survivors Suffering from Chronic Pain: An Explorative Case-Control Study
Authors: Tümkaya Yılmaz Sevilay , Elma Ömer , Nijs Jo , Clarys Peter , Coppieters Iris , Deliens Tom , Calders Patrick , Naert Eline , Malfliet Anneleen
Published: November 2024

Background/Objectives: Dietary factors may significantly influence pain management in cancer survivors. However, a substantial gap exists regarding the relationship between nutrition and chronic pain in this population. This study examined differences in diet quality and dietary intake between breast cancer survivors (BCS) experiencing chronic pain and healthy controls (HC). It also aimed to understand the associations between dietary elements and pain-related outcomes within the BCS group. Methods: A case-control study was conducted with 12 BCS experiencing chronic pain and 12 HC (ages 18–65). Data collection included body composition, experimental pain assessments, pain-related questionnaires, and a 3-day food diary to calculate diet quality using the Healthy Eating Index-2015 (HEI-2015) and Dietary Inflammatory Index (DII). Statistical analyses evaluated group differences and associations between dietary factors and pain within the BCS group. Results: There were no significant differences in HEI-2015 scores between BCS and HC, but BCS had a significantly lower DII score (p = 0.041), indicating a more anti-inflammatory diet. BCS also showed higher intake of omega-3, vitamins B6, B12, A, D, and magnesium (p < 0.05). While total diet quality scores did not correlate with pain outcomes, several HEI-2015 and DII components, such as dairy, sodium, protein, vitamin C, and vitamin D, showed moderate positive or negative correlations with pain measures. Conclusions: Despite no overall differences in diet quality, BCS with chronic pain consumed more anti-inflammatory nutrients than HC. Complex correlations between specific dietary components and pain outcomes emphasise the need for further research to explore these links for chronic pain management in BCS.