bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Discrimination Limit Analysis of Macrophage Phagocytosis Between Target Antigens and Non-Target Objects Using Microcapillary Manipulation Assay
Authors: Ando Maiha , Horonushi Dan , Yuki Haruka , Kato Shinya , Yoshida Amane , Yasuda Kenji
Published: November 2024

During phagocytosis, the FcGR–IgG bond is thought to be necessary to promote cell-membrane extension as the zipper mechanism. However, does this zipper mechanism provide a spatial antigen discrimination capability that allows macrophages to selectively phagocytose only antigens, especially for clusters with a mixture of antigens and non-antigens? To elucidate the ability and limitation of the zipper mechanism, we fed a coupled 2 μm IgG-coated and 4.5 μm non-coated polystyrene bead mixtures to macrophages and observed their phagocytosis. Macrophage engulfed the mixed clusters, including the 4.5 μm non-coated polystyrene part, indicating that the non-coated particles can be engulfed even without the zipper mechanism as far as coupled to the opsonized particles. In contrast, when the non-opsonized particle part was held by the microcapillary manipulation assay, macrophages pinched off the non-coated polystyrene particle part and internalized the opsonized particle part only. The results suggest that (1) an IgG-coated surface is needed to anchor phagocytosis by cell-membrane protrusion; however, (2) once the antibody-dependent cell phagocytosis is started, phagocytosis can proceed with the uncoated objects as the followers of the internalizing opsonized particles even without the support of the zipper mechanism. They may also indicate the concern of misleading the immune system to target unexpected objects because of their aggregation with target pathogens and the possibility of new medical applications to capture the non-opsonized target objects by the aggregation with small antigens to activate an immune response.
Multifunctional Downhole Drilling Motor Speed Sensor Based on Triboelectric Nanogenerator
Authors: Zhang Yanbo , Su Shida , Zhang Lei , Gao Yulin , Wu Chuan
Published: November 2024

The measurement of downhole drilling motor rotational speed is crucial for optimizing drilling operations, improving work efficiency, and preventing equipment failures. However, traditional downhole rotational speed sensors suffer from power supply limitations, which can increase drilling costs. To address this issue, this study presents a novel multifunctional rotational speed sensor based on triboelectric nanogenerator (TENG) technology, enabling the self-powered measurement of rotational speed, direction, and angle. Our experimental results demonstrate that the sensor operates stably within a temperature range of 0 to 150 °C and a humidity range of 0 to 90%. It achieves rotational speed measurement with an accuracy of less than 2.5% error within a range of 0 to 1000 rpm, angular measurement with a resolution of 60 degrees and an error of less than 2% within a range of 0 to 360 degrees, and rotational direction measurement. Furthermore, the sensor exhibits self-powered functionality, achieving a maximum power output of 29.1 μW when the external load is 10 MΩ. Compared to conventional rotational speed sensors, this sensor possesses the unique advantage of integrating the measurement of rotational speed, angle, and direction, while simultaneously harnessing downhole working conditions for self-power generation. These characteristics make it highly suitable for practical downhole environments.
Network Analysis of Pathogenesis Markers in Murine Chagas Disease Under Antimicrobial Treatment
Authors: Dias Nayra , Dias Marina , Ribeiro Andressa , Gomes Nélio , Moraes Aline , Wesley Moisés , Gonzaga Carlito , Ramos Doralina do Amaral Rabello , Braz Shélida , Dallago Bruno , de Carvalho Juliana Lott , Hagström Luciana , Nitz Nadjar , Hecht Mariana
Published: November 2024

Chagas disease (CD), a disease affecting millions globally, remains shrouded in scientific uncertainty, particularly regarding the role of the intestinal microbiota in disease progression. This study investigates the effects of antibiotic-induced microbiota depletion on parasite burden, immune responses, and clinical outcomes in BALB/c mice infected with either the Trypanosoma cruzi Colombiana or CL Brener strains. Mice were treated with a broad-spectrum antibiotic cocktail before infection, and parasite burden was quantified via qPCR at 30 and 100 days post-infection (dpi). Immune responses were analyzed using flow cytometry and ELISA, while histopathology was conducted on cardiac and intestinal tissues. Antibiotic treatment uncovered strain-specific correlations, with Colombiana infections affecting Bifidobacterium populations and CL Brener infections linked to Lactobacillus. Microbiota depletion initially reduced parasite burden in the heart and intestine, but an increase was observed in the chronic phase, except in the CL Brener-infected gut, where an early burden spike was followed by a decline. Antibiotic-induced bacterial shifts, such as reductions in Bacteroides and Bifidobacterium, promoted a more pro-inflammatory immune profile. These findings highlight the importance of microbiota and strain-specific factors in CD and suggest further research into microbiota manipulation as a potential therapeutic strategy.
Unraveling the Role of the Human Gut Microbiome in Health and Diseases
Authors: Khalil Mohamad , Di Ciaula Agostino , Mahdi Laura , Jaber Nour , Di Palo Domenica Maria , Graziani Annarita , Baffy Gyorgy , Portincasa Piero
Published: November 2024

The human gut is a complex ecosystem that supports billions of living species, including bacteria, viruses, archaea, phages, fungi, and unicellular eukaryotes. Bacteria give genes and enzymes for microbial and host-produced compounds, establishing a symbiotic link between the external environment and the host at both the gut and systemic levels. The gut microbiome, which is primarily made up of commensal bacteria, is critical for maintaining the healthy host’s immune system, aiding digestion, synthesizing essential nutrients, and protecting against pathogenic bacteria, as well as influencing endocrine, neural, humoral, and immunological functions and metabolic pathways. Qualitative, quantitative, and/or topographic shifts can alter the gut microbiome, resulting in dysbiosis and microbial dysfunction, which can contribute to a variety of noncommunicable illnesses, including hypertension, cardiovascular disease, obesity, diabetes, inflammatory bowel disease, cancer, and irritable bowel syndrome. While most evidence to date is observational and does not establish direct causation, ongoing clinical trials and advanced genomic techniques are steadily enhancing our understanding of these intricate interactions. This review will explore key aspects of the relationship between gut microbiota, eubiosis, and dysbiosis in human health and disease, highlighting emerging strategies for microbiome engineering as potential therapeutic approaches for various conditions.
Establishing a UG2 Pillar Strength Formula in South African Platinum Mines
Authors: Watson Bryan , Maphosa Tatenda , Theron Willie , Fernandes Noel , Stacey Thomas , Morgan Andrew , Carpede Andrew , Betz Gunther
Published: November 2024

In this study, the peak strength of chromitite pillars in South African platinum mines is re-examined by comparing laboratory tests to the Upper Group 2 (UG2) PlatMine pillar strength formula and underground measurements. The laboratory results were stronger than the underground measurements and the strength predicted by the PlatMine formula. The rock mass strength in the PlatMine formula (‘k-value’) was about 70% of the laboratory tests performed on a 50 mm diameter sample. This finding agrees with other researchers who have compared the rock mass strength to laboratory-determined uniaxial compressive strengths. The laboratory tests, underground measurements, and the PlatMine formula all show that the pillars are significantly stronger than traditionally accepted. This finding can help the UG2 mining industry to improve extraction ratios significantly by adopting the PlatMine formula, particularly at deeper levels where bord-and-pillar workings are used. The results presented in this paper will achieve significant revenue creation in the mine where the underground measurements were made.
Geophysical Methods Applied to the Mineralization Discovery of Rare-Earth Elements at the Fazenda Buriti Alkaline Complex, Goiás Alkaline Province, Brazil
Authors: dos Santos Fabrício Pereira , Leão-Santos Marcelo Henrique , Borges Welitom Rodrigues , Borges Patrícia Caixeta
Published: November 2024

In this case study, exploratory techniques were applied for the selection of potential targets for rare-earth elements (REEs) in the Fazenda Buriti Mafic–Ultramafic Complex, part of the Goiás Alkaline Province. The results of the processing and interpretation of aeromagnetic and radiometric data associated with the direct measurements of magnetic susceptibility and radiometry in rock samples collected in the study area allowed for the characterization and delimitation of the geological units. The application of Boolean logic in the radiometric data of uranium (U), thorium (Th), and the U/Th ratio allowed for the generation of a prospective map with the delimitation of two exploration targets. A 100 m deep exploratory drill hole was drilled at the main target, intercepting REE mineralization and validating the developed prospective technique. The results contributed to the detailing of a 1:25,000 scale geological map and the interpretation of shallow and deep magnetic structures. Petrophysical data allowed for the estimation of the magnetite content in the main units of the study area. The delimitation of targets with the applied method proved to be efficient after positive geochemical results for REE from the drilled rocks. The total sum of ∑REEs reached 19,629 ppm in the superficial part of the hole and 3,560 ppm in the fresh rock. Mineralogical results in two follow-up drill core samples indicated that monazite was the main REE mineral. Total REE ranged from 34,746 ppm in HG1 to 30,017 ppm in HG2, with LREEs in its majority. The bulk and clay XRD analyses indicated that monazite consisted of 5.7% (HG1) and 5.1% (HG2). The mineral abundance from the TIMA-X analysis indicated 4.2% (HG1) and 4.4% (HG2) in monazite content.
Flotation Enrichment of Micro- and Nanosilica Formed During the Production of Silicon and Ferrosilicon
Authors: Karlina Antonina I. , Karlina Yuliya I. , Gladkikh Vitaliy A.
Published: November 2024

This paper presents the results of experiments conducted on the flotation separation of cyclone dust particles. The flotation process was conducted using a laboratory flotation apparatus comprising three chambers. Experimental tests supported theoretical results of the theoretical reasoning and justification for the choice of parameters that the flotation process should have in order to extract particles of such small sizes. Furthermore, this work elucidates the concept of “nanobubbles” and substantiates their viability for use in the flotation of nanoparticles, given that bubbles of such a magnitude are firmly affixed to the hydrophobic surface of particles. Bubbles of a larger size than nanoparticles will float both hydrophobic and hydrophilic particles. The effective flotation of cyclone dust from the gas cleaning of silicon and ferroalloy production provided two materials as a result. The experiments yielded insights into the rational technological parameters of the flotation mode for obtaining new products. These insights were gleaned from the preliminary conditioning (conditioning time from 0.5 to 1.5 h) of wet cyclone dust (dry dust weight of 4 kg) with liquid glass (1.4 g per 1 dm3 of pulp) in a cavitation unit at a pH value of 8.5. The flotation process was conducted in a three-chamber flotation apparatus with a volume of 0.02 m3 for a duration of 90 min, utilizing a pneumohydraulic aerator with air suction from the atmosphere. In this instance, the pulp was conveyed via a pump at a pressure of 0.4 MPa from the initial cleansing chamber into the aerator. During the flotation process, kerosene (1 mg per 1 dm3 of pulp) and pine oil (2 mg per 1 dm3 of pulp) were added as additives. The resulting products were silicon dioxide (95%) and carbon nanoparticles (94%).
DFT Study on the Interaction Between Flotation Agents and Lepidolite-1M Surfaces
Authors: Zhang Xujun , He Guichun , Du Changzhen
Published: November 2024

The surface chemical properties of Lepidolite-1M crystals are closely related to their flotation properties. This paper uses density functional theory (DFT) to analyze the band structure, population, and state density of ideal Lepidolite-1M crystals. The results show that lepidolite-1M is an insulator, and its most probable positively charged active site is Al, and its negatively charged active sites are O and F. To further investigate the adsorption mechanism of Lepidolite-1M during comminution and flotation processes, we calculated the surface energy, population, state density, and differential charge density of its most common (001) surface. The results show that its surface energy is 0.9934 J/m2, occurred in the valence electron configurations, population values, and bond lengths of the surface atoms. Furthermore, oxygen atoms on the (001) surface showed different activities, with F and O atoms in the lithium-rich region showing significant electron enrichment. Overall, our results demonstrated that anion collectors react mainly with the Al sites on the surface of Lepidolite-1M, and the cationic collectors and metal ion activators can be adsorbed on the surface of Lepidolite-1M to produce better trapping and activation capabilities.
Ore Formation and Mineralogy of the Alattu–Päkylä Gold Occurrence, Ladoga Karelia, Russia
Authors: Ivashchenko Vasily I.
Published: November 2024

The Alattu–Päkylä gold occurrence is located in the Northern Lake Ladoga area, in the Raaha-Ladoga suprasubduction zone, at the Karelian Craton (AR)—Svecofennian foldbelt (PR1) boundary. Its gold ore mineral associations are of two types of mineralization: (1) copper–molybdenum–porphyry with arsenopyrite and gold (intrusion-related) and (2) gold–arsenopyrite–sulfide in shear zones. Optical and scanning electron microscopy, X-ray fluorescence spectrometry, inductively coupled plasma mass spectrometry (ICP-MS), instrumental neutron activation analysis (INAA) and fire analysis with AAS finishing were used to study them. Type 1 was provoked by shallow-depth tonalite intrusion (~1.89 Ga) and type 2 by two stages of Svecofennian metamorphism (1.89–1.86 and 1.83–1.79 Ga) with the possible influence of the impactogenesis of the Janisjärvi astrobleme (age ~1 Ga). Intrusive and host rocks were subjected to shearing accompanied by the formation of ore-bearing metasomatic rocks of the propylite-beresite series (depending on substrate) and quartz–sericite, quartz and sericite–tourmaline veins and streaks. Ore mineralization is present as several consecutive mineral associations: pyritic–molybdenite with arsenopyrite and gold; gold–arsenopyrite; quartz–arsenopyrite with antimony sulfosalts of lead; gold–polysulfide with tetrahedrite –argentotetrahedrite series minerals and gold–antimony with Pb–Sb–S system minerals and native antimony. Arsenopyrite contains invisible (up to 234 ppm) and visible gold. Metamorphosed domains in arsenopyrite and rims with visible gold around it are usually enriched in As, indicating higher (up to >500 °C) temperatures of formations than original arsenopyrite with invisible gold (<500 °C). A paragenetic sequence associated with the deposition of invisible and visible gold established at the Alattu–Päkylä ore occurrence: pyrrhotite + unaltered arsenopyrite (with invisible gold) → altered arsenopyrite (As-enriched) + pyrite ± pyrrhotite + visible gold. Gold, associated with gudmundite, sphalerite and native antimony, seems to be due to cainotypic rhyodacitic porphyry cutting tonalite intrusion or with a retrograde stage in post-Svecofennian metamorphism. The isotopic composition of Pb and 238U/204Pb (9.4–9.75) for the feldspar of the tonalite intrusion and the pyrite of gold mineralization, εNd (−4 up to −5) for tonalites and ẟ34S values of −2.10–+4.99 for arsenopyrite, indicate the formation of gold occurrence provoked by Svecofennian magmatic and tectono-thermal processes with the involvement of matter from a mantle-lower crustal reservoir into magma formation and mineralization.
Catalytic Methane Decomposition on In Situ Reduced FeCo Alloy Catalysts Derived from Layered Double Hydroxides
Authors: Cao Dianfeng , Li Yuwen , Lv Chao , An Yongtao , Song Jiangfeng , Li Mingcan , Zhang Xin
Published: November 2024

Catalytic methane decomposition (CMD) reaction is considered a promising process for converting greenhouse gas CH4 into hydrogen and high-value-added carbon materials. In this work, a series of Al2O3-supported FeCo alloy catalysts were successfully prepared in the CMD process. Compared to the pre-reduced catalysts, the in situ reduced FeCo alloy catalysts showed higher methane conversion rates, with the highest reaching 83% at 700 °C, due to the finer active nanoparticle size and greater exposure of active site. Furthermore, the time-on-stream tests demonstrated that the catalytic activity of in situ reduced FeCo alloy catalysts could remain above 92.3% of the highest catalytic activity after 10 h. In addition, TEM analyses of the carbon products from the CMD in situ reduced catalysts revealed the production of carbon nanofibers and nanotubes several microns in length after the reaction. This indicates that the in situ reduced FeCo alloy catalysts more effectively promoted the growth of carbon nanofibers. These results could provide a viable strategy for future methane decomposition development aimed at producing hydrogen and high-value carbon.
Gold Nanoprobes for Robust Colorimetric Detection of Nucleic Acid Sequences Related to Disease Diagnostics
Authors: Enea Maria , Leite Andreia , Franco Ricardo , Pereira Eulália
Published: November 2024

Gold nanoparticles (AuNPs) are highly attractive for applications in the field of biosensing, particularly for colorimetric nucleic acid detection. Their unique optical properties, which are highly sensitive to changes in their environment, make them ideal candidates for developing simple, rapid, and cost-effective assays. When functionalized with oligonucleotides (Au-nanoprobes), they can undergo aggregation or dispersion in the presence of complementary sequences, leading to distinct color changes that serve as a visual signal for detection. Aggregation-based assays offer significant advantages over other homogeneous assays, such as fluorescence-based methods, namely, label-free protocols, rapid interactions in homogeneous solutions, and detection by the naked eye or using low-cost instruments. Despite promising results, the application of Au-nanoprobe-based colorimetric assays in complex biological matrices faces several challenges. The most significant are related to the colloidal stability and oligonucleotide functionalization of the Au-nanoprobes but also to the mode of detection. The type of functionalization method, type of spacer, the oligo–AuNPs ratio, changes in pH, temperature, or ionic strength influence the Au-nanoprobe colloidal stability and thus the performance of the assay. This review elucidates characteristics of the Au-nanoprobes that are determined for colorimetric gold nanoparticles (AuNPs)-based nucleic acid detection, and how they influence the sensitivity and specificity of the colorimetric assay. These characteristics of the assay are fundamental to developing low-cost, robust biomedical sensors that perform effectively in biological fluids.
Micro- and Nanostructured Biomaterials for Biomedical Applications and Regenerative Medicine
Authors: Bianchi Michele , Carnevale Gianluca
Published: November 2024

Over the past two decades, research on innovative micro- and nano-biomaterials has seen a significant surge in the bioengineering, biomedicine, and regenerative medicine fields [...]
Antimicrobial Resistance Profile of Zoonotic Clinically Relevant WHO Priority Pathogens
Authors: Meade Elaine , Slattery Mark Anthony , Garvey Mary
Published: November 2024

The World Health Organization announced critically important bacterial and fungal pathogens displaying alarming levels of antimicrobial resistance, which currently represent difficult-to-treat cases of morbidity. Within this grouping, the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are causative of significant morbidity and mortality. Studies described herein demonstrate the presence of critically important fungal and ESKAPE bacterial species in companion animals which are zoonotic in nature. The relationship between the environment, animals, and human infectious disease has long been recognized as part of One Health. This research investigates the resistance patterns of isolated zoonotic pathogens using recognized in vitro methodologies, namely disk diffusion, minimum inhibitory concentration testing, and genetic screening. Antibiotic susceptibility testing and gene analysis demonstrated an association between multi-drug resistance and extended beta spectrum lactamase production in critical-priority bacteria. Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa exhibit great levels of multi-drug resistance. Fungal isolates demonstrated high levels of resistance, with Amphotericin B proving the most effective antifungal agent investigated. The level of antimicrobial resistance present in clinically relevant bacterial and fungal pathogens isolated from animal cases of morbidity in this study is alarming. In conclusion, this study shows that animals can act as a reservoir facilitating the transmission of antibiotic-resistant pathogens and genes zoonotically.
Tick-Borne Encephalitis Virus Infection in a Two-Year-Old Child Returning from Switzerland (July–August 2023): Is It Time for TBE Immunization of Serbian Travelers?
Authors: Simin Verica , Ležakov Ognjen , Bogdan Ivana , Mijatović Dragana , Gazibara Dragana , Popović-Dragonjić Lidija , Vijatov Đurić Gordana , Milanović Borko , Kesić Jelena , Đuretić Andrea , Ábrahám Ágota , Lanszki Zsófia , Kemenesi Gábor , Zana Brigitta , Bányai Krisztián , Zając Zbigniew , Jakimovski Dejan , Cabezas-Cruz Alejandro , Banović Pavle
Published: November 2024

Tick-borne encephalitis (TBE) is a vaccine-preventable viral infection that poses significant public health challenges, particularly in regions where tick-borne diseases are endemic. This case report describes a 2-year-old boy with confirmed abortive TBEV infection following a tick bite during travel to Switzerland. The patient developed fever and mild symptoms but did not exhibit central nervous system involvement. The case underscores the importance of raising awareness among healthcare providers and travelers from non-endemic areas, such as Serbia, about TBE risk and the potential benefits of preventive vaccination. Strategic immunization campaigns could mitigate the public health impact of travel-related TBE.
In Silico Study of the Potential Inhibitory Effects on Escherichia coli DNA Gyrase of Some Hypothetical Fluoroquinolone–Tetracycline Hybrids
Authors: Lungu Ioana-Andreea , Oancea Octavia-Laura , Rusu Aura
Published: November 2024

Background/Objectives: Despite the discovery of antibiotics, bacterial infections persist globally, exacerbated by rising antimicrobial resistance that results in millions of cases, increased healthcare costs, and more extended hospital stays. The urgent need for new antibacterial drugs continues as resistance evolves. Fluoroquinolones and tetracyclines are versatile antibiotics that are effective against various bacterial infections. A hybrid antibiotic combines two or more molecules to enhance antimicrobial effectiveness and combat resistance better than monotherapy. Fluoroquinolones are ideal candidates for hybridization due to their potent bactericidal effects, ease of synthesis, and ability to form combinations with other molecules. Methods: This study explored the mechanisms of action for 40 hypothetical fluoroquinolone–tetracycline hybrids, all of which could be obtained using a simple, eco-friendly synthesis method. Their interaction with Escherichia coli DNA Gyrase and similarity to albicidin were evaluated using the FORECASTER platform. Results: Hybrids such as Do-Ba, Mi-Fi, and Te-Ba closely resembled albicidin in physicochemical properties and FITTED Scores, while Te-De surpassed it with a better score. Similar to fluoroquinolones, these hybrids likely inhibit DNA synthesis by binding to enzyme–DNA complexes. Conclusions: These hybrids could offer broad-spectrum activity and help mitigate bacterial resistance, though further in vitro and in vivo studies are needed to validate their potential.
Complexity of the Therapeutic Regimen in Older Adults with Cancer: Associated Factors
Authors: Oliveira Rita F. , Oliveira Ana I. , Cruz Agostinho , Ribeiro Oscar , Afreixo Vera , Pimentel Francisco
Published: November 2024

Background/Objectives: Population aging is a worldwide phenomenon and is often associated with multimorbidity and polypharmacy. Complex medication regimens are common among older adults and contribute to the occurrence of harmful health outcomes. Age is one of the main risk factors for cancer. This study aimed to determine and characterize the therapeutic complexity in older patients with cancer, and analyze the factors associated with high complexity and the impact of the oncological context. Methods: A cross-sectional study with patients aged ≥65 years with cancer was conducted in three hospitals in northern Portugal. Data collection was obtained using self-reports. The medication regimen complexity was assessed using the Medication Regimen Complexity Index (MRCI). Descriptive and association statistical analysis were performed. Logistic, linear, simple and multiple regression analysis were conducted, with and without automatic variable selection. Results: A total of 552 patients were included (median age, 71; IQR, 68–76). The mean MRCI before the oncological context was 18.67 (SD 12.60) and 27.39 (SD 16.67) after the oncological context, presenting a statistically significant difference in the values obtained (p < 0.001). An elevated complexity was significantly associated with polypharmacy, chronic diseases and with the administration of high-risk medications (p < 0.05). High MRCI values showed a relationship with the occurrence of potential drug interactions (p < 0.001). There was no relationship with the existence of cardiac risk comorbidity. Conclusions: This study demonstrated the existence of high therapeutic complexity in older patients with cancer, suggesting the need for intervention to prevent medication-related problems in this vulnerable population.
Predicting Structural Consequences of Antibody Light Chain N-Glycosylation in AL Amyloidosis
Authors: Morgan Gareth J. , Yung Zach , Spencer Brian H. , Sanchorawala Vaishali , Prokaeva Tatiana
Published: November 2024

Background/Objectives: Antibody light chains form amyloid fibrils that lead to progressive tissue damage in amyloid light chain (AL) amyloidosis. The properties of each patient’s unique light chain appear to determine its propensity to form amyloid. One factor is N-glycosylation, which is more frequent in amyloid-associated light chains than in light chains from the normal immune repertoire. However, the mechanisms underlying this association are unknown. Here, we investigate the frequency and position within the light chain sequence of the N-glycosylation sequence motif, or sequon. Methods: Monoclonal light chains from AL amyloidosis and multiple myeloma were identified from the AL-Base repository. Polyclonal light chains were obtained from the Observed Antibody Space resource. We compared the fraction of light chains from each group harboring an N-glycosylation sequon, and the positions of these sequons within the sequences. Results: Sequons are enriched among AL-associated light chains derived from a subset of precursor germline genes. Sequons are observed at multiple positions, which differ between the two types of light chains, κ and λ, but are similar between light chains from AL amyloidosis and multiple myeloma. Positions of sequons map to residues with surface-exposed sidechains that are compatible with the folded structures of light chains. Within the known structures of λ AL amyloid fibrils, many residues where sequons are observed are buried, inconsistent with N-glycosylation. Conclusions: There is no clear structural rationale for why N-glycosylation of κ light chains is associated with AL amyloidosis. A better understanding of the roles of N-glycosylation in AL amyloidosis is required before it can be used as a marker for disease risk.
Adaptation to Sodium Hypochlorite and Potassium Permanganate May Lead to Their Ineffectiveness Against Candida albicans
Authors: Karpiński Tomasz M. , Korbecka-Paczkowska Marzena , Ożarowski Marcin , Włodkowic Donald , Wyganowska Marzena Liliana , Seremak-Mrozikiewicz Agnieszka , Cielecka-Piontek Judyta
Published: November 2024

Background/Objectives: Adaptation can reduce or completely eliminate the effectiveness of antibiotics and antiseptics at clinical concentrations. To our knowledge, no studies have examined fungal adaptation to antiseptics. This study aimed to preliminarily investigate the potential for Candida albicans adaptation to eight antiseptics. Methods: The minimal inhibitory concentration (MIC), drug susceptibility, adaptation to antiseptics, and Karpinski Adaptation Index (KAI) of C. albicans strains were assessed. Results: The antiseptics with the most effective MICs activity against C. albicans were octenidine dihydrochloride (OCT), chlorhexidine digluconate (CHX), and polyhexamethylene biguanide (polyhexanide, PHMB). Sodium hypochlorite (NaOCl) and ethacridine lactate (ET) demonstrated moderate activity, while boric acid (BA), povidone–iodine (PVI), and potassium permanganate (KMnO4) showed the weakest activity. The MIC values for NaOCl and KMnO4 were close to or equal to the clinical concentrations used in commercial products. The studied strains were susceptible to econazole, miconazole, and voriconazole. Resistance to other drugs occurred in 10–30% of the strains. Antifungal resistance remained unchanged after antiseptic adaptation testing. The lowest KAI values, indicating very low resistance risk, were observed for CHX, OCT, and PHMB. PVI and BA presented a low risk, ET a moderate risk. KMnO4 and NaOCl had the highest KAI values, indicating high and very high resistance risk in Candida yeasts. Conclusions: C. albicans strains can adapt to antiseptics to varying extents. For most antiseptics, adaptation does not significantly affect their clinical efficacy. However, due to adaptation, NaOCl and KMnO4 may become ineffective against C. albicans strains even at clinical concentrations.
Structure of a Cyclic Peptide as an Inhibitor of Mycobacterium tuberculosis Transcription: NMR and Molecular Dynamics Simulations
Authors: Stephanie Filia , Tambunan Usman Sumo Friend , Kuczera Krzysztof , Siahaan Teruna J.
Published: November 2024

Background and Objectives: A novel antitubercular cyclic peptide, Cyclo(1,6)-Ac-CLYHFC-NH2, was designed to bind at the rifampicin (RIF) binding site on the RNA polymerase (RNAP) of Mycobacterium tuberculosis (MTB). This peptide inhibits RNA elongation in the MTB transcription initiation assay in the nanomolar range, which can halt the MTB transcription initiation complex, similar to RIF. Therefore, determining the solution conformation of this peptide is useful in improving the peptide’s binding affinity to the RNAP. Methods: Here, the solution structure of Cyclo(1,6)-Ac-CLYHFC-NH2 was determined by two-dimensional (2D) NMR experiments and NMR-restrained molecular dynamic (MD) simulations. Results: All protons of Cyclo(1,6)-Ac-CLYHFC-NH2 were assigned using TOCSY and NOE NMR spectroscopy. The NOE cross-peak intensities were used to calculate interproton distances within the peptide. The JNH-HCα coupling constants were used to determine the possible Phi angles within the peptide. The interproton distances and calculated Phi angles from NMR were used in NMR-restrained MD simulations. The NOE spectra showed NH-to-NH cross-peaks at Leu2-to-Tyr3 and Tyr3-to-His4, indicating a βI-turn formation at the Cys1-Leu2-Tyr3-His4 sequence. Conclusions: The NMR-restrained MD simulations showed several low-energy conformations that were congruent with the NMR data. Finally, the conformation of this peptide will be used to design derivatives that can better inhibit RNAP activity.
Lung Toxicity Occurring During Enfortumab Vedotin Treatment: From a Priming Case Report to a Retrospective Analysis
Authors: Desimpel Grégoire , Zammit François , Lejeune Sarah , Grisay Guillaume , Seront Emmanuel
Published: November 2024

Background/Objectives: Enfortumab vedotin (EV) is an antibody-drug conjugate (ADC) that combines monomethyl auristatin E (MMAE), a potent cytotoxic agent, with a monoclonal antibody targeting Nectin-4. It has emerged as a promising therapy for metastatic urothelial carcinoma (mUC), either as monotherapy or in combination with pembrolizumab, improving significantly the overall survival of these patients. EV is associated with common adverse events, including skin reactions, glucose imbalance, and peripheral neuropathy, which are usually mild in severity and easily manageable. Methods: Following an initial case of pleuro-pneumopathy occurring in a patient treated with EV, we conducted a retrospective analysis of EV effects on pulmonary imaging. Results: In a cohort of 20 all-comers mUC patients, we identified three cases of potentially EV-related lung toxicity, resulting in a pleuro-pneumopathy rate of 15%. Two of these cases appeared highly symptomatic and required high steroid doses, with a rapid resolution of symptoms and normalization of radiological findings. In one patient, rechallenge of EV was associated with reoccurrence of pneumopathy. We described the clinical and radiological features of these cases, as well as their evolution after EV discontinuation and rechallenge. Conclusions: This case series underscores the importance of close pulmonary monitoring during EV treatment.
Quantitative Approach to Explore Regulatory T Cell Activity in Immuno-Oncology
Authors: Serrano Alejandro , Zalba Sara , Lasarte Juan Jose , Troconiz Iñaki F. , Riva Natalia , Garrido Maria J.
Published: November 2024

The failure of immunotherapies in cancer patients is being widely studied due to the complexities present in the tumor microenvironment (TME), where regulatory T cells (Treg) appear to actively participate in providing an immune escape mechanism for tumors. Therefore, therapies to specifically inhibit tumor-infiltrating Treg represent a challenge, because Treg are distributed throughout the body and provide physiological immune homeostasis to prevent autoimmune diseases. Characterization of immunological and functional profiles could help to identify the mechanisms that need to be inhibited or activated to ensure Treg modulation in the tumor. To address this, quantitative in silico approaches based on mechanistic mathematical models integrating multi-scale information from immune and tumor cells and the effect of different therapies have allowed the building of computational frameworks to simulate different hypotheses, some of which have subsequently been experimentally validated. Therefore, this review presents a list of diverse computational mathematical models that examine the role of Treg as a crucial immune resistance mechanism contributing to the failure of immunotherapy. In addition, this review highlights the relevance of certain molecules expressed in Treg that are associated with the TME immunosuppression, which could be incorporated into the mathematical model for a better understanding of the contribution of Treg modulation. Finally, different preclinical and clinical combinations of molecules are also included to show the trend of new therapies targeting Treg.
Development of a Water-Soluble Nanomicellar Formulation Loaded with Trans-Resveratrol Using Polyethylene Glycol Monostearate for the Treatment of Intracerebral Hemorrhage
Authors: Banshoya Kengo , Machida Aoi , Kawamura Saki , Yamada Tetsuhiro , Okada Riko , Kawamoto Yui , Kimura Hikaru , Shibata Sachi , Hieda Yuhzo , Kaneo Yoshiharu , Tanaka Tetsuro , Ohnishi Masatoshi
Published: November 2024

Background/Objectives: Trans-resveratrol (Res) has been reported to possess many biological activities, including neuroprotective effects, owing to its anti-inflammatory and antioxidant properties. However, Res has very low water solubility, which limits its therapeutic application. In this work, we formulated water-soluble micellar formulations incorporating Res using polyethylene glycol monostearate (stPEG). Methods: These formulations (stPEG/Res) were developed using five types of stPEG containing 10, 25, 40, 55 and 140 PEG repeat units. The formulations were characterized for Res content, water solubility, particle size, zeta potential, precipitation, biodistribution, and efficacy against neuronal and motor dysfunction in intracerebral hemorrhage (ICH). Results: Intravenous administration of stPEG40/Res, which demonstrated particle size, water solubility, and biodistribution properties suitable for intravenous administration, suppressed neurological and motor dysfunction following in a collagenase-induced ICH mouse model. These effects were inhibited by zinc protoporphyrin-9, an inhibitor of the antioxidant enzyme heme oxygenase-1, suggesting that Res contributes to antioxidant enzyme expression and anti-inflammatory activity. Conclusions: The stPEG/Res micellar formulation developed in this study may offer a promising therapeutic approach for ICH treatment.
Green Synthesis of Zinc Oxide Nanoparticles Using Puerarin: Characterization, Antimicrobial Potential, Angiogenesis, and In Ovo Safety Profile Assessment
Authors: Liga Sergio , Vodă Raluca , Lupa Lavinia , Paul Cristina , Nemeş Nicoleta Sorina , Muntean Delia , Avram Ștefana , Gherban Mihaela , Péter Francisc
Published: November 2024

Background: Zinc oxide nanobiocomposites were successfully synthesized using a green synthesis approach. The process involves the utilization of the isoflavone puerarin, resulting in the formation of PUE-ZnO NPs. Methods: Physico-chemical and biological characterization techniques including X-ray dif-fraction (XRD), UV-vis spectroscopy, Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), atomic force microscopy (AFM), and in ovo methods were employed to study the main characteristics of this novel hybrid material. Results: The PUE-ZnO NPs were confirmed to have been successfully synthesized with a UV absorption peak at 340 nm, the XRD analysis demonstrating their high purity and crystallinity. The energy band-gap value of 3.30 eV suggests possible photocatalytic properties. Both SEM and AFM images revealed the nanoparticle`s quasi-spherical shape, roughness, and size. Good tolerability and anti-irritative effects were recorded in ovo on the chorioallantoic membrane (CAM). Conclusions: According to these results, the synthesis of green PUE-ZnO NPs may be a promising future approach for biomedical and personal care applications.
Peptide-Based Biomaterials for Combatting Infections and Improving Drug Delivery
Authors: Lombardi Lucia , Li Jiaxu , Williams Daryl R.
Published: November 2024

This review explores the potential of peptide-based biomaterials to enhance biomedical applications through self-assembly, biological responsiveness, and selective targeting. Peptides are presented as versatile agents for antimicrobial activity and drug delivery, with recent approaches incorporating antimicrobial peptides into self-assembling systems to improve effectiveness and reduce resistance. The review also covers peptide-based nanocarriers for cancer drug delivery, highlighting their improved stability, targeted delivery, and reduced side effects. The focus of this work is on the bioactive properties of peptides, particularly in infection control and drug delivery, rather than on their structural design or material characteristics. Additionally, it examines the role of peptidomimetics in broadening biomaterial applications and enhancing resistance to enzymatic degradation. Finally, the review discusses the commercial prospects and challenges of translating peptide biomaterials into clinical applications.
Antibacterial and Inhibitory Activity of Nora and Mepa Efflux Pumps of Estragole Complexed to β-Cyclodextrin (ES/β-CD) In Vitro Against Staphylococcus aureus Bacteria, Molecular Docking and MPO-Based Pharmacokinetics Prediction
Authors: Costa Roger Henrique Sousa da , Pessoa Renata Torres , Silva Eduardo dos Santos , Araujo Isaac Moura , Gonçalves Sheila Alves , Rocha Janaína Esmeraldo , Pereira Junior Francisco Nascimento , Oliveira Naiara Cipriano , Oliveira Victor Moreira de , Rocha Matheus Nunes da , Marinho Emmanuel Silva , Kelly Gomes de Carvalho Natália , Galberto Martins da Costa José , Santos Hélcio Silva dos , Menezes Irwin Rose Alencar de
Published: November 2024

Background/Objectives: The work investigates the effect of the estragole complex encapsulated in beta-cyclodextrin (ES/β-CD) in modulating bacterial resistance, specifically in Staphylococcus aureus strains expressing NorA and MepA efflux pumps. Efflux pumps are mechanisms that bacteria use to resist antibiotics by expelling them from the cell. Methodology: Several compounds and antibiotics, such as ciprofloxacin and norfloxacin, were used to evaluate the antimicrobial activity and the ability of the ES/β-CD complex to reverse resistance. Methods: The study included scanning electron microscopy assays, minimum inhibitory concentration (MIC) determination, and efflux pump inhibition tests. Results: The ES/β-CD complex did not show significant direct antibacterial activity. However, it modulated the action of norfloxacin, decreasing the MIC when combined with this antibiotic in the 1199B (NorA) strain. These results suggest a potential for synergy but not a direct inhibition of efflux pumps. Conclusion: ES/β-CD can potentiate the efficacy of some antibiotics but does not directly act as an efflux pump inhibitor; it is more of an antibiotic potentiator than a direct solution to bacterial resistance. The molecular docking simulation data suggest its high affinity for forming the ES/β-CD complex. The pharmacokinetic predictions based on MPO suggest that the compound has moderate lipophilicity, highly effective cellular permeability, and low incidence of organic toxicity, pointing to a promising pharmacological principle with controlled daily oral dosing. Conclusions: These results indicate this complex’s possible and relevant association as an adjuvant in antibiotic therapy to reduce multidrug-resistant bacteria; however, new in vivo assays are necessary to confirm this effect.
Investigation of Antimicrobial and Anti-Inflammatory Efficacy of Newly Synthesized Pyrogallol-Coumarin Hybrids: In Vitro and In Silico Studies
Authors: Simijonović Dušica , Avdović Edina , Milić Sandra Jovičić , Antonijević Marko , Milenković Dejan , Marković Katarina , Grujović Mirjana , Stojković Danijela Lj. , Dekić Milan , Marković Zoran
Published: November 2024

Background: The aim of this study is to present the synthesis of two new compounds with promising antimicrobial and anti-inflammatory properties using precursors that contain pyrogallol and coumarin units. Methods: The characterization of the obtained compounds (PCHs) (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-2,3,4-trihydroxybenzohydrazide (PCH-1) and (E)-N′-(1-(2,4-dioxochroman-3-ylidene)ethyl)-3,4,5-trihydroxybenzohydrazide (PCH-2) was performed using various spectroscopic methods in combination with the DFT methods. To evaluate antimicrobial and anti-inflammatory activities, PCHs were tested against 13 different types of microorganisms and soybean lipoxygenase. To determine the specific mechanisms of anti-LOX activity, molecular docking and molecular dynamics studies were performed. Results: These compounds had the most potent antibacterial activity against the bacterium Proteus mirabilis ATCC 12453, with a MIC value of 31.125 µg/mL. In addition, three standard bacterial species were chosen to evaluate the antibiofilm activity of tested substances. The results showed that the strongest effect of PCH-2 was noticed on the biofilm formation of Staphylococcus aureus ATCC 25923 (BIC50 at 378 µg/mL). The anti-LOX results indicate that PCHs have excellent activity with the IC50 value for PCH-1 = 38.12 μM and PCH-2 = 34.12 μM. Conclusions: The obtained in vitro and in silico results confirm the strong inhibitory potential of the investigated compounds.
Response of Typical Shrubs Growth and Soil Nutrients to Graphene Addition in Impoverished Land of the Ulan Buh Desert
Authors: Mu Ren , Qiao Jun , Kong Chuijiu , Hao Xuting , Xu Guangfu , Han Jingfu , Li Xinle
Published: November 2024

Graphene can promote plant growth and improve soil conditions, but its effectiveness in enhancing infertile soils in arid regions remains unclear. This study selected three typical shrubs from the Ulan Buh Desert Nitraria tangutorum, Xanthoceras sorbifolium, and Amygdalus mongolica as research subjects. Five graphene addition levels were set: 0 mg/L (C0), 25 mg/L (C1), 50 mg/L (C2), 100 mg/L (C3), and 200 mg/L (C4).A pot experiment was conducted in June 2023 to investigate the effects of graphene addition on shrub growth and soil nutrients. The results showed that the optimal graphene addition levels for A. mongolica, X. sorbifolium, and N. tangutorum were C2, C2, and C3, respectively. Compared with the control, the total biomass of the different shrubs increased by 185.31%, 50.86%, and 161.10%, respectively. However, when the graphene addition exceeded the optimal level, shrub biomass showed a decreasing trend with increasing graphene concentration. Total shrub biomass was positively correlated with soil available nitrogen and potassium, while redundancy analysis indicated that soil organic matter was the primary factor influencing shrub growth. This suggests that graphene promotes shrub growth by affecting soil organic matter and available nutrients. Therefore, graphene addition can enhance soil fertility in barren lands in arid regions and significantly promote shrub growth. However, due to soil leaching effects, this growth-promoting effect may decrease over time.
Impacts of Climate Change-Induced Temperature Rise on Phenology, Physiology, and Yield in Three Red Grape Cultivars: Malbec, Bonarda, and Syrah
Authors: Dominguez Deolindo L. E. , Cirrincione Miguel A. , Deis Leonor , Martínez Liliana E.
Published: November 2024

Climate change has significant implications for agriculture, especially in viticulture, where temperature plays a crucial role in grapevine (Vitis vinifera) growth. Mendoza’s climate is ideal for producing high-quality wines, but 21st-century climate change is expected to have negative impacts. This study aimed to evaluate the effects of increased temperature on the phenology, physiology, and yield of Malbec, Bonarda, and Syrah. A field trial was conducted over two seasons (2019–2020 and 2020–2021) in an experimental vineyard with an active canopy heating system (+2–4 °C). Phenological stages (budburst, flowering, fruit set, veraison, harvest), shoot growth (SG), number of shoots (NS), stomatal conductance (gs), chlorophyll content (CC), chlorophyll fluorescence (CF), and water potential (ψa) were measured. Additionally, temperature, relative humidity, light intensity, and canopy temperature were recorded. Heat treatment advanced all phenological stages by approximately two weeks, increased SG and NS, and reduced gs and ψa during the hottest months. CC and CF remained unaffected. The treatment also resulted in lower yields, reduced acidity, and increased °Brix in both seasons. Overall, rising temperatures due to climate change advance the phenological phases of Malbec, Syrah, and Bonarda, leading to lower yields, higher °Brix, and lower acidity, although physiological variables remained largely unchanged.