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Search Results (1,235)

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22 pages, 688 KiB  
Review
The Evolving Treatment Landscape for the Elderly Multiple Myeloma Patient: From Quad Regimens to T-Cell Engagers and CAR-T
by Matthew James Rees and Hang Quach
Cancers 2025, 17(15), 2579; https://doi.org/10.3390/cancers17152579 - 5 Aug 2025
Abstract
Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, [...] Read more.
Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article
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19 pages, 10865 KiB  
Article
Evaluation of Immunoprotective Activities of White Button Mushroom (Agaricus bisporus) Water Extract Against Major Pathogenic Bacteria (Aeromonas hydrophila or Vibrio fluvialis) in Goldfish (Carassius auratus)
by Shujun Sun, Jing Chen, Pan Cui, Xiaoxiao Yang, Yuhan Zheng, Zijian Ma, Yong Liu and Xiang Liu
Animals 2025, 15(15), 2257; https://doi.org/10.3390/ani15152257 - 1 Aug 2025
Viewed by 168
Abstract
The white button mushroom (Agaricus bisporus) is a widely cultivated edible and medicinal mushroom, which contains various active substances, and has application value against pathogenic bacteria in aquaculture. Firstly, A. bisporus water extract (AB-WE) was prepared. Through the detection kits, it [...] Read more.
The white button mushroom (Agaricus bisporus) is a widely cultivated edible and medicinal mushroom, which contains various active substances, and has application value against pathogenic bacteria in aquaculture. Firstly, A. bisporus water extract (AB-WE) was prepared. Through the detection kits, it was found that the polysaccharide, protein, and polyphenol components of AB-WE were 9.11%, 3.3%, and 1.5%, respectively. The 246 compounds were identified in AB-WE, and the major small-molecule components included L-Isoleucine, L-Tyrosine, L-Valine, and Linoleic acid by HPLC-Q Exactive-Orbitrap-MS. Secondly, the AB-WE was evaluated for its immunological activities through dietary administration and pathogen challenge (Aeromonas hydrophila and Vibrio fluvialis) in goldfish (Carassius auratus). The results showed that the levels of immune factors of acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM) increased (p < 0.05) in goldfish, and the relative percentage survival of AB-WE against A. hydrophila and V. fluvialis were 80.00% (p < 0.05) and 81.82% (p < 0.05), respectively. The AB-WE reduced the bacterial content in renal tissue, enhanced the phagocytic activity of leukocytes, and exhibited antioxidant and anti-inflammatory effects by reducing the expression of antioxidant-related factors and inflammatory factors. Through histopathological and immunofluorescence techniques, it was found that AB-WE maintained the integrity of visceral tissues and reduced renal tissue apoptosis and DNA damage. Therefore, AB-WE exhibits immunoprotective activity against A. hydrophila and V. fluvialis infections in fish, and holds promise as an immunotherapeutic agent against major pathogenic bacteria in aquaculture. Full article
(This article belongs to the Section Aquatic Animals)
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23 pages, 1337 KiB  
Review
Balancing Innovation and Safety: Prediction, Prevention, and Management of Pneumonitis in Lung Cancer Patients Receiving Novel Anti-Cancer Agents
by Sarah Liu, Daniel Wang, Andrew Robinson, Mihaela Mates, Yuchen Li, Negar Chooback, Pierre-Olivier Gaudreau, Geneviève C. Digby, Andrea S. Fung and Sofia Genta
Cancers 2025, 17(15), 2522; https://doi.org/10.3390/cancers17152522 - 30 Jul 2025
Viewed by 315
Abstract
Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as [...] Read more.
Pneumonitis is characterized as inflammation of the lung parenchyma, and a potential adverse effect of several anti-cancer therapies. Diagnosing pneumonitis can be particularly challenging in lung cancer patients due to inherent similarities in symptoms and radiological presentation associated with pneumonitis, as well as other common conditions such as infection or disease progression. Furthermore, many lung cancer patients have underlying pulmonary conditions that might render them more susceptible to severe or fatal outcomes from pneumonitis. Novel anti-cancer agents, such as antibody–drug conjugates (ADCs) and bispecific antibodies (BsAbs), are being incorporated into the treatment of lung cancer; therefore, understanding the risk and mechanisms underlying the potential development of pneumonitis with these new therapies is important to ensure continuous improvements in patient care. This narrative review provides an overview of the incidence of pneumonitis observed with novel anti-cancer agents, characterizes potential pathophysiological mechanisms underlying pneumonitis risk and emerging predictive biomarkers, highlights management strategies, and explores future directions for minimizing the risk of pneumonitis for lung cancer patients. Full article
(This article belongs to the Special Issue Cancer Immunotherapy in Clinical and Translational Research)
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26 pages, 12786 KiB  
Article
EMB System Design and Clamping Force Tracking Control Research
by Junyi Zou, Haojun Yan, Yunbing Yan and Xianping Huang
Modelling 2025, 6(3), 72; https://doi.org/10.3390/modelling6030072 - 25 Jul 2025
Viewed by 339
Abstract
The electromechanical braking (EMB) system is an important component of intelligent vehicles and is also the core actuator for longitudinal dynamic control in autonomous driving motion control. Therefore, we propose a new mechanism layout form for EMB and a feedforward second-order linear active [...] Read more.
The electromechanical braking (EMB) system is an important component of intelligent vehicles and is also the core actuator for longitudinal dynamic control in autonomous driving motion control. Therefore, we propose a new mechanism layout form for EMB and a feedforward second-order linear active disturbance rejection controller based on clamping force. This solves the problem of excessive axial distance in traditional EMB and reduces the axial distance by 30%, while concentrating the PCB control board for the wheels on the EMB housing. This enables the ABS and ESP functions to be integrated into the EMB system, further enhancing the integration of line control and active safety functions. A feedforward second-order linear active disturbance rejection controller (LADRC) based on the clamping force of the brake caliper is proposed. Compared with the traditional clamping force control methods three-loop PID and adaptive fuzzy PID, it improves the response speed, steady-state error, and anti-interference ability. Moreover, the LADRC has more advantages in parameter adjustment. Simulation results show that the response speed is increased by 130 ms, the overshoot is reduced by 9.85%, and the anti-interference ability is increased by 41.2%. Finally, the feasibility of this control algorithm was verified through the EMB hardware-in-the-loop test bench. Full article
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22 pages, 5945 KiB  
Article
Immunogenicity Risk Assessment of Biotherapeutics Using an Ex Vivo B Cell Assay
by Kevin M. Budge, Ross Blankenship, Patricia Brown-Augsburger and Lukasz K. Chlewicki
Antibodies 2025, 14(3), 62; https://doi.org/10.3390/antib14030062 - 22 Jul 2025
Viewed by 368
Abstract
Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization [...] Read more.
Background/Objectives: Anti-drug antibody (ADA) formation can impact the safety, pharmacokinetics, and/or efficacy of biotherapeutics, including monoclonal antibodies (mAbs). Current strategies for ADA/immunogenicity risk prediction of mAbs include in silico algorithms, T cell proliferation assays, MHC-associated peptide proteomics assays (MAPPs), and dendritic cell internalization assays. However, B cell-mediated responses are not assessed in these assays. B cells are professional antigen-presenting cells (APCs) and secrete antibodies toward immunogenic mAbs. Therefore, methods to determine B cell responses would be beneficial for immunogenicity risk prediction and may provide a more comprehensive assessment of risk. Methods: We used a PBMC culture method with the addition of IL-4, IL-21, B cell activating factor (BAFF), and an anti-CD40 agonist mAb to support B cell survival and activation. Results: B cells in this assay format become activated, proliferate, and secrete IgG. A panel of 51 antibodies with varying clinical immunogenicity rates were screened in this assay with IgG secretion used as a readout for immunogenicity risk. IgG secretion differed among test articles but did not correlate with the clinical immunogenicity rating. Conclusions: This dataset highlights the challenges of developing a B cell assay for immunogenicity risk prediction and provides a framework for further refinement of a B cell-based assay for immunogenicity risk prediction of mAbs. Full article
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20 pages, 6280 KiB  
Article
The V5-Epitope Tag for Cell Engineering and Its Use in Immunohistochemistry and Quantitative Flow Cytometry
by Katja Fritschle, Marion Mielke, Olga J. Seelbach, Ulrike Mühlthaler, Milica Živanić, Tarik Bozoglu, Sarah Dötsch, Linda Warmuth, Dirk H. Busch, Arne Skerra, Christian Kupatt, Wolfgang A. Weber, Richard E. Randall, Katja Steiger and Volker Morath
Biology 2025, 14(7), 890; https://doi.org/10.3390/biology14070890 - 20 Jul 2025
Viewed by 432
Abstract
Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterologous fusion proteins assembled from interchangeable building blocks is of high importance. The V5 [...] Read more.
Synthetic biology has fundamentally advanced cell engineering and helped to develop effective therapeutics such as chimeric antigen receptor (CAR)-T cells. For these applications, the detection, localization, and quantification of heterologous fusion proteins assembled from interchangeable building blocks is of high importance. The V5 tag, a 14-residue epitope tag, offers promising characteristics for these applications but has only rarely been used in this context. Thus, we have systematically evaluated the murine anti-V5 tag antibody mu_SV5-Pk1 as well as its humanized version, hu_SV5-Pk1, to analyze cells expressing V5-tagged receptors in samples from various in vitro and in vivo experiments. We found that the V5 tag signal on cells is affected by certain fixation and detachment reagents. Immunohistochemistry (IHC) on formalin-fixed paraffin-embedded (FFPE) mouse tissue samples was performed to sensitively detect cells in tissue. We improved IHC by applying the hu_SV5-Pk1 monoclonal antibody (mAb) to avoid cross-reactivity within and unspecific background signals arising on fixed mouse tissue. Conversely, the absence of unspecific binding by the mu_SV5-Pk1 mAb was evaluated on 46 human normal or cancer tissues. Our findings present a robust toolbox for utilizing the V5 tag and cognate antibodies in synthetic biology applications. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)
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34 pages, 17167 KiB  
Article
An Enhanced ABS Braking Control System with Autonomous Vehicle Stopping
by Mohammed Fadhl Abdullah, Gehad Ali Qasem and Mazen Farid
World Electr. Veh. J. 2025, 16(7), 400; https://doi.org/10.3390/wevj16070400 - 16 Jul 2025
Viewed by 358
Abstract
This study explores the design and implementation of a control system integrating the anti-lock braking system (ABS) with frequency-modulated continuous wave (FMCW) radar technology to enhance safety and performance in autonomous vehicles. The proposed system employs a hybrid fuzzy logic controller (FLC) and [...] Read more.
This study explores the design and implementation of a control system integrating the anti-lock braking system (ABS) with frequency-modulated continuous wave (FMCW) radar technology to enhance safety and performance in autonomous vehicles. The proposed system employs a hybrid fuzzy logic controller (FLC) and proportional-integral-derivative (PID) controller to improve braking efficiency and vehicle stability under diverse driving conditions. Simulation results showed significant enhancements in stopping performance across various road conditions. The integrated system exhibited a marked improvement in braking performance, achieving significantly shorter stopping distances across all evaluated surface conditions—including dry concrete, wet asphalt, snowy roads, and icy roads—compared with scenarios without ABS. These results highlight the system’s ability to dynamically adapt braking forces to different conditions, significantly improving safety and stability for autonomous vehicles. The limitations are acknowledged, and directions for real-world validation are outlined to ensure system robustness under diverse environmental conditions. Full article
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18 pages, 1680 KiB  
Article
IL-2 Complex Therapy Mitigates Humoral Rejection of Fully Mismatched Skin Allografts by Inhibiting IgG Alloantibody Formation
by Konstantinos Mengrelis, Mario Wiletel, Romy Steiner, Anna M. Weijler, Laurenz Wolner, Valentina Stolz, Milos Nikolic, Daniel Simon, Florian Frommlet, Jonathan Sprent, Hannes Stockinger and Nina Pilat
Cells 2025, 14(14), 1086; https://doi.org/10.3390/cells14141086 - 16 Jul 2025
Viewed by 472
Abstract
Antibody-mediated rejection (ABMR) caused by donor-specific Abs (DSAs) is still the leading cause of late graft loss following clinical organ transplantation, and effective strategies to combat ABMR are still elusive. We previously showed that rIL-2 complexed with anti-IL-2 mAb clone JES6-1A12 (IL-2 cplx) [...] Read more.
Antibody-mediated rejection (ABMR) caused by donor-specific Abs (DSAs) is still the leading cause of late graft loss following clinical organ transplantation, and effective strategies to combat ABMR are still elusive. We previously showed that rIL-2 complexed with anti-IL-2 mAb clone JES6-1A12 (IL-2 cplx) leads to the selective expansion of regulatory T cells (Tregs) and the prolonged survival of MHC-mismatched skin allografts. Although the grafts were eventually rejected, mice failed to develop DSAs. Here, we investigated the impact of IL-2 cplx on the humoral response and germinal center (GC) reaction during allograft rejection. IL-2 cplx treatment prevents Bcl-6 upregulation, leading to suppressed development of GC T and B cells. The IL-2 cplx-induced impairment of GC development limits IgG allo-Ab production but allows for IgM synthesis. By employing a hapten–carrier system to investigate affinity maturation, we found that IL-2 cplx induces a distinct shift in specific Ab production favoring low-affinity IgM while simultaneously decreasing IgG responses. These findings illuminate the potential of IL-2 cplx therapy for inducing humoral tolerance, potentially paving the way for refining strategies aimed at preventing and treating ABMR. Full article
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25 pages, 24158 KiB  
Communication
Generation of Novel Monoclonal Antibodies Recognizing Rabbit CD34 Antigen
by Jaromír Vašíček, Miroslav Bauer, Eva Kontseková, Andrej Baláži, Andrea Svoradová, Linda Dujíčková, Eva Tvrdá, Jakub Vozaf, Peter Supuka and Peter Chrenek
Biomolecules 2025, 15(7), 1021; https://doi.org/10.3390/biom15071021 - 15 Jul 2025
Viewed by 419
Abstract
The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have [...] Read more.
The rabbit is a widely used experimental model for human translational research and stem cell therapy. Many studies have focused on rabbit mesenchymal stem cells from different biological sources for their possible application in regenerative medicine. However, a minimal number of studies have been published aimed at rabbit hematopoietic stem/progenitor cells, mainly due to the lack of specific anti-rabbit CD34 antibodies. In general, CD34 antigen is commonly used to identify and isolate hematopoietic stem/progenitor cells in humans and other animal species. The aim of this study was to develop novel monoclonal antibodies highly specific to rabbit CD34 antigen. We used hybridoma technology, two synthetic peptides derived from predicted rabbit CD34 protein, and a recombinant rabbit CD34 protein as immunogens to produce monoclonal antibodies (mAbs) specific to rabbit CD34. The produced antibodies were screened for their binding activity and specificity using ELISA, flow cytometry, and Western blot analysis. Finally, four mAbs (58/47/26, 58/47/34, 182/7/80, and 575/36/8) were selected for the final purification process. The purified mAbs recognized up to 2–3% of total rabbit bone marrow cells, while about 2% of those cells exhibited CD45 expression, which are likely rabbit primitive hematopoietic stem cells and their hematopoietic progenitors, respectively. The newly generated and purified mAbs specifically recognize CD34 antigen in rabbit bone marrow or peripheral blood and can be therefore used for further immunological applications, to study rabbit hematopoiesis or to establish a new animal model for hematopoietic stem cell transplantation studies. Full article
(This article belongs to the Section Biomacromolecules: Proteins, Nucleic Acids and Carbohydrates)
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17 pages, 1438 KiB  
Review
Pathogenesis of Autoimmunity/Systemic Lupus Erythematosus (SLE)
by Shunichi Shiozawa
Cells 2025, 14(14), 1080; https://doi.org/10.3390/cells14141080 - 15 Jul 2025
Viewed by 596
Abstract
SLE is characterized by the generation of a variety of autoantibodies including anti-dsDNA autoantibodies, causing damage in various organs. If autoimmunity is defined by the generation of a variety of autoantibodies against the self, SLE is the only disease to qualify. Identification of [...] Read more.
SLE is characterized by the generation of a variety of autoantibodies including anti-dsDNA autoantibodies, causing damage in various organs. If autoimmunity is defined by the generation of a variety of autoantibodies against the self, SLE is the only disease to qualify. Identification of the SLE-causing factor must fulfill the following criteria: (i) the factor induces SLE, (ii) the factor is operating in active SLE and (iii) SLE heals after removal of the factor. All candidate factors are reviewed from this viewpoint in this review. As to the cause of SLE, high levels of interferon α can induce SLE; however, interferon α in most patients did not reach this high level. BAFF (B cell activating factor of the TNF family) is increased in SLE. BAFF itself induced some manifestation of SLE, whereas removal of interferon α or BAFF by an antibody (Ab) did not heal SLE. BXSB male mice with a duplicated TLR7 gene develop SLE; however, the gene Sle1 is also required for the development of SLE. In addition, sanroque mice develop a variety of autoantibodies and SLE; the sanroque mutation, which disrupts one of the repressors of ICOS, results in increased CCR7lo CXCR5+Tfh cells, IL-21 and SLE. ICOS+T follicular helper (Tfh) cells increase in SLE and SLE-model (NZBxNZW)F1 mice, and the blockade of Tfh development ameliorated SLE, indicating the importance of Tfh cells in the pathogenesis of SLE. Self-organized criticality theory shows that SLE is caused by repeated infection, wherein SLE-inducing pathogens can vary individually depending on one’s HLA; however, the pathogen presented on HLA stimulates the T cell receptor (TCR) strongly beyond self-organized criticality. This stimulation generates TCR-revised, autoreactive DOCK8+Tfh cells, which induced a variety of autoantibodies and SLE. The SARS-CoV-2 virus is an example pathogen because SLE occurs after SARS-CoV-2 infection and vaccination. DOCK8+Tfh cells and SLE decreased after conventional or anti-DOCK Ab therapies. Thus, DOCK8+Tfh cells newly generated after repeated infection fulfill the criteria (i), (ii) and (iii) as the cause of SLE. Full article
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20 pages, 2298 KiB  
Review
CD20+ T Cells in Multiple Sclerosis: From Pathogenesis to Treatment-Induced Depletion
by Anna Chiara Mazzeo, Laura Calabresi, Valentina Damato, Gregorio Spagni, Luca Massacesi and Alice Mariottini
Int. J. Mol. Sci. 2025, 26(14), 6655; https://doi.org/10.3390/ijms26146655 - 11 Jul 2025
Viewed by 430
Abstract
The traditional paradigm of multiple sclerosis (MS) as a T cell-mediated disorder has been challenged by the effectiveness of monoclonal antibodies (mAbs) targeting CD20-expressing lymphocytes. Although these are mostly represented by B cells, the CD20 marker is expressed by 2–6% of T cells [...] Read more.
The traditional paradigm of multiple sclerosis (MS) as a T cell-mediated disorder has been challenged by the effectiveness of monoclonal antibodies (mAbs) targeting CD20-expressing lymphocytes. Although these are mostly represented by B cells, the CD20 marker is expressed by 2–6% of T cells (CD20+ T), which are effectively depleted in serum and cerebrospinal fluid of MS patients by anti-CD20 mAbs. CD20+ T cells are characterized by a pro-inflammatory phenotype and increased potential for migrating and invading the central nervous system (CNS) compared to CD20− T cells. Furthermore, CD20+ T cells are detected within brain inflammatory lesions from MS patients and actively participate in the experimental MS model. This review aims to summarize the current knowledge on CD20+ T cells, from their identification and characterization to evidence of depletion by disease-modifying treatments (DMTs), likely contributing to therapeutic efficacy. Conflicting hypotheses on the origin and development of CD20+ T cells will also be discussed, as well as evidence from clinical and preclinical studies supporting their pathogenetic role in MS. Full article
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13 pages, 4275 KiB  
Article
Integrating Recycled Acrylonitrile–Butadiene–Styrene Plastics from Electronic Waste with Carbon Black for Sustainable Asphalt Production
by Sepehr Mohammadi, Dongzhao Jin and Zhanping You
Infrastructures 2025, 10(7), 181; https://doi.org/10.3390/infrastructures10070181 - 11 Jul 2025
Cited by 1 | Viewed by 333
Abstract
As the global demand for electronic equipment continues to grow, many devices are being replaced more frequently, resulting in a rapid rise in electronic waste (e-waste), now the fastest growing waste stream worldwide. Motivated by this, the objective of this study is to [...] Read more.
As the global demand for electronic equipment continues to grow, many devices are being replaced more frequently, resulting in a rapid rise in electronic waste (e-waste), now the fastest growing waste stream worldwide. Motivated by this, the objective of this study is to present an environmentally friendly method to recycle acrylonitrile–butadiene–styrene (ABS), one of the most common e-waste plastics, by using it for asphalt production. In contrast to earlier methods of plastic-modified asphalt production involving complex pretreatments or complimentary additives unsuitable for plant-scale use, this study aims to demonstrate a practical, low-cost solution through the use of carbon black. This approach included physically pretreating ABS plastics for size reduction and incorporating waste tire-derived carbon black to promote effective dispersion in asphalt during wet modification. The rheological properties of the e-waste-modified asphalt were subsequently assessed. The test results indicated that recycling ABS plastics with a blending content of 5% alongside 5% carbon black can enhance cold-weather cracking resistance and high-temperature anti-rutting performance of asphalt. The enhancement can be attributed to the proper preparation procedures of ABS plastics and the addition of carbon black, which can further improve the performance by promoting the proper dispersion of plastic particles in asphalt. The outcome of this study indicates that recycling e-waste plastics through asphalt production can lead to more green and sustainable asphalt construction, reduce total construction costs, and most importantly enhance performance. Full article
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11 pages, 1069 KiB  
Article
Evaluation of Torquetenovirus (TTV) Particle Integrity Utilizing PMAxx™
by Giuseppe Sberna, Claudia Minosse, Cosmina Mija, Eliana Specchiarello, Pietro Giorgio Spezia, Sara Belladonna, Giulia Berno, Lavinia Fabeni, Giulia Matusali, Silvia Meschi, Daniele Focosi and Fabrizio Maggi
Int. J. Mol. Sci. 2025, 26(13), 6542; https://doi.org/10.3390/ijms26136542 - 7 Jul 2025
Viewed by 442
Abstract
Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To [...] Read more.
Torquetenovirus (TTV) is a ubiquitous, non-pathogenic DNA virus that has been suggested as a biomarker of immune competence, with the viral load correlating with the level of immunosuppression. However, by detecting non-intact viral particles, standard PCR-based quantification may overestimate the TTV viremia. To improve the clinical relevance of TTV quantification, in this study, we investigated the use of PMAxx™, a virion viability dye that selectively blocks the amplification of compromised virions. Serum samples from 10 Hepatitis C Virus-positive (HCV+) individuals, 81 liver transplant recipients (LTRs), and 40 people with HIV (PWH) were treated with PMAxx™ and analyzed for TTV DNA loads by digital droplet PCR (ddPCR). Furthermore, anti-SARS-CoV-2 IgG levels and neutralizing antibody (nAbs) titers were measured post-COVID-19 vaccination. Using ddPCR, the PMAxx™ treatment significantly reduced the TTV DNA levels in all the groups (mean reduction: 0.66 Log copies/mL), indicating the abundant presence of non-intact, circulating viral genomes. However, correlations between TTV DNA and SARS-CoV-2 IgG or nAbs were weak or absent in both PMAxx™-treated and untreated samples. These findings suggest that while PMAxx™ enhanced the specificity of TTV quantification, it did not improve the predictive value of TTV viremia at assessing vaccine-induced humoral responses. Full article
(This article belongs to the Section Molecular Microbiology)
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12 pages, 926 KiB  
Review
Nanotechnology Approaches for Mitigating Biologic Immunogenicity: A Literature Review
by Jouri Alanazi, Fadilah Sfouq Aleanizy and Fulwah Yahya Alqahtani
Pharmaceutics 2025, 17(7), 888; https://doi.org/10.3390/pharmaceutics17070888 - 7 Jul 2025
Viewed by 487
Abstract
Biologic therapeutics, particularly monoclonal antibodies (mAbs), have revolutionized disease treatment paradigms; however, their clinical success is often hindered by immunogenicity. Host immune recognition of these biologics can induce anti-drug antibody (ADA) formation, leading to reduced therapeutic efficacy, altered pharmacokinetics and serious adverse events, [...] Read more.
Biologic therapeutics, particularly monoclonal antibodies (mAbs), have revolutionized disease treatment paradigms; however, their clinical success is often hindered by immunogenicity. Host immune recognition of these biologics can induce anti-drug antibody (ADA) formation, leading to reduced therapeutic efficacy, altered pharmacokinetics and serious adverse events, such as infusion reactions and loss of response. Overcoming these immunogenicity challenges is essential to maximize the clinical effect of biologics and ensure patient safety. This paper offers an overview of the mechanisms underlying the formation of anti-drug antibodies and explores potential nanotechnology-based strategies to reduce or eliminate these responses. Specifically, the review examines how the immune system recognizes biologics and develops ADAs, which can impact drug efficacy and safety. The review then investigates various nanotechnology approaches aimed at mitigating ADA formation, potentially improving the therapeutic outcomes of biologic drugs. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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8 pages, 278 KiB  
Article
Antibiotic Prescription in Dentistry: Trends, Patient Demographics, and Drug Preferences in Germany
by Lisa Lotta Cirkel, Jens Martin Herrmann, Claudia Ringel, Bernd Wöstmann and Karel Kostev
Antibiotics 2025, 14(7), 676; https://doi.org/10.3390/antibiotics14070676 - 3 Jul 2025
Viewed by 438
Abstract
Background and objectives: ABs are widely used in dental practice in the treatment of odontogenic infections and as systemic prophylaxis in high-risk patients. However, AB overuse contributes to antimicrobial resistance (AMR), which is a major global concern. This study examined dental AB prescribing [...] Read more.
Background and objectives: ABs are widely used in dental practice in the treatment of odontogenic infections and as systemic prophylaxis in high-risk patients. However, AB overuse contributes to antimicrobial resistance (AMR), which is a major global concern. This study examined dental AB prescribing trends in Germany in 2024, focusing on the share of overall AB prescriptions, patient demographics, and commonly used agents. Methods: This retrospective cross-sectional study used data from the IQVIA Longitudinal Prescription Database (LRx), covering approximately 80% of prescriptions reimbursed by statutory health insurance funds in Germany. Patients with at least one AB prescription (ATC code: J01) issued by a dentist in 2024 were analyzed. Descriptive statistics covered age, sex, and prescribed substances. Results: In 2024, German dentists prescribed ABs to 2,325,500 patients, accounting for 13.9% of all patients in the database who received AB prescriptions. Dentists were the second-largest group of AB prescribers, surpassed only by general physicians. Amoxicillin (54.2%) was most frequently prescribed, followed by amoxicillin with clavulanic acid (24.5%) and clindamycin (21.0%). Dental patients receiving AB prescriptions were older (mean age: 49.8 years) than the general antibiotic patient population (44.7 years). Interestingly, dental AB prescriptions increased during the COVID-19 pandemic, in contrast to the sharp overall decline in AB prescriptions. Between 2015 and 2019, the proportion of dental antibiotic prescriptions showed a moderate upward tendency, followed by a marked increase during the COVID-19 pandemic and a subsequent decline. In contrast, the number of patients receiving antibiotic prescriptions from other medical disciplines decreased over the same period. One particularly notable finding was the extended use of clindamycin, a reserve AB with known side effects and resistance risks, in dentistry. Conclusions: Dentists are responsible for a significant share of AB prescriptions in Germany. The rise in dental AB prescriptions, particularly the frequent prescription of clindamycin, underscores the need for interventions such as updated clinical guidelines and awareness campaigns concerning AB-related risks and their mitigation directed at dentists. These could focus on microbial culture and sensitivity testing and patient adherence education and control for targeted AB interventions. Emphasizing preventive and alternative anti-infective treatment strategies in dentistry may also help to contain AMR. Full article
(This article belongs to the Special Issue Managing Appropriate Antibiotic Prescribing and Use in Primary Care)
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