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Search Results (902)

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Keywords = death preparation

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15 pages, 397 KB  
Article
The Grieving Process of a Family Caregiver: Experience Before Influences What Happens Next—A Grounded Theory
by Catarina Simões, Margarida Vieira and Ana Paula Sapeta
Nurs. Rep. 2026, 16(6), 201; https://doi.org/10.3390/nursrep16060201 (registering DOI) - 12 Jun 2026
Abstract
Background/Objectives: Recognizing and managing grief is particularly important in nursing, especially from the perspective of family caregivers. In this qualitative study, we aim to understand the grieving process of family caregivers, focusing on what happens before the death of an adult family member [...] Read more.
Background/Objectives: Recognizing and managing grief is particularly important in nursing, especially from the perspective of family caregivers. In this qualitative study, we aim to understand the grieving process of family caregivers, focusing on what happens before the death of an adult family member due to chronic illness, and to identify the factors influencing the grieving process in this context. Methods: This study is an outcome of a broader study which aimed to understand how family caregivers grieve during the first year following the death of an adult family member due to a chronic illness. This article will only address the influencing conditions that emerged from data related to events that occurred prior to the person’s death. A theoretical sample was gathered through semi-structured interviews with 20 bereaved family caregivers. Data were collected and then analyzed independently by the research team using the three stages and principles of Strauss and Corbin’s grounded theory. Results: Adaptation was identified as the central category. Before death, the family caregiver undergoes two adaptive processes: adapting to their new role and preparing for the imminent loss. As they adapt to this loss, they become aware of the seriousness of the illness and the inevitability of death, opening the possibility for the grieving process to begin. The process is influenced by personal and contextual factors as well as interaction-related factors, including access to information, satisfaction with the care provided, recognition of their efforts, and feelings of abandonment or interaction with healthcare professionals. A wide range of emotions and feelings are experienced. This experience is colored by hope and anticipatory grief. The meaning of the dying process is explored and expectations are redefined. Conclusions: The grieving process experienced by family caregivers is an adaptive process that begins before the patient’s death. Some conditions can be modified before the patient’s death; in this case, nurse interventions can enhance the experience of family caregivers. Full article
23 pages, 459 KB  
Article
Analytical Lindblad Dynamics of Field-Controlled Entanglement and State Fidelity in the Hydrogen Electron-Proton Spins: Interplay of Hyperfine Coupling, Zeeman Effects, and Pure Dephasing
by Kamal Berrada and Smail Bougouffa
Axioms 2026, 15(6), 431; https://doi.org/10.3390/axioms15060431 - 10 Jun 2026
Viewed by 72
Abstract
In this paper, we investigate the dynamics of quantum correlations in the ground-state hyperfine manifold of the hydrogen atom subjected to a static external magnetic field and local pure dephasing. The electron–proton spin pair is modeled as a bipartite two-qubit system evolving under [...] Read more.
In this paper, we investigate the dynamics of quantum correlations in the ground-state hyperfine manifold of the hydrogen atom subjected to a static external magnetic field and local pure dephasing. The electron–proton spin pair is modeled as a bipartite two-qubit system evolving under the combined effects of hyperfine coupling, Zeeman splitting, and a Lindblad master equation that describes Markovian dissipative processes. Employing exact analytical solutions for the time-dependent density matrix elements (derived in the Markovian open-system framework), we quantify entanglement persistence via concurrence and state stability via Uhlmann fidelity with respect to the initial preparation. For an initial Werner state, numerical results reveal that the external magnetic field substantially modifies the system dynamics: Both concurrence and fidelity exhibit pronounced dependence on the Zeeman parameter, producing field-controlled oscillations, delayed entanglement sudden death, and altered decoherence rates. This behavior originates from Zeeman-induced lifting of hyperfine degeneracies, symmetry breaking of the isotropic Werner state, and redistribution of populations and coherences. Unlike previous studies that treat hyperfine interactions, Zeeman splitting, or decoherence in isolation, the present work provides a unified analytical treatment that simultaneously incorporates all three mechanisms. The findings underscore the competition between coherent hyperfine coupling and environmental noise and open new pathways for precision spectroscopy and robust quantum information protocols based on atomic spin degrees of freedom. Full article
(This article belongs to the Section Mathematical Physics)
19 pages, 1572 KB  
Article
Minimal Photovoltaic Solar Cooker for a Catalytic Effect on Energy Poverty
by Antonio Lecuona-Neumann, José-Ignacio Nogueira-Goriba and Jean Boubour
Energies 2026, 19(11), 2720; https://doi.org/10.3390/en19112720 - 4 Jun 2026
Viewed by 331
Abstract
One to four million annual premature deaths are associated with household air pollution. This indoor pollution is mainly generated by traditional biomass cookstoves. Thus, solar cooking can significantly reduce this toll. Its proliferation would also mitigate deforestation pressures. Additionally, for developing countries, it [...] Read more.
One to four million annual premature deaths are associated with household air pollution. This indoor pollution is mainly generated by traditional biomass cookstoves. Thus, solar cooking can significantly reduce this toll. Its proliferation would also mitigate deforestation pressures. Additionally, for developing countries, it would alleviate the fuel collection workload, mainly borne by women responsible for fuel collection. Electric cooking provides a clean and controllable alternative to thermal cookers for indoor food preparation, sterilization and heating. This study presents a minimal, off-grid photovoltaic solar cooker that operates without batteries and power electronics. Such a cooker constitutes a low-cost and high-reliability solution for electrically decentralized locations. The system encompassing the cooker is conceived as an accessible entry point for household-level photovoltaic (PV) adoption. So, it offers the potential to catalyze the uptake of clean-energy technologies and to support sustainable development. The proposed design dissipates PV power into heat using commercial positive temperature coefficient (PTC) resistors operating near their Curie temperature. A simplified theoretical model is formulated to easily estimate the thermal power and heat-transfer conductances required for achieving cooking temperatures. An instrumented prototype allows for characterizing the transient temperature evolution during controlled heating and cooling experiments in the laboratory, facilitating development in an initial step avoiding the PV panel. The results demonstrate that the minimal PV configuration is technically feasible, robust, and compatible with low-resource settings. This encourages its adoption in communities experiencing energy poverty. Full article
(This article belongs to the Collection Featured Papers in Solar Energy and Photovoltaic Systems Section)
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15 pages, 13547 KB  
Article
Protective Effects of Vitis coignetiae Vine Stem Extract Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice
by Nam-Kyu Yoon, Jeongjun Lee, Hunsuk Chung, Jae-Kwang Kim and Sae-Kwang Ku
Antioxidants 2026, 15(5), 651; https://doi.org/10.3390/antiox15050651 - 21 May 2026
Viewed by 378
Abstract
Vitis coignetiae Pulliat ex Planch, commonly referred to as “meoru” in Korea (crimson glory vine), is a grape species belonging to the Vitaceae family, native to East Asia. This study investigated the protective effects of a hot water extract prepared from the vine [...] Read more.
Vitis coignetiae Pulliat ex Planch, commonly referred to as “meoru” in Korea (crimson glory vine), is a grape species belonging to the Vitaceae family, native to East Asia. This study investigated the protective effects of a hot water extract prepared from the vine stems of V. coignetiae (CG) in a model of CCl4-induced acute liver injury. Mice received oral administration of CG (100, 200, and 400 mg/kg) or silymarin (200 mg/kg) once daily for 7 consecutive days, followed by intraperitoneal injection of CCl4 (0.5 mL/kg). CG attenuated CCl4-induced oxidative stress, as indicated by reduced hepatic malondialdehyde production and decreased 4-hydroxynonenal-positive cells. These effects were accompanied by restoration of antioxidant defense systems, including increased glutathione levels and superoxide dismutase and catalase activities, along with increased nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression. Hepatic inflammatory responses were also attenuated by CG treatment, with reductions in TNF-α, interleukin (IL)-1β, and IL-6 levels, inflammatory cell infiltration, and nuclear factor-κB (NF-κB) mRNA expression. Furthermore, CG attenuated apoptotic cell death, as evidenced by decreased cleaved caspase-3-positive and cleaved poly(ADP-ribose) polymerase (PARP)-positive cells. CG also lowered serum aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase levels, and alleviated hepatocellular degeneration in histopathological analysis. Collectively, these findings suggest that CG may exert protective effects against CCl4-induced liver injury by regulating oxidative stress, inflammation, and apoptosis. Full article
(This article belongs to the Special Issue Oxidative Stress in Hepatic Diseases)
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22 pages, 360 KB  
Article
From Nihilism to Realism: Joseph Edkins’ Interpretation of Buddhist Nirvana and Death
by Yuan Li
Religions 2026, 17(5), 622; https://doi.org/10.3390/rel17050622 - 21 May 2026
Viewed by 357
Abstract
In the nineteenth century, the emergence of Western Buddhist studies generated sustained debate over nirvana, one of the central doctrines of Buddhism. The British Protestant missionary Joseph Edkins actively participated in this intellectual discussion and developed a distinctive interpretation of the concept. Early [...] Read more.
In the nineteenth century, the emergence of Western Buddhist studies generated sustained debate over nirvana, one of the central doctrines of Buddhism. The British Protestant missionary Joseph Edkins actively participated in this intellectual discussion and developed a distinctive interpretation of the concept. Early in his writings, Edkins largely followed the prevailing tendency in European scholarship to interpret nirvana through a philosophical framework that equated it with nihilism. However, through extensive engagement with Chinese Buddhist texts and direct interactions with Chinese Buddhists, he gradually revised this view. Approaching the issue from the perspectives of common sense and religion, Edkins argued that nirvana, as understood in Chinese Buddhism, retained a form of practical realism rather than complete annihilation. Although he ultimately rejected the idea that nirvana could provide genuine salvation, Edkins discerned the Western Heaven (Pure Land) within his own construction of a Buddhist theory of death and interpreted it as a potential preparation for Christianity. By situating Northern Buddhism within a broader biblical narrative, he sought to reconcile tensions between nirvana and other Buddhist conceptions of the afterlife, as well as the wider doctrinal tensions between Buddhism and Christianity. As an intermediary in Sino-Western intellectual exchange, Edkins’ creative interpretation of nirvana not only reflects the imprint of Western intellectual traditions but also illuminates the complex negotiations between Christianity and Buddhism, and between faith and reason, in the nineteenth-century construction of Buddhist knowledge. Full article
24 pages, 310 KB  
Review
Compassionate Extracorporeal Membrane Oxygenation Discontinuation: A Narrative Review and Practical Process Model for Reliable End-of-Life Care
by Kinsley Hubel, Raju Reddy, Akram Khan, Jonathan Pak and Nehan Sher
Healthcare 2026, 14(9), 1249; https://doi.org/10.3390/healthcare14091249 - 6 May 2026
Viewed by 574
Abstract
Background and Objectives: Extracorporeal membrane oxygenation (ECMO) provides temporary respiratory or circulatory support when conventional therapies fail. Some patients do not recover and are not candidates for transplant or durable mechanical support. In these cases, continuing ECMO may no longer align with the [...] Read more.
Background and Objectives: Extracorporeal membrane oxygenation (ECMO) provides temporary respiratory or circulatory support when conventional therapies fail. Some patients do not recover and are not candidates for transplant or durable mechanical support. In these cases, continuing ECMO may no longer align with the patient’s goals. Compassionate ECMO discontinuation (CED) is the planned withdrawal of extracorporeal support with death anticipated. The term “compassionate” refers to the goal of minimizing suffering in the end-of-life process. This review proposes a reliability-oriented framework to standardize CED and reduce preventable distress for patients, families, and clinicians. Materials and Methods: We conducted a targeted narrative review of ethical analyses, consensus guidance, and empirical literature on planned ECMO withdrawal. The results of the narrative review were combined with our existing practical process for CED into this proposed reliability-oriented framework as a guide for clinicians. Recommendations were organized into a four-phase process model that emphasizes operational implementation, anticipatory guidance, and quality improvement. We included modality-specific considerations for veno-arterial (VA), veno-venous (VV) ECMO, and extracorporeal cardiopulmonary resuscitation (ECPR). Results: The framework includes four phases. Phase I, Anticipation and Alignment, emphasizes structured shared decision-making, early expectation setting, time-limited trials, palliative care integration, and predefined pathways for managing disagreement. Phase II, Preparation, includes interdisciplinary role assignment, a pre-withdrawal time out, family coaching on expected physiological changes, and preemptive comfort medications that account for ECMO-altered pharmacokinetics. Phase III, Implementation, prioritizes comfort first, pacing with explicit pause points, environmental controls to reduce alarms and visual distress, and modality-tailored sequencing. Phase VI, Aftercare and Learning Capture, includes bereavement support, standardized documentation, structured team debriefing, and recommended process measures to guide improvement. Conclusions: Viewing CED as a low-frequency, high-stakes clinical process supported by scripts, checklists, and iterative feedback can improve goal-concordant end-of-life (EOL) care, reduce suffering and family trauma, support clinicians, and strengthen ECMO program learning systems. Full article
16 pages, 732 KB  
Systematic Review
COVID-19 in Space: Possible Health Risks and Preparedness Guidelines
by Ishan Vashishat, Sanghyun Eddie Han and Barnabe D. Assogba
Pathogens 2026, 15(5), 498; https://doi.org/10.3390/pathogens15050498 - 6 May 2026
Cited by 1 | Viewed by 501
Abstract
Background: The COVID-19 pandemic resulted in over 705 million infections and 7 million deaths, underscoring the importance of understanding disease behavior across diverse environments. As NASA, SpaceX, and ISRO prepare for more frequent missions, managing health risks for astronauts and space tourists is [...] Read more.
Background: The COVID-19 pandemic resulted in over 705 million infections and 7 million deaths, underscoring the importance of understanding disease behavior across diverse environments. As NASA, SpaceX, and ISRO prepare for more frequent missions, managing health risks for astronauts and space tourists is essential. Objective: This study reviews the literature on airborne infections in space, identifies research gaps, and establishes preparedness strategies for potential COVID-19 outbreaks during space missions. Methods: A systematic literature review was conducted to identify studies examining airborne infectious diseases in space. To compare these findings with Earth-based data, pathogen safety data sheets were used. A separate systematic review was conducted to explore similarities between COVID-19 and the identified airborne infectious diseases. A comparative approach was used to predict COVID-19’s potential behavior in microgravity. Existing guidelines for managing airborne diseases in space and on Earth were reviewed and compared to develop a set of preparedness recommendations for COVID-19 in space. Results: Nine airborne infectious diseases occurring in space were identified. Six tentative effects of COVID-19 in a microgravity environment were theorized in this study. We propose recommendations to improve current space travel health guidelines and address the identified risks. Conclusions: The results of this study will change the course of human space exploration by assisting in the protection of space travelers and guiding the development of new protocols that include comprehensive safety features. Full article
(This article belongs to the Collection SARS-CoV Infections)
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25 pages, 4638 KB  
Article
Functionalization of Chitosan with Asparagus (Asparagus officinalis L.) Waste Extract as a Potential Additive for Active Food Packaging Application: Preparation and Characterization of Antioxidant and Antibacterial Properties
by Ana L. Moreno-Robles, Leslie V. Acuña-Pacheco, Maribel Plascencia-Jatomea, Saúl Sánchez-Valdes, María J. Moreno-Vásquez, José A. Tapia-Hernández, Rosario M. Robles-Sánchez, Idania E. Quintero-Reyes and Abril Z. Graciano-Verdugo
Polysaccharides 2026, 7(2), 52; https://doi.org/10.3390/polysaccharides7020052 - 3 May 2026
Viewed by 590
Abstract
In this study, we investigate the valorization of asparagus processing by-products—cut-off waste (CAW) and whole asparagus waste (WAW)—as sources of bioactive compounds, primarily polyphenolics, and their conjugation with chitosan (CS) to enhance their antioxidant and antibacterial properties, with potential applications as a food-preservation [...] Read more.
In this study, we investigate the valorization of asparagus processing by-products—cut-off waste (CAW) and whole asparagus waste (WAW)—as sources of bioactive compounds, primarily polyphenolics, and their conjugation with chitosan (CS) to enhance their antioxidant and antibacterial properties, with potential applications as a food-preservation additive. Aqueous (CAWaq, WAWaq) and ethanolic (CAWet, WAWet) extracts were prepared and characterized to determine total phenol and flavonoid content, antioxidant capacity, and polyphenolic compound profile. Among the extracts, WAWaq exhibited the highest antioxidant activity, with a total phenolic content of 9.93 mg gallic acid equivalents/g DW, and quercetin, rutin, and phenolic acids were identified as major constituents. A novel conjugate (WAWaq–CS) was synthesized via free-radical-mediated chemical modification of chitosan with WAWaq and characterized by means of ultraviolet-visible (UV–vis) and Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and determination of bioactive properties. WAWaq-CS improved the antioxidant activity of chitosan and exhibited selective inhibition of Staphylococcus aureus across all tested concentrations, inducing cell death, as confirmed by resazurin viability and optical density measurements. Conversely, Pediococcus acidilactici maintained viability at low concentrations, preserving probiotic functionality in antibacterial systems. These findings indicate the potential of asparagus waste extract–chitosan conjugates as sustainable materials with dual functionality, highlighting the transformation of agro-industrial residues into functional materials for active food packaging and food preservation. Full article
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12 pages, 352 KB  
Article
Assessment of Risks and Outcomes of Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Stem Cell Transplant Recipients Including Potentially Undiagnosed Cases—A Multicenter Canadian Study
by Emily Trus, Alexander Ruzic, Ram Vasudevan Nampoothiri, Gregory R. Pond, Vinita Dhir, Andrew Poskus, Louise Bordeleau and Michael Trus
Curr. Oncol. 2026, 33(5), 261; https://doi.org/10.3390/curroncol33050261 - 30 Apr 2026
Viewed by 671
Abstract
Background and Methods: Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a severe complication of allogeneic stem cell transplant (allo-SCT). Given the increased use of allo-SCT and variability of SOS/VOD incidence in published reports, cases of allo-SCT from two major transplant centers in Ontario, Canada [...] Read more.
Background and Methods: Sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a severe complication of allogeneic stem cell transplant (allo-SCT). Given the increased use of allo-SCT and variability of SOS/VOD incidence in published reports, cases of allo-SCT from two major transplant centers in Ontario, Canada (2019–2021), were reviewed to identify risk factors prognostic for SOS/VOD onset and to assess outcomes. Results: This study included 536 allo-SCT cases, with a mean age of 53.4 years [min–max: 17–76], including 322 male recipients and 214 female recipients. There were 17 SOS/VOD cases diagnosed during the first 100 days, representing 3% of allo-SCT cases, with a median age of 48 years [18–72] and equally distributed between genders. All cases were classical SOS/VOD, with onset prior to day 21 [1–20]. These cases were graded as one mild, six moderate, six severe, and four very severe cases. The mild case of SOS/VOD recovered after treatment with diuretics. In respect to the 16 cases graded as ≥moderate SOS/VOD, the average inpatient stay was 56 days [24–178], and eight patients were in the ICU for an average of 6 days [0–42], with a median of zero days. Five of the sixteen ≥moderate SOS/VOD patients died within 100 days [9–59]—four from SOS/VOD. After day +100, five remained alive, and six died between days 125 and 419. Treatments for ≥moderate SOS/VOD included diuretics [n = 15], steroids [n = 3], and defibrotide [n = 9]. The nine patients treated with defibrotide were graded as moderate [n = 2], severe [n = 4], and very severe [n = 3]. Three of the nine patients treated with defibrotide died before day 100, and the other six survived beyond day 100. None of the six surviving patients died from SOS/VOD. Univariable regression analysis identified a higher baseline absolute neutrophil count (ANC) of 4.2 × 109/L compared to 2.6 × 109/L [p = 0.035] and lower baseline platelet count of 104 × 109/L compared to 140 × 109/L [p = 0.034] in SOS/VOD and non-SOS/VOD cases, respectively, as independent risks for ≥moderate SOS/VOD. Treatment with inotuzumab ozogamicin was also identified as a risk factor for ≥moderate SOS/VOD (p = 0.016). The absence of late-onset SOS/VOD in the cohort of 536 patients prompted a retrospective analysis of the data to identify potentially missed cases. Seven cases were identified as meeting the diagnostic criteria for SOS/VOD: four classical and three late-onset. One case would have been graded as severe, and the remaining six would have been graded as very severe. Six patients were reported to have died between days 11 and 107, with four deaths before day 100. The clinical diagnoses of patients meeting diagnostic criteria for SOS/VOD included infection (n = 3), graft-versus-host disease (GVHD) (n = 3), and pulmonary hemorrhage (n = 1). The inclusion of potentially missed cases in the analysis again suggested a lower baseline platelet count (p = 0.002) and prior treatment with inotuzumab ozogamicin (p = 0.003) as potential risk factors for SOS/VOD. The baseline ANC was lower in this combined cohort but did not reach statistical significance (p = 0.089) as it did in the confirmed SOS/VOD cohort (p = 0.035). Additional clinical features that were identified as statistically significant for the onset of SOS/VOD (potential and confirmed cases) included a lower Karnofsky Performance Status (p = 0.01), the presence of pulmonary hypertension (p = 0.012), lower baseline hemoglobin (p = 0.017), and higher baseline serum ferritin (p = 0.01). Conclusions: The incidence of classical SOS/VOD in this cohort was consistent with recent published reports and carried a high fatality rate. A higher ANC, lower platelet count at the start of the preparative regimen, and prior treatment with inotuzumab ozogamicin were identified as potential risk factors for diagnosed SOS/VOD. Hospital and intensive care unit stays were longer in SOS/VOD patients. There were no cases of late-onset VOD diagnosed within the first 100 days of allo-SCT transplant, which is inconsistent with recently reported incidence rates. Potentially missed cases of SOS/VOD were identified, suggesting that this disease may be under-diagnosed and underscoring the need for ongoing education and resources to allow for early intervention. Full article
(This article belongs to the Section Cell Therapy)
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23 pages, 4615 KB  
Article
Coumarin–Thiourea Hybrids: Structural Features Governing CA Inhibition and Antiproliferative Effects
by Alma Fuentes-Aguilar, Rebecca Colombo, Aday González-Bakker, Adrián Puerta, Penélope Merino-Montiel, Sara Montiel-Smith, José L. Vega-Báez, Simone Giovannuzzi, Alessio Nocentini, José G. Fernández-Bolaños, Claudiu T. Supuran, José M. Padrón and Óscar López
Int. J. Mol. Sci. 2026, 27(9), 3743; https://doi.org/10.3390/ijms27093743 - 23 Apr 2026
Viewed by 272
Abstract
Selective inhibition of the tumour-associated carbonic anhydrase (CA) isoforms IX and XII, which are overexpressed in hypoxic tumours, has emerged as a promising strategy for the development of novel anticancer agents. Among the diverse CA inhibitors reported to date, coumarins have attracted particular [...] Read more.
Selective inhibition of the tumour-associated carbonic anhydrase (CA) isoforms IX and XII, which are overexpressed in hypoxic tumours, has emerged as a promising strategy for the development of novel anticancer agents. Among the diverse CA inhibitors reported to date, coumarins have attracted particular attention. These chromenone derivatives, widely distributed in phytochemicals, display a broad range of biological activities and are known to act as suicide inhibitors of CAs. Following the tail approach, we designed a series of hybrid compounds combining a coumarin core with an N-arylthioureido scaffold located at the C-7 position and investigated how structural variations—including substituents on the coumarin and aromatic moieties, tether length, and urea/thiourea isosterism—influence their biological properties (CA inhibition and antiproliferative activity). Substituted coumarins at C-3 and C-4 were efficiently prepared via Pechmann condensation, while the thioureido motif was introduced using various aryl isothiocyanates as key synthetic intermediates. The lead compound, featuring a dimethylated coumarin, a pentyl linker, and an N-(p-tolyl)thioureido residue, inhibited the target enzymes in the low- to mid-nanomolar range (Ki = 6.0 and 49.9 nM, respectively), displaying selectivity indexes (S.I.s) surpassing those of the reference drug acetazolamide (AAZ). Moreover, it exhibited potent antiproliferative activity, with GI50 values in the low micromolar range (1.9–3.5 µM) against both drug-sensitive and multidrug-resistant cancer cell lines. Label-free three-dimensional holotomographic microscopy revealed that this compound triggers slow apoptosis, leading to cell death after approximately 20 h of exposure. Full article
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15 pages, 945 KB  
Article
The Role of Drug-Coated Balloons in an All-Comer Population: Outcomes from a Two-Center Real-World Registry
by Florin-Leontin Lazar, Teodor Paul Kacso, Calin Homorodean, Horea-Laurentiu Onea, Ioan-Cornel Bitea, Mihai Ober, Oana Stoia, Minodora Teodoru and Dan-Mircea Olinic
Medicina 2026, 62(4), 769; https://doi.org/10.3390/medicina62040769 - 16 Apr 2026
Viewed by 1096
Abstract
Background and Objectives: Drug-coated balloons (DCBs) represent a novel, attractive strategy for coronary revascularization; however, data supporting their use in complex real-world populations remain limited. We aimed to evaluate the safety and efficacy of a DCB-first strategy in a predominantly acute coronary syndrome [...] Read more.
Background and Objectives: Drug-coated balloons (DCBs) represent a novel, attractive strategy for coronary revascularization; however, data supporting their use in complex real-world populations remain limited. We aimed to evaluate the safety and efficacy of a DCB-first strategy in a predominantly acute coronary syndrome (ACS) and multivessel disease (MVD) population. Materials and Methods: We conducted a prospective two-center observational registry including 115 consecutive patients treated with a DCB-first strategy (DCB-only in 44 patients and a hybrid DCB–drug-eluting stent in 71 patients) for both de novo and in-stent coronary lesions. Bailout stenting was performed when required according to predefined criteria. Results: The study population was characterized by high clinical complexity, with 78.3% MVD and 67.8% presenting with ACS, including 10.5% ST-segment elevation myocardial infarctions. Bailout stenting was required in 12.2% of lesions. At 18 months, the target lesion revascularization (TLR) rate was 2.83%, while the device-oriented composite endpoint (DOCE; cardiac death, target vessel myocardial infarction or TLR) occurred in 4.7% of patients. The cumulative major adverse cardiovascular event (MACE) rate at 18 months was 14.8%, largely driven by the high-risk clinical profile of the cohort. Patients treated with a DCB-only strategy had a shorter duration of dual antiplatelet therapy compared with those treated with a hybrid strategy. Conclusions: In this two-center real-world registry including predominantly ACS and MVD patients, a DCB-first strategy was associated with low lesion-level event rates and acceptable mid-term clinical outcomes. These findings support the feasibility of a leave-nothing-behind approach in complex coronary disease when meticulous lesion preparation and provisional bailout stenting are applied. Full article
(This article belongs to the Section Cardiology)
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24 pages, 3132 KB  
Article
BSA-Based Nanoparticles for Dual Loading of Pazopanib and Enzalutamide: Formulation Optimization and In Vitro Evaluation in Breast Cancer Cells
by Gizem Ruya Topal, Kubra Kilic, Meral Sarper, Ozgur Esim, Ayhan Savaser and Yalcin Ozkan
Pharmaceutics 2026, 18(4), 475; https://doi.org/10.3390/pharmaceutics18040475 - 13 Apr 2026
Viewed by 753
Abstract
Objectives: Limited intracellular exposure can reduce the in vitro activity of pazopanib (PAZ) and enzalutamide (ENZ). This study developed bovine serum albumin (BSA) particles co-encapsulating PAZ and ENZ (PE-BSA) and evaluated physicochemical properties, release kinetics, 4T1 cellular uptake, and in vitro cytotoxicity versus [...] Read more.
Objectives: Limited intracellular exposure can reduce the in vitro activity of pazopanib (PAZ) and enzalutamide (ENZ). This study developed bovine serum albumin (BSA) particles co-encapsulating PAZ and ENZ (PE-BSA) and evaluated physicochemical properties, release kinetics, 4T1 cellular uptake, and in vitro cytotoxicity versus free drugs and single-drug particles. Methods: Drug-loaded BSA particles were prepared using a crosslinking-based method. Particle size (PS), polydispersity index (PDI), zeta potential (ZP), and encapsulation efficiency (EE) were determined. In vitro release was assessed over 48 h and fitted to kinetic models. 4T1 uptake was quantified after 2 and 4 h by intracellular drug levels. Cytotoxicity was measured by MTT at 24 and 72 h (1–100 µg/mL). Moreover, cell death analyses were conducted. Stability studies at +4 °C and serum were also carried out. Results: PE-BSA was nanoscale and monodisperse (PS 128.7 ± 2.6 nm; PDI 0.026 ± 0.01) with ZP −31.65 ± 1.13 mV and high EE (PAZ 98.59 ± 1.78%; ENZ 69.79 ± 0.02%). At 24/48 h, cumulative release from PE-BSA was 11.96/12.31% for PAZ and 52.26/85.95% for ENZ. The release kinetics were best described by the Korsmeyer–Peppas model for PAZ (r2 = 0.9578) and the Higuchi model for ENZ (r2 = 0.9605), indicating diffusion-controlled release. PE-BSA increased 4T1 uptake versus free drugs (2 h: 10.02% PAZ and 21.9% ENZ; 1.77-fold and 4.15-fold), with sustained enhancement at 4 h (2.2- and 4.69-fold, respectively). After 24 h, PE-BSA induced a markedly higher apoptotic response in 4T1 cells (32.5% early apoptosis and 0.8% late apoptosis/early necrosis) compared with free-PAZ (6.6% early apoptosis) and P-BSA (7.3% early apoptosis). Particles were stable. Conclusions: PE-BSA produced BSA particles with diffusion-governed release and enhanced 4T1 internalization, supporting albumin particles as a delivery platform to increase intracellular exposure of PAZ/ENZ in vitro. Full article
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17 pages, 7119 KB  
Article
Pathway-Guided Medium Engineering for Enhanced Prodiginine Production in Spartinivicinus ruber MCCC 1K03745T
by Xiaosi Lin, Liping Xiao, Jingru Xiao and Congjie Dai
Fermentation 2026, 12(4), 192; https://doi.org/10.3390/fermentation12040192 - 9 Apr 2026
Viewed by 515
Abstract
Cycloheptylprodigiosin is a promising anticancer candidate that induces cancer cell death accompanied by severe Golgi stress. Although the soybean oil-based optimized MB2216 medium produced a total prodiginine titer approximately three times that of the basal MB2216 medium, the overall production level remained limited. [...] Read more.
Cycloheptylprodigiosin is a promising anticancer candidate that induces cancer cell death accompanied by severe Golgi stress. Although the soybean oil-based optimized MB2216 medium produced a total prodiginine titer approximately three times that of the basal MB2216 medium, the overall production level remained limited. In addition, a substantial fraction of the pigments partitioned into floating oil droplets, hindering efficient recovery by simple centrifugation. In this study, a novel medium was rationally formulated based on genomic insights derived from homology analysis of conserved biosynthetic genes involved in cycloheptylprodigiosin production in Spartinivicinus ruber MCCC 1K03745T. Sequential optimization through single-factor experiments, full factorial designs, steepest ascent experiments and response surface methodology identified an optimal medium consisting of peptone (5 g/L), yeast extract (1 g/L), peanut meal (7.611 g/L), and L-Proline (0.695 g/L) prepared in seawater at pH 7.6. Under the optimized conditions, the total prodiginine titer reached 53.33 mg/L, which was 11.37 times that of the basal MB2216 medium and 3.29 times that of the soybean oil-based MB2216 medium. Moreover, the pigment-associated biomass could be efficiently recovered by centrifugation. This study provides a genomics-informed strategy for improving prodiginine production in S. ruber and facilitates downstream pigment recovery. Full article
(This article belongs to the Section Fermentation Process Design)
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17 pages, 5018 KB  
Article
A Rabies Virus Glycoprotein Subunit Vaccine Produced in Pichia pastoris Induces Neutralizing Antibodies in Mice
by Ye Yang, Ruo Mo, Zhuoran Hou, Han Wang, Peng Sun, Ruixi Liu, Tiantian Wang, Bin Zhang, Xuchen Hou, Yongkun Zhao, Jun Wu and Bo Liu
Vaccines 2026, 14(4), 322; https://doi.org/10.3390/vaccines14040322 - 4 Apr 2026
Viewed by 1122
Abstract
Background: Rabies is a highly fatal zoonotic disease that causes approximately 59,000 human deaths worldwide each year. Current inactivated rabies vaccines require multiple doses and are associated with high costs. The full-length rabies virus glycoprotein (RVG), a membrane protein, exhibits substantial instability [...] Read more.
Background: Rabies is a highly fatal zoonotic disease that causes approximately 59,000 human deaths worldwide each year. Current inactivated rabies vaccines require multiple doses and are associated with high costs. The full-length rabies virus glycoprotein (RVG), a membrane protein, exhibits substantial instability in its trimeric structure during recombinant expression. This instability makes it difficult to obtain high-purity, correctly folded antigens. Objectives: This study focuses on the preparation of a full-length recombinant RVG subunit vaccine candidate expressed in a glycoengineered Pichia pastoris system with mammalian-like glycosylation. Methods: The full-length RVG gene (including the transmembrane domain and cytoplasmic tail) from the Challenge Virus Standard-11 (CVS-11) strain was codon-optimized and inserted into the pPICZαA vector to construct the recombinant expression plasmid pPICZαA-RVG. The plasmid was transformed into glycoengineered Pichia pastoris X33-7 (low-mannose type) by electroporation for inducible expression. The target protein was purified by nickel affinity chromatography, anion-exchange chromatography, and Superdex-200 size-exclusion chromatography. The structural characteristics of the purified protein were analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The purified antigen was formulated with the adjuvants AS03 or MF59. BALB/c mice (n = 5 per group) were immunized intramuscularly following a four-dose schedule (days 0, 7, 14, and 28). Antigen-specific IgG antibody titers were measured by ELISA, and neutralizing antibody titers were determined using the rapid fluorescent focus inhibition test (RFFIT). Results: Glycoengineered Pichia pastoris yeast strains expressing wild-type RVG (RVG-WT) or a mutant variant (RVG-M6: R84S, R199S, H270P, R279S, K300S, and R463S) were successfully constructed. The purified RVG antigen formed nanoparticles with an average particle size of approximately 75 nm. Immunized mice generated robust RVG-specific IgG responses, with titers reaching approximately 6.31 × 105 for RVG-WT after the fourth immunization, compared to 3.16 × 103 for RVG-M6 and 5.62 × 103 for the RVG-WT-PEG control. Two weeks after the fourth immunization, RVG-WT formulated with AS03 or MF59 induced significant neutralizing antibody responses compared with the control group (p < 0.0001 and p < 0.01, respectively). The neutralizing antibody titers reached 1:79.43 in the AS03 group and 1:33.11 in the MF59 group, whereas the WT-PEG + AS03 control group showed a low titer of 1:3.72. In contrast, RVG-M6 formulated with MF59 failed to induce detectable neutralizing antibodies (1:3.02). Furthermore, RVG-WT + AS03 induced significantly higher neutralizing antibody responses than the WT-PEG + AS03 control group (p < 0.0001), and a significant difference was also observed between the RVG-WT + MF59 and RVG-M6 + MF59 groups (p < 0.01). Conclusions: The glycoengineered Pichia pastoris expression system successfully produced uniform full-length rabies virus glycoprotein nanoparticles with high purity. When formulated with the AS03 adjuvant, RVG-WT induced high-titer neutralizing antibodies in mice, suggesting a promising strategy for the development of recombinant subunit vaccines against rabies. However, this study is limited by the absence of challenge studies and validation in target animal species, which will be further investigated in future work. Full article
(This article belongs to the Section Vaccine Advancement, Efficacy and Safety)
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10 pages, 463 KB  
Article
Epidemiology of Foodborne Botulism Outbreaks in Romania, 2007–2024
by Bianca Georgiana Enciu, Rodica Popescu, Alina Daniela Zaharia, Barbara Schimmer, Daniela Pițigoi, Anca Mirela Sîrbu and Adriana Pistol
Microorganisms 2026, 14(4), 819; https://doi.org/10.3390/microorganisms14040819 - 2 Apr 2026
Viewed by 925
Abstract
Foodborne botulism, caused by ingestion of pre-formed botulinum neurotoxin, is the most common form of botulism. While large outbreaks linked to commercial foods are rare, smaller outbreaks associated with home-processed products are more frequent, reflecting local dietary habits and traditional preservation practices. The [...] Read more.
Foodborne botulism, caused by ingestion of pre-formed botulinum neurotoxin, is the most common form of botulism. While large outbreaks linked to commercial foods are rare, smaller outbreaks associated with home-processed products are more frequent, reflecting local dietary habits and traditional preservation practices. The aim of this paper is to provide a public health overview of reported foodborne botulism outbreaks in Romania over an 18-year period to raise awareness among clinicians and public health officials. Between 2007 and 2024, a total of 337 foodborne botulism cases were reported in Romania, of which 43% (147) were related to 55 outbreaks (median number of cases per outbreak: 2; IQR: 2–3). Most outbreaks were reported in Bihor County (11 outbreaks with 29 cases) and its neighboring county, Satu Mare (seven outbreaks, accounting for a total number of 20 cases). Outbreak-related cases were observed in younger persons with a median age of 31 years (compared to 45 years for sporadic cases) and were statistically significantly associated with consumption of pork products (p < 0.001). Fifteen deaths occurred (case fatality ratio: 4%), including three outbreak-related cases (case fatality ratio: 2%). These findings highlight the ongoing public health challenge of foodborne botulism in Romania and the need for robust surveillance, targeted educational initiatives in high-incidence counties to deliver information about safe food preparation and preservation practices, and the continuous availability of botulinum antitoxin supplies. Full article
(This article belongs to the Special Issue Infectious Disease Surveillance in Romania: Third Edition)
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