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Search Results (15,786)

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19 pages, 3470 KB  
Article
Immunomodulatory Effects of Poly-D,L-Lactic Acid on LL-37-Driven Rosacea-like Inflammation via Suppression of mTORC1 Signaling
by Kyung-A Byun, Jeyoung Park, Seyeon Oh, Jiyeon Shin, Suk Bae Seo, Kuk Hui Son and Kyunghee Byun
Int. J. Mol. Sci. 2026, 27(14), 6425; https://doi.org/10.3390/ijms27146425 (registering DOI) - 19 Jul 2026
Abstract
Rosacea is a chronic inflammatory skin disorder driven by dysregulated cathelicidin processing and excessive LL-37, which triggers a circuit involving Toll-like receptor 2 (TLR2)/kallikrein-5 (KLK5)-dependent amplification and downstream mechanistic target of rapamycin complex 1 (mTORC1), NF-κB, and NLR family pyrin domain containing 3 [...] Read more.
Rosacea is a chronic inflammatory skin disorder driven by dysregulated cathelicidin processing and excessive LL-37, which triggers a circuit involving Toll-like receptor 2 (TLR2)/kallikrein-5 (KLK5)-dependent amplification and downstream mechanistic target of rapamycin complex 1 (mTORC1), NF-κB, and NLR family pyrin domain containing 3 (NLRP3) inflammasome pathways. We hypothesized that poly-D,L-lactic acid (PDLLA) could attenuate this inflammatory cascade by inducing macrophage-derived interleukin (IL)-10. PDLLA increased IL-10 secretion from THP-1-derived macrophages in a dose-dependent manner. In LL-37-stimulated HaCaT keratinocytes, LL-37 decreased phosphorylated signal transducer and activator of transcription (pSTAT3)/STAT3, DNA damage-inducible transcript 4 (DDIT4), and phosphorylated AMP-activated protein kinase (pAMPK)/AMPK while increasing phosphorylated protein kinase B (pAKT)/AKT and mTORC1 activation; conditioned media from PDLLA-treated macrophages (CMPDLLA) restored pSTAT3/STAT3, DDIT4, and pAMPK/AMPK, reduced pAKT/AKT, and suppressed pmTOR/mTOR. CMPDLLA attenuated downstream inflammatory responses, including NF-κB nuclear translocation, VEGF production, and NLRP3-inflammasome-mediated IL-18 secretion. These findings were validated using an intradermal LL-37-injected mouse model. Compared with the normal control/saline group, LL-37/saline decreased IL-10, pSTAT3/STAT3, DDIT4, and pAMPK/AMPK while increasing pAKT/AKT, pmTOR/mTOR, pS6K/S6K, TLR2/KLK5/LL-37, NF-κB, VEGF, and NLRP3 inflammasome/IL-18 signaling; PDLLA partially restored the STAT3/DDIT4–AMPK regulatory pattern and suppressed these disease-associated signals. Consequently, PDLLA treatment led to a pronounced reduction in clinical lesion area. Overall, PDLLA may attenuate LL-37-driven cutaneous inflammation by promoting an IL-10-linked STAT3/DDIT4–AKT/AMPK program that suppresses mTORC1 and disrupts cathelicidin amplification, supporting its potential as an injectable immunomodulatory approach for rosacea-like skin inflammation. Full article
(This article belongs to the Section Molecular Immunology)
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21 pages, 1067 KB  
Entry
Biodegradation: A Pharmaceutical Journey
by Thomas I. Wilkes
Encyclopedia 2026, 6(7), 159; https://doi.org/10.3390/encyclopedia6070159 (registering DOI) - 19 Jul 2026
Definition
Pharmaceuticals are essential to modern healthcare but increasingly represent a pervasive and biologically active class of environmental contaminants. Following administration, many drugs are incompletely metabolised in the human body and are excreted as parent compounds or active metabolites, subsequently entering municipal wastewater treatment [...] Read more.
Pharmaceuticals are essential to modern healthcare but increasingly represent a pervasive and biologically active class of environmental contaminants. Following administration, many drugs are incompletely metabolised in the human body and are excreted as parent compounds or active metabolites, subsequently entering municipal wastewater treatment plants (WWTPs). Conventional treatment processes only partially remove many pharmaceuticals, resulting in chronic sub-therapeutic exposure of microbial communities which act as both functional agents of biodegradation and sensitive ecological targets. Such exposure alters microbial structure and function, reduces biotransformation capacity, promotes the persistence of recalcitrant compounds such as carbamazepine and diclofenac, and drives the selection and dissemination of antibiotic resistance genes. These effects may propagate across aquatic, terrestrial, agricultural, and food systems via treated effluents and biosolids, linking human medical practices to environmental and public health outcomes. By integrating Pharmaceutical science, wastewater engineering, microbiome ecology, and antimicrobial resistance research, this work frames pharmaceutical pollution as a closed-loop OneHealth challenge. Full article
(This article belongs to the Collection Encyclopedia of One Health)
17 pages, 3169 KB  
Article
The microRNA Expression Signature of Lung Adenocarcinoma Harboring EGFR Mutations: Identification of Therapeutic Targets for EGFR-TKI Combination Therapy
by Takuya Tokunaga, Yuya Tomioka, Aya Harada Takeda, Yuka Ishihara, Ayako Nagata, Mayuko Kato, Takayuki Suetsugu, Keiko Mizuno, Masaya Aoki, Kazuhiro Ueda and Naohiko Seki
Int. J. Mol. Sci. 2026, 27(14), 6412; https://doi.org/10.3390/ijms27146412 (registering DOI) - 19 Jul 2026
Abstract
Approximately half of Japanese patients with lung adenocarcinoma (LUAD) have epi-dermal growth factor receptor (EGFR) gene mutations. Therefore, EGFR is the most critical therapeutic target in treating LUAD. This study’s purpose is to explore novel therapeutic targets for LUAD and further [...] Read more.
Approximately half of Japanese patients with lung adenocarcinoma (LUAD) have epi-dermal growth factor receptor (EGFR) gene mutations. Therefore, EGFR is the most critical therapeutic target in treating LUAD. This study’s purpose is to explore novel therapeutic targets for LUAD and further improve EGFR inhibitor combination therapy. We created microRNA (miRNA) expression signatures from clinical specimens of LUAD patients harboring EGFR gene mutations using RNA sequencing. Based on the miRNA signature, we focused on miR-206, which had the most downregulated expression. We searched for its target gene in LUAD cells by facilitating transfection of miR-206 into the EGFR mutant cell line PC9 and searching for genes with suppressed expression. A total of 821 genes were downregulated in PC9 cells. Through molecular classification of these genes, we revealed that 18 genes were closely related to the cell cycle. Among these genes, we focused on cyclin-dependent kinase 4 (CDK4) and investigated the synergistic effects of a CDK4/6 inhibitor (abemaciclib or palbociclib) and osimertinib, an EGFR inhibitor in LUAD cells. In vitro and three-dimensional culture analyses showed that combination therapy with a CDK4/6 inhibitor and an EGFR inhibitor synergistically suppressed proliferation of LUAD cells with EGFR mutations. Our miRNA-based analysis is an excellent strategy for identifying therapeutic targets for LUAD. Continued analysis will reveal target molecules that enhance the therapeutic effects of EGFR inhibitors. Full article
(This article belongs to the Special Issue Advances in Molecular Biomarkers in Cancer and Metabolic Diseases)
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22 pages, 3132 KB  
Article
Prognostic Value of Morphological Characteristics and Immune Microenvironment in High-Grade Serous Cancer (HGSC)
by Danijel Antonio Grubišić, Branka Petrić Miše, Toni Čeprnja, Vesna Telesmanić Dobrić, Vesna Čapkun and Snježana Tomić
Cancers 2026, 18(14), 2327; https://doi.org/10.3390/cancers18142327 (registering DOI) - 19 Jul 2026
Abstract
Background/Objectives: High-grade serous ovarian carcinoma (HGSC) is the most aggressive subtype of epithelial ovarian cancer and is characterized by marked heterogeneity of the tumor immune microenvironment. SET morphology has been associated with homologous recombination deficiency and BRCA1/2 mutations; however, its relationship with the [...] Read more.
Background/Objectives: High-grade serous ovarian carcinoma (HGSC) is the most aggressive subtype of epithelial ovarian cancer and is characterized by marked heterogeneity of the tumor immune microenvironment. SET morphology has been associated with homologous recombination deficiency and BRCA1/2 mutations; however, its relationship with the immune microenvironment and progression-free survival (PFS) remains insufficiently understood. This study investigated the association between SET morphology, immune microenvironment characteristics, and PFS in patients with advanced-stage HGSC. Methods: A retrospective cohort of 305 patients with FIGO stage III–IV HGSC treated with primary surgery between 1996 and 2021 was analyzed. Histopathological assessment included evaluation of SET morphology, stromal and intraepithelial tumor-infiltrating lymphocytes (sTILs and itTILs), tumor immune phenotype, and lymphoid aggregates. Immunohistochemical analyses included CD8 and PD-L1 expression. Associations between SET morphology and immune parameters were evaluated using χ2 and logistic regression analyses. PFS was assessed using Kaplan–Meier analysis, log-rank testing, and Cox proportional hazards regression. Results: SET morphology was significantly associated with higher sTIL and itTIL levels, increased stromal and intraepithelial CD8+ T-cell infiltration, higher PD-L1 TPS and CPS, more frequent primary and secondary lymphoid aggregates, and a predominance of the inflamed immune phenotype (all p < 0.05). Despite these features of an immune-active tumor microenvironment, SET morphology, CD8+ T-cell density, PD-L1 expression, lymphoid aggregates, and immune phenotype were not independently associated with prolonged PFS. In contrast, age remained an independent prognostic factor, with patients older than 55 years having a 50% higher risk of disease progression than younger patients (HR = 1.5, 95% CI: 1.1–2.1; p = 0.012). Higher intraepithelial TIL levels (>10%) were independently associated with improved PFS (HR = 2.1, 95% CI: 1.0–4.4; p = 0.045). Conclusions: SET morphology identifies an immune-active subtype of HGSC characterized by increased immune infiltration and PD-L1 expression but does not independently predict prolonged PFS. The dissociation between immune cell abundance and clinical outcome suggests that immune cell functionality, rather than immune infiltration alone, may determine prognosis. Routine histopathological assessment of SET morphology may facilitate biological characterization of HGSC and provide a practical surrogate marker for future biomarker-driven studies evaluating immunotherapy and targeted treatment strategies. Full article
(This article belongs to the Special Issue The Tumor Microenvironment: Interplay Between Immune Cells)
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38 pages, 582 KB  
Review
Hydrodynamic Cavitation in Water and Wastewater Treatment: A Critical Review of Applications, Reactor Design, and Process Function
by Lorenzo Albanese
Pollutants 2026, 6(3), 37; https://doi.org/10.3390/pollutants6030037 (registering DOI) - 18 Jul 2026
Abstract
Hydrodynamic cavitation has attracted increasing attention in water and wastewater treatment because it can generate localized shear, pressure fluctuations, interfacial renewal, and reactive species in relatively simple continuous-flow devices. This review critically examines its main application domains, including microbial disinfection, cyanobacterial bloom control, [...] Read more.
Hydrodynamic cavitation has attracted increasing attention in water and wastewater treatment because it can generate localized shear, pressure fluctuations, interfacial renewal, and reactive species in relatively simple continuous-flow devices. This review critically examines its main application domains, including microbial disinfection, cyanobacterial bloom control, organic micropollutant degradation, real wastewater treatment, sludge pretreatment for energy recovery, and hybrid process configurations. Rather than treating hydrodynamic cavitation as a single treatment mode, the discussion compares applications in relation to reactor design, matrix characteristics, treatment target, operating conditions, and assigned process function. The analysis shows that performance depends strongly on the interaction among device geometry, treated matrix, process configuration, and evaluation metrics. The same nominal process may therefore act as direct treatment, pretreatment, mass-transfer intensifier, oxidant-activation module, or support to downstream biological and polishing steps. The most consolidated evidence concerns microbial disinfection, sludge pretreatment, and several classes of organic contaminants, whereas PFAS treatment, field-scale validation, and system-level assessment remain less mature. Overall, hydrodynamic cavitation is best interpreted as a process-intensification platform rather than as a universally applicable stand-alone solution. Further progress will require more transparent assessment criteria, more comparable metrics, stronger validation in real matrices, more controllable reactors, and more rigorous energy, techno-economic, and scale-up evaluation. Full article
(This article belongs to the Section Water Pollution)
27 pages, 986 KB  
Systematic Review
Dual-Track Synergistic Regulation of Data and Algorithms in Connected and Autonomous Vehicles: A Systematic Literature Review
by Jingwen Cai, Yifen Yin, Yuanyuan Yu, Haoqian Hu, Wai In Ho and Chunning Wang
World Electr. Veh. J. 2026, 17(7), 372; https://doi.org/10.3390/wevj17070372 (registering DOI) - 18 Jul 2026
Abstract
Connected and Automated Electric Vehicles (CAEVs) are rapidly evolving into complex Cyber-Physical-Social Systems (CPSS), generating structural tensions between technological innovation and public safety. Current research in public governance exhibits significant fragmentation. Scholars frequently isolate data privacy compliance from algorithmic safety auditing, treating them [...] Read more.
Connected and Automated Electric Vehicles (CAEVs) are rapidly evolving into complex Cyber-Physical-Social Systems (CPSS), generating structural tensions between technological innovation and public safety. Current research in public governance exhibits significant fragmentation. Scholars frequently isolate data privacy compliance from algorithmic safety auditing, treating them as distinct silos. To bridge this gap, this study applies the PRISMA framework to systematically synthesize 135 core peer-reviewed articles, exposing the endogenous limitations of unidimensional regulatory paradigms. Our analysis yields three central insights. First, traditional “notice-and-consent” models fail under the ubiquitous data collection demands of modern V2X environments. Macro-level policies must translate into foundational Privacy-Enhancing Technologies (PETs) through “Law-as-Code” mechanisms. Second, the opacity of end-to-end algorithmic decision-making deconstructs traditional tort liability systems. This necessitates ex-ante quantitative auditing mechanisms—such as Explainable Artificial Intelligence (XAI) and enhanced Threat Analysis and Risk Assessment (TARA 2.0)—to mitigate adversarial attacks and physical-level safety hazards. Third, overcoming cross-national regulatory fragmentation requires constructing a “dual-track synergistic” governance architecture. This framework institutionalizes the coupling of data lifecycle quality workflows with the algorithmic Safety of the Intended Functionality (SOTIF). Ultimately, this review advocates for adaptive regulatory sandboxes and advances the harmonization and mutual recognition of global standards (e.g., ISO/SAE 21434, UN R155/156). Addressing current methodological and empirical data constraints, future academic inquiry must pivot. Researchers should target the value alignment challenges of Large Language Models (LLMs) in autonomous driving and implement multi-stakeholder participatory policy pilots designed to reconcile diverse social values. Full article
(This article belongs to the Section Automated and Connected Vehicles)
65 pages, 2253 KB  
Review
Mechanism-First Psychobiotics: Fermented Vegetables, Dairy, and Soy for Depression and Anxiety
by Masaru Tanaka, Claudia Rucco Penteado Detregiachi, Vitor C. Strozze Catharin, Eliana de Souza Bastos Mazuqueli, Cristiano Machado Galhardi, Tereza L. Menegucci Zutin, Mariana Hirata, Karina Quesada, Virginia M. C. Strozze Catharin, Rafael S. de Argollo Haber, Vitor Fernando Bordin Miola and Sandra Maria Barbalho
Int. J. Mol. Sci. 2026, 27(14), 6399; https://doi.org/10.3390/ijms27146399 (registering DOI) - 18 Jul 2026
Abstract
Depression and anxiety are increasingly understood to involve systemic biological processes, where chronic stress, immune dysregulation, and vascular dysfunction converge on brain-relevant symptoms. Fermented foods are widely studied as psychobiotic candidates, yet results remain inconsistent because products vary in chemistry, viability, sodium, and [...] Read more.
Depression and anxiety are increasingly understood to involve systemic biological processes, where chronic stress, immune dysregulation, and vascular dysfunction converge on brain-relevant symptoms. Fermented foods are widely studied as psychobiotic candidates, yet results remain inconsistent because products vary in chemistry, viability, sodium, and biogenic amines, and trials often rely on broad symptom outcomes without exposure verification. A major gap is the lack of a reusable, mechanism-first framework that links what a product delivers to barrier, endothelial, and neurovascular target engagement. As a narrative and conceptual review rather than a systematic review, the article integrates mechanistic evidence into a conceptual framework rather than undertaking quantitative evidence synthesis. It addresses that gap by treating fermented vegetables, dairy, soy, and selected Brazilian cassava ferments and artisanal cheeses as metabolite-engineering platforms mapped onto a tri-barrier remodeling axis from gut epithelium to endothelium and platelets to the blood–brain barrier. We synthesize dosing-resolved metabolite modules, including short-chain fatty acids, tryptophan-derived indoles, bile acids, neuroactive small molecules, and peptide and exopolysaccharide fingerprints, and align them with interpretable readouts for permeability, endotoxemia proxies, endothelial activation, immunothrombosis, and epigenetic aging pace. Here we highlight how this modular framework converts heterogeneous food studies into testable exposure hypotheses, guides comparator design and phenotype stratification, and clarifies why null results can be informative. To maintain a focused scope, the review uses selected fermented-food families as representative test platforms rather than attempting a complete survey of global fermented foods. The emphasis is therefore placed on mechanisms, exposure verification, and trial-design principles that can be transferred to other products. Full article
30 pages, 1088 KB  
Review
Research Trends in Wastewater Treatment for Sustainable Environmental Management of the Black Sea Basin—A Bibliometric Analysis
by Elena Bisinicu, Elena Ristea and Luminita Lazar
Water 2026, 18(14), 1742; https://doi.org/10.3390/w18141742 (registering DOI) - 18 Jul 2026
Abstract
The Black Sea is a semi-enclosed basin that has experienced significant environmental degradation driven by nutrient enrichment and pollution from insufficiently treated wastewater discharges. While previous reviews have focused primarily on ecological impacts and eutrophication dynamics, no bibliometric study has systematically examined the [...] Read more.
The Black Sea is a semi-enclosed basin that has experienced significant environmental degradation driven by nutrient enrichment and pollution from insufficiently treated wastewater discharges. While previous reviews have focused primarily on ecological impacts and eutrophication dynamics, no bibliometric study has systematically examined the representation of wastewater treatment technologies within this literature. This review addresses that gap, providing the first bibliometric synthesis to jointly analyse environmental research trends and wastewater treatment technology development in the Black Sea basin. A total of 1002 peer-reviewed publications indexed in the Web of Science Core Collection between January 2000 and March 2026 were analysed using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-based framework to examine research trends, thematic clusters, and geographic distribution. A targeted subset of 101 publications directly addressing wastewater treatment technologies was extracted for detailed technological classification. The results reveal a clear increase in research output over the past two decades, with eutrophication, nutrient enrichment, and water-quality degradation as dominant themes. Geographic analysis shows that Türkiye (n = 383), Russia (n = 232), and Romania (n = 129) are the leading contributors, with riparian countries accounting for 83.8% of publications. However, only 101 of the 1002 publications (10.1%) directly address wastewater treatment technologies, with most studies focused on conventional WWTP infrastructure (75.2%) and biological nutrient removal (22.8%). Advanced treatment technologies and nature-based solutions each represent only 3.0% of the wastewater subset. These findings are consistent with a meaningful gap in the regional evidence base for technological approaches to reducing nutrient inputs to the Black Sea, though it should be noted that publication volume alone cannot fully characterise the state of technological development in the region, as it is also shaped by funding structures, disciplinary traditions, and indexing practices. Nevertheless, expanding research on innovative and sustainable wastewater treatment technologies could play an important role in improving wastewater management and supporting long-term ecosystem recovery. Full article
(This article belongs to the Section Wastewater Treatment and Reuse)
25 pages, 2420 KB  
Systematic Review
Enfortumab Vedotin in Advanced or Metastatic Urothelial Carcinoma: A Systematic Review of Efficacy, Safety, and Clinical Perspectives
by Julia Piekarz, Natalia Picheta, Jakub Pobideł, Karolina Daniłowska, Natalia Gierulska, Katarzyna Szklener and Magdalena Skórzewska
Cancers 2026, 18(14), 2324; https://doi.org/10.3390/cancers18142324 (registering DOI) - 18 Jul 2026
Abstract
Background: Urothelial carcinoma (UC) is a significant clinical problem, especially in locally advanced and metastatic stages, where the prognosis remains poor despite advances in immunotherapy. Enfortumab vedotin (EV), an antibody–drug conjugate (ADC) targeting Nectin-4, extends beyond direct cytotoxicity by actively modulating the immunosuppressive [...] Read more.
Background: Urothelial carcinoma (UC) is a significant clinical problem, especially in locally advanced and metastatic stages, where the prognosis remains poor despite advances in immunotherapy. Enfortumab vedotin (EV), an antibody–drug conjugate (ADC) targeting Nectin-4, extends beyond direct cytotoxicity by actively modulating the immunosuppressive tumor microenvironment (TME) in preclinical models, creating a strong rationale for combination strategies. This systematic review aimed to evaluate the clinical efficacy, safety, and hypothesized immune-modulating potential of EV in the treatment of UC, particularly in combination with immunotherapy. Materials and Methods: The review was conducted in accordance with the PRISMA 2020 guidelines. PubMed, Web of Science, and ClinicalTrials.gov databases were searched to identify interventional clinical studies published between 2020 and 2026. Studies evaluating EV used as monotherapy or in combination with immunotherapy in adult patients with UC were analyzed. ORR, PFS, OS, and the incidence of treatment-related adverse events were evaluated. Individual publications originating from the same clinical trial programs were treated as linked records and analyzed collectively. Results: The analysis was primarily based on key clinical trial programs, including EV-103, EV-301, and EV-302, along with their subgroup analyses, follow-up reports, and patient-reported outcomes. EV demonstrated significant clinical efficacy in the treatment of locally advanced UC (laUC). In the EV-301 study, EV therapy significantly prolonged overall survival compared to chemotherapy (12.88 vs. 8.97 months). In the EV-302 study, EV combination therapy with pembrolizumab showed a significant improvement in progression-free survival and overall survival compared to platinum-based chemotherapy. Conclusions: EV represents a significant therapeutic advance not only as a cytotoxic agent but as a potent immune modulator with clinical efficacy that may be enhanced by its biologically hypothesized immunomodulatory mechanisms in mUC. Its clinical development reflects a critical shift from later-line monotherapy toward earlier-line combination strategies designed to target both tumor cells and the microenvironment. Further studies are needed to better define its role in the context of alternative treatment approaches and across different stages of disease. Full article
(This article belongs to the Special Issue Advances in Clinical and Treatment of Bladder Cancer)
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25 pages, 3246 KB  
Article
Characterization of Spent Coffee Grounds’ Polyphenol Fraction and Its Potential as a Low-Cost Tool for Bioactivity-Guided Nephroprotective Modulation of Gut–Kidney Axis and NF-κB/Nrf2/TGF-β Signaling in Hypertension-Associated Kidney Injury
by Fahrul Nurkolis, Dante Saksono Harbuwono, Yulia Wardhani, Edwin Hadinata, Siti Nur Rohmah, Metalia Puspitasari, Lucia De Luca, Raffaele Romano, Danny Pratama Kuswadi, Raymond Rubianto Tjandrawinata, Eka Ginanjar, Pringgodigdo Nugroho and Antonello Santini
Antioxidants 2026, 15(7), 889; https://doi.org/10.3390/antiox15070889 (registering DOI) - 17 Jul 2026
Abstract
Background: Hypertension-associated kidney injury is driven by oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins via the gut–kidney axis. Spent coffee grounds (SCG) represent a sustainable source of bioactive polyphenols with potential nephroprotective effects. This study aimed to characterize a bioactivity-guided SCG polyphenol [...] Read more.
Background: Hypertension-associated kidney injury is driven by oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins via the gut–kidney axis. Spent coffee grounds (SCG) represent a sustainable source of bioactive polyphenols with potential nephroprotective effects. This study aimed to characterize a bioactivity-guided SCG polyphenol fraction and evaluate its therapeutic potential. Methods: Bioactivity-guided fractionation was performed to enrich active polyphenols, followed by in silico target prediction and in vivo validation using L-NAME-induced hypertensive rats treated for 8 weeks. Renal function, oxidative stress, inflammatory and fibrotic markers, gut-derived metabolites, and endothelial function were assessed. Results: The enriched fraction was dominated by chlorogenic acid derivatives and showed predicted interactions with NF-κB, Keap1/Nrf2, TGF-β receptor, ACE, and AT1 receptor. In hypertensive rats, treatment significantly lowered blood pressure, improved renal function, reduced oxidative stress, inflammation, fibrosis, and gut-derived uremic toxins, while restoring Nrf2 activity, short-chain fatty acid production, and endothelial function. Across multiple biological endpoints, the polyphenol-enriched fraction consistently demonstrated greater efficacy than the crude extract. Conclusion: SCG polyphenol fraction shows strong nephroprotective potential via gut–kidney axis modulation and NF-κB/Nrf2/TGF-β regulation, supporting its development as a low-cost therapeutic candidate. Full article
(This article belongs to the Special Issue Oxidative Stress and Inflammation in Kidney Diseases)
22 pages, 587 KB  
Review
Beyond Carrier Design: Fabrication Method as the Hidden Driver of NSAID Nanomedicine Performance
by Ana-Maria Raluca Pauna, Liliana Mititelu-Tartau, Angy Abu Koush, Roxana Ionela Vasluianu, Jamal Al Ashkar, Ruxandra Teodora Stan, Viorel Radu, Marius Constantin Moraru, Cosmin Gabriel Popa, Roxana Florentina Gavril, Dragos Valentin Crauciuc, Andreea Ludusanu, Cristinel Ionel Stan and Alin Mihai Vasilescu
Pharmaceutics 2026, 18(7), 877; https://doi.org/10.3390/pharmaceutics18070877 (registering DOI) - 17 Jul 2026
Abstract
Background/Objectives: Diclofenac (DCF) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management; however, their clinical significance is limited by poor aqueous solubility, short biological half-life, and dose-dependent gastrointestinal, renal, and cardiovascular adverse effects. Nanocarrier-based delivery systems have been [...] Read more.
Background/Objectives: Diclofenac (DCF) and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for pain and inflammation management; however, their clinical significance is limited by poor aqueous solubility, short biological half-life, and dose-dependent gastrointestinal, renal, and cardiovascular adverse effects. Nanocarrier-based delivery systems have been extensively explored because they can enhance the apparent solubility of poorly water-soluble NSAIDs, provide controlled and sustained drug release, prolong systemic circulation, and improve drug localization at the site of action. By reducing peak plasma concentrations and off-target exposure, these systems may decrease dose-dependent gastrointestinal and systemic adverse effects while maintaining therapeutic efficacy. Most studies focus on optimizing formulation composition, while the manufacturing process is often treated as a secondary parameter. The research critically evaluates conventional and emerging fabrication methods for NSAID nanocarriers, using DCF as the principal reference compound, with emphasis on their impact on physicochemical characteristics, reproducibility, scalability, and translational potential. Methods: A structured literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science (2015–2026, with emphasis on 2022–2026) for DCF and NSAID-loaded submicron delivery systems reporting quantitative formulation data and clearly defined fabrication methods, resulting in a narrative review of approximately 375–395 eligible studies, comprising 75 DCF-specific studies and approximately 300–320 studies involving other NSAIDs that were included as representative surrogate systems when DCF-specific evidence was unavailable for particular fabrication approaches. The review followed Scale for the Assessment of Narrative Review Articles (SANRA) recommendations. Studies were analyzed using a standardized seven-parameter framework including encapsulation efficiency, release profile, particle size control, polydispersity, scalability, reproducibility, and process complexity. Results: Batch-based techniques, such as thin-film hydration for chitosan-coated liposomal systems, consistently provide high encapsulation efficiency, sustained drug release, and good biocompatibility. However, these methods are often associated with batch-to-batch variability, operator dependence, and limited scalability. In contrast, continuous manufacturing approaches, including microfluidic mixing, nanostructured lipid carriers, and Quality-by-Design (QbD)–guided processes, demonstrate improved control over particle size distribution and polydispersity, enhanced reproducibility, and better scalability potential. Conclusions: Manufacturing methodology is an important determinant of DCF and NSAID nanocarrier performance alongside formulation composition. Continuous manufacturing approaches offer promising improvements in reproducibility, process control, and scalability, but current evidence remains uneven across different nanocarrier classes. Further standardized comparative studies are needed to support their broader translation into clinical applications Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
27 pages, 3062 KB  
Article
Group-Aware Registration for Lesion-Level Quantitative Motion Correction in Respiratory-Gated PET/CT Biomedical Imaging
by Hui Zhou, Longxi He, Yangsheng Hu, Zhouyuan Qin, Feng Wang and Jianfeng He
Sensors 2026, 26(14), 4554; https://doi.org/10.3390/s26144554 (registering DOI) - 17 Jul 2026
Abstract
Respiratory-gated PET/CT generates phase-resolved biomedical imaging data, but respiratory motion can cause spatial mismatch and lesion-level quantitative instability, especially for small thoracoabdominal lesions. This study proposes SCAR-Net, a Similarity-Constrained Adaptive Respiratory Registration Network, for retrospective phase-to-reference correction of respiratory-gated 18F-FDG PET/CT. SCAR-Net [...] Read more.
Respiratory-gated PET/CT generates phase-resolved biomedical imaging data, but respiratory motion can cause spatial mismatch and lesion-level quantitative instability, especially for small thoracoabdominal lesions. This study proposes SCAR-Net, a Similarity-Constrained Adaptive Respiratory Registration Network, for retrospective phase-to-reference correction of respiratory-gated 18F-FDG PET/CT. SCAR-Net treats motion correction as a quantitative stability problem in phase-resolved PET/CT rather than only a generic registration task. It combines sampled group-aware feature encoding with adaptive group-attentive modulation to represent structured respiratory deformation and enhance motion-sensitive correspondence. The method was evaluated using controlled respiratory simulations and a retrospective two-center clinical cohort of 100 patients, jointly assessing lesion-level SUV repeatability, spatial correspondence, image similarity, deformation plausibility, center-stratified performance with B-spline FFD as a conventional reference, cross-dataset testing without target-domain fine-tuning, ablation behavior, and computational efficiency. In the independent clinical test set, lesion-level evaluation included 20 patients, 43 independent PET-avid lesions, and 245 evaluable lesion-phase pairs. In small-lesion phase pairs, SCAR-Net reduced median phase-to-reference variability to 6.45% for |ΔSUVmax| and 4.73% for |ΔSUVmean|, and increased median lesion Dice from 0.55 to 0.72. In large-lesion phase pairs, SCAR-Net achieved a post-correction Dice of 0.89 and remained competitive for SUV repeatability. Descriptive center-stratified analysis showed a consistent lesion-level performance pattern across the two clinical acquisition settings. These findings suggest that SCAR-Net can improve phase consistency and quantitative stability in respiratory-gated PET/CT, with the clearest benefit observed in small-lesion assessment. Downstream clinical endpoints, such as diagnostic accuracy, tumor staging, PERCIST-based response assessment, and patient outcomes, were not evaluated and require future prospective validation. Full article
(This article belongs to the Special Issue Advanced Biomedical Imaging and Signal Processing)
31 pages, 20802 KB  
Article
Robust Optimization of an Electromechanical Linear Actuator Under Experimental-Budget Constraints
by Mario Đurić, Drago Bračun and Marjan Jenko
Actuators 2026, 15(7), 401; https://doi.org/10.3390/act15070401 (registering DOI) - 17 Jul 2026
Abstract
The design optimization of electromechanical linear actuators (EMLAs) is challenged by coupled tribological, thermal, and dynamic effects. Such interactions can violate the additivity assumptions of compact orthogonal designs. Factor ranking may become unreliable when residual variance includes non-additive contributions rather than stochastic noise [...] Read more.
The design optimization of electromechanical linear actuators (EMLAs) is challenged by coupled tribological, thermal, and dynamic effects. Such interactions can violate the additivity assumptions of compact orthogonal designs. Factor ranking may become unreliable when residual variance includes non-additive contributions rather than stochastic noise alone. This study presents an Extended Orthogonal Experimental Matrix (E-OEM) framework for robust factor screening under experimental-budget constraints. It preserves the reduced effort of an orthogonal design while using a latent allocation term to retain structured non-additive variation that would otherwise be treated as residual error. It combines compact experimentation, fitted probability distributions, Monte Carlo simulation, and weighted multi-criteria ranking under push force, robustness, and cost targets. The framework is demonstrated on 90 automotive EMLAs considering lubricant type, drive frequency, and operating temperature. E-OEM was benchmarked against the full-factorial experiment (27 combinations, 810 push-force measurements). Under the selected weighting strategy, both E-OEM and the benchmark identified the same nominal optimum (590 Hz, +25 °C, Addinol lubricant), with a measured push force of 77.32 ± 2.05 N (1.01% deviation from the prediction). The results show that E-OEM provides an efficient screening and decision-support approach for actuator design when full-factorial testing is constrained by time and cost. Full article
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22 pages, 2050 KB  
Article
Computational Assessment of Electrical and Thermal Effects of Epicardial Pulsed Field Ablation Adjacent to Stented Arteries
by Francisco Estevez-Laborí, Maite Izquierdo, Ken Coffey, Barry O’Brien and Ana González-Suárez
Bioengineering 2026, 13(7), 825; https://doi.org/10.3390/bioengineering13070825 (registering DOI) - 17 Jul 2026
Abstract
Background: Current ablation strategies for the treatment of cardiac arrhythmias remain suboptimal. Treating cardiac arrhythmias using epicardial pulsed field ablation (PFA) selectively targets ganglionated plexi (GPs) within epicardial fat, offering a promising alternative to thermal ablation. Previous computational studies lacked physiological realism, excluding [...] Read more.
Background: Current ablation strategies for the treatment of cardiac arrhythmias remain suboptimal. Treating cardiac arrhythmias using epicardial pulsed field ablation (PFA) selectively targets ganglionated plexi (GPs) within epicardial fat, offering a promising alternative to thermal ablation. Previous computational studies lacked physiological realism, excluding catheter geometry, fluid flow and post-PFA thermal latency. This study aimed to develop a realistic 3D epicardial PFA model integrating a clinical catheter, clinical PFA parameters and a sequentially coupled electro-thermal-fluid dynamics model, including thermal latency, to assess electrical and thermal collateral effects near stented coronary arteries. Methods: The model included epicardial fat, myocardium, blood, and the left circumflex artery containing a metallic stent positioned 0.25 mm beneath the catheter electrodes. Pulses of 1000, 2000, and 2500 V (60 pulses × 100 µs, 1 Hz) were simulated to analyze electric field distribution, PFA-induced lesion volume, temperature evolution, and Arrhenius-based thermal damage, including a 90 s post-pulse period to account for thermal latency. The PFA-threshold of 1000 V/cm was considered. Results: The artery reduced PFA-induced lesion size mainly by occupying fat tissue volume, while the stent shielded the lumen without altering fat lesion volume. The presence of a stent produced localized electric field enhancement at the arterial wall, with up to 3.83% of the arterial wall volume affected by PFA in the worst-case configuration. At clinical settings (1000 V), temperature remained below 40 °C and no collateral damage occurred. Voltages > 2000 V increased arterial wall heating, with thermal damage expanding up to five-fold during latency in the epicardial fat. Myocardium remained unaffected in all cases. Conclusions: The computational model developed in this study indicates that clinically relevant PFA parameters (1000 V) produce localized electric field enhancement at the stent–artery interface, resulting in limited collateral electrical effects in the arterial wall, while avoiding collateral thermal effects and preserving the myocardium. However, the use of higher pulse voltages can lead to delayed thermal damage within the epicardial fat. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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30 pages, 2853 KB  
Article
Deep Reinforcement Learning-Based Path-Following Control for Underactuated Autonomous Underwater Vehicles
by Xin Pan, Lin Huang, Liangjin Li and Song Wang
Sensors 2026, 26(14), 4548; https://doi.org/10.3390/s26144548 (registering DOI) - 17 Jul 2026
Abstract
Autonomous Underwater Vehicles (AUVs) face significant challenges in path-following control due to strong environmental disturbances and model uncertainties. To address these issues, this paper proposes a model-free deep reinforcement learning framework, named ILLT (Improved LOS-LSTM-TD3), which integrates an integral line-of-sight (LOS) guidance law [...] Read more.
Autonomous Underwater Vehicles (AUVs) face significant challenges in path-following control due to strong environmental disturbances and model uncertainties. To address these issues, this paper proposes a model-free deep reinforcement learning framework, named ILLT (Improved LOS-LSTM-TD3), which integrates an integral line-of-sight (LOS) guidance law with the twin delayed deep deterministic policy gradient (TD3) algorithm. The framework treats the LOS look-ahead distance as a learnable optimization variable and incorporates an LSTM network to capture temporal motion dependencies. A progressive unfreezing transfer learning strategy, combined with attention-based feature–current fusion, is designed to enhance domain adaptation under varying ocean currents. Simulation results demonstrate that ILLT reduces the average cross-track error by 48.5% compared to the baseline ILT algorithm and by 66.4% compared to traditional PID control, while achieving significantly faster convergence in target domains. Physical experiments in tank and lake environments further validate the algorithm’s feasibility and robustness, with tracking errors approaching simulation results under moderate current conditions. These findings confirm the effectiveness of the proposed framework for underactuated AUV path-following tasks. Full article
(This article belongs to the Section Navigation and Positioning)
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