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19 pages, 5488 KiB  
Article
Treatment of Recycled Metallurgical By-Products for the Recovery of Fe and Zn Through a Plasma Reactor and RecoDust
by Wolfgang Reiter, Loredana Di Sante, Vincenzo Pepe, Marta Guzzon and Klaus Doschek-Held
Metals 2025, 15(8), 867; https://doi.org/10.3390/met15080867 (registering DOI) - 1 Aug 2025
Viewed by 95
Abstract
The 1.9 billion metric tons of steel globally manufactured in 2023 justify the steel industry’s pivotal role in modern society’s growth. Considering the rapid development of countries that have not fully taken part in the global market, such as Africa, steel production is [...] Read more.
The 1.9 billion metric tons of steel globally manufactured in 2023 justify the steel industry’s pivotal role in modern society’s growth. Considering the rapid development of countries that have not fully taken part in the global market, such as Africa, steel production is expected to increase in the next decade. However, the environmental burden associated with steel manufacturing must be mitigated to achieve sustainable production, which would align with the European Green Deal pathway. Such a burden is associated both with the GHG emissions and with the solid residues arising from steel manufacturing, considering both the integrated and electrical routes. The valorisation of the main steel residues from the electrical steelmaking is the central theme of this work, referring to the steel electric manufacturing in the Dalmine case study. The investigation was carried out from two different points of view, comprising the action of a plasma electric reactor and a RecoDust unit to optimize the recovery of iron and zinc, respectively, being the two main technologies envisioned in the EU-funded research project ReMFra. This work focuses on those preliminary steps required to detect the optimal recipes to consider for such industrial units, such as thermodynamic modelling, testing the mechanical properties of the briquettes produced, and the smelting trials carried out at pilot scale. However, tests for the usability of the dusty feedstock for RecoDust are carried out, and, with the results, some recommendations for pretreatment can be made. The outcomes show the high potential of these streams for metal and mineral recovery. Full article
15 pages, 5596 KiB  
Article
Effects of Hypertension Induced by 0.3% Saline Loading on Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats
by Rina Takagi, Yoshiaki Tanaka, Tetsuya Hasegawa, Masami Shinohara, Yasushi Kageyama, Tomohiko Sasase, Takeshi Ohta, Shin-ichi Muramatsu, Nobuhiko Ohno, Akihiro Kakehashi and Toshikatsu Kaburaki
Diabetology 2025, 6(8), 73; https://doi.org/10.3390/diabetology6080073 (registering DOI) - 1 Aug 2025
Viewed by 149
Abstract
Objective: This study aimed to determine the possibility of creating a new animal model in which diabetic retinopathy (DR) progresses due to hypertension caused by salt loading. Methods: Male Spontaneously Diabetic Torii (SDT) fatty rats were divided into two groups: one group received [...] Read more.
Objective: This study aimed to determine the possibility of creating a new animal model in which diabetic retinopathy (DR) progresses due to hypertension caused by salt loading. Methods: Male Spontaneously Diabetic Torii (SDT) fatty rats were divided into two groups: one group received 0.3% saline water starting at 8 weeks of age for a duration of 16 weeks (salt SDT fatty group), while the control group was provided with tap water (SDT fatty group). In addition, Sprague-Dawley (SD) rats receiving tap water served as normal controls. Retinal function was assessed by electroretinography (ERG) at 8 and 24 weeks of age. At 24 weeks, following perfusion with fluorescein dextran, the eyes were enucleated, and retinal flat mounts were prepared for vascular evaluation. Retinal thickness and the number of retinal folds were assessed histologically, and ultrastructural changes in the retina were examined using transmission electron microscopy. Results: Saline administration did not lead to significant changes in food consumption or body weight among the groups. In the salt SDT fatty group, blood pressure was significantly elevated, while blood glucose levels showed a slight reduction. ERG analysis showed that the amplitude of oscillatory potential (OP)1 waves was suppressed, and the latencies of OP3, OP4, and OP5 waves were prolonged. Although no significant changes were noted in retinal thickness or the number of retinal folds, thickening of the retinal capillary basement membrane was evident in the salt SDT fatty group. Conclusions: Hypertension induced by 0.3% saline promotes DR progression in SDT fatty rats. This model may help clarify the role of hypertension in DR. Full article
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15 pages, 495 KiB  
Article
Perceptions of Infant Cry Sounds Among Tobacco and Cannabis Using Mothers and Their Association with Tobacco and Cannabis Cravings
by Pamela Schuetze, Madison R. Kelm, Olivia Bell and Rina D. Eiden
Children 2025, 12(8), 1006; https://doi.org/10.3390/children12081006 - 31 Jul 2025
Viewed by 169
Abstract
Background/Objectives: We examined maternal perceptions of infant cries as a mediator between maternal tobacco/cannabis use, psychological distress (depression/anger/hostility) and reported cravings for cigarettes and/or cannabis across two time points. Methods: A total of 96 substance-using mothers (35 tobacco-only and 61 tobacco/cannabis) [...] Read more.
Background/Objectives: We examined maternal perceptions of infant cries as a mediator between maternal tobacco/cannabis use, psychological distress (depression/anger/hostility) and reported cravings for cigarettes and/or cannabis across two time points. Methods: A total of 96 substance-using mothers (35 tobacco-only and 61 tobacco/cannabis) were recruited in pregnancy. Maternal substance use and psychological distress were measured when their children were school age (5–6 years, T1). At the middle childhood assessment (9–12 years, T2), mothers listened to a standardized set of newborn cries and, afterwards, rated their aversiveness, impact on negative affect, and their tobacco/cannabis cravings. Results: Higher levels of maternal depressive symptoms at T1 were associated with perceptions of cries as being more aversive at T2, which, in turn, were associated with increased cannabis cravings at T2. At T1, higher depressive symptoms predicted increased tobacco cravings and higher maternal anger/hostility predicted increased cannabis cravings. Conclusions: Results highlight the role that infant cries and psychological distress play in cravings among tobacco/cannabis-using mothers. Full article
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20 pages, 3857 KiB  
Article
Temporal and Sex-Dependent N-Glycosylation Dynamics in Rat Serum
by Hirokazu Yagi, Sachiko Kondo, Reiko Murakami, Rina Yogo, Saeko Yanaka, Fumiko Umezawa, Maho Yagi-Utsumi, Akihiro Fujita, Masako Okina, Yutaka Hashimoto, Yuji Hotta, Yoichi Kato, Kazuki Nakajima, Jun-ichi Furukawa and Koichi Kato
Int. J. Mol. Sci. 2025, 26(15), 7266; https://doi.org/10.3390/ijms26157266 - 27 Jul 2025
Viewed by 390
Abstract
We conducted systematic glycomic and glycoproteomic profiling to characterize the dynamic N-glycosylation landscape of rat serum, with particular focus on sex- and time-dependent variations. MALDI-TOF-MS analysis revealed that rat serum N-glycans are predominantly biantennary, disialylated complex-type structures with extensive O-acetylation [...] Read more.
We conducted systematic glycomic and glycoproteomic profiling to characterize the dynamic N-glycosylation landscape of rat serum, with particular focus on sex- and time-dependent variations. MALDI-TOF-MS analysis revealed that rat serum N-glycans are predominantly biantennary, disialylated complex-type structures with extensive O-acetylation of Neu5Ac residues, especially in females. LC-MS/MS-based glycoproteomic analysis of albumin/IgG-depleted serum identified 87 glycoproteins enriched in protease inhibitors (e.g., serine protease inhibitor A3K) and immune-related proteins such as complement C3. Temporal analyses revealed stable sialylation in males but pronounced daily fluctuations in females, suggesting hormonal influence. Neu5Gc-containing glycans were rare and mainly derived from residual IgG, as confirmed by glycomic analysis. In contrast to liver-derived glycoproteins, purified IgG exhibited Neu5Gc-only sialylation without O-acetylation, underscoring distinct sialylation profiles characteristic of B cell-derived glycoproteins. Region-specific glycosylation patterns were observed in IgG, with the Fab region carrying more disialylated structures than Fc. These findings highlight cell-type and sex-specific differences in sialylation patterns between hepatic and immune tissues, with implications for hormonal regulation and biomarker research. This study provides a valuable dataset on rat serum glycoproteins and underscores the distinctive glycosylation features of rats, reinforcing their utility as model organisms in glycobiology and disease research. Full article
(This article belongs to the Special Issue Glycobiology of Health and Diseases)
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16 pages, 2379 KiB  
Article
Atractylodes lancea (Thunb.) DC. [Asteraceae] Rhizome-Derived Exosome-like Nanoparticles Suppress Lipopolysaccharide-Induced Inflammation by Reducing Toll-like Receptor 4 Expression in BV-2 Murine Microglial Cells
by Mizusa Hyodo, Kei Kawada, Tomoaki Ishida, Yuki Izawa-Ishizawa, Ryoko Matoba, Rina Okamoto, Kohei Jobu, Io Horikawa, Fuka Aizawa, Kenta Yagi, Takahiro Niimura, Yayoi Kawano, Shinji Abe, Yukihiro Hamada, Mitsuhiro Goda and Keisuke Ishizawa
Pharmaceuticals 2025, 18(8), 1099; https://doi.org/10.3390/ph18081099 - 24 Jul 2025
Viewed by 261
Abstract
Background/Objectives: Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR)-derived exosome-like nanoparticles (ALR-ELNs) exhibit anti-neuroinflammatory effects in microglial cells. However, the associated mechanisms and pathways are unknown. We aimed to characterize the effects of ALR-ELNs on inflammatory responses of BV-2 microglial cells to lipopolysaccharide (LPS) [...] Read more.
Background/Objectives: Atractylodes lancea (Thunb.) DC. [Asteraceae] (ALR)-derived exosome-like nanoparticles (ALR-ELNs) exhibit anti-neuroinflammatory effects in microglial cells. However, the associated mechanisms and pathways are unknown. We aimed to characterize the effects of ALR-ELNs on inflammatory responses of BV-2 microglial cells to lipopolysaccharide (LPS) using RNA sequencing. Methods: ALR-ELNs were fractionated from ALR. BV-2 microglial murine cells were stimulated with LPS after treatment with ALR-ELNs. RNA sequencing was performed to analyze variations in mRNA levels. Ingenuity pathway analysis (IPA) was performed to investigate the mechanism of action of ALR-ELNs. mRNA expression was assessed using real-time quantitative polymerase chain reaction (qPCR). Results: The expression of 651 genes was downregulated, whereas that of 1204 genes was upregulated in LPS-stimulated BV2 cells pretreated with ALR-ELNs. The IPA showed that the effects of ALR-ELNs on inflammation took place through pathogen-influenced signaling. Network analysis via IPA showed that the Toll-like receptor (TLR) is involved in the suppression of inflammation by ALR-ELNs. The qPCR analysis showed that pretreatment with ALR-ELNs significantly reduced TLR4 mRNA expression. Conclusions: ALR-ELNs suppress the release of inflammatory mediators by downregulating TLR4 expression, which is a novel mechanism by which ALR-ELNs act on microglia. Identifying active ingredients in ALR-ELNs that downregulate TLR4 expression can advance the development of therapeutic drugs for neuroinflammatory diseases. Full article
(This article belongs to the Section Natural Products)
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26 pages, 312 KiB  
Article
REN+HOMES Positive Carbon Building Methodology in Co-Design with Residents
by Dorin Beu, Alessio Pacchiana, Elena Rastei, Horaţiu Albu and Theodor Contolencu
Architecture 2025, 5(3), 51; https://doi.org/10.3390/architecture5030051 - 23 Jul 2025
Viewed by 214
Abstract
This article demonstrates how positioning residents as active co-designers fundamentally transforms both the process and outcomes of carbon-positive building development. Through structured collaborative workshops, shared decision-making protocols, and continuous partnership throughout the building lifecycle, the REN+HOMES Positive Carbon Building methodology challenges the conventional [...] Read more.
This article demonstrates how positioning residents as active co-designers fundamentally transforms both the process and outcomes of carbon-positive building development. Through structured collaborative workshops, shared decision-making protocols, and continuous partnership throughout the building lifecycle, the REN+HOMES Positive Carbon Building methodology challenges the conventional expert-driven approach to sustainable construction. Developed and validated through the H2020 REN+HOMES project, this resident-centered approach achieved remarkable technical performance—65.9% reduction in final energy demand—while simultaneously enhancing community ownership and long-term sustainability practices. By integrating participatory design with Zero Emissions Building (ZEB) criteria, renewable energy systems, and national carbon offset programs, the methodology proves that resident collaboration is not merely beneficial but essential for creating buildings that truly serve both environmental and human needs. This research establishes a new paradigm where technical excellence emerges from authentic partnership between residents and sustainability experts, offering a replicable framework for community-driven environmental regeneration. Full article
13 pages, 1791 KiB  
Article
Hydrogen Gas Inhalation Improved Intestinal Microbiota in Ulcerative Colitis: A Randomised Double-Blind Placebo-Controlled Trial
by Takafumi Maruyama, Dai Ishikawa, Rina Kurokawa, Hiroaki Masuoka, Kei Nomura, Mayuko Haraikawa, Masayuki Orikasa, Rina Odakura, Masao Koma, Masashi Omori, Hirotaka Ishino, Kentaro Ito, Tomoyoshi Shibuya, Wataru Suda and Akihito Nagahara
Biomedicines 2025, 13(8), 1799; https://doi.org/10.3390/biomedicines13081799 - 23 Jul 2025
Viewed by 300
Abstract
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of [...] Read more.
Background/Objective: Dysbiosis is implicated in the pathogenesis of ulcerative colitis. Hydrogen has been reported to promote intestinal microbiota diversity and suppress ulcerative colitis progression in mice models. In this study, we investigated changes in the intestinal microbiota, therapeutic effects, and safety of hydrogen inhalation in patients with ulcerative colitis. Methods: In this randomised, double-blind, placebo-controlled trial, 10 active patients with ulcerative colitis (aged ≥20 years; Lichtiger’s clinical activity index, 3–10; and Mayo endoscopic subscores ≥1) participated, and they were assigned to either a hydrogen or air inhalation group (hydrogen and placebo groups, respectively). All patients inhaled gas for 4 h every day for 8 weeks. Subsequently, we performed clinical indices and microbiota analyses using the metagenomic sequencing of stool samples before and after inhalation. Results: There was significant difference in the sum of the Mayo endoscopic subscores before and after inhalation in the clinical assessment indices. The hydrogen group showed higher α-diversity (p = 0.19), and the variation in β-diversity was markedly different, compared to the placebo group, in intestinal microbiota analysis (p = 0.02). Functional gene analysis revealed 115 significant genetic changes in the hydrogen group following treatment. No inhalation-related adverse events were observed. Conclusions: Hydrogen inhalation appeared to improve intestinal microbiota diversity; however, no clear therapeutic effect on ulcerative colitis was observed. Further studies are needed, and hydrogen inhalation may possibly lead to a logical solution combined with microbiome therapy, such as faecal microbiota transplantation, with fewer adverse events. Full article
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2 pages, 192 KiB  
Correction
Correction: Wiedermann et al. Health Information Use and Trust: The Role of Health Literacy and Patient Activation in a Multilingual European Region. Int. J. Environ. Res. Public Health 2025, 22, 570
by Christian J. Wiedermann, Verena Barbieri, Stefano Lombardo, Timon Gärtner, Patrick Rina, Klaus Eisendle, Giuliano Piccoliori, Adolf Engl and Dietmar Ausserhofer
Int. J. Environ. Res. Public Health 2025, 22(8), 1165; https://doi.org/10.3390/ijerph22081165 - 23 Jul 2025
Viewed by 125
Abstract
In the original publication [...] Full article
34 pages, 2026 KiB  
Review
Review of Applications of Zeolites in Dermatology: Molecular Perspectives and Translational Potentials
by James Curtis Dring, Matthew Kaczynski, Rina Maria Zureikat, Michael Kaczynski, Alicja Forma and Jacek Baj
Int. J. Mol. Sci. 2025, 26(14), 6821; https://doi.org/10.3390/ijms26146821 - 16 Jul 2025
Viewed by 465
Abstract
Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, [...] Read more.
Zeolites, microporous aluminosilicates with tuneable physicochemical properties, have garnered increasing attention in dermatology due to their antimicrobial, detoxifying, and drug delivery capabilities. This review evaluates the structural characteristics, therapeutic mechanisms, and clinical applications of zeolites—including clinoptilolite, ZSM-5, ZIF-8, and silver/zinc-functionalized forms—across skin infections, wound healing, acne management, and cosmetic dermatology. Zeolites demonstrated broad-spectrum antibacterial and antifungal efficacy, enhanced antioxidant activity, and biocompatible drug delivery in various dermatological models. Formulations such as silver–sulfadiazine–zeolite composites, Zn–clinoptilolite for acne, and zeolite-integrated microneedles offer innovative avenues for targeted therapy. Zeolite-based systems represent a promising shift toward multifunctional, localized dermatologic treatments. However, further research into long-term safety, formulation optimization, and clinical validation is essential to transition these materials into mainstream therapeutic use. Full article
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25 pages, 23420 KiB  
Article
Proposal of a Socio-Ecological Resilience Integrated Index (SERII) for Colombia, South America (1985–2022)
by Cesar Augusto Ruiz-Agudelo
Sustainability 2025, 17(14), 6461; https://doi.org/10.3390/su17146461 - 15 Jul 2025
Viewed by 506
Abstract
Colombia is a megadiverse, multiethnic, and multicultural country with a tremendous socio-ecological systems (SESs) diversity, which faces essential challenges arising from human activities, low levels of sustainable economic development, poverty, and social inequality rates, and the persistence of multiple forms of military, political, [...] Read more.
Colombia is a megadiverse, multiethnic, and multicultural country with a tremendous socio-ecological systems (SESs) diversity, which faces essential challenges arising from human activities, low levels of sustainable economic development, poverty, and social inequality rates, and the persistence of multiple forms of military, political, and social violence. Understanding the resilience of this complex system is both fundamental and challenging due to the contradictory effects of economic development and regional ecosystem degradation. This research proposes the Socio-Ecological Resilience Integrated Index (SERII) to assess historical changes in socio-ecological resilience in Colombia’s departments (political-administrative units) between 1985–2022. The SERII considers the trade-offs between ecosystems, social systems, and production systems, providing a complete perspective of integrated management with a geographic resolution at the level of general political-administrative units. The results reveal a spatial variation in the SERII, with worse conditions in the Caribbean, the Pacific, and the Colombian Amazon (on the country periphery) and better conditions in departments of the country center. From 1985 to 2022, the SERII experienced a decrease (51.5%), driven by ecosystem degradation, increased extractive activities (illegal and illegal), and the persistence of military, political, and social violence. While the limitations of the proposed indicator are described, the SERII effectively replicates the overall resilience of Colombia’s departments to external shocks and allows for suggesting regional management priorities for the targeted promotion of sustainable development. Full article
(This article belongs to the Special Issue Ecosystem Services and Sustainable Development of Human Health)
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21 pages, 3110 KiB  
Article
Long-Chain Fatty Acids Alter Estrogen Receptor Expression in Breast Cancer Cells
by Ruiko Ogata, Yi Luo, Rina Fujiwara-Tani, Rika Sasaki, Ayaka Ikemoto, Kaho Maehana, Ayaka Sasaki, Takamitsu Sasaki, Kiyomu Fujii, Hitoshi Ohmori and Hiroki Kuniyasu
Int. J. Mol. Sci. 2025, 26(14), 6722; https://doi.org/10.3390/ijms26146722 - 13 Jul 2025
Viewed by 448
Abstract
Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid [...] Read more.
Long-chain fatty acids (LCFAs) have emerged as important regulators of cancer metabolism, but their impact on hormone receptor expression in breast cancer (BCA) remains poorly understood. In this study, we investigated the effects of five LCFAs—linoleic acid (LA), oleic acid (OA), elaidic acid (EA), palmitic acid (PA), and α-linolenic acid (LNA)—on two BCA cell lines: luminal-type MCF7 and triple-negative MDA-MB-231 (MB231). All LCFAs suppressed cell viability and mitochondrial function in a dose-dependent manner, accompanied by decreased membrane potential, increased reactive oxygen species production, and a metabolic shift. Notably, OA reduced both mRNA and nuclear protein levels of estrogen receptor alpha (ERα) in MCF7 cells, leading to impaired responses to estradiol and tamoxifen. In contrast, PA induced nuclear ERα expression in MB231 cells, although ER signaling remained inactive. MicroRNA profiling revealed that OA upregulated ER-suppressive miR-22 and miR-221 in MCF7, while PA increased miR-34a in MB231, contributing to ERα induction. These findings suggest that specific LCFAs modulate ER expression through epigenetic and post-transcriptional mechanisms, altering hormonal responsiveness in BCA. Our results offer new insights into how dietary lipids may influence therapeutic efficacy and tumor behavior by regulating nuclear receptor signaling. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Targeted Therapies of Breast Cancer)
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18 pages, 695 KiB  
Review
Vital Role of Visceral Adipose Tissue in Maintaining Cognitive Functions
by Rina Shirafuji, Yoko Amagase, Ai Goto and Yoshinori Takei
Int. J. Mol. Sci. 2025, 26(14), 6597; https://doi.org/10.3390/ijms26146597 - 9 Jul 2025
Viewed by 488
Abstract
The aging process involves a decline in certain cognitive abilities. Cognitive aging progresses more quickly with obesity and more slowly with exercise and fasting. All of these conditions have strong impacts on white adipose tissue, which suggests that this tissue may play a [...] Read more.
The aging process involves a decline in certain cognitive abilities. Cognitive aging progresses more quickly with obesity and more slowly with exercise and fasting. All of these conditions have strong impacts on white adipose tissue, which suggests that this tissue may play a pivotal role in the progression of cognitive aging. Brain-derived neurotrophic factor (BDNF), a neurotrophin indispensable for maintaining brain functions, becomes insufficient with age. Obesity also decreases the BDNF level in the hippocampus. This deficiency not only results in cognitive impairment but increases susceptibility to obesity. Both exercise and fasting increase the BDNF level in the hippocampus. Our study demonstrates that the chemokine ligand CX3CL1 in white adipose tissue is involved in the regulation of the BDNF level in the hippocampus. Aging reduces CX3CL1 expression, interfering with the mechanisms. Other studies have suggested that obesity increases adipose CX3CL1 expression; however, CX3CL1 augmented under obese condition may not contribute to the promotion of the BDNF level in the hippocampus. This suggests that the malfunction of the adipose CX3CL1-mediated mechanism could be involved in the downregulation of the hippocampus BDNF level under obese conditions. Studies have also suggested that the adipose CX3CL1-mediated mechanism appears to be involved in the exercise-induced promotion of BDNF expression in the hippocampus. Its involvement in the fasting-induced BDNF promotion is still unknown. Therefore, aging, obesity, and exercise appear to affect white adipose tissue to regulate the hippocampus BDNF level. While further studies are required to elucidate the precise role of the adipose CX3CL1-mediated regulation of BDNF expression, studies on white adipose tissue may provide new therapeutic targets for preventing age-associated cognitive decline. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2025)
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22 pages, 1359 KiB  
Article
A Meta-Learning-Based Ensemble Model for Explainable Alzheimer’s Disease Diagnosis
by Fatima Hasan Al-bakri, Wan Mohd Yaakob Wan Bejuri, Mohamed Nasser Al-Andoli, Raja Rina Raja Ikram, Hui Min Khor, Zulkifli Tahir and The Alzheimer’s Disease Neuroimaging Initiative
Diagnostics 2025, 15(13), 1642; https://doi.org/10.3390/diagnostics15131642 - 27 Jun 2025
Viewed by 578
Abstract
Background/Objectives: Artificial intelligence (AI) models for Alzheimer’s disease (AD) diagnosis often face the challenge of limited explainability, hindering their clinical adoption. Previous studies have relied on full-scale MRI, which increases unnecessary features, creating a “black-box” problem in current XAI models. Methods: This study [...] Read more.
Background/Objectives: Artificial intelligence (AI) models for Alzheimer’s disease (AD) diagnosis often face the challenge of limited explainability, hindering their clinical adoption. Previous studies have relied on full-scale MRI, which increases unnecessary features, creating a “black-box” problem in current XAI models. Methods: This study proposes an explainable ensemble-based diagnostic framework trained on both clinical data and mid-slice axial MRI from the ADNI and OASIS datasets. The methodology involves training an ensemble model that integrates Random Forest, Support Vector Machine, XGBoost, and Gradient Boosting classifiers, with meta-logistic regression used for the final decision. The core contribution lies in the exclusive use of mid-slice MRI images, which highlight the lateral ventricles, thus improving the transparency and clinical relevance of the decision-making process. Our mid-slice approach minimizes unnecessary features and enhances model explainability by design. Results: We achieved state-of-the-art diagnostic accuracy: 99% on OASIS and 97.61% on ADNI using clinical data alone; 99.38% on OASIS and 98.62% on ADNI using only mid-slice MRI; and 99% accuracy when combining both modalities. The findings demonstrated significant progress in diagnostic transparency, as the algorithm consistently linked predictions to observed structural changes in the dilated lateral ventricles of the brain, which serve as a clinically reliable biomarker for AD and can be easily verified by medical professionals. Conclusions: This research presents a step toward more transparent AI-driven diagnostics, bridging the gap between accuracy and explainability in XAI. Full article
(This article belongs to the Special Issue Explainable Machine Learning in Clinical Diagnostics)
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17 pages, 654 KiB  
Article
Phenotypic and Genotypic Characterization of 171 Patients with Syndromic Inherited Retinal Diseases Highlights the Importance of Genetic Testing for Accurate Clinical Diagnosis
by Sofia Kulyamzin, Rina Leibu, Hadas Newman, Miriam Ehrenberg, Nitza Goldenberg-Cohen, Shiri Zayit-Soudry, Eedy Mezer, Ygal Rotenstreich, Iris Deitch, Daan M. Panneman, Dinah Zur, Elena Chervinsky, Stavit A. Shalev, Frans P. M. Cremers, Dror Sharon, Susanne Roosing and Tamar Ben-Yosef
Genes 2025, 16(7), 745; https://doi.org/10.3390/genes16070745 - 26 Jun 2025
Viewed by 531
Abstract
Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals [...] Read more.
Background: Syndromic inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of disorders, involving the retina and additional organs. Over 80 forms of syndromic IRD have been described. Methods: We aimed to phenotypically and genotypically characterize a cohort of 171 individuals from 140 Israeli families with syndromic IRD. Ophthalmic examination included best corrected visual acuity, fundus examination, visual field testing, retinal imaging and electrophysiological evaluation. Most participants were also evaluated by specialists in fields relevant to their extra-retinal symptoms. Genetic analyses included haplotype analysis, homozygosity mapping, Sanger sequencing and next-generation sequencing. Results: In total, 51% of the families in the cohort were consanguineous. The largest ethnic group was Muslim Arabs. The most common phenotype was Usher syndrome (USH). The most common causative gene was USH2A. In 29% of the families, genetic analysis led to a revised or modified clinical diagnosis. This included confirmation of an atypical USH diagnosis for individuals with late-onset retinitis pigmentosa (RP) and/or hearing loss (HL); diagnosis of Heimler syndrome in individuals with biallelic pathogenic variants in PEX6 and an original diagnosis of USH or nonsyndromic RP; and diagnosis of a mild form of Leber congenital amaurosis with early-onset deafness (LCAEOD) in an individual with a heterozygous pathogenic variant in TUBB4B and an original diagnosis of USH. Novel genotype–phenotype correlations included biallelic pathogenic variants in KATNIP, previously associated with Joubert syndrome (JBTS), in an individual who presented with kidney disease and IRD, but no other features of JBTS. Conclusions: Syndromic IRDs are a highly heterogeneous group of disorders. The rarity of some of these syndromes on one hand, and the co-occurrence of several syndromic and nonsyndromic conditions in some individuals, on the other hand, complicates the diagnostic process. Genetic analysis is the ultimate way to obtain an accurate clinical diagnosis in these individuals. Full article
(This article belongs to the Special Issue Advances in Medical Genetics)
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14 pages, 1234 KiB  
Article
Metabolic Engineering of Escherichia coli for De Novo Biosynthesis of Mandelic Acid
by Chang Liu, Xuefeng Xiao, Wanbin Xing, Rina Na, Yunuo Song, Guoqiang Cao and Pengchao Wang
Fermentation 2025, 11(6), 331; https://doi.org/10.3390/fermentation11060331 - 9 Jun 2025
Viewed by 879
Abstract
Mandelic acid (MA) is a valuable α-hydroxy acid with applications in pharmaceuticals, cosmetics, and fine chemicals. While chemical synthesis is well established, concerns over toxicity and sustainability have driven interest in microbial production. Here, we engineered Escherichia coli for de novo MA biosynthesis [...] Read more.
Mandelic acid (MA) is a valuable α-hydroxy acid with applications in pharmaceuticals, cosmetics, and fine chemicals. While chemical synthesis is well established, concerns over toxicity and sustainability have driven interest in microbial production. Here, we engineered Escherichia coli for de novo MA biosynthesis by integrating enzyme screening, metabolic flux optimization, and pathway regulation. We first screened and identified an efficient hydroxymandelate synthase (HMAS) homolog from Actinosynnema mirum for MA synthesis, and subsequently enhanced the shikimate pathway along with the supply of the precursors erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP). Additionally, CRISPR interference (CRISPRi) was employed to repress competing pathways and redirect flux toward MA production. High-cell-density cultivation (HCDC) in a 5 L bioreactor demonstrated the strain’s industrial potential, achieving an MA titer of 9.58 g/L, the highest reported for microbial production. This study provides a systematic metabolic engineering approach for efficient MA biosynthesis from glucose, offering a foundation for sustainable large-scale production, demonstrating not only genetic-level optimizations, but also effective process scaling through high-cell-density cultivation, highlighting the power of pathway engineering in microbial cell factories. Full article
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)
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