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20 pages, 404 KB

Open AccessArticle

Individual Behavior or Collective Phenomenon: Peer Effects in the Coordinated Intelligentization and Greenization of Chinese Manufacturing Firms

by Liangfeng Hao, Xinyuan Li and Zhongjuan Ji

Sustainability 2025, 17(24), 11013; https://doi.org/10.3390/su172411013 (registering DOI) - 9 Dec 2025

Abstract

Artificial intelligence technology plays an important role in driving the coordinated development of intelligentization and greenization in China’s manufacturing industry. However, there may be differences in enterprises’ capabilities to advance this coordinated development, and it remains unclear whether promoting such dual transformation is [...] Read more.

Artificial intelligence technology plays an important role in driving the coordinated development of intelligentization and greenization in China’s manufacturing industry. However, there may be differences in enterprises’ capabilities to advance this coordinated development, and it remains unclear whether promoting such dual transformation is an individual behavior or a collective phenomenon. This paper employs the entropy weight method and the coupling coordination degree model to measure the level of coordinated development between enterprise intelligentization and greenization, and examines the peer effects of dual transformation among enterprises. The findings show that enterprise intelligentization lags behind greenization, with the two aspects being in a state of low-level coupling but steadily improving. Additionally, there are significant peer effects in the coordinated development of enterprise intelligentization and greenization, with their formation mechanisms primarily reflected in intelligentization enabling greenization, intra-industry competition, and the learning effect of followers from leaders. Heterogeneity analysis shows that the peer effects in the coordinated development of intelligentization and greenization are more pronounced among state-owned enterprises and technology-intensive firms. Moreover, enterprises located in the same province, within the same large-scale city, or within the same interlocking directorate network are more likely to exhibit peer effects in dual transformation. Full article

(This article belongs to the Special Issue AI for Sustainable Development: Applications and Impacts across Industries)

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18 pages, 4761 KB

Open AccessArticle

Energy Efficiency of Road Lighting Without Specific Numerical Indicators

by Catalin Daniel Galatanu and Irena Fryc

Energies 2025, 18(24), 6442; https://doi.org/10.3390/en18246442 (registering DOI) - 9 Dec 2025

Abstract

Energy efficiency in road lighting is increasingly critical for sustainable urban development, yet numerical indicators essential for objective evaluation are often misunderstood or misapplied. This paper addresses fundamental misconceptions in interpreting the Power Density Indicator (PDI), a key metric for assessing lighting system [...] Read more.

Energy efficiency in road lighting is increasingly critical for sustainable urban development, yet numerical indicators essential for objective evaluation are often misunderstood or misapplied. This paper addresses fundamental misconceptions in interpreting the Power Density Indicator (PDI), a key metric for assessing lighting system efficiency. Through analysis of Romanian street lighting modernization projects and extensive literature review, we demonstrate widespread misunderstanding of PDI’s properties, including inappropriate summation across streets and failure to recognize its independence from road class. We present a comprehensive methodology for PDI interpretation and optimization through spatial visualization of Luminous Intensity Distribution Curves (LIDCs) using MATLAB’s MESH function. The theoretical framework derives minimum achievable PDI values as a function of LED-specific efficacy and system utilance. Case studies from 181 streets in Romanian cities reveal significant optimization potential. Finally, we demonstrate, through computational simulation, the theoretical ideal: a perfectly adapted LIDC achieving unitary utilance, confirming that minimum PDI depends solely on LED efficacy and optical efficiency. These findings provide practical guidance for designers to optimize energy efficiency while meeting photometric requirements. Full article

(This article belongs to the Collection Energy Use Efficiency)

14 pages, 1230 KB

Open AccessCommunication

Individual Genomic Distinctness of Rice Germplasm as Measured with an Average Pairwise Dissimilarity of Genome-Wide SNPs and Structural Variants

by Yong-Bi Fu

Plants 2025, 14(24), 3750; https://doi.org/10.3390/plants14243750 (registering DOI) - 9 Dec 2025

Abstract

The average pairwise dissimilarity (APD) between one plant sample and other assayed samples based on genetic markers was developed in 2006 to assess genetic distinctness and genetic redundancy in a plant germplasm collection. With the availability of abundant genomic variants across a genome, [...] Read more.

The average pairwise dissimilarity (APD) between one plant sample and other assayed samples based on genetic markers was developed in 2006 to assess genetic distinctness and genetic redundancy in a plant germplasm collection. With the availability of abundant genomic variants across a genome, APD can be expanded to measure individual genomic distinctness. This study was conducted to assess the applicability of APD estimates in measuring the individual genomic distinctness of 1789 indica and 854 japonica rice samples based on published genome-wide single-nucleotide polymorphism (SNP) and structural variant (SV) data. It was found that the acquired APD estimates were weakly or not correlated between the SNP and SV data sets in the indica or japonica samples, respectively. For the indica samples, the APD estimates based on the SNP and SV data ranged from 0.1779 to 0.3277 and from 0.2297 to 0.4096, respectively. For the japonica samples, the SNP-based and SV-based APD estimates varied from 0.1774 to 0.3029 and from 0.1534 to 0.3459, respectively. These APD estimates were highly negatively correlated with the estimates of individual inbreeding coefficients and can identify the most genomically distinct rice germplasm that are compatible with those revealed through principal component analysis. Also, a reliable APD estimation was found to require 5000 to 10,000 random genomic SNPs or SVs. These findings together are significant, not only in demonstrating the informativeness of APD estimates in the identification of individuals with variable genomic distinctness, but also in providing guidance for APD applications to measure individual genomic distinctness. Full article

(This article belongs to the Section Plant Genetics, Genomics and Biotechnology)

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46 pages, 2441 KB

Open AccessReview

A State-of-the-Art Overview on (Epi)Genomics and Personalized Skin Rejuvenating Strategies

by Roxana-Georgiana Tauser, Ioana-Mirela Vasincu, Andreea-Teodora Iacob, Maria Apotrosoaei, Bianca-Ștefania Profire, Florentina-Geanina Lupascu, Oana-Maria Chirliu and Lenuta Profire

Pharmaceutics 2025, 17(12), 1585; https://doi.org/10.3390/pharmaceutics17121585 (registering DOI) - 9 Dec 2025

Abstract

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks [...] Read more.

This article aims to point out new perspectives opened by genomics and epigenomics in skin rejuvenation strategies which target the main hallmarks of the ageing. In this respect, this article presents a concise overview on: the clinical relevance of the most important clocks and biomarkers used in skin anti-ageing strategy evaluation, the fundamentals, the main illustrating examples preclinically and clinically tested, the critical insights on knowledge gaps and future research perspectives concerning the most relevant skin anti-ageing and rejuvenation strategies based on novel epigenomic and genomic acquisitions. Thus the review dedicates distinct sections to: senolytics and senomorphics targeting senescent skin cells and their senescent-associated phenotype; strategies targeting genomic instability and telomere attrition by stimulation of the deoxyribonucleic acid (DNA) repair enzymes and proteins essential for telomeres’ recovery and stability; regenerative medicine based on mesenchymal stem cells or cell-free products in order to restore skin-resided stem cells; genetically and chemically induced skin epigenetic partial reprogramming by using transcription factors or epigenetic small molecule agents, respectively; small molecule modulators of DNA methylases, histone deacetylases, telomerases, DNA repair enzymes or of sirtuins; modulators of micro ribonucleic acid (miRNA) and long-non-coding ribonucleic acid (HOTAIR’s modulators) assisted or not by CRISPR-gene editing technology (CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats); modulators of the most relevant altered nutrient-sensing pathways in skin ageing; as well as antioxidants and nanozymes to address mitochondrial dysfunctions and oxidative stress. In addition, some approaches targeting skin inflammageing, altered skin proteostasis, (macro)autophagy and intercellular connections, or skin microbiome, are very briefly discussed. The review also offers a comparative analysis among the newer genomic/epigenomic-based skin anti-ageing strategies vs. classical skin rejuvenation treatments from various perspectives: efficacy, safety, mechanism of action, evidence level in preclinical and clinical data and regulatory status, price range, current limitations. In these regards, a concise overview on senolytic/senomorphic agents, topical nutrigenomic pathways’ modulators and DNA repair enzymes, epigenetic small molecules agents, microRNAs and HOTAIRS’s modulators, is illustrated in comparison to classical approaches such as tretinoin and peptide-based cosmeceuticals, topical serum with growth factors, intense pulsed light, laser and microneedling combinations, chemical peels, botulinum toxin injections, dermal fillers. Finally, the review emphasizes the future research directions in order to accelerate the clinical translation of the (epi)genomic-advanced knowledge towards personalization of the skin anti-ageing strategies by integration of individual genomic and epigenomic profiles to customize/tailor skin rejuvenation therapies. Full article

(This article belongs to the Topic Challenges and Opportunities in Drug Delivery Research)

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9 pages, 479 KB

Open AccessArticle

Rapamycin Modulates the Polarisation of CD4+ T Cells Towards T_H1 Cells in Patients with Active Granulomatosis with Polyangiitis and Microscopic Polyangiitis

by Jang Woo Ha, Taejun Yoon, Oh Chan Kwon, Yong-Beom Park and Sang-Won Lee

J. Clin. Med. 2025, 14(24), 8720; https://doi.org/10.3390/jcm14248720 (registering DOI) - 9 Dec 2025

Abstract

Objective: This study investigated whether rapamycin could modulate the polarisation of CD4+ T cells towards T_H1, T_H2, T_H17, and Treg cells using peripheral blood mononuclear cell (PBMC) obtained from patients with granulomatosis with polyangiitis and microscopic polyangiitis [...] Read more.

Objective: This study investigated whether rapamycin could modulate the polarisation of CD4+ T cells towards T_H1, T_H2, T_H17, and Treg cells using peripheral blood mononuclear cell (PBMC) obtained from patients with granulomatosis with polyangiitis and microscopic polyangiitis (GPA/MPA). Methods: Twenty patients with GPA/MPA were included in this study. Their stored PBMCs were cultured and stimulated with anti-CD3 and anti-CD28 antibodies for 72 h in the presence or absence of rapamycin (10 nM). The cells were stained for surface markers with anti-CD4-FITC and anti-CD25-APC, followed by intracellular staining using anti-interferon (IFN)-γ-PE, anti-IL-4-PerCP-Cy5, anti-IL17A-APC, and anti-Foxp3-PE. The stained cells were analysed using a flow cytometer. Results: The median age of the 20 GPA/MPA patients (10 men and 10 women) was 65.5 years. Rapamycin treatment significantly modulated the polarisation of CD4+IFN-γ+ T (T_H1) cells compared to no treatment among GPA/MPA patients. In addition, the polarisation of CD4+IFN-γ+ T (T_H1) cells was also significantly reduced in rapamycin-treated PBMC obtained from active patients compared to untreated PBMC from the same patients; however, these alterations were not observed in inactive patients. Conversely, rapamycin treatment did not affect the polarisation of CD4+IL-4+ T (T_H2), CD4+IL-17+ T (T_H17), or CD4+FoxP3+CD25+ T (Treg) cells, regardless of GPA/MPA activity. Conclusions: This study was the first pilot study to demonstrate that rapamycin modulates the polarisation of CD4+ T cells towards CD4+IFN-γ+ T cells in active GPA/MPA. Full article

(This article belongs to the Section Immunology & Rheumatology)

26 pages, 4520 KB

Open AccessArticle

Simulation and Optimization of Collaborative Scheduling of AGV and Yard Crane in U-Shaped Automated Terminal Based on Deep Reinforcement Learning

by Yongsheng Yang, Feiteng Zhao, Junkai Feng, Shu Sun, Wenying Lu and Shanghao Chen

J. Mar. Sci. Eng. 2025, 13(12), 2344; https://doi.org/10.3390/jmse13122344 (registering DOI) - 9 Dec 2025

Abstract

In U-shaped automated container terminals (U-shaped ACTs), automated guided vehicles (AGVs) need to frequently interact with yard cranes (YCs), and separate scheduling of the two devices will affect terminal efficiency. Therefore, this study explores the coordinated scheduling problem between the two devices. To [...] Read more.

In U-shaped automated container terminals (U-shaped ACTs), automated guided vehicles (AGVs) need to frequently interact with yard cranes (YCs), and separate scheduling of the two devices will affect terminal efficiency. Therefore, this study explores the coordinated scheduling problem between the two devices. To solve this problem, a high-precision simulation model of the U-shaped ACTs is established, which incorporates real operational logic. Second, an Improved Non-dominated Sorting Genetic Algorithm II based on Proximal Policy Optimization (INSGAII-PPO) is proposed. The algorithm uses PPO to realize dynamic genetic operator selection and makes related improvements, which improve the multi-objective optimization ability of NSGAII, and solve the collaborative scheduling problem by combining simulation. Finally, a hybrid weighted Technique for Order Preference by Similarity to Ideal Solution with preferences is proposed to select the final solution. The experimental results show that the scheme obtained by INSGAII-PPO exhibits better convergence and diversity, and offers significant advantages compared with the comparison algorithms. Moreover, the energy consumption and waiting time of the final solution selected by the proposed method are reduced by 3.42% and 4.87% on average. The proposed method has the capability of providing a theoretical reference for the AGVs and YCs collaborative scheduling of U-shaped ACTs. Full article

(This article belongs to the Special Issue Maritime Logistics: Shipping and Port Management)

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11 pages, 7223 KB

Open AccessCase Report

Primary Pericardial Well-Differentiated Papillary Mesothelioma in a Spotted Hyena (Crocuta crocuta)

by Louise van der Weyden, Dewald Keet and Nicolize O’Dell

Vet. Sci. 2025, 12(12), 1170; https://doi.org/10.3390/vetsci12121170 (registering DOI) - 9 Dec 2025

Abstract

There have been few reports of neoplasia in hyenas to date. In this report, we describe a captive adult female spotted hyena (Crocuta crocuta) that developed inappetence, lethargy and marked abdominal distension over a 3-day period. The hyena was chemically immobilised [...] Read more.

There have been few reports of neoplasia in hyenas to date. In this report, we describe a captive adult female spotted hyena (Crocuta crocuta) that developed inappetence, lethargy and marked abdominal distension over a 3-day period. The hyena was chemically immobilised to allow clinical investigation of the severe symptoms; however, she died before any internal examination occurred. At necropsy, severe serosanguinous hydropericardium was evident, as well as pulmonary congestion and oedema, ascites and chronic passive congestion of the liver with mild fibrosis. Histopathological examination of the pericardial surface revealed fibrous proliferations lined by mostly a single layer of large proliferating neoplastic mesothelial cells forming papillary projections into the lumen of the pericardial sac as well as infiltration into the pericardial connective tissue, with innumerable haemosiderin-laden macrophages in places, suggestive of chronic haemorrhage. The liver revealed severe congestion and interstitial fibrosis, and the lung revealed congestion and oedema, with moderate numbers of alveolar macrophages and marked anthracosis. The diagnosis was pericardial well-differentiated papillary mesothelioma, with death under anaesthesia caused by cardiogenic shock due to pericardial mesothelioma-associated cardiac tamponade. As primary pericardial mesothelioma (PPM) is a rare tumour type for both animals and humans, and this is the first report of a PPM in a hyena, we compare the clinical findings with those seen in other species. Full article

(This article belongs to the Section Anatomy, Histology and Pathology)

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14 pages, 1637 KB

Open AccessArticle

Orthodontic Implants: Novelty and Evolution in Veterinary Orthodontics—Retrospective Case Series Report

by Raluca-Ioana Nedelea, Mihai Marian Borzan, Cristinel Cezar Mătură and Ioan Marcus

Vet. Sci. 2025, 12(12), 1169; https://doi.org/10.3390/vetsci12121169 (registering DOI) - 9 Dec 2025

Abstract

Orthodontic implants (OIs) are endosseous devices designed to provide stable skeletal anchorage in orthodontic treatment. A variety of terms have been proposed for these devices; however, such terminology may lead to OIs being confused with conventional dental implants. Therefore, the similarities and distinctions [...] Read more.

Orthodontic implants (OIs) are endosseous devices designed to provide stable skeletal anchorage in orthodontic treatment. A variety of terms have been proposed for these devices; however, such terminology may lead to OIs being confused with conventional dental implants. Therefore, the similarities and distinctions between OIs and dental implants will be examined in this research. Three representative clinical cases will be presented, illustrating the application of OIs for mandibular incisor teeth lingualizations, distalization of a maxillary canine tooth, and palatal flap protection for palatoschizis closure in a cat, describing a custom-made protection shield held in place with four OIs. This article will cover the criteria for OI selection, the determination of optimal insertion sites, and the placement technique. Given that a key prerequisite for a successful outcome is primary stability, several complications may occur such as local inflammation, injury to adjacent anatomical structures, implant fracture, loss of stability, or challenges in attaching elastic chains due to interference from surrounding soft tissues. The prevention and management of such complications will be addressed. Full article

(This article belongs to the Special Issue Advanced Therapy in Companion Animals—2nd Edition)

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15 pages, 2268 KB

Open AccessArticle

Ameliorating Acute Kidney Injury Induced by Ischemia-Reperfusion by Targeting Purine Metabolism

by Limei Zhao, Tingting Zhang and Xiaoshuang Zhou

Int. J. Mol. Sci. 2025, 26(24), 11886; https://doi.org/10.3390/ijms262411886 (registering DOI) - 9 Dec 2025

Abstract

In the pathological process of acute kidney injury (AKI) and its transition to chronic kidney disease, the uric acid (UA) metabolic pathway plays a significant role. UA is produced as the last oxidative product in the metabolism of purine nucleotides. Prolonged organ ischemia [...] Read more.

In the pathological process of acute kidney injury (AKI) and its transition to chronic kidney disease, the uric acid (UA) metabolic pathway plays a significant role. UA is produced as the last oxidative product in the metabolism of purine nucleotides. Prolonged organ ischemia promotes the breakdown of nucleotides into adenosine, hypoxanthine, xanthine, and UA. In this study, animal models of ischemia–reperfusion-induced AKI and renal tubular epithelial cells subjected to hypoxia–reoxygenation injury exhibited significantly reduced ATP levels, along with elevated concentrations of purine catabolites, including AMP, hypoxanthine, xanthine, and UA. Concurrently, the expression of xanthine oxidase (XO), a key enzyme in purine catabolism, was upregulated, peaking at 3 h after reoxygenation, accompanied by increased reactive oxygen species (ROS) production. Treatment with the XO inhibitor febuxostat in hypoxia–reoxygenated HK-2 cells led to a marked reduction in UA, inflammatory cytokines, and ROS levels, along with decreased apoptosis and enhanced proliferative capacity. Clinical data analysis revealed that 59.4% of AKI patients presented with hyperuricemia. UA levels demonstrated a linear correlation with the estimated glomerular filtration rate (eGFR) and the tissue necrosis marker lactate dehydrogenase (LDH). A random forest model constructed based on UA, LDH, age, diabetes, and hypertension accurately predicted the eGFR. These findings indicate that patients with I/R-induced AKI exhibit enhanced purine catabolism, and purine metabolic breakdown products are closely associated with the severity of renal injury in I/R AKI. For high-risk AKI populations or patients diagnosed with AKI with significantly elevated UA levels, febuxostat may be considered to prevent AKI onset and improve renal function. Furthermore, in AKI patients where creatinine data are unavailable or not significantly elevated despite markedly increased UA levels, a comprehensive assessment incorporating relevant indicators of glomerular filtration function is recommended. Full article

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32 pages, 4759 KB

Open AccessArticle

Development of a Bayesian Network and Information Gain-Based Axis Dynamic Mechanism for Ankle Joint Rehabilitation

by Huiguo Ma, Yuqi Bao, Jingfu Lan, Xuewen Zhu, Pinwei Wan, Raquel Cedazo León, Shuo Jiang, Fangfang Chen, Jun Kang, Qihan Guo, Peng Zhang and He Li

Biomimetics 2025, 10(12), 823; https://doi.org/10.3390/biomimetics10120823 (registering DOI) - 9 Dec 2025

Abstract

In response to the personalized and precise rehabilitation needs for motor injuries and stroke associated with population aging, this study proposes a design method for an intelligent rehabilitation trainer that integrates Bayesian information gain (BIG) and axis matching techniques. Grounded in the biomechanical [...] Read more.

In response to the personalized and precise rehabilitation needs for motor injuries and stroke associated with population aging, this study proposes a design method for an intelligent rehabilitation trainer that integrates Bayesian information gain (BIG) and axis matching techniques. Grounded in the biomechanical characteristics of the human ankle joint, the design fully draws upon biomimetic principles, constructing a 3-PUU-R hybrid serial–parallel bionic mechanism. By mimicking the dynamic variation of the ankle’s instantaneous motion axis and its balance between stiffness and compliance, a three-dimensional digital model was developed, and multi-posture human factor simulations were conducted, thereby achieving a rehabilitation process more consistent with natural human movement patterns. Natural randomized disability grade experimental data were collected for 100 people to verify the validity of the design results. On this basis, a Bayesian information gain framework was established by quantifying the reduction of uncertainty in rehabilitation outcomes through characteristic parameters, enabling the dynamic optimization of training strategies for personalized and precise ankle rehabilitation. The rehabilitation process was modeled as a problem of uncertainty quantification and information gain optimization. Prior distributions were constructed using surface EMG (electromyography) signals and motion trajectory errors, and mutual information was used to drive the dynamic adjustment of training strategies, ultimately forming a closed-loop control architecture of “demand perception–strategy optimization–execution adaptation.” This innovative integration of probabilistic modeling and cross-joint bionic design overcomes the limitations of single-joint rehabilitation and provides a new paradigm for the development of intelligent rehabilitation devices. The deep integration mechanism-based dynamic axis matching and Bayesian information gain holds significant theoretical value and engineering application prospects for enhancing the effectiveness of neural plasticity training. Full article

(This article belongs to the Special Issue Advanced Service Robots: Exoskeleton Robots 2025)

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21 pages, 842 KB

Open AccessReview

Analysis of qPCR Data: From PCR Efficiency to Absolute Target Quantity

by Jan M. Ruijter and Maurice J. B. van den Hoff

Int. J. Mol. Sci. 2025, 26(24), 11885; https://doi.org/10.3390/ijms262411885 (registering DOI) - 9 Dec 2025

Abstract

Quantitative Polymerase Chain Reaction (qPCR) is a very sensitive method to determine small amounts of DNA or RNA in experimental, environmental, veterinary, forensic and clinical samples. Despite efforts from the qPCR community to address qPCR variability by recommending standardization of reporting of all [...] Read more.

Quantitative Polymerase Chain Reaction (qPCR) is a very sensitive method to determine small amounts of DNA or RNA in experimental, environmental, veterinary, forensic and clinical samples. Despite efforts from the qPCR community to address qPCR variability by recommending standardization of reporting of all steps of a qPCR experiment, most reported qPCR results are still grossly biased. The first part of this paper describes two decades of efforts to remedy this situation by promoting so-called efficiency-corrected qPCR data analysis. Although such analysis leads to less variable qPCR results, the outcome, fluorescence at cycle zero, is difficult to grasp. In the second part, we outline how qPCR analyses can result in N_copy, the number of copies of the target at the start of the reaction. A newly developed theoretical approach determines N_copy using the characteristics of the amplification curve and the known concentrations of all reaction components. By including these reaction-mix characteristics in the analysis, this N_copy is assay-, machine- and laboratory-independent and thus allows direct worldwide comparisons. Moreover, N_copy provides a very intuitive and easy-to-interpret absolute quantitative result. Full article

(This article belongs to the Special Issue Advancing Molecular Science Through Reproducible qPCR: MIQE Guidelines and Beyond)

32 pages, 1788 KB

Open AccessReview

Luteinizing Hormone-Releasing Hormone (LHRH)-Targeted Treatment in Ovarian Cancer

by Pallavi Nayak, Michela Varani, Anna Giorgio, Giuseppe Campagna, Donatella Caserta and Alberto Signore

Int. J. Mol. Sci. 2025, 26(24), 11884; https://doi.org/10.3390/ijms262411884 (registering DOI) - 9 Dec 2025

Abstract

Ovarian cancer remains one of the most lethal gynecologic malignancies and requires more effective and targeted treatment strategies. Luteinizing hormone-releasing hormone (LHRH), or gonadotropin-releasing hormone (GnRH), receptors are expressed in approximately 80% of ovarian tumors, representing a promising target for targeted drug delivery. [...] Read more.

Ovarian cancer remains one of the most lethal gynecologic malignancies and requires more effective and targeted treatment strategies. Luteinizing hormone-releasing hormone (LHRH), or gonadotropin-releasing hormone (GnRH), receptors are expressed in approximately 80% of ovarian tumors, representing a promising target for targeted drug delivery. This narrative review aimed to explore the development and advancements of LHRH-receptor targeted therapies in ovarian cancer. A bibliographic search was performed using PubMed, Scopus, Google Scholar, and Web of Science. The search strategy included studies on LHRH-peptide drug delivery systems and LHRH-conjugate nanosystems. Literature search covered in vitro studies, preclinical models, and ongoing clinical trials from 2000 to 2025. A total of 19 studies were included for peptide-drug delivery, and 30 studies were included for LHRH-conjugated nanosystems. Overall findings demonstrated enhanced preclinical efficacy, achieving ~50–80% tumor-growth inhibition and 2–4-fold higher cellular uptake, alongside reduced systemic toxicity. Early clinical studies, although limited, reported an overall response/disease-control rate of approximately 50%, supporting improved tumor accumulation of drugs, small interfering RNA (siRNA), and diagnostic agents. Ovarian cancer-specific therapy, targeting LHRH receptors, represents a promising strategy to enhance therapeutic outcomes. Further efforts in preclinical and clinical research are essential to refine personalized treatments and integrate them with a combination of therapies. Full article

(This article belongs to the Special Issue Current Research on Cancer Biology and Therapeutics: Fourth Edition)

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10 pages, 6321 KB

Open AccessArticle

Novel Preparation and Characterization of an Organic-Vermiculite Intercalated by Hexadecyltrimethylammonium Bromide

by Liang Zhang, Ben Wang, Xiaomei Shao and Wei Han

Processes 2025, 13(12), 3979; https://doi.org/10.3390/pr13123979 (registering DOI) - 9 Dec 2025

Abstract

A novel and rapid ball-milling approach was developed in this study to efficiently intercalate hexadecyltrimethylammonium bromide (HDTMA-Br) into vermiculite (VMT) within only 15 min. The raw granular VMT (2–3 mm) was first ground into fine powder using an airflow pulverizer. A suspension containing [...] Read more.

A novel and rapid ball-milling approach was developed in this study to efficiently intercalate hexadecyltrimethylammonium bromide (HDTMA-Br) into vermiculite (VMT) within only 15 min. The raw granular VMT (2–3 mm) was first ground into fine powder using an airflow pulverizer. A suspension containing VMT and HDTMA-Br (1 CEC) in deionized water was then subjected to planetary ball milling at 450 r/min (25 °C), followed by washing and drying to obtain organo-vermiculite (OVMT) with a particle size of 44–5 µm. X-ray diffraction, Fourier-transform Infrared Spectroscopy and Thermogravimetric Analysis analyses confirmed successful intercalation, with the basal spacing

d_{(001)}

expanding from 1.46 nm to 4.51 nm. Transmission Electron Microscopy observations further revealed partial delamination of lamellar structures and a pronounced reduction in particle size, supporting the structural reorganization induced by the mechanochemical process. In addition, nitrogen adsorption analysis showed that the BET surface area decreased by 4.05 m²·g⁻¹, while the average pore diameter increased by 3.2 nm, indicating the development of a more hydrophobic interlayer environment. Overall, this approach offers a practical route for producing organophilic silicate materials and shows strong potential for wastewater treatment applications, particularly for the adsorption of organic pollutants and heavy-metal ions. Full article

(This article belongs to the Special Issue Advanced Water Monitoring and Treatment Technologies)

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14 pages, 2644 KB

Open AccessArticle

A Mathematical Model for the Variation of Cerebral Electrical Conductivity and the Amount of β-Amyloid Protein Values Due to Alzheimer’s Disease

by Emmanouil Perakis and Panagiotis Vlamos

Brain Sci. 2025, 15(12), 1313; https://doi.org/10.3390/brainsci15121313 (registering DOI) - 9 Dec 2025

Abstract

Background/Objectives: This study presents a time-dependent mathematical model that describes how progressive amyloid-β (Aβ) accumulation drives the gradual decline of cerebral electrical conductivity during Alzheimer’s disease (AD). Methods: The formulation captures the coupled evolution of molecular burden and electrophysiological function through a pair [...] Read more.

Background/Objectives: This study presents a time-dependent mathematical model that describes how progressive amyloid-β (Aβ) accumulation drives the gradual decline of cerebral electrical conductivity during Alzheimer’s disease (AD). Methods: The formulation captures the coupled evolution of molecular burden and electrophysiological function through a pair of interconnected dynamical processes, enabling a mechanistic link between early biochemical alterations and large-scale neural degradation. Results: Simulations reveal a characteristic pattern in which Aβ levels rise steadily toward a pathological plateau, while conductivity follows a delayed but persistent downward trajectory that stabilizes at an impaired state consistent with advanced neurodegeneration. The model reproduces key phenomena reported in experimental and clinical studies, including the slow, irreversible reduction in cortical conductivity and the strong inverse relationship between amyloid burden and electrophysiological integrity. Conclusions: Although intentionally minimal, the framework offers a tractable basis for interpreting disease progression and can be extended to incorporate additional pathological pathways such as tau aggregation, inflammatory responses, or spatial heterogeneity. By providing a compact yet biologically meaningful representation of the interplay between molecular pathology and electrical dysfunction, the model supports the development of computational biomarkers and contributes to a more integrated understanding of AD progression. Full article

(This article belongs to the Section Computational Neuroscience, Neuroinformatics, and Neurocomputing)

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20 pages, 3720 KB

Open AccessArticle

The Double-K Fracture Toughness of Concrete with Different Coarse Aggregate Volume Fractions

by Xiao Li, Ying Zhang, Yanwei Chen, Ying Yuan, Jili Feng and Zhiguang Li

Materials 2025, 18(24), 5526; https://doi.org/10.3390/ma18245526 (registering DOI) - 9 Dec 2025

Abstract

This study examines how coarse aggregate volume fraction (V_a) affects the double-K fracture toughness and fundamental mechanical properties of concrete. Wedge-splitting tests were conducted on specimens with six different V_a values: 19%, 25%, 31%, 37%, 43%, and 50%. [...] Read more.

This study examines how coarse aggregate volume fraction (V_a) affects the double-K fracture toughness and fundamental mechanical properties of concrete. Wedge-splitting tests were conducted on specimens with six different V_a values: 19%, 25%, 31%, 37%, 43%, and 50%. The results indicate that compressive strength (f_c) and elastic modulus (E) consistently increase with V_a, reaching 59.8 MPa and 37.9 GPa at V_a = 50%, respectively. Conversely, tensile strength (f_t), double-K fracture toughness (including initiation toughness

K_{IC}^{ini}

and unstable toughness

K_{IC}^{un}

), and fracture energy (G_IF) initially increase before decreasing, peaking at an optimal V_a of 37%. Specifically,

K_{IC}^{ini}

,

K_{IC}^{un}

, and G_IF reached their maximum values of 0.54 MPa·m^1/2, 1.20 MPa·m^1/2, and 225.0 N/m at V_a = 37%. The tortuosity of crack paths follows a similar trend, becoming more pronounced up to V_a = 37% before diminishing. Furthermore, quantitative exponential relationships were established between f_t and

K_{IC}^{ini}

,

K_{IC}^{un}

, and G_IF. A safety warning parameter (δ), derived from the double-K fracture toughness, was proposed to quantitatively assess the pre-peak ductility, with values ranging from 0.88 to 0.72 in this study. The findings offer valuable guidance for optimizing concrete mix design, suggesting that a V_a range of 25% to 31% provides an optimal balance between high crack initiation resistance and adequate safety warning capacity for critical engineering structures. Full article

(This article belongs to the Section Construction and Building Materials)

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32 pages, 37329 KB

Open AccessArticle

Movement Artifact Direction Estimation Based on Signal Processing Analysis of Single-Frame Images

by Woottichai Nonsakhoo and Saiyan Saiyod

Sensors 2025, 25(24), 7487; https://doi.org/10.3390/s25247487 (registering DOI) - 9 Dec 2025

Abstract

Movement artifact direction and magnitude are critical parameters in noise detection and image analysis, especially for single-frame images where temporal information is unavailable. This paper introduces the Movement Artifact Direction Estimation (MADE) algorithm, a signal processing-based approach that performs 3D geometric analysis to [...] Read more.

Movement artifact direction and magnitude are critical parameters in noise detection and image analysis, especially for single-frame images where temporal information is unavailable. This paper introduces the Movement Artifact Direction Estimation (MADE) algorithm, a signal processing-based approach that performs 3D geometric analysis to estimate both the direction (in degrees) and weighted quantity (in pixels) of movement artifacts. Motivated by computational challenges in medical image quality assessment systems such as LUIAS, this work investigates directional multiplicative noise characterization using controlled experimental conditions with optical camera imaging. The MADE algorithm operates on multi-directional quantification outputs from a preprocessing pipeline—MAPE, ROPE, and MAQ. The methodology is designed for computational efficiency and instantaneous processing, providing interpretable outputs. Experimental results using precision-controlled apparatus demonstrate robust estimation of movement artifact direction and magnitude across a range of image shapes and velocities, with principal outputs aligning closely to ground truth parameters. The proposed MADE algorithm offers a methodological proof of concept for movement artifact analysis in single-frame images, emphasizing both directional accuracy and quantitative assessment under controlled imaging conditions. Full article

(This article belongs to the Special Issue Innovative Sensing Methods for Motion and Behavior Analysis)

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14 pages, 830 KB

Open AccessReview

Cancer-Associated Fibroblasts and Epithelial–Mesenchymal Transition as Critical Contributors to Renal Cell Carcinoma Progression

by Sergii Vernygorodskyi, Anton B. Tonchev, Nikolai T. Evtimov and Kameliya Zhechkova Bratoeva

J. Mol. Pathol. 2025, 6(4), 31; https://doi.org/10.3390/jmp6040031 (registering DOI) - 9 Dec 2025

Abstract

Renal cell carcinoma (RCC) features a complex tumor microenvironment, where cancer-associated fibroblasts (CAFs) play key roles in tumor progression, epithelial–mesenchymal transition (EMT), immune evasion, and resistance to treatment. This article updates our understanding of CAF origins, diversity, and functions in RCC, incorporating recent [...] Read more.

Renal cell carcinoma (RCC) features a complex tumor microenvironment, where cancer-associated fibroblasts (CAFs) play key roles in tumor progression, epithelial–mesenchymal transition (EMT), immune evasion, and resistance to treatment. This article updates our understanding of CAF origins, diversity, and functions in RCC, incorporating recent single-cell RNA sequencing (scRNA-seq) data that refine CAF subtypes. The paper explores the mechanistic interactions between CAFs and EMT, focusing on CAF-derived signaling pathways like TGF-β, IL-6/STAT3, HGF/c-MET, and Wnt/β-catenin, as well as extracellular-vesicle-mediated transfer of miRNAs and lncRNAs that promote metastatic behavior in RCC. It also addresses how CAF-driven remodeling of the extracellular matrix, metabolic changes, and activation of YAP/TAZ contribute to invasion and resistance to therapies, particularly in relation to tyrosine kinase inhibitors, mTOR inhibitors, and immune checkpoint blockade. The review highlights emerging therapeutic strategies targeting CAFs, such as inhibiting specific signaling pathways, disrupting CAF–tumor cell communication, and selectively depleting CAFs. In conclusion, it identifies limitations in current CAF classification systems and proposes future research avenues to improve RCC-specific CAF profiling and exploit the CAF–EMT axis for therapeutic gain. Full article

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17 pages, 3211 KB

Open AccessArticle

Spatial Analysis of Extreme Coastal Water Levels and Dominant Forcing Factors Along the Senegalese Coast

by Cheikh Omar Tidjani Cissé, Rafael Almar and Abdoulaye Ndour

J. Mar. Sci. Eng. 2025, 13(12), 2342; https://doi.org/10.3390/jmse13122342 (registering DOI) - 9 Dec 2025

Abstract

Coastal flooding risk is intensifying under climate change, especially along the low sandy Senegalese coastline. This study explores the spatiotemporal variability of extreme coastal water levels (ECWL) from 1993 to 2023 by combining ERA5 reanalysis (waves, wind, pressure), tide gauge and meteorological data, [...] Read more.

Coastal flooding risk is intensifying under climate change, especially along the low sandy Senegalese coastline. This study explores the spatiotemporal variability of extreme coastal water levels (ECWL) from 1993 to 2023 by combining ERA5 reanalysis (waves, wind, pressure), tide gauge and meteorological data, and applying a generalized Pareto distribution (GPD) to estimate the 99th percentile and return levels for 50 and 100 year events. The analysis of the upper 1% of ECWLs reveals significant spatial heterogeneity: 99th percentile values exceed 1.2 m in the Dakar region (Yoff, Ouakam, Ngor) and around Saint-Louis/Langue de Barbarie, with 95% confidence intervals ranging from approximately 1.15 m to 1.30 m, while Casamance and the Saloum Delta exhibit much lower extremes (0.8–1.0 m). For return periods, ECWLs vary between 1.6 m and 2.3 m, with the 100 year return level (T100) exceeding 2.25 m in Dakar, above 2.0 m in Saint-Louis, and intermediate values (1.5–1.9 m) along the Petite Côte (Mbour–Toubab Dialaw) and in the Saloum Delta. The 50 year return level (T50) follows a similar spatial pattern but is 5–10 cm lower than T100 in the most exposed areas. Sensitivity analysis shows that ECWLs are primarily controlled by astronomical tide along much of the coast, whereas wave runup dominates in the southern estuarine zones (Saloum, Casamance, Mbour). Trend analysis using the Mann–Kendall test reveals a latitudinal gradient: stronger positive slopes in the south, weaker trends in central and northern sections, but all p values lie between 0.1 and 0.4, meaning none of the trends reach conventional significance. These findings point to a potential intensification of extreme water levels in socio-economically critical areas (Dakar, Saint-Louis, Mbour) but should be interpreted with caution given the lack of robust statistical significance. The results provide a quantitative basis for coastal risk management in light of projected sea level rise. Full article

(This article belongs to the Section Coastal Engineering)

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18 pages, 2140 KB

Open AccessArticle

Development and Experimental Validation of an Integrated Evaluation Framework for EMS Smartwear Electrodes

by Gihyun Lee, Uri Chae, Jungmin Yun, Donghyeon Seo, Inyoung Jang, Geunho Ham, Taehoon Kim and Hongbum Kim

Sensors 2025, 25(24), 7484; https://doi.org/10.3390/s25247484 (registering DOI) - 9 Dec 2025

Abstract

This study presents an integrated evaluation framework for textile-based electrical muscle stimulation smartwear electrodes, combining physiological and user-centered assessments to ensure comprehensive performance analysis. Four electrode types—lock stitch, knit, hot stamping, and moss stitch—were examined using a systematic five-step process with nine participants. [...] Read more.

This study presents an integrated evaluation framework for textile-based electrical muscle stimulation smartwear electrodes, combining physiological and user-centered assessments to ensure comprehensive performance analysis. Four electrode types—lock stitch, knit, hot stamping, and moss stitch—were examined using a systematic five-step process with nine participants. Quantitative measurements were obtained using electromyography to determine maximum voluntary contraction and tensiomyography to assess muscle contraction velocity. The knit electrode demonstrated a statistically significant reduction in maximum voluntary contraction following stimulation (W = 2.0, p = 0.012, Cohen’s d = 0.58), indicating effective neuromuscular activation and fatigue induction. The moss stitch electrode also showed a notable trend toward reduced muscle activation (W = 6.0, p = 0.055, d = 0.37). In contrast, the lock stitch and hot stamping electrodes exhibited negligible changes. User experience surveys revealed overall high acceptance across all electrode types (4.0–4.5 of mean scores on a 5-point scale), with the moss stitch electrode receiving the highest ratings for perceived safety and minimal skin discomfort, while the hot stamping electrode scored lowest in breathability. The proposed framework enables balanced evaluation of both functional performance and user experience, offering practical design guidance for optimizing textile electrodes across applications ranging from high-intensity athletic training to low-intensity rehabilitation. Full article

(This article belongs to the Special Issue Innovative Applications of Wearable Sensors in Musculoskeletal Biomechanics and Rehabilitation)

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16 pages, 238 KB

Open AccessArticle

The Development in Heidegger’s Thinking of Truth: From the 1930 Drafts of on the Essence of Truth to the Published 1943/49 Version

by Asadullah Khan

Philosophies 2025, 10(6), 132; https://doi.org/10.3390/philosophies10060132 (registering DOI) - 9 Dec 2025

Abstract

This paper traces the development in Heidegger’s thinking of truth from the early drafts of “On the Essence of Truth” (1930) to the published essay of 1943/49. It argues that the shift from the early thinking of truth, which understands truth as disclosure [...] Read more.

This paper traces the development in Heidegger’s thinking of truth from the early drafts of “On the Essence of Truth” (1930) to the published essay of 1943/49. It argues that the shift from the early thinking of truth, which understands truth as disclosure in terms of horizonal projection, to the later conception, which understands truth as disclosure granted by the open-region (die Gegnet), marks a deepening that entails significant development in Heidegger’s thinking as a whole. This paper follows the development of the relation between comportment, letting-be, disclosure, and concealment in early drafts, and shows how the later published version rethinks these in light of a more primordial openness that had remained unthought in the early drafts. Full article

(This article belongs to the Special Issue Interpreting the New Heidegger)

20 pages, 5782 KB

Open AccessArticle

Sr²⁺ and Eu³⁺ Co-Doped Whitlockite Phosphates Ca_8−xSr_xZnEu(PO₄)₇: Bioactivity, Antibacterial Potential, and Luminescence Properties for Biomedical Applications

by Dina V. Deyneko, Vladimir N. Lebedev, Ivan V. Nikiforov, Vladimir V. Titkov, Roman Yu. Shendrik, Katia Barbaro, Daniela Caciolo, Sergey M. Aksenov, Marco Fosca, Bogdan I. Lazoryak and Julietta V. Rau

Coatings 2025, 15(12), 1453; https://doi.org/10.3390/coatings15121453 (registering DOI) - 9 Dec 2025

Abstract

Calcium phosphates are one of the main materials used in biomedicine for bone regeneration purposes. To improve the properties of biocompatible β-Ca₃(PO₄)₂, doping by bioactive, antibacterial is actively used, as well as luminescent ions. Co-doped phosphates Ca [...] Read more.

Calcium phosphates are one of the main materials used in biomedicine for bone regeneration purposes. To improve the properties of biocompatible β-Ca₃(PO₄)₂, doping by bioactive, antibacterial is actively used, as well as luminescent ions. Co-doped phosphates Ca_8−xSr_xZnEu(PO₄)₇ with a β-Ca₃(PO₄)₂ (β-TCP)-type structure were synthesized through solid-state synthesis. The β-TCP-type structure was confirmed using X-ray powder diffraction and FTIR spectroscopy. Photoluminescence data, including excitation and emission spectra, decay curves, lifetime values and quantum yields, were collected for all samples. Ca_8−xSr_xZnEu(PO₄)₇ phosphates exhibit strong red-emission due to 4f-4f transitions of Eu³⁺ ions in disordered oxygen surrounding, with quantum yields reaching 54%. The phosphates demonstrated biocompatibility through MTT assay, with successful differentiation of aMSCs into the osteogenic lineage. Antibacterial activity was tested against four bacteria (E. coli, S. aureus, P. aeruginosa, and E. faecalis) and a fungus (C. albicans). It was found that the samples demonstrated antibacterial properties. The growth of E. coli and E. faecalis is significant inhibited by Ca_8−xSr_xZnEu(PO₄)₇ samples with 0 ≤ x ≤ 6.0. Analysis of mixed salt solubility using Eu³⁺ ions as a fluorescent probe showed that increasing Sr²⁺ concentration in Ca_8−xSr_xZnEu(PO₄)₇ delays both β-TCP phase resorption and HAP phase precipitation. These results demonstrate the potential of Ca_8−xSr_xZnEu(PO₄)₇ phosphates for bioimaging and bone healing control. Full article

(This article belongs to the Special Issue Advanced Coatings and Materials for Biomedical Applications)

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28 pages, 1941 KB

Open AccessFeature PaperArticle

Optimal Choice of Crop Insurance: The Case of Winter Barley in France

by Diana Dorobantu and Gia Hien Pham

Risks 2025, 13(12), 244; https://doi.org/10.3390/risks13120244 (registering DOI) - 9 Dec 2025

Abstract

This paper analyzes how the agricultural insurance market is adapting to climate change, particularly as extreme weather events become more frequent and severe. We focus on the optimal decision faced by a risk-averse farmer who wants to insure their crop while making savings. [...] Read more.

This paper analyzes how the agricultural insurance market is adapting to climate change, particularly as extreme weather events become more frequent and severe. We focus on the optimal decision faced by a risk-averse farmer who wants to insure their crop while making savings. They can choose between a traditional loss-based insurance, index-based insurance or a mix of both. By maximizing the farmer’s CARA utility function, we show that in some cases, a mixed insurance strategy is more advantageous than a single contract. In our model, the farmer insures only part of the crop when the market interest rate is strictly positive. Demand for traditional and index insurance depends on their respective prices. Highly risk-averse farmers prefer traditional insurance. A numerical application to the French agriculture sector indicates that mean spring temperature primarily affects winter barley yield and could therefore be the main indicator for index-based insurance design. Insurance simulations using the theoretical model and the estimated results further illustrate these findings. Full article

41 pages, 1213 KB

Open AccessArticle

Mathematical Stability Analysis of the Full SREBP-2 Pathway Model: Insights into Cholesterol Homeostasis

by Mostafa Bachar

Axioms 2025, 14(12), 905; https://doi.org/10.3390/axioms14120905 (registering DOI) - 9 Dec 2025

Abstract

We present a mathematical analysis of the sterol regulatory element-binding protein 2 (SREBP-2) pathway, a key regulator of intracellular cholesterol homeostasis. Using a compartment model formulated as a nonlinear system of ordinary differential equations, we investigate stability via M-matrix theory and norm-based [...] Read more.

We present a mathematical analysis of the sterol regulatory element-binding protein 2 (SREBP-2) pathway, a key regulator of intracellular cholesterol homeostasis. Using a compartment model formulated as a nonlinear system of ordinary differential equations, we investigate stability via M-matrix theory and norm-based criteria. We show that the Frobenius norm

{∥ B ∥}_{F} \geq 1

cannot ensure stability, whereas the infinity norm condition

{∥ B ∥}_{\infty} < 1

provides a practical guarantee that the spectral radius

ρ (B) < 1

. The spectral norm

{∥ B ∥}_{2}

yields sharper intermediate bounds. Numerical simulations confirm these results, highlighting parameter regions of stability and showing that the dissociation rate

k_{- 1}

has the strongest influence on system behavior. These findings demonstrate the robustness of the

ℓ_{\infty}

criterion, clarify the role of dissociation kinetics in cholesterol regulation, and provide a rigorous framework for assessing homeostatic control in the SREBP-2 pathway. Full article

(This article belongs to the Special Issue New Perspectives in Bifurcations Analysis of Dynamical Systems)

24 pages, 6350 KB

Open AccessArticle

Composites Derived from Aluminium-Modified Biphasic Calcium-Phosphate for Bone Regeneration

by Raluca Lucacel-Ciceo, Roxana Dudric, Razvan Hirian, Iulia Lupan, Oana Koblicska, Roxana Strimbu, Radu George Hategan, Dorina Simedru and Zorita Diaconeasa

Biomimetics 2025, 10(12), 824; https://doi.org/10.3390/biomimetics10120824 (registering DOI) - 9 Dec 2025

Abstract

In this research, aluminium-doped biphasic calcium phosphate (Al-BCP) was synthesized by co-precipitation and formulated with hydrolyzed collagen and acetylsalicylic acid (ASA) to yield composites designed as a new class of bone-regenerative biomaterials with enhanced biological performance. Undoped and Al-modified powders (5/10 wt% Al [...] Read more.

In this research, aluminium-doped biphasic calcium phosphate (Al-BCP) was synthesized by co-precipitation and formulated with hydrolyzed collagen and acetylsalicylic acid (ASA) to yield composites designed as a new class of bone-regenerative biomaterials with enhanced biological performance. Undoped and Al-modified powders (5/10 wt% Al precursor) were prepared at 40 °C (pH ~ 11) and calcined at 700 °C, and composites were produced at a 1:1:0.1 mass ratio (ceramic–collagen–ASA). Structure and chemistry were assessed by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) and Raman spectroscopies, and X-ray photoelectron spectroscopy (XPS). Morphology and elemental distribution were examined by scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDX). Biological performance was preliminarily evaluated using HaCaT (immortalized human keratinocytes) viability and antibacterial assays against Staphylococcus aureus and Escherichia coli. XRD confirmed a biphasic hydroxyapatite/β-tricalcium phosphate system and showed that Al incorporation shifted the phase balance toward hydroxyapatite (HAp fraction 54.8% in BCP vs. ~68.6–68.7% in Al-doped samples). FTIR/Raman preserved BCP vibrational signatures and revealed collagen/ASA bands in the composites. XPS/EDX verified the expected composition, including surface N 1s from organics and Al at ~2–5 at% for doped samples, with surface Ca/P ≈ 1.15–1.16. SEM revealed multigranular microstructures with homogeneous Al distribution. All composites were non-cytotoxic (≥70% viability); M_Al10_Col_ASA exceeded 90% viability at 12.5% dilution. Preliminary antibacterial assays against Gram-positive and Gram-negative strains showed modest, time-dependent reductions in CFU relative to controls. These results corroborate the compositional/structural profile and preliminary biological performance of Al-BCP–collagen–ASA composites as multifunctional bone tissue engineering materials that foster a bone-friendly microenvironment, warranting further evaluation for bone regeneration. Full article

(This article belongs to the Special Issue Advances in Bioceramics for Bone Regeneration: 2nd Edition)

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33 pages, 1099 KB

Open AccessReview

Targeting Cathepsins in Neurodegeneration: Biochemical Advances

by Francesca Di Matteo, Mariapia Vietri, Simone D’Alessio, Tania Ciaglia, Erica Federica Vestuto, Giacomo Pepe, Ornella Moltedo, Veronica Di Sarno, Simona Musella, Carmine Ostacolo, Fabio Cominelli, Pietro Campiglia, Alessia Bertamino, Maria Rosaria Miranda and Vincenzo Vestuto

Biomedicines 2025, 13(12), 3019; https://doi.org/10.3390/biomedicines13123019 (registering DOI) - 9 Dec 2025

Abstract

Background/Objectives: Cathepsins, lysosomal proteases crucial for neuronal proteostasis, mediate the clearance of misfolded and aggregated proteins. Their dysregulation is implicated in neurodegenerative and neuropsychiatric disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. These conditions are characterized by toxic protein accumulation and impaired [...] Read more.

Background/Objectives: Cathepsins, lysosomal proteases crucial for neuronal proteostasis, mediate the clearance of misfolded and aggregated proteins. Their dysregulation is implicated in neurodegenerative and neuropsychiatric disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases. These conditions are characterized by toxic protein accumulation and impaired clearance, which exacerbate cellular stress responses, including the unfolded protein response (UPR), oxidative damage, and mitochondrial dysfunction. This review aims to summarize current knowledge on cathepsin roles in these pathways and assess their therapeutic potential. Methods: A comprehensive literature review was conducted, focusing on recent in vitro and in vivo studies investigating cathepsin function, inhibition, and modulation. Mechanistic insights and pharmacological approaches targeting cathepsins were analyzed, with attention to challenges in translating preclinical findings to clinical settings. Results: Cathepsins demonstrate a dual role: their proteolytic activity supports neuronal health by degrading toxic aggregates, but altered or insufficient activity may worsen proteotoxic stress. Studies reveal that cathepsins regulate autophagy, apoptosis, and neuroinflammation both intracellularly and extracellularly. Despite promising mechanistic data, clinical translation is hindered by issues such as poor inhibitor selectivity, limited brain penetration, and variability across preclinical models. Conclusions: Targeting cathepsins presents a promising strategy for treating neurodegenerative and neuropsychiatric disorders, but significant challenges remain. Future research should focus on improving drug specificity and delivery, and on developing standardized models to better predict clinical outcomes. Full article

(This article belongs to the Special Issue New Horizons in Enzyme Inhibitor Discovery: Targets, Design and Evaluation)

25 pages, 1201 KB

Open AccessArticle

Temporal Variability of Arsenic in the Caplina Aquifer, La Yarada Los Palos, Peru: Implications for Risk-Based Drinking Water Management

by Luis Johnson Paúl Mori Sosa, Dante Ulises Morales Cabrera and Walter Dimas Florez Ponce De León

Sustainability 2025, 17(24), 11025; https://doi.org/10.3390/su172411025 (registering DOI) - 9 Dec 2025

Abstract

Arsenic (As) in groundwater often fluctuates around the 10 µg/L health-based guideline, complicating compliance assessment and risk-based management. This study investigates the short-term temporal behavior of As and its implications for compliance at three supply wells in the Caplina aquifer (La Yarada Los [...] Read more.

Arsenic (As) in groundwater often fluctuates around the 10 µg/L health-based guideline, complicating compliance assessment and risk-based management. This study investigates the short-term temporal behavior of As and its implications for compliance at three supply wells in the Caplina aquifer (La Yarada Los Palos, Tacna, Peru), based on a one-year fortnightly time series. At each visit, in situ electrical conductivity (EC), total dissolved solids (TDS), pH, and temperature were measured, and total As was determined by inductively coupled plasma–mass spectrometry (ICP–MS). The dataset was evaluated using robust descriptive statistics, exceedance proportions with Wilson 95% confidence intervals, Spearman rank correlations, simple time-series diagnostics, and comparisons of deterministic monthly schemes against the fortnightly reference. Exceedances were widespread—100% at Point 1 and 91.7% at Points 2 and 3—yielding 94.4% at the network scale, with no consistent seasonal signal. Relative variability was low yet operationally decisive (coefficient of variation (CV) ≈ 7–10%; interquartile range ≈ 1.3–1.6 µg/L), and typical fortnightly oscillations of ~0.5–1.5 µg/L were sufficient to flip compliance labels under monthly sampling. Point-wise associations were generally weak, except for a moderate As–TDS correlation at Point 1, supporting an interpretation dominated by geogenic As under arid, alkaline, and saline conditions, modulated by redox processes, anion competition, and mixing/pumping dynamics. The findings support risk-based monitoring with a fortnightly baseline and adaptive escalation when predefined activation criteria and action thresholds are met, using EC/TDS, pH, and simple redox indicators as operational early warnings. To reduce exposure in such settings, priority should be given to source management, pre-oxidation of As(III) to As(V), and adsorption onto iron media (or membranes where appropriate), while future work should integrate high-frequency sensing, in situ or inline speciation, reactive-transport modeling, and locally trained risk mapping to strengthen contributions to Sustainable Development Goals 3 (Good Health and Well-Being) and 6 (Clean Water and Sanitation). Full article

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