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20 pages, 2931 KiB

Open AccessArticle

Assessment of Biological Activity of Low Molecular Weight 1,4-Benzoquinone Derivatives

by Marija Bartolić, Ana Matošević, Nikola Maraković, Irena Novaković, Dušan Sladić, Suzana Žunec, Dejan Opsenica and Anita Bosak

Biomolecules 2025, 15(8), 1162; https://doi.org/10.3390/biom15081162 (registering DOI) - 14 Aug 2025

Abstract

In this paper, we aimed to evaluate whether simple, low molecular mass benzoquinone derivatives, featuring different substituents in para- and meta-position relative to the tert-butyl group, possess biological activities against major targets associated with Alzheimer’s disease. The 1,4-benzoquinone derivatives studied [...] Read more.

In this paper, we aimed to evaluate whether simple, low molecular mass benzoquinone derivatives, featuring different substituents in para- and meta-position relative to the tert-butyl group, possess biological activities against major targets associated with Alzheimer’s disease. The 1,4-benzoquinone derivatives studied herein inhibited both cholinesterases in the micromolar concentration range, generally showing a preference for butyrylcholinesterase over acetylcholinesterase; formed complexes with biometal ions Fe²⁺, Cu²⁺ and Zn²⁺; and displayed a certain BACE1 inhibition. Moreover, the tested compounds displayed certain antioxidant activity via either electron transfer or hydrogen atom transfer mechanisms. The antioxidant capacity of the unsubstituted tert-butyl-1,4-benzoquinone (compound 1) was three times lower than that of the standard antioxidant BHT, while 2,6-disubstituted derivatives (compounds 15 and 7) exhibited peroxyl radical scavenging activity comparable to that of Trolox. Taken together with in silico-predicted low toxicity, good intestinal absorption and favorable oral bioavailability, the presented 1,4-benzoquinone derivatives are promising scaffolds for the design of more complex molecules with enhanced cholinesterase and BACE1 inhibitory activity. Furthermore, they could serve as functional substituents in other structural scaffolds to combine and enhance their biological activities. Full article

(This article belongs to the Section Molecular Medicine)

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16 pages, 6065 KiB

Open AccessArticle

Bi-Allelic Loss-of-Function Variant in MAN1B1 Cause Rafiq Syndrome and Developmental Delay

by Liyu Zang, Yaoling Han, Qiumeng Zhang, Si Luo, Zhengmao Hu, Kun Xia, Ashfaque Ahmed and Qi Tian

Int. J. Mol. Sci. 2025, 26(16), 7820; https://doi.org/10.3390/ijms26167820 (registering DOI) - 14 Aug 2025

Abstract

Rafiq syndrome (RAFQS) is a rare autosomal recessive disorder that is classified as a type II congenital disorder of glycosylation (CDG-II), and caused by MAN1B1 gene mutation. To date, 24 pathogenic MAN1B1 mutations have been reported in association with MAN1B1-CDG. However, the underlying [...] Read more.

Rafiq syndrome (RAFQS) is a rare autosomal recessive disorder that is classified as a type II congenital disorder of glycosylation (CDG-II), and caused by MAN1B1 gene mutation. To date, 24 pathogenic MAN1B1 mutations have been reported in association with MAN1B1-CDG. However, the underlying pathogenic mechanisms remain poorly understood. In this study, we recruited a consanguineous family from Pakistan with multiple affected individuals exhibiting mild facial dysmorphism, developmental delay, and intellectual disability. Utilizing exome sequencing and homozygosity mapping, we identified a novel MAN1B1 mutation (c.772_775del) that co-segregated with RAFQS in this family. Analysis of public single-cell transcriptomic data revealed that MAN1B1 is predominantly expressed in dorsal progenitors and intermediate excitatory neurons during human brain development. Knockdown of Man1b1 in primarily cultured mouse excitatory neurons disrupted axon growth, dendrite formation, and spine maturation, and could not be rescued by truncated variants identified in the family. Furthermore, in utero, electroporation experiments revealed that Man1b1 knockdown in the murine cortex impaired neural stem cells’ proliferation and differentiation, as well as cortical neuron migration. Collectively, these findings elucidate a critical role for MAN1B1 in the etiology of RAFQS and demonstrate that loss-of-function mutation in MAN1B1 disrupt neuro-developmental processes, providing mechanistic insights into the pathogenesis of this disorder. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

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20 pages, 973 KiB

Open AccessReview

New Vaccine Introduction in Middle-Income Countries Across the Middle East and North Africa—Progress and Challenges

by Chrissy Bishop, Deeksha Parashar, Diana Kizza, Motuma Abeshu, Miloud Kaddar, Abdallah Bchir, Atef El Maghraby, Hannah Schirrmacher, Zicheng Wang, Ulla Griffiths, Shahira Malm, Sowmya Kadandale and Saadia Farrukh

Vaccines 2025, 13(8), 860; https://doi.org/10.3390/vaccines13080860 (registering DOI) - 14 Aug 2025

Abstract

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical [...] Read more.

Background/Objectives: The middle-income countries (MICs) in the Middle East and North Africa (MENA) region face multifaceted challenges—including fiscal constraints, conflict, and vaccine hesitancy—that impede the timely introduction of critical vaccines. This study examines the status, barriers, and facilitators to introducing three critical vaccines—human papillomavirus vaccine (HPV), pneumococcal conjugate vaccine (PCV), and rotavirus vaccine (RV)—across seven MENA MICs, to identify actionable solutions to enhance vaccine uptake and immunisation coverage. Methods: Using the READ methodology (ready materials, extract, analyse, and distil data), this review systematically analysed policy documents, reports, and the literature on the introduction of HPV, PCV, and RV vaccines in seven MENA MICs. A data extraction framework was designed to capture the status of vaccine introduction and barriers and facilitators to introduction. Findings and data gaps were validated with stakeholder consultations. Results: Of the seven study countries, progress in introducing PCV and RV has been uneven across the region (five countries have introduced PCV, four have introduced RV, and only a single country has introduced HPV at time of writing), hindered by vaccine hesitancy, fiscal challenges, and insufficient epidemiological data. Morocco is the only country to introduce all three vaccines, while Egypt has yet to introduce any. Other common barriers include the impact of conflict and displacement on healthcare infrastructure, delayed introduction due to the 2020 COVID-19 pandemic, and limited local production facilities and regional cooperation. In addition, not all countries eligible for Gavi MICs support have applied. These findings provide a roadmap for policymakers to accelerate equitable vaccine introduction in the MENA region. Conclusions: Targeted efforts, such as addressing fiscal constraints, improving local manufacturing, tackling gender barriers, and fostering public trust, paired with regional collaboration, can help bridge gaps and ensure no community is left behind in preventing vaccine-preventable diseases. Full article

(This article belongs to the Section Vaccines and Public Health)

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17 pages, 813 KiB

Open AccessReview

Kidney Stone Disease: Epigenetic Dysregulation in Homocystinuria and Mitochondrial Sulfur Trans-Sulfuration Ablation Driven by COVID-19 Pathophysiology

by Anmol Babbarwal, Mahavir Singh, Utpal Sen, Mahima Tyagi and Suresh C. Tyagi

Biomolecules 2025, 15(8), 1163; https://doi.org/10.3390/biom15081163 (registering DOI) - 14 Aug 2025

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought to light unexpected complications beyond respiratory illness, including effects on kidney function and a potential link to kidney stone disease (KSD). This review proposes a novel [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought to light unexpected complications beyond respiratory illness, including effects on kidney function and a potential link to kidney stone disease (KSD). This review proposes a novel framework connecting COVID-19-induced epigenetic reprogramming to disruptions in mitochondrial sulfur metabolism and the pathogenesis of kidney stones. We examine how SARS-CoV-2 interferes with host methylation processes, leading to elevated homocysteine (Hcy) levels and impairment of the trans-sulfuration pathway mechanisms particularly relevant in metabolic disorders such as homocystinuria. These epigenetic and metabolic alterations may promote specific kidney stone subtypes through disrupted sulfur and oxalate handling. Additionally, we explore the role of COVID-19-associated gut dysbiosis in increasing oxalate production and driving calcium oxalate stone formation. Together, these pathways may accelerate the transition from acute kidney injury (AKI) to chronic KSD, linking viral methylation interference, sulfur amino acid imbalance, mitochondrial dysfunction, and microbiota changes. Unlike earlier reviews that address these mechanisms separately, this work offers an integrated hypothesis to explain post-viral renal lithogenesis and highlights the potential of targeting sulfur metabolism and redox pathways as therapeutic strategies for KSD triggered or aggravated by viral infections such as COVID-19. Full article

(This article belongs to the Special Issue Acute Kidney Injury and Mitochondrial Involvement)

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14 pages, 6195 KiB

Open AccessArticle

Analysis of Groundwater Chemical Characteristics and Boron Sources in the Oasis Area of the Cherchen River Basin in Xinjiang, China

by Jiangwei Dong, Fuxiang Gao, Jinlong Zhou, Jiang Li and Yinzhu Zhou

Water 2025, 17(16), 2397; https://doi.org/10.3390/w17162397 (registering DOI) - 14 Aug 2025

Abstract

The oasis area of the Cherchen River Basin (OACRB) is located in the southeast edge of the Tarim Basin in Xinjiang, China. High boron (B) groundwater is observed in the OACRB according to 40 groundwater samples collected in May 2023. Identification of the [...] Read more.

The oasis area of the Cherchen River Basin (OACRB) is located in the southeast edge of the Tarim Basin in Xinjiang, China. High boron (B) groundwater is observed in the OACRB according to 40 groundwater samples collected in May 2023. Identification of the chemical characteristics and B sources of groundwater in the OACRB is of great significance for the sustainable development and utilization of groundwater resources and the protection of animals, plants and human health. To explore the chemical characteristics and main B sources of groundwater, Piper three-line diagram, Gibbs diagram, correlation analysis, hydrogeochemical simulation and absolute principal component analysis (PCA-APCS-MLR) were used for analysis. The contribution of different factors to groundwater B was quantitatively evaluated. The results showed that the groundwater is weakly alkaline (with an average pH of 7.94) and mainly brackish water and saline water with Cl⁻ and Na⁺ as the main anions and cations. The groundwater is dominated by SO₄ · Cl-Na type. The average concentration (ρ) of groundwater B in the study area was 1.48 mg·L⁻¹ with the over-standard rate was 45.0%. The APCS-MLR receptor model analysis revealed that groundwater chemical components including B were mainly derived from leaching-enrichment, human activity, primary geological factors, and unknown sources. Groundwater B is obviously greater than the standard limit, which is mainly due to agricultural activities (fertilizers and pesticides) and unknown sources. Full article

(This article belongs to the Topic The Hydrosphere in Crisis: Human Impact, Climate Change, and Pathways to Resilience, 2nd Edition)

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13 pages, 581 KiB

Open AccessArticle

Delayed vs. Concomitant Urethrectomy for Non-Metastatic Urothelial Carcinoma of the Urinary Bladder Undergoing Radical Cystectomy: Perioperative and Survival Outcomes from a Single Tertiary Centre in the United Kingdom

by Francesco Del Giudice, Mohamed Gad, Valerio Santarelli, Rajesh Nair, Yasmin Abu-Ghanem, Elsie Mensah, Ben Challacombe, Jonathan Kam, Youssef Ibrahim, Basil Lufti, Amir Khan, Akra Yeasmin, Kathryn Chatterton, Suzanne Amery, Katarina Spurna, Romerr Alao, Syed Ghazi Ali Kirmani, Felice Crocetto, Biagio Barone, Bernardo Rocco, Alessandro Sciarra, Benjamin I. Chung, Ramesh Thurairaja and Muhammad Shamim Khan Show full author list Hide full author list

J. Pers. Med. 2025, 15(8), 375; https://doi.org/10.3390/jpm15080375 (registering DOI) - 14 Aug 2025

Abstract

Introduction: The role of urethrectomy at the time of Robotic-Assisted or Open Radical Cystectomy (RARC, ORC) is controversial. Whether urethrectomy should be performed at the time of RARC/ORC or delayed up to a 3–6 month interval is unclear. We performed a retrospective cohort [...] Read more.

Introduction: The role of urethrectomy at the time of Robotic-Assisted or Open Radical Cystectomy (RARC, ORC) is controversial. Whether urethrectomy should be performed at the time of RARC/ORC or delayed up to a 3–6 month interval is unclear. We performed a retrospective cohort analysis of perioperative and survival outcomes in patients with high-risk NMIBCs or non-metastatic MIBCs at our institution who underwent either concomitant or deferred urethrectomy after RC. Materials and Methods: cTis-T1 or cT2-T4, N0-1, M0 BC patients who underwent RARC or ORC from 2009 to 2024 were reviewed. Clinical, demographic, tumour, and patient characteristics and perioperative variables were assessed across concomitant and delayed urethrectomy groups. Multivariate logistic analysis was performed to estimate the impact of significant variables on intraoperative and postoperative outcomes. Univariable Kaplan–Meier and multivariable Cox regression modelling was implemented to explore the relative effect of time of urethrectomy on progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Results: A total of n = 58 patients (n = 47 delayed vs. n = 11 concomitant) with similar demographic characteristics were included. The concomitant urethrectomy group experienced longer operative time and greater blood loss (379 ± 65 min and 430 ± 101 mL vs. 342 ± 82 min and 422 ± 125 mL, with p = 0.049 and p = 0.028, respectively). Hospital readmission rates were higher in the concomitant urethrectomy group (36.4% vs. 8.5%, p = 0.016; OR: 17.9; 95% CI 1.2–265; p = 0.036). In Cox regression analysis, the timing of urethrectomy had no influence on PFS, CSS, or OS (all p > 0.05). Conclusions: Our study suggests that urethrectomy can be safely deferred unless urothelial disease is clearly present pre- or intraoperatively without compromising survival outcome and with the advantage of reducing surgical morbidity at the time of RC. Full article

(This article belongs to the Special Issue Targeted Surgery and Artificial Intelligence in Personalized Medicine and Robotic Surgery: Current Challenges and Future Prospects)

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25 pages, 405 KiB

Open AccessArticle

Chemical Composition, Antioxidant and Antimicrobial Activity of Piper carpunya and Simira ecuadorensis: A Comparative Study of Four Extraction Methods

by María del Cisne Guamán-Balcázar, Diana Hualpa, Garlet Infante, Luis Luzuriaga, José Luis Riofrío, Anderli Jarro, Estefany Lopez, Verónica Salas-Gomez, Rómulo Salazar, Jorge F. Reyes and Miguel A. Meneses

Plants 2025, 14(16), 2526; https://doi.org/10.3390/plants14162526 (registering DOI) - 14 Aug 2025

Abstract

In this in vitro experimental study, we compared four extraction techniques -dynamic maceration (DME), ultrasound-assisted (UAE), microwave-assisted (MAE), and pressurized liquid extraction (PLE)- to obtain bioactive extracts from two native Ecuadorian plants, Piper carpunya and Simira ecuadorensis. The effect of extraction techniques was [...] Read more.

In this in vitro experimental study, we compared four extraction techniques -dynamic maceration (DME), ultrasound-assisted (UAE), microwave-assisted (MAE), and pressurized liquid extraction (PLE)- to obtain bioactive extracts from two native Ecuadorian plants, Piper carpunya and Simira ecuadorensis. The effect of extraction techniques was evaluated separately for each specie based on extraction yield, total phenolic content (TPC), antioxidant capacity (DPPH, ABTS, FRAP, and ORAC assays), antimicrobial activity, and chemical composition. All analyses were performed in triplicate and analyzed statistically (ANOVA, p < 0.05). UAE and MAE exhibited the highest extraction yield, while PLE provided extracts with the greatest TPC. However, UAE extracts, particularly for S. ecuadorensis, exhibited superior antioxidant capacity across assays. GC/MS analysis revealed alkanes as predominant constituents, along with minor phenolic and ester compounds. Antimicrobial activity was observed in both species, especially against Listeria monocytogenes and Pseudomonas aeruginosa, with UAE and MAE extracts being most effective. Compounds such as isoelemicin, phytol, and ethyl linolenate may contribute to the observed bioactivities. These findings highlight the potential of P. carpunya and S. ecuadorensis as natural sources of antioxidants and antimicrobials for food and pharmaceutical applications. Full article

(This article belongs to the Special Issue Analysis of Phenolic Compounds and Antioxidant Capacity in Native Plants: Characterization and Biological Effects)

26 pages, 3685 KiB

Open AccessArticle

Research on Parameter Optimization and Control Strategy of Air Source Heat Pump Coupled with Thermal Energy Storage System

by Xuan Liu, Wei Chen, Feng Li, Saisai Du, Ge Yao, Pengfei Zhang, Kaiwen Xu and Zhihua Wang

Buildings 2025, 15(16), 2870; https://doi.org/10.3390/buildings15162870 (registering DOI) - 14 Aug 2025

Abstract

The air source heat pump coupled with energy storage system is a key technology for flexibly utilizing clean energy. The capacity configuration parameters and control strategies of this coupled system are two important aspects that significantly affect its performance. In order to explore [...] Read more.

The air source heat pump coupled with energy storage system is a key technology for flexibly utilizing clean energy. The capacity configuration parameters and control strategies of this coupled system are two important aspects that significantly affect its performance. In order to explore the methods of setting configuration parameters and provide reasonable operation strategies, a simulation model of the coupled system under a time-of-use electricity pricing strategy is established and verified with measured data. Through multi-objective optimization of the system, configuration schemes considering economy, energy saving, and flexibility are given. Subsequently, based on the load prediction model, an optimal control strategy is proposed with the objective function of minimizing the operating cost. The optimization amplitude of the schemes considering the three indicators reached 11.09%, 13.37%, and 29.03%, respectively. Under the proposed control strategies, the typical daily electricity consumption decreased by 14.65% to 24.06%, and the operating electricity cost is saved by approximately 17.32%. By reasonably designing the parameters of the coupled system, its economic, energy-saving performance, and flexibility can be improved by more than 11% compared to a system designed using traditional methods. By adopting the control strategy based on hourly load prediction, the operating cost can be reduced significantly. Full article

(This article belongs to the Special Issue Performance Analysis and Design Optimization of Renewable Energy Heating Systems)

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19 pages, 310 KiB

Open AccessArticle

Novel Finite Sum Identities Involving Reciprocals of Binomial Coefficients

by Necdet Batır and Junesang Choi

Symmetry 2025, 17(8), 1318; https://doi.org/10.3390/sym17081318 (registering DOI) - 14 Aug 2025

Abstract

Finite sums involving reciprocals of binomial coefficients have long intrigued mathematicians, owing to their elegant structure and unexpected identities. In this work, we present a comprehensive general formula that unifies and extends several results previously studied in the literature. To demonstrate the breadth [...] Read more.

Finite sums involving reciprocals of binomial coefficients have long intrigued mathematicians, owing to their elegant structure and unexpected identities. In this work, we present a comprehensive general formula that unifies and extends several results previously studied in the literature. To demonstrate the breadth and utility of our approach, we also investigate a variety of significant special cases, shedding light on deeper patterns and connections. This unified perspective aims to appeal to researchers interested in combinatorics, number theory, and special functions. Full article

(This article belongs to the Special Issue Symmetries of Difference Equations, Special Functions and Orthogonal Polynomials: 3rd Edition)

41 pages, 974 KiB

Open AccessReview

Confronting Melanoma Radioresistance: Mechanisms and Therapeutic Strategies

by Ielizaveta Gorodetska, Alexander Schulz, Gerhard Behre and Anna Dubrovska

Cancers 2025, 17(16), 2648; https://doi.org/10.3390/cancers17162648 (registering DOI) - 14 Aug 2025

Abstract

Melanoma is a highly aggressive skin cancer with survival rates varying significantly based on stage and genomic characteristics. While localized melanoma has favorable outcomes, metastatic melanoma is associated with poor prognosis and limited treatment options. Radiotherapy (RT), one of the most commonly used [...] Read more.

Melanoma is a highly aggressive skin cancer with survival rates varying significantly based on stage and genomic characteristics. While localized melanoma has favorable outcomes, metastatic melanoma is associated with poor prognosis and limited treatment options. Radiotherapy (RT), one of the most commonly used cancer treatments, is less effective in melanoma due to its intrinsic radioresistance. This review discusses the current knowledge about the biological mechanisms contributing to melanoma radioresistance, including the role of cancer stem cells (CSCs), DNA repair mechanisms, hypoxia, altered metabolism, and melanin production. It also examines preclinical and clinical studies on novel therapeutic approaches, such as targeting CSC pathways, inhibiting DNA repair, modulating hypoxia-induced metabolic shifts, and combining RT with immunotherapies or targeted therapies. Promising strategies, such as RT-induced immune responses and advanced RT techniques, show the potential to overcome resistance. However, melanoma’s heterogeneity and the limited clinical validation of these approaches remain significant challenges. Integrated therapeutic strategies targeting the multifaceted mechanisms of melanoma radioresistance are essential to improve treatment outcomes. Further clinical validation and personalized approaches are needed to address the heterogeneity of melanoma and enhance the efficacy of novel interventions. Full article

(This article belongs to the Special Issue Emerging Paradigms for Cancer Therapy: Promises and Challenges)

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15 pages, 1864 KiB

Open AccessArticle

Interaction Between Two Independent Chaotic Neural Networks Installed in the Motion Control Systems of Two Roving Robots

by Shigetoshi Nara, Naoya Miyahara, Yutaka Yamaguti and Ichiro Tsuda

Dynamics 2025, 5(3), 32; https://doi.org/10.3390/dynamics5030032 (registering DOI) - 14 Aug 2025

Abstract

The high-dimensional chaos generated in a neural network consisting of pseudo-neuron devices invented by one of the authors (S.N.) has been successfully applied to control the complex motion of a roving robot, e.g., to solve a maze, as reported in the previous papers. [...] Read more.

The high-dimensional chaos generated in a neural network consisting of pseudo-neuron devices invented by one of the authors (S.N.) has been successfully applied to control the complex motion of a roving robot, e.g., to solve a maze, as reported in the previous papers. On the basis of successful works and the concept that chaos plays important functional roles in biological systems, in the present paper, we report new experiments to show the functional aspects of chaos via behavioral interactions in an ill-posed context and solve problems with chaotic neural networks. Explicitly, experiments on two roving robots in a maze (labyrinth) are reported, in which both seek to catch each other or one chases and the other flees, mimicking the survival activities of insects in natural environments. The two-dimensional robot motion is controlled with motion control systems, each of which is equipped with a chaotic neural network to generate autonomous and adaptive actions depending on sensor inputs of obstacles and/or target detection information including uncertainty. We report both computer experiments and practical hardware implementations, where for the latter, only the chaotic neural network is run on a desktop computer, the motion signals are coded into two-dimensional space, and sensor signals are transferred via Bluetooth device between robots and computers. Full article

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26 pages, 6989 KiB

Open AccessArticle

Model-Based and Data-Driven Global Optimization of Rainbow-Trapping Mufflers

by Cédric Maury, Teresa Bravo, Daniel Mazzoni, Muriel Amielh and Antonio J. Reinoso

Technologies 2025, 13(8), 356; https://doi.org/10.3390/technologies13080356 (registering DOI) - 14 Aug 2025

Abstract

Compared to rigidly-backed absorbers, the selection of appropriate optimization techniques for the optimal design of broadband acoustic mufflers remains under-investigated. This study determines the most effective optimization strategy for maximizing the total dissipation of rainbow-trapping silencers (RTSs), composed of graded side-branch cavities that [...] Read more.

Compared to rigidly-backed absorbers, the selection of appropriate optimization techniques for the optimal design of broadband acoustic mufflers remains under-investigated. This study determines the most effective optimization strategy for maximizing the total dissipation of rainbow-trapping silencers (RTSs), composed of graded side-branch cavities that enable broadband dissipation of sound through visco-thermal effects. Model-based and data-driven optimization strategies are compared, particularly in high-dimensional design spaces with flat cost function landscapes where gradient-based approaches are inadequate. It is found that model-based particle swarm optimization (PSO) outperforms simulated annealing, genetic algorithm, and surrogate method in maximizing RTS total dissipation, especially in high-dimensional designs. PSO uniquely handles flat or valleyed cost landscapes through efficient exploration–exploitation trade-offs. Data-driven approaches using Bayesian regularization neural networks (BRNNs) drastically reduce computational cost in high-dimensional spaces, though they require large datasets to avoid over-smoothing. In low dimensions, direct optimization on BRNN outputs suffices, making global search unnecessary. Both model-based and BRNN methods show robustness to input errors, but data-driven approaches handle output noise better. These findings, validated using transfer matrix models, offer strategic guidance for selecting optimization methods, especially when using computationally expensive visco-thermal finite element simulations. Full article

(This article belongs to the Section Environmental Technology)

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16 pages, 964 KiB

Open AccessArticle

Intersection Between Eco-Anxiety and Lexical Labels: A Study on Mental Health in Spanish-Language Digital Media

by Alicia Figueroa-Barra, David Guerrero-Mardones, Camila Vargas-Castillo, Luis Millalonco-Martínez, Angel Roco-Videla, Emmanuel Méndez and Sergio Flores-Carrasco

Behav. Sci. 2025, 15(8), 1102; https://doi.org/10.3390/bs15081102 (registering DOI) - 14 Aug 2025

Abstract

Background: Eco-anxiety and solastalgia are psychological responses to environmental degradation and climate change. This study examines how these concepts are represented in Spanish-language digital media, considering both emotional dimensions and the profiles of content producers. Methods: We conducted an inductive qualitative content analysis [...] Read more.

Background: Eco-anxiety and solastalgia are psychological responses to environmental degradation and climate change. This study examines how these concepts are represented in Spanish-language digital media, considering both emotional dimensions and the profiles of content producers. Methods: We conducted an inductive qualitative content analysis of 120 Spanish-language items (online news articles and selected posts from digital platforms) published between October 2023 and March 2024. Items were identified using a Boolean search strategy and initially filtered by LIWC to detect high emotional-and-anxiety term density; final coding followed grounded-theory procedures, resulting in four thematic categories. Results: The most frequent theme was environmental activism (41%), followed by catastrophic thinking (29%), coping strategies (25%), and loss of meaningful places (6%). Among content producers, citizen participants represented 40%, youth activists 25%, and scientists 15%. Digital media function both as sources of anxiety-inducing content and as spaces for awareness-raising and support. Conclusions: While eco-anxiety is not a clinical diagnosis, it exerts a significant psychological impact—particularly on youth and vulnerable groups. Spanish-language digital platforms play an ambivalent role, amplifying distress yet enabling resilience and collective action. Future interventions should leverage these channels to foster environmental awareness, emotional resilience, and civic engagement. Full article

(This article belongs to the Special Issue Mental Health and the Natural Environment)

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12 pages, 627 KiB

Open AccessArticle

Relationship Between Total 25-Hydroxyvitamin D and Parathyroid Hormone Concentrations During Early Gestation in Indian Women

by Nandini Chopra, Fathima Ayoob, Roopashree C, Shashikala Karanth, Manjula Harish, Annamma Thomas, Vasista Adiga, Annapurna Vyakarnam, Catherine Hawrylowicz, Anura V. Kurpad and Pratibha Dwarkanath

Nutrients 2025, 17(16), 2626; https://doi.org/10.3390/nu17162626 (registering DOI) - 14 Aug 2025

Abstract

Background: A high prevalence of vitamin D deficiency (VDD) during early pregnancy has been reported globally, along with a high risk of adverse pregnancy and birth outcomes. The present cut-off to diagnose VDD during pregnancy is <20 ng/mL of serum 25-hydroxyvitamin-D (25(OH)D) concentration, [...] Read more.

Background: A high prevalence of vitamin D deficiency (VDD) during early pregnancy has been reported globally, along with a high risk of adverse pregnancy and birth outcomes. The present cut-off to diagnose VDD during pregnancy is <20 ng/mL of serum 25-hydroxyvitamin-D (25(OH)D) concentration, but there is a lack of consensus on this value. We evaluated this diagnostic cut-off specifically during early pregnancy among apparently healthy Indian women. Methods: Demographic details, obstetrics history, anthropometric measurements, and blood samples were collected from 395 apparently healthy pregnant Indian women at ≤14 weeks of gestation, after obtaining written informed consent. The inverse relationship between 25(OH)D and parathyroid hormone (PTH) concentrations was examined to define the breakpoint at which PTH was maximally suppressed using a segmented regression analysis. Covariate exposures associated with VDD were also examined. Results: The breakpoint at which a sharp increase in PTH was observed in response to decreasing 25(OH)D concentrations occurred at 15.76 ng/mL (95%CI: 12.3–19.2; p < 0.001). Using this diagnostic threshold, 66.1% of pregnant women were VDD compared to 82.0% when using the present cut-off. Statistically significant associations between VDD and parity (p = 0.011), season (winter: p = 0.001; post-monsoon: p < 0.001), anemia status (p = 0.044), and physical activity (p = 0.045) were also found. Conclusions: Our diagnostic cut-off for VDD, derived from PTH regulation in early pregnancy, is lower than the currently recommended threshold. Although assessing vitamin D status may be challenging due to the influence of modifiable and non-modifiable factors such as parity, anemia, season, and physical activity. These findings underscore the need to re-evaluate existing cut-offs through well-designed longitudinal studies to prove causality between this threshold and adverse pregnancy outcomes. Full article

(This article belongs to the Section Nutrition and Public Health)

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13 pages, 431 KiB

Open AccessSystematic Review

The Role of lncRNAs in Complicated Pregnancy: A Systematic Review

by Antonio Cerillo, Rossella Molitierno, Pasquale De Franciscis, Debora Damiana Nunziata, Mario Fordellone, Carlo Capristo, Maria Maddalena Marrapodi, Andrea Etrusco, Antonio Simone Laganà and Marco La Verde

Genes 2025, 16(8), 959; https://doi.org/10.3390/genes16080959 (registering DOI) - 14 Aug 2025

Abstract

Background/Objectives: Long non-coding RNAs (lncRNAs) play a crucial role in trophoblast invasion, immune tolerance, and placental angiogenesis. To delineate their diagnostic and pathological significance, we critically evaluated the evidence for correlations between circulating or placental lncRNA profiles with pregnancy complications. Methods: Five databases [...] Read more.

Background/Objectives: Long non-coding RNAs (lncRNAs) play a crucial role in trophoblast invasion, immune tolerance, and placental angiogenesis. To delineate their diagnostic and pathological significance, we critically evaluated the evidence for correlations between circulating or placental lncRNA profiles with pregnancy complications. Methods: Five databases were searched from inception through September 2024. We included only the studies that assessed the expression of the lncRNA-complicated pregnancies versus a control group. Results: Three single-center case–control studies fulfilled the inclusion criteria. Eight serum lncRNAs that present <20 weeks of gestation were elevated in subsequent pregnancy-induced hypertension or preeclampsia. The three lncRNAs in intrahepatic cholestasis of pregnancy were consistently decreased with a negative correlation with bile acids. Gestational diabetes was characterized by the elevation of MALAT1. Conclusions: Different lncRNAs showed a potential for use as non-invasive markers as well as for risk stratification for pregnancy-induced hypertension or preeclampsia, metabolic, and hepatobiliary pregnancy complications. There is a need for large-scale, multi-ethnic, prospective cohorts to include lncRNA as screening or therapeutic targeting in obstetric practice. Full article

(This article belongs to the Section RNA)

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15 pages, 2140 KiB

Open AccessArticle

B-Mode Ultrasound May Be an Early Marker in Acute Kidney Injury

by André Luiz Sampaio Fernandes, Fernanda Gosuen Gonçalves Dias, Marcela Aldrovani Rodrigues, Ewaldo de Mattos-Junior, Alef Winter Alvarenga, Maria Eduarda Raffaini de Oliveira Cunha, Marjury Cristina Maronesi and Leandro Zuccolotto Crivellenti

Diagnostics 2025, 15(16), 2034; https://doi.org/10.3390/diagnostics15162034 (registering DOI) - 14 Aug 2025

Abstract

Background/Objectives: This study evaluated the applicability of B-mode ultrasound, Doppler, and elastography in the early diagnosis of non-azotemic acute kidney injury (AKI) in rats induced with cyclophosphamide. Methods: The prospective, randomized, and blinded experiment involved groups receiving cyclophosphamide (CG, n = 12) and [...] Read more.

Background/Objectives: This study evaluated the applicability of B-mode ultrasound, Doppler, and elastography in the early diagnosis of non-azotemic acute kidney injury (AKI) in rats induced with cyclophosphamide. Methods: The prospective, randomized, and blinded experiment involved groups receiving cyclophosphamide (CG, n = 12) and saline (control, SG, n = 9). Serum biomarkers (urea, creatinine, and symmetric dimethylarginine) were assessed, along with renal histological analysis to classify AKI severity and distribution. Results: B-mode ultrasound revealed a significantly higher corticomedullary ratio at 24 and 72 h and increased renal width at 48 h in the cyclophosphamide group compared to controls. Biochemical analyses showed no significant differences between groups in early stages. Although B-mode ultrasound detected early morphological changes—specifically in corticomedullary ratio and renal size—Doppler and elastography demonstrated limited diagnostic utility in early AKI detection. Conclusions: Overall, B-mode ultrasound provided valuable early indicators of renal injury, whereas Doppler and elastography showed minimal clinical benefit at this stage. Full article

(This article belongs to the Special Issue Advances in the Diagnosis and Management of Kidney Diseases—2nd Edition)

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14 pages, 464 KiB

Open AccessArticle

The Relationship Between Men’s Self-Perceived Attractiveness and Ratings of Women’s Sexual Intent

by Peter O. Rerick, Tyler N. Livingston and Jonathan Singer

Behav. Sci. 2025, 15(8), 1101; https://doi.org/10.3390/bs15081101 (registering DOI) - 14 Aug 2025

Abstract

Sexual and romantic partners tend to match on various dimensions of mate value including physical attractiveness. Men may be motivated to inflate their self-perceived physical attractiveness to justify pursuing highly attractive women. In the present research, heterosexual men (N = 180) received [...] Read more.

Sexual and romantic partners tend to match on various dimensions of mate value including physical attractiveness. Men may be motivated to inflate their self-perceived physical attractiveness to justify pursuing highly attractive women. In the present research, heterosexual men (N = 180) received random assignment to a two-way between-participants factorial design that tested the effects of a woman’s physical attractiveness (low vs. high) and the recipient of her ambiguous sexual behavior (the participant himself or another man) on men’s ratings of her sexual intent. Participants rated that attractive women had greater sexual intent compared to unattractive women, but only when the participant himself was the recipient of women’s behavior. Men’s self-perceived physical attractiveness did not vary as a function of the woman’s physical attractiveness except when another man was the recipient of a physically attractive woman’s behavior, which reduced men’s perceptions of their physical attractiveness. Findings suggested that men’s self-perceptions and women’s appearance may bias men’s sexual judgment. Full article

(This article belongs to the Special Issue Psychology of Mate Choice, Romantic Relationships and Sexuality)

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43 pages, 3473 KiB

Open AccessReview

Biochips on the Move: Emerging Trends in Wearable and Implantable Lab-on-Chip Health Monitors

by Nikolay L. Kazanskiy, Pavel A. Khorin and Svetlana N. Khonina

Electronics 2025, 14(16), 3224; https://doi.org/10.3390/electronics14163224 (registering DOI) - 14 Aug 2025

Abstract

Wearable and implantable Lab-on-Chip (LoC) biosensors are revolutionizing healthcare by enabling continuous, real-time monitoring of physiological and biochemical parameters in non-clinical settings. These miniaturized platforms integrate sample handling, signal transduction, and data processing on a single chip, facilitating early disease detection, personalized treatment, [...] Read more.

Wearable and implantable Lab-on-Chip (LoC) biosensors are revolutionizing healthcare by enabling continuous, real-time monitoring of physiological and biochemical parameters in non-clinical settings. These miniaturized platforms integrate sample handling, signal transduction, and data processing on a single chip, facilitating early disease detection, personalized treatment, and preventive care. This review comprehensively explores recent advancements in LoC biosensing technologies, emphasizing their application in skin-mounted patches, smart textiles, and implantable devices. Key innovations in biocompatible materials, nanostructured transducers, and flexible substrates have enabled seamless integration with the human body, while fabrication techniques such as soft lithography, 3D printing, and MEMS have accelerated development. The incorporation of nanomaterials significantly enhances sensitivity and specificity, supporting multiplexed and multi-modal sensing. We examine critical application domains, including glucose monitoring, cardiovascular diagnostics, and neurophysiological assessment. Design considerations related to biocompatibility, power management, data connectivity, and long-term stability are also discussed. Despite promising outcomes, challenges such as biofouling, signal drift, regulatory hurdles, and public acceptance remain. Future directions focus on autonomous systems powered by AI, hybrid wearable–implantable platforms, and wireless energy harvesting. This review highlights the transformative potential of LoC biosensors in shaping the future of smart, patient-centered healthcare through continuous, minimally invasive monitoring. Full article

(This article belongs to the Special Issue Lab-on-Chip Biosensors)

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10 pages, 411 KiB

Open AccessArticle

Statin Treatment for Reducing Mortality Risk in Individuals over 75 Years of Age: A Large-Scale Retrospective Analysis

by Noy Nachmias, Sher Matsri, Maisaa Sharary, Noam Yaniv, Tal Netser, Assaf Buch, Yona Greenman, Elena Izkhakov and Eugene Feigin

J. Clin. Med. 2025, 14(16), 5739; https://doi.org/10.3390/jcm14165739 (registering DOI) - 14 Aug 2025

Abstract

Background: Despite the worldwide increase in life expectancy, individuals aged 75 years and older with an unknown history of cardiovascular disease often receive suboptimal statin treatment for primary prevention, reflecting uncertainties regarding statin efficacy and safety in this aging group. We aimed [...] Read more.

Background: Despite the worldwide increase in life expectancy, individuals aged 75 years and older with an unknown history of cardiovascular disease often receive suboptimal statin treatment for primary prevention, reflecting uncertainties regarding statin efficacy and safety in this aging group. We aimed to assess the impact of statin treatment on all-cause mortality among individuals aged 75 years and older without prior cardiovascular diagnoses. Methods: This retrospective study utilized real-world data from a large cohort of individuals aged 75 years and older who were treated as outpatients in or were admitted to the Tel Aviv Sourasky Medical Center. Extracted variables included demographic details, Charlson Comorbidity Index (CCI), chronic medication regimens, mortality outcomes and blood test results (high-density lipoprotein, low-density lipoprotein and creatinine). Patients with a prior diagnosis of angina, myocardial infarction or stroke were excluded from the study. Results: A total of 98,502 patients were included in the study, of whom 37,171 (mean age 80.67 ± 4.73 years) were treated with statins and 6804 (18.3%) of the latter patients were aged 85 years and above. The majority of the statin-treated patients (72.6%) had received high-intensity statins. The non-statin-treated group comprised 61,331 subjects with a mean age of 82.69 ± 5.77 years, of whom 19,253 (31.39%) were aged 85 years and above. The risk of all-cause mortality was significantly lower in the statin-treated group compared to the non-statin-treated group (adjusted odds ratio [aOR] 0.715, 95% confidence interval [CI] [0.671–0.761], p < 0.001). This trend persisted after stratification for age 85 years and above (aOR 0.7, 95% CI [0.606–0.809], p < 0.001), and for a low CCI (≤4) or a high CCI (>4) score (aOR 0.766, 95% CI [0.708–0.803]; aOR 0.648, 95% CI [0.585–0.717], respectively, p < 0.001). Conclusions: Provision of statin therapy contributes to a reduction in risk of all-cause mortality in individuals aged 75 years and above who have an unknown history of cardiovascular disease, regardless of the type of statin or the patient’s CCI score. Full article

(This article belongs to the Section Geriatric Medicine)

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15 pages, 2344 KiB

Open AccessArticle

Design and Verification of Beam Diagnostics System for Pepper-Pot Method

by Xianfang Bao, Peng Lu, Renli Zhu, Yuzhong Qian, Lizhen Liang and Lan Tian

Appl. Sci. 2025, 15(16), 8952; https://doi.org/10.3390/app15168952 (registering DOI) - 14 Aug 2025

Abstract

The pepper-pot method is a beam diagnostics technique used to measure the transverse beam profile, divergence angle, and envelope in particle accelerators. However, its practical application faces challenges, such as insufficient point recognition accuracy and signal quality degradation in complex environments. Based on [...] Read more.

The pepper-pot method is a beam diagnostics technique used to measure the transverse beam profile, divergence angle, and envelope in particle accelerators. However, its practical application faces challenges, such as insufficient point recognition accuracy and signal quality degradation in complex environments. Based on the Boron Neutron Capture Therapy (BNCT) facility at the Hefei Comprehensive National Science Center—Energy Research Institute (Anhui Energy Laboratory), this study developed an improved pepper-pot beam diagnostics system to optimize the beam quality of the accelerator ion source. The key innovation is adaptive threshold segmentation for spot segmentation, and the experimental results indicate that the enhanced image segmentation method outperforms traditional methods in terms of segmentation accuracy and robustness. Full article

(This article belongs to the Section Applied Physics General)

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13 pages, 1290 KiB

Open AccessSystematic Review

Immunogenicity as a Predictor of Influenza Vaccine Efficacy: A Systematic Review

by André Miguel Martins, Luis Félix Valero Juan, Marlene Santos and João P. Martins

Vaccines 2025, 13(8), 859; https://doi.org/10.3390/vaccines13080859 (registering DOI) - 14 Aug 2025

Abstract

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy [...] Read more.

Background/Objectives: Influenza represents a significant burden on global public health, and vaccination is the most effective strategy to reduce it. The large investment in vaccination programs and the need for adjustments in vaccine serotypes are important reasons for evaluating the influenza vaccine’s efficacy every year. Establishing a relationship between immunogenicity data and efficacy is also crucial for predicting the efficacy of a vaccine during its development. Antibody response measurement is one of the most common methods for evaluating immunogenicity, particularly in vaccines and biologics. The aim of this systematic review was to define a model that relates the immunogenicity of a given vaccine to its efficacy, based on hemagglutination inhibition titer levels. Methods: To achieve this goal, information was gathered from articles linking immunogenicity with the efficacy of the influenza vaccine in the Medline and Scopus databases. Different mathematical models were developed and applied to assess the relationship between HAI titers and the effectiveness of the flu vaccine. This analysis was conducted for the various existing vaccines, for the different influenza virus strains, and for their efficacy in paediatric populations. Results: The r² obtained ranged from 0.2579 to 0.966, which points to the importance of this immunological factor in the efficacy of the influenza vaccine. Conclusions: The efficacy values for titer level 40 confirm the validity of the data provided by Hobson. Full article

(This article belongs to the Special Issue Influenza Virus Vaccines and Vaccination)

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19 pages, 1620 KiB

Open AccessArticle

Impact of Water Velocity on Litopenaeus vannamei Behavior Using ByteTrack-Based Multi-Object Tracking

by Jiahao Zhang, Lei Wang, Zhengguo Cui, Hao Li, Jianlei Chen, Yong Xu, Haixiang Zhao, Zhenming Huang, Keming Qu and Hongwu Cui

Fishes 2025, 10(8), 406; https://doi.org/10.3390/fishes10080406 (registering DOI) - 14 Aug 2025

Abstract

In factory-controlled recirculating aquaculture systems, precise regulation of water velocity is crucial for optimizing shrimp feeding behavior and improving aquaculture efficiency. However, quantitative analysis of the impact of water velocity on shrimp behavior remains challenging. This study developed an innovative multi-objective behavioral analysis [...] Read more.

In factory-controlled recirculating aquaculture systems, precise regulation of water velocity is crucial for optimizing shrimp feeding behavior and improving aquaculture efficiency. However, quantitative analysis of the impact of water velocity on shrimp behavior remains challenging. This study developed an innovative multi-objective behavioral analysis framework integrating detection, tracking, and behavioral interpretation. Specifically, the YOLOv8 model was employed for precise shrimp detection, ByteTrack with a dual-threshold matching strategy ensured continuous individual trajectory tracking in complex water environments, and Kalman filtering corrected coordinate offsets caused by water refraction. Under typical recirculating aquaculture system conditions, three water circulation rates (2.0, 5.0, and 10.0 cycles/day) were established to simulate varying flow velocities. High-frequency imaging (30 fps) was used to simultaneously record and analyze the movement trajectories of Litopenaeus vannamei during feeding and non-feeding periods, from which two-dimensional behavioral parameters—velocity and turning angle—were extracted. Key experimental results indicated that water circulation rates significantly affected shrimp movement velocity but had no significant effect on turning angle. Importantly, under only the moderate circulation rate (5.0 cycles/day), the average movement velocity during feeding was significantly lower than during non-feeding periods (p < 0.05). This finding reveals that moderate water velocity constitutes a critical hydrodynamic window for eliciting specific feeding behavior in shrimp. These results provide core parameters for an intelligent Litopenaeus vannamei feeding intensity assessment model based on spatiotemporal graph convolutional networks and offer theoretically valuable and practically applicable guidance for optimizing hydrodynamics and formulating precision feeding strategies in recirculating aquaculture systems. Full article

(This article belongs to the Special Issue Application of Artificial Intelligence in Aquaculture)

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23 pages, 2768 KiB

Open AccessArticle

Nonlinear Algebraic Parameter Estimation of Doubly Fed Induction Machine Based on Rotor Current Falling Curves

by Alexander Glazyrin, Dmitriy Bunkov, Evgeniy Bolovin, Yusup Isaev, Vladimir Kopyrin, Sergey Kladiev, Alexander Filipas, Sergey Langraf, Rustam Khamitov, Vladimir Kovalev, Evgeny Popov, Semen Popov and Marina Deneko

Energies 2025, 18(16), 4316; https://doi.org/10.3390/en18164316 (registering DOI) - 14 Aug 2025

Abstract

Currently, wind turbines utilize doubly fed induction machines that incorporate a frequency converter in the rotor circuit to manage slip energy. This setup ensures a stable voltage amplitude and frequency that align with the alternating current. It is crucial to accurately determine the [...] Read more.

Currently, wind turbines utilize doubly fed induction machines that incorporate a frequency converter in the rotor circuit to manage slip energy. This setup ensures a stable voltage amplitude and frequency that align with the alternating current. It is crucial to accurately determine the parameters of the equivalent circuit from the rotor side of the vector control system of the frequency converter. The objective of this study is to develop a method for the preliminary identification of the doubly fed induction machines parameters by analyzing the rotor current decay curves using Newton’s method. The numerical estimates of the equivalent circuit parameters a doubly fed induction machines with a fixed short-circuited rotor are obtained during the validation of the results on a real plant. It is along with the integral errors of deviation between the experimental rotor current decay curve and the response of the adaptive regression model. The integral errors do not exceed 4% in nearly all sections of the curves. It is considered acceptable in engineering practice. The developed algorithm for the preliminary identification for the parameters of the doubly fed induction machines substitution scheme can be applied with the configuring machines control systems, including a vector control system. Full article

(This article belongs to the Special Issue Advanced Control Strategies for Multiphase Induction Generators: Design, Optimization, and Application 2024)

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16 pages, 487 KiB

Open AccessReview

TNFR2 Agonism: Basic Science and Promising Treatment for Multiple Sclerosis and Related Diseases

by Denise L. Faustman, Miriam Davis and Willem M. Kuhtreiber

Int. J. Mol. Sci. 2025, 26(16), 7839; https://doi.org/10.3390/ijms26167839 (registering DOI) - 14 Aug 2025

Abstract

The three pathological hallmarks of multiple sclerosis (MS) are inflammation, demyelination, and progressive neurodegeneration. None of the approved disease-modifying therapies for MS counters all three pathologies, and, more specifically, none is approved for neuroprotection. Axonal loss is the most significant contributor to chronic [...] Read more.

The three pathological hallmarks of multiple sclerosis (MS) are inflammation, demyelination, and progressive neurodegeneration. None of the approved disease-modifying therapies for MS counters all three pathologies, and, more specifically, none is approved for neuroprotection. Axonal loss is the most significant contributor to chronic and irreversible disability in MS. A tantalizing molecular target has emerged to uniquely counter all three MS pathologies: tumor necrosis factor receptor 2 (TNFR2). Agonism or activation of TNFR2 has been shown in MS models to induce immunosuppression, oligodendrocyte precursor differentiation, and neuroprotection. Further, in basic science studies stemming from the past 15 years, TNFR2 agonism is known to be a strong inducer of T-regulatory cells (Tregs). Treg cells, and especially those expressing TNFR2, are known to confer the strongest suppression per cell type. TNFR2 is even more attractive as a therapeutic target because of its restricted expression by only a handful of CNS and immune cell subsets, thereby minimizing the likelihood of systemic and other adverse effects. Recent antibody design work suggests many of the hurdles of Treg agonism may have been overcome. This review covers the current treatment landscape for MS, the basic science of TNFR2, the rationale for and evidence behind TNFR2 agonism to treat multiple sclerosis, the design of potent TNFR2 agonist antibodies, and the treatment applications for other neurological, autoimmune, or inflammatory diseases. Full article

(This article belongs to the Special Issue Pathophysiological Insights, Biomarkers and New Therapeutic Strategies in Immune-Mediated Disorders and Neurodegenerative Diseases)

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10 pages, 2113 KiB

Open AccessArticle

Generation of 27 nm Spectral Bandwidth, Two-Port Output Pulses Directly from a Yb-Doped Fiber Laser

by Junyu Chen, Mengyun Hu, Jianing Chen, Chixuan Zou, Zichen Zhao, Gantong Zhong and Shuai Yuan

Photonics 2025, 12(8), 812; https://doi.org/10.3390/photonics12080812 (registering DOI) - 14 Aug 2025

Abstract

We reported on a generation of 27 nm spectral bandwidth, two-port output ultrashort pulses directly from an all-normal-dispersion passively mode-locked Yb-fiber laser. Based on the nonlinear polarization rotation (NPR) mode-locking technique, high pump power and optical devices with high damage thresholds were introduced [...] Read more.

We reported on a generation of 27 nm spectral bandwidth, two-port output ultrashort pulses directly from an all-normal-dispersion passively mode-locked Yb-fiber laser. Based on the nonlinear polarization rotation (NPR) mode-locking technique, high pump power and optical devices with high damage thresholds were introduced to achieve broad spectral bandwidth and strong output power. The dual wavelengths were emitted from the clockwise and counterclockwise ports, respectively, and self-started mode-locking was achieved. The bidirectional output laser generates stable pulses with up to 223.5 mW average power at a 46.04 MHz repetition rate, corresponding to a pulse energy of 5 nJ. The bidirectional ultrashort outputs of the laser provide potential applications in supercontinuum generation and medical and biological applications. Full article

(This article belongs to the Special Issue Advances in Ultrafast Laser Science and Applications)

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11 pages, 209 KiB

Open AccessArticle

Between Uncertainty and Responsibility: A Philosophical Inquiry into Climate Change Projections

by Fernando Watson-Hernández and Isabel Guzmán-Arias

Philosophies 2025, 10(4), 91; https://doi.org/10.3390/philosophies10040091 (registering DOI) - 14 Aug 2025

Abstract

This paper explores how uncertainty in climate change projections both shapes and is shaped by key epistemic, methodological, ethical, and political concerns. Drawing on a review of key philosophical sources, it examines the relationship between scientific objectivity and the influence of social, ethical, [...] Read more.

This paper explores how uncertainty in climate change projections both shapes and is shaped by key epistemic, methodological, ethical, and political concerns. Drawing on a review of key philosophical sources, it examines the relationship between scientific objectivity and the influence of social, ethical, and political values in contexts of deep uncertainty. Authors such as Wendy Parker and Heather Douglas debate the role that social values play in the estimation and communication of scientific uncertainty, particularly when decisions carry significant ethical and political consequences. At the same time, several studies emphasize that, beyond the influence of values, there are structural limitations inherent to complex climate models that prevent uncertainty from being fully reduced. Taken together, these perspectives suggest that both evaluative judgments and technical constraints must be considered when interpreting and managing uncertainty in climate science, especially insofar as it informs collective decision-making processes. The article also examines how certain institutional practices tend to downplay uncertainty, generating biases that affect both scientific communication and public decision-making. It, therefore, explores potential solutions through more integrative approaches, such as robust modeling, risk assessments focused on low-probability but high-impact events (HILL), and collective ethical deliberation. The paper further discusses the concept of normative uncertainty, illustrated through the case of the Tempisque River water conflict, which highlights the difficulty of reconciling competing values. It concludes that, far from being eliminated, uncertainty must be managed through tools that integrate technical rationality, ethical sensitivity, and adaptive governance. Full article

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