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17 pages, 632 KB

Open AccessArticle

Comparison of Different Surgical Techniques for Osia^® System Implantation—Experience from Two European Clinical Centers

by Wojciech Gawęcki, Ann-Kathrin Rauch, Marta Pietraszek, Maria Jaworska and Susan Arndt

J. Clin. Med. 2026, 15(1), 57; https://doi.org/10.3390/jcm15010057 (registering DOI) - 21 Dec 2025

Abstract

Background/Objectives: This study aimed to compare two surgical techniques for Osia^® system implantation performed at two European clinical centers: Poznań (Poland) and Freiburg (Germany). Methods: The study included 83 patients who underwent Osia^® OSI200 and OSI300 implantation (89 implants). [...] Read more.

Background/Objectives: This study aimed to compare two surgical techniques for Osia^® system implantation performed at two European clinical centers: Poznań (Poland) and Freiburg (Germany). Methods: The study included 83 patients who underwent Osia^® OSI200 and OSI300 implantation (89 implants). The analysis focused on surgical technique, postoperative healing, and long-term skin integrity and aesthetic outcomes. Results: The centers differed in their surgical approaches, particularly regarding skin incision design and bone preparation. Most patients experienced no complications. Implant explantation was required in two cases, and one patient with recurrent seroma underwent revision surgery. Both centers achieved excellent postoperative skin integrity, with minimal scar visibility in most patients. Patients treated in Freiburg showed significantly better outcomes in terms of retroauricular bump visibility or palpability (p < 0.05) and postoperative pain (p < 0.05). Conversely, patients operated on in Poznań reported numbness less frequently (p < 0.05). Conclusions: Osia^® system implantation is a safe and well-tolerated procedure, with postoperative complications occurring in only a small proportion of cases. The Freiburg technique appears to reduce visibility and palpability of retroauricular bump and postoperative pain, but may slightly increase the risk of numbness and, in some cases, lead to a more visible scar compared to the Poznań approach. Optimal outcomes may be achieved by combining elements of both surgical techniques. Full article

(This article belongs to the Special Issue Hearing Disorders: Diagnosis, Management, and Future Opportunities: 4th Edition)

18 pages, 3482 KB

Open AccessSystematic Review

Efficacy and Safety of Newly Diagnosed Multiple Myeloma Combination Therapies: A Systematic Review Integrating Network Meta-Analysis and Real-World Vigilance Study

by Yanjun Liu, Ying Zhang, Wenhui Yang, Haoyan Du, Shijie Sun, Zuojing Li and Dongsheng Zong

Pharmaceuticals 2026, 19(1), 18; https://doi.org/10.3390/ph19010018 (registering DOI) - 21 Dec 2025

Abstract

Background: Although anti-CD38 monoclonal antibody-based regimens are standard care for newly diagnosed multiple myeloma (NDMM), direct comparative efficacy and comprehensive real-world safety data remain scarce. Methods: We conducted a systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs). [...] Read more.

Background: Although anti-CD38 monoclonal antibody-based regimens are standard care for newly diagnosed multiple myeloma (NDMM), direct comparative efficacy and comprehensive real-world safety data remain scarce. Methods: We conducted a systematic review and Bayesian network meta-analysis (NMA) of randomized controlled trials (RCTs). Efficacy was assessed using hazard ratios (HRs) for progression-free survival and odds ratios (ORs) for response rates, with treatment rankings evaluated by Surface Under the Cumulative Ranking (SUCRA) values. Separately, adverse event reports for daratumumab, bortezomib, lenalidomide, and dexamethasone (D_VRd) regimens were extracted from the US FDA Adverse Event Reporting System (FAERS) (Q1 2015–Q2 2025). Statistical analyses were performed using R (4.3.3) and STATA (16.0). Results: The NMA included 33 RCTs. For the primary efficacy endpoints, compared to the standard bortezomib, lenalidomide, and dexamethasone (VRd) regimen, both D_VRd (OR = 3.21, 95% CI: 2.46–4.26; HR = 0.48, 95% CI: 0.38–0.63) and isatuximab plus VRd (Isa_VRd) (OR = 1.71, 95% CI: 1.25–2.32; HR = 0.66, 95% CI: 0.51–0.85) regimens demonstrated superior efficacy. Subsequent pharmacovigilance analysis of D_VRd identified 11,714 FAERS reports, yielding 197 significant adverse drug event signals (64 unlabeled). These signals primarily affected elderly males and showed a bimodal distribution pattern. Conclusions: Combination regimens containing anti-CD38 monoclonal antibodies demonstrate superiority in achieving deep remission and survival benefits, with D_VRd and Isa_VRd regimens showing particularly outstanding performance. However, efficacy and safety profiles vary across different combination regimens. Real-world data analysis further indicates that the D_VRd regimen carries several safety risk signals that remain underappreciated and exhibits a bimodal time distribution pattern. These findings provide new evidence to guide clinical decision-making and risk-stratified monitoring. Full article

(This article belongs to the Section Biopharmaceuticals)

22 pages, 1745 KB

Open AccessArticle

Governance on Point? An Assessment of the Permitting, Supervision and Enforcement Processes for Point Source Discharges in the Netherlands

by Arnoud Klok, Carel Dieperink and Tessa Rötscheid

Water 2026, 18(1), 27; https://doi.org/10.3390/w18010027 (registering DOI) - 21 Dec 2025

Abstract

The European Water Framework Directive (2000/60/EC) (WFD) aims to protect inland surface waters, transitional waters, coastal waters and groundwater. The overarching goal of the WFD is to reach a good aquatic ecosystem throughout all of Europe. With the aim of reaching this goal, [...] Read more.

The European Water Framework Directive (2000/60/EC) (WFD) aims to protect inland surface waters, transitional waters, coastal waters and groundwater. The overarching goal of the WFD is to reach a good aquatic ecosystem throughout all of Europe. With the aim of reaching this goal, article 4 of the WFD sets certain environmental objectives. According to article 4 of the WFD, all the surface water bodies falling under its scope should be of good chemical and ecological quality by the end of 2027, as most extension deadlines will expire. For artificial and heavily modified surface water bodies—which make up the vast majority in the Netherlands—the goal is not to achieve a good ecological status but instead a good ecological potential and a good chemical status. Point source discharges may have a major impact on water quality and in order to progress, a well-functioning permitting, supervision and enforcement (PSE) process is of considerable interest. So far little academic attention has been paid to the functioning and quality of the governance processes underlying the PSE process. This paper aims to reduce this knowledge gap by conducting a case study on Sitech, the wastewater company for the Chemelot industrial complex in Geleen in the province of Limburg, the Netherlands. We first elaborate on an assessment framework consisting of 18 good governance criteria. The framework is used to assess the permitting, supervision and enforcement process concerning the discharges of Chemelot industrial plant. Our assessment reveals that, despite significant improvements over the last decade, good governance in this case is only partially achieved. While in terms of accountability and resilience the process shows robust strengths, gaps are found in its inclusiveness, effectiveness and transparency. We conclude our paper with some reflections on the generalizability of our findings and some suggestions for further research and policymaking. Full article

(This article belongs to the Section Water Resources Management, Policy and Governance)

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15 pages, 1653 KB

Open AccessArticle

Slow Releasing CO Donor Modulates Susceptibility to Seizures in Rats with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: Behavioral and EEG Study

by Nikola Šutulović, Neriman Ezgin, Emilija Djuric, Milena Vesković, Dušan Mladenović, Zorica Nestorović, Aleksandra Rašić-Marković, Olivera Stanojlović and Dragan Hrnčić

Medicina 2026, 62(1), 15; https://doi.org/10.3390/medicina62010015 (registering DOI) - 21 Dec 2025

Abstract

Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that involves changes in multiple organs and even the central nervous system (CNS). CP/CPPS may elevate seizure risk via neuroinflammatory mechanisms within the CNS. Neuroprotective effects of CO-releasing molecules [...] Read more.

Background and Objectives: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that involves changes in multiple organs and even the central nervous system (CNS). CP/CPPS may elevate seizure risk via neuroinflammatory mechanisms within the CNS. Neuroprotective effects of CO-releasing molecules (CORMs) were demonstrated in inflammation-driven conditions, while CORMs potential to ameliorate seizure susceptibility in inflammatory states, like CP/CPPS, remains unclear. Therefore, we investigated effects of CORM-A1 on susceptibility to lindane–induced seizures in rats with CP/CPPS through behavioral and electroencephalographic (EEG) study. Materials and Methods: Wistar rats were divided into four groups (n = 8/group): Sham-PBS, Sham-CORM, CP/CPPS-PBS and CP/CPPS-CORM. The CP/CPPS model was created by injection of 3% λ-carrageenan and its development assessed by mechanical pain threshold. CORM-A1 (2 mg/kg/day, i.p.) or vehicle (PBS) was given during seven postoperative days. Hereupon, subconvulsive dose of lindane (4 mg/kg, i.p.) was administered and behavioral features of seizures were observed alongside with EEG recordings. Results: Our data showed that the incidence and severity of lindane-induced seizures was significantly higher in the CP/CPPS-PBS group than in the Sham-PBS group. CORM-A1 treatment significantly decreased seizure incidence, prolonged seizure latency, and reduced seizure severity in CP/CPPS rats compared to vehicle treatment (CP/CPPS-CORM vs. CP/CPPS-PBS). Also, CORM-A1 treatment significantly reduced the number and duration of ictal periods induced by lindane in CP/CPPS animals compared to vehicle treatment. Conclusions: It could be concluded that CORM-A1 treatment reduced both behavioral and EEG signs of increased seizure susceptibility in rats with CP/CPPS, thus it could be a potential therapeutic target. Full article

(This article belongs to the Section Psychiatry)

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41 pages, 572 KB

Open AccessReview

Future Directions for Sustainable Poultry Feeding and Product Quality: Alternatives from Insects, Algae and Agro-Industrial Fermented By-Products

by Petru Alexandru Vlaicu, Raluca Paula Turcu, Mihaela Dumitru, Arabela Elena Untea and Alexandra Gabriela Oancea

Agriculture 2026, 16(1), 25; https://doi.org/10.3390/agriculture16010025 (registering DOI) - 21 Dec 2025

Abstract

Due to global increases in poultry meat and egg production, consumers request sustainable agricultural practices, requiring alternative solutions for future feeding. Global egg production increased by over 41% between 2000 and 2020, from 51 to 87 million tonnes, at an average increasing rate [...] Read more.

Due to global increases in poultry meat and egg production, consumers request sustainable agricultural practices, requiring alternative solutions for future feeding. Global egg production increased by over 41% between 2000 and 2020, from 51 to 87 million tonnes, at an average increasing rate of 3%. Similarly, the production of poultry meat reached 145 million tonnes in 2023 and continues to increase, which amplifies the pressure on sustainable alternative feed solutions. Commercial poultry diets are typically based on a cereal (corn or wheat) as an energy source and a quality protein source, especially soybean meal (SBM), to provide essential amino acids. Soybean production is associated with deforesting and land use in several countries, sensitiveness to supply chains and price volatility. As a response to these challenges over the last decade, research and commercial innovation have intensively focused on alternative and novel feed resources that can be integrated into both broiler and layer diets. Some future candidate ingredients are insect meal, algae, agro-industrial by-products such as distiller’s dried grains with solubles (DDGS), brewery spent grains (BSG) and fermented feedstuffs (oilseed cakes/meals). Literature data showed that moderate inclusion of these alternative ingredients can be partly integrated in poultry diets, without compromising egg or meat quality. In some cases, studies showed improvements of productive performances and specific quality traits (yolk color, fatty acids and antioxidant compounds), offering potential to valorize waste streams, improve local circularity and provide functional ingredients for animals and humans. However, challenges still remain, especially in terms of nutrient variability, digestibility limitations, higher processing costs and still-evolving regulations which constrain mainstream adoption of some of these potential future alternatives. Full article

(This article belongs to the Special Issue Alternative and Novel Feeds for Poultry: Nutritive Value, Product Quality and Environmental Aspects)

40 pages, 3141 KB

Open AccessArticle

Extending the Migration from Asynchronous to Reactive Programming in Java: A Performance Analysis of Caching, CPU-Bound, and Blocking Scenarios

by Andrei Zbarcea, Cătălin Tudose and Alexandru Boicea

Appl. Sci. 2026, 16(1), 90; https://doi.org/10.3390/app16010090 (registering DOI) - 21 Dec 2025

Abstract

Modern distributed systems increasingly rely on reactive programming to meet the demands of high throughput and low latency under extreme concurrency. While the theoretical advantages of non-blocking I/O are well-established, empirical understanding of its behavior across heterogeneous enterprise workloads remains fragmented. This study [...] Read more.

Modern distributed systems increasingly rely on reactive programming to meet the demands of high throughput and low latency under extreme concurrency. While the theoretical advantages of non-blocking I/O are well-established, empirical understanding of its behavior across heterogeneous enterprise workloads remains fragmented. This study presents a unified architectural evaluation of asynchronous (thread-per-request) and reactive (event-loop) paradigms within a functionally equivalent Java microservice environment. Unlike prior studies that isolate specific workloads, this research benchmarks the architectural crossover points across three distinct operational categories: distributed caching, CPU-bound processing, and blocking I/O, under loads up to 1000 concurrent users. The results quantify specific boundary conditions: the reactive model demonstrates superior elasticity in I/O-bound caching scenarios, achieving 75% higher throughput and 68% lower memory footprint. However, this advantage is strictly workload-dependent; both paradigms converge to an identical CPU wall at processor saturation, where the reactive model incurs a quantifiable latency penalty due to event-loop contention. Furthermore, under blocking conditions, the reactive model’s memory efficiency (reducing footprint by ~50%) provides resilience against Out-Of-Memory (OOM) failures, even as throughput gains plateau. These findings move beyond generic performance comparisons to provide precise, data-driven guidelines for hybrid architectural adoption in complex distributed systems. Full article

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23 pages, 4099 KB

Open AccessArticle

Scaphoid Fracture Detection and Localization Using Denoising Diffusion Models

by Zhih-Cheng Huang, Tai-Hua Yang, Zhen-Li Yang and Ming-Huwi Horng

Diagnostics 2026, 16(1), 26; https://doi.org/10.3390/diagnostics16010026 (registering DOI) - 21 Dec 2025

Abstract

Background/Objectives: Scaphoid fractures are a common wrist injury, typically diagnosed and treated through X-ray imaging, a process that is often time-consuming. Among the various types of scaphoid fractures, occult and nondisplaced fractures pose significant diagnostic challenges due to their subtle appearance and variable [...] Read more.

Background/Objectives: Scaphoid fractures are a common wrist injury, typically diagnosed and treated through X-ray imaging, a process that is often time-consuming. Among the various types of scaphoid fractures, occult and nondisplaced fractures pose significant diagnostic challenges due to their subtle appearance and variable bone density, complicating accurate identification via X-ray images. Therefore, creating a reliable assist diagnostic system based on deep learning for the scaphoid fracture detection and localization is critical. Methods: This study proposes a scaphoid fracture detection and localization framework based on diffusion models. In Stage I, we augment the training data set by embedding fracture anomalies. Pseudofracture regions are generated on healthy scaphoid images, producing healthy and fractured data sets, forming a self-supervised learning strategy that avoids the complex and time-consuming manual annotation of medical images. In Stage II, a diffusion-based reconstruction model learns the features of healthy scaphoid images to perform high-quality reconstruction of pseudofractured scaphoid images, generating healthy scaphoid images. In Stage III, a U-Net-like network identifies differences between the target and reconstructed images, using these differences to determine whether the target scaphoid image contains a fracture. Results: After model training, we evaluated its diagnostic performance on real scaphoid images by comparing the model’s results with precise fracture locations further annotated by physicians. The proposed method achieved an image area under the receiver operating characteristic curve (AUROC) of 0.993 for scaphoid fracture detection, corresponding to an accuracy of 0.983, recall of 1.00, and precision of 0.975. For fracture localization, the model achieved a pixel AUROC of 0.978 and a pixel region overlap of 0.921. Conclusions: This study shows promise as a reliable, powerful, and scalable solution for the scaphoid fracture detection and localization. Experimental results demonstrate the strong performance of the denoising diffusion models; these models can significantly reduce diagnostic time while precisely localizing potential fracture regions, identifying conditions overlooked by the human eye. Full article

(This article belongs to the Special Issue 3rd Edition: AI/ML-Based Medical Image Processing and Analysis)

23 pages, 4585 KB

Open AccessArticle

UCST-Activated Network Reinforcement in Hybrid Microgels for Smart Plugging

by Mingliang Du, Huifeng He, Qingchen Wang, Keming Sheng, Guancheng Jiang and Yinbo He

Gels 2026, 12(1), 8; https://doi.org/10.3390/gels12010008 (registering DOI) - 21 Dec 2025

Abstract

Conventional polymer-based plugging materials often fail in deep-well environments due to passive thermal softening and network relaxation, which significantly compromise mechanical integrity and interfacial retention. To address this challenge, a novel smart Upper Critical Solution Temperature (UCST)-responsive hybrid microgel (SUPA) was synthesized for [...] Read more.

Conventional polymer-based plugging materials often fail in deep-well environments due to passive thermal softening and network relaxation, which significantly compromise mechanical integrity and interfacial retention. To address this challenge, a novel smart Upper Critical Solution Temperature (UCST)-responsive hybrid microgel (SUPA) was synthesized for adaptive plugging in complex formations. The distinctive UCST responsiveness was conferred by incorporating N-(2-amino-2-oxoethyl)acrylamide (NAGA) and N-(2-hydroxypropyl) methacrylamide (HPMA) functional units into a robust dual-crosslinked network. Particle size analysis and oscillatory rheology in saline solution revealed the thermal activation mechanism: surpassing the critical temperature triggers the dissociation of intramolecular hydrogen bonds, driving polymer chain extension and volumetric expansion. This conformational transition induces dynamic network reinforcement, quantified by a significant ~7.5-fold increase in the storage modulus (G′). Consequently, the SUPA-enhanced fluid exhibited superior rheological performance, including a 4.4-fold increase in low-shear viscosity and rapid thixotropic recovery (ratio of 1.06). Crucially, lost circulation tests confirmed reliable and highly efficient sealing performance under harsh conditions of 150 °C and 5 MPa, even in fractured models. This study validates a design strategy centered on UCST-activated network reinforcement, offering a robust, mechanism-driven solution for severe lost circulation control in deep-well drilling. Full article

(This article belongs to the Section Gel Applications)

27 pages, 1187 KB

Open AccessArticle

An Empirical Data Model for Spare Parts Management: Linking Maintenance, Logistics, Inventory, and Equipment Data to Bridge Information Silos and Reduce Data-Gathering Efforts

by Simon Klarskov Didriksen, Kristoffer Wernblad Sigsgaard, Niels Henrik Mortensen and Christian Brunbjerg Jespersen

Appl. Sci. 2026, 16(1), 94; https://doi.org/10.3390/app16010094 (registering DOI) - 21 Dec 2025

Abstract

Effective spare parts management (SPM) is imperative for equipment-intensive organizations to reduce equipment downtime through maintenance. Despite the extensive availability of data-driven SPM methodologies, decision-makers are challenged and tend to rely on tacit knowledge and simple approaches due to extensive data-gathering requirements and [...] Read more.

Effective spare parts management (SPM) is imperative for equipment-intensive organizations to reduce equipment downtime through maintenance. Despite the extensive availability of data-driven SPM methodologies, decision-makers are challenged and tend to rely on tacit knowledge and simple approaches due to extensive data-gathering requirements and fragmented information across multiple organizational IT systems and departmental knowledge silos. A review of 60 academic SPM contributions demonstrated that data remains siloed and that research is limited in integrating data across SPM-relevant knowledge areas. This study proposes an empirical SPM data model to address this gap by consolidating and linking spare parts with maintenance, logistics, inventory, and equipment data, thus forming a coherent database across the identified SPM knowledge areas to bridge data silos and reduce data-gathering requirements. A case study assesses the effects of model implementation for decision-making on 10,843 spare parts and shows that model implementation led to a 15.1% stock value reduction, a 76–91% full-time equivalent resource improvement, a 4–5% decision quality improvement, and an enhancement of decision-maker engagement. The data model reduces data-gathering efforts, enhances data accessibility, and improves decision quality and consistency. Full article

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23 pages, 3451 KB

Open AccessArticle

Load Flexibilities from Charging Processes by Electric Vehicles at the Workplace: A Case Study in Southern Germany

by Ronald Opoku and Patrick Jochem

Energies 2026, 19(1), 42; https://doi.org/10.3390/en19010042 (registering DOI) - 21 Dec 2025

Abstract

The workplace, as a promising location for Electric Vehicle Supply Equipment (EVSE), presents a particular challenge, as different user requirements (e.g., parking and charging durations) meet a spatially and quantitatively limited offer of EVSE. However, integrating electric vehicles synergistically into the energy system [...] Read more.

The workplace, as a promising location for Electric Vehicle Supply Equipment (EVSE), presents a particular challenge, as different user requirements (e.g., parking and charging durations) meet a spatially and quantitatively limited offer of EVSE. However, integrating electric vehicles synergistically into the energy system of the employer can increase the profitability of the system and, correspondingly, increase the number of EVSE. For this, a deep understanding of employees’ charging behavior is key. For providing some evidence of empirical charging patterns at the workplace, this work examined a dataset of 23.9 million observations on empirical charging processes at workplaces in 2023. To identify user groups, a probabilistic model (Gaussian Mixture Model) and a K-Means clustering approach were applied and the results compared. Eight groups were identified, including full-time and part-time employees, pool vehicle users, and opportunists. The group-specific probability distributions are used to publish a synthetic dataset of parking and charging patterns at workplaces. The openly provided dataset helps to identify the right composition of EVSE in the employee context and to optimize potential fields of action. Full article

(This article belongs to the Topic Electric Vehicles Smart Charging: Strategies, Technologies, and Challenges)

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17 pages, 1233 KB

Open AccessArticle

Consistency Testing Method for Energy Storage Systems with Time-Series Properties

by Nan Wang and Zhen Li

Energies 2026, 19(1), 46; https://doi.org/10.3390/en19010046 (registering DOI) - 21 Dec 2025

Abstract

As a cushion for the volatility of renewable energy, energy storage systems can achieve peak shaving and valley filling, thereby improving the operational efficiency and economic performance of the power grid. In addition, energy storage systems can absorb renewable energy production, thereby enhancing [...] Read more.

As a cushion for the volatility of renewable energy, energy storage systems can achieve peak shaving and valley filling, thereby improving the operational efficiency and economic performance of the power grid. In addition, energy storage systems can absorb renewable energy production, thereby enhancing the safety and reliability of the electrical power system. Nowadays, energy storage systems are facing severe problems such as explosions that are caused by overcharging and discharging. The main reason for the overcharging and discharging of energy storage systems is the inconsistency in the state of the electric core in the charging and discharging process, which not only affects the safety of the electric core, but also influences the overall charging and discharging capacity of the energy storage system. To address this inconsistency of energy storage cores, this paper proposes an energy storage consistency monitoring method under the framework of clustering-classification, which adopts the Belief Peaks Evidential Clustering and Evidential K-Nearest Neighbors classification algorithm. This paper proposes a BPEC-EKNN-based method for battery inconsistency detection and localization. The proposed approach first constructs battery performance evaluation coefficients to characterize inter-cell behavioral differences, and then integrates an enhanced k-nearest neighbor strategy to identify abnormal cells. It also identifies and locates inconsistent battery cells by analyzing the magnitude of the confidence level m (Ω), without relying on predefined thresholds. Also, time-series data as opposed to the evaluation of voltage data at a singular point is engaged to realize the detection and localization of energy storage core consistency anomalies under the consideration of time-series data. The proposed algorithm is capable of identifying inconsistencies among energy storage batteries, with the parameter m (Ω) serving as an indicator of the likelihood of inconsistency. Experimental results on battery pack datasets demonstrate that the proposed method achieves higher detection accuracy and robustness compared with representative statistical threshold-based methods and machine learning approaches, and it can more accurately identify inconsistent battery cells. By applying perturbation analysis to real-time operational data, the algorithm proposed in this paper can detect inconsistencies in battery cells reliably. Full article

(This article belongs to the Section D: Energy Storage and Application)

22 pages, 4393 KB

Open AccessArticle

Construction and Characterization of PDA@MnO₂-Cored Multifunctional Targeting Nanoparticles Loaded with Survivin siRNA for Breast Tumor Therapy

by Jing Zhang, Wenhao Jiang, Lei Hu, Qing Du, Nina Filipczak, Satya Siva Kishan Yalamarty and Xiang Li

Pharmaceutics 2026, 18(1), 10; https://doi.org/10.3390/pharmaceutics18010010 (registering DOI) - 21 Dec 2025

Abstract

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO₂) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. [...] Read more.

Objective: This study aims to engineer a novel nanoparticle formulation for combined tumor therapy, designated as PDA@Mn-siSur-c-NPs, which comprises a polydopamine/manganese dioxide (PDA@MnO₂) core alongside survivin-targeting siRNA and cyclo(RGD-DPhe-K)-targeting moiety. Methods: The PDA@Mn-siSur-c-NPs were constructed and subjected to detailed characterization. Inductively coupled plasma optical emission spectroscopy (ICP-OES) was employed to quantify manganese content. To assess siRNA stability within the system, samples were incubated with 50% fetal bovine serum (FBS) before agarose gel electrophoresis analysis. Additionally, cellular internalization by 4T1 cells and in vitro photothermal conversion efficiency of the formulation were evaluated. ICP-OES was further utilized to investigate the in vivo pharmacokinetics and tissue distribution of manganese. Animal model studies were conducted to assess the anti-breast cancer efficacy of PDA@Mn-siSur-c-NPs in combination with infrared irradiation. Results: The newly developed PDA@Mn-siSur-c-NPs demonstrated superior siRNA protection, reduced toxicity, and high photothermal conversion capacity. When combined with photothermal therapy (PTT), these nanoparticles exerted enhanced synergistic anti-tumor effects. Delivery of survivin siRNA resulted in a significant downregulation of survivin protein expression in tumor tissues. Moreover, magnetic resonance imaging (MRI) confirmed that the nanoparticles possess favorable imaging properties. Conclusions: This research demonstrates that the integration of PDA@Mn-siSur-c-NPs with PTT holds considerable therapeutic promise for improved breast cancer treatment. Full article

(This article belongs to the Special Issue Hybrid Nanoparticles for Cancer Therapy)

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17 pages, 11314 KB

Open AccessArticle

Integrated Network Toxicology and Metabolomics Reveal the Ovarian Toxicity Mechanisms of Chronic Carbofuran Exposure in Female Mice

by Di Liang, Hongyu Su and Xian Ju

Int. J. Mol. Sci. 2026, 27(1), 90; https://doi.org/10.3390/ijms27010090 (registering DOI) - 21 Dec 2025

Abstract

Carbofuran, a widely used carbamate pesticide, is an endocrine disruptor with documented reproductive toxicity, yet the mechanisms underlying its ovarian toxicity remain incompletely understood. This study employed integrated network toxicology and untargeted metabolomics to investigate these mechanisms in female C57BL/6J mice that had [...] Read more.

Carbofuran, a widely used carbamate pesticide, is an endocrine disruptor with documented reproductive toxicity, yet the mechanisms underlying its ovarian toxicity remain incompletely understood. This study employed integrated network toxicology and untargeted metabolomics to investigate these mechanisms in female C57BL/6J mice that had been chronically exposed to carbofuran (0.5 or 2.0 mg/kg for 45 days, once daily). Methods included histopathological evaluation, serum hormone ELISA, network prediction of toxicity targets, molecular docking, and metabolomics profiling. Results demonstrated that carbofuran exposure induced dose-dependent ovarian damage, including reduced follicular reserve, increased atresia, abnormal corpus luteum, and disrupted hormone levels. Network toxicology identified 38 common targets, with EGFR, GSK3B, APP, and JAK2 as core proteins, indicating potential high affinity. Metabolomics suggests significant alterations in pathways such as phenylalanine, tyrosine, tryptophan biosynthesis and arginine/proline metabolism. Our collective evidence indicates that carbofuran may induce ovarian toxicity through multifaceted mechanisms involving endocrine disruption, oxidative stress, inflammatory activation, and metabolic disturbance. This study provides novel experimental insights into the reproductive toxicity mechanisms of carbofuran, offering a theoretical basis for health risk assessment and intervention strategies. Full article

(This article belongs to the Section Molecular Toxicology)

15 pages, 3387 KB

Open AccessArticle

Transcriptome Dynamics and Regulatory Networks of Postnatal Muscle Development in Leizhou Black Goats

by Jiancheng Han, Jing Huang, Mengning Xu, Yuelang Zhang, Ke Wang and Hanlin Zhou

Int. J. Mol. Sci. 2026, 27(1), 88; https://doi.org/10.3390/ijms27010088 (registering DOI) - 21 Dec 2025

Abstract

Postnatal muscle development involves complex transcriptional regulation that remains poorly characterized in goats. This study employed RNA-Seq to profile the Longissimus dorsitranscriptome of Leizhou Black goats across three developmental stages: birth, six months, and two years. We identified dynamic gene expression patterns, widespread [...] Read more.

Postnatal muscle development involves complex transcriptional regulation that remains poorly characterized in goats. This study employed RNA-Seq to profile the Longissimus dorsitranscriptome of Leizhou Black goats across three developmental stages: birth, six months, and two years. We identified dynamic gene expression patterns, widespread alternative splicing events, and stage-specific co-expression networks that collectively orchestrate muscle maturation. A significant transcriptional shift occurred between six months and two years, marked by the downregulation of proliferation-related genes (e.g., RRM2, TOP2A) and the activation of pathways governing muscle contraction and energy metabolism. Functional enrichment analyses highlighted the importance of PI3K-Akt, PPAR, and calcium signaling pathways throughout development. Additionally, 905 novel transcripts were discovered, many enriched in mitochondrial functions, indicating incompleteness in the current goat genome annotation. Weighted gene co-expression network analysis revealed modules correlated with developmental stages, and protein–protein interaction analysis identified hub genes regulating cell cycle progression and muscle function. Key results were validated via qRT-PCR, confirming the temporal expression patterns of genes such as CYP4B1, HACD1, and ACTC1. These findings provide mechanistic insights into the transcriptional reprogramming driving postnatal muscle development and offer valuable genetic resources for improving meat production in goats through molecular breeding. Full article

(This article belongs to the Special Issue Domestic Animal Genetics, Genomics, and Molecular Breeding)

9 pages, 365 KB

Open AccessArticle

Gauge Function as a New and Powerful Tool to Study the Van der Pol Oscillator

by Rupam Das and Zdzislaw E. Musielak

Mathematics 2026, 14(1), 27; https://doi.org/10.3390/math14010027 (registering DOI) - 21 Dec 2025

Abstract

A gauge function for the van der Pol oscillator is constructed and used to perform stability analysis of this system as well as to determine its dynamical states without solving the corresponding equation of motion. Despite previous claims that the oscillator is a [...] Read more.

A gauge function for the van der Pol oscillator is constructed and used to perform stability analysis of this system as well as to determine its dynamical states without solving the corresponding equation of motion. Despite previous claims that the oscillator is a non-Lagrangian system, it is shown that the gauge function allows deriving its first Lagrangian. The presented results demonstrate that the gauge function is a new and powerful tool to study this system and that it gives deeper physical insights into the system’s nature than any tool previously used. Full article

(This article belongs to the Section E4: Mathematical Physics)

15 pages, 4424 KB

Open AccessArticle

Application of NDVI-Based Crop Sensor in Alfalfa Selection for Improving Breeding Process

by Marijana Tucak, Katarina Perić, Tihomir Čupić, Goran Krizmanić, Luka Andrić, Marko Ivić, Marija Ravlić and Vladimir Meglič

Agronomy 2026, 16(1), 22; https://doi.org/10.3390/agronomy16010022 (registering DOI) - 21 Dec 2025

Abstract

Alfalfa (Medicago sativa) is a globally important forage crop; however, improvements in its biomass yield have stagnated due to its complex genetic architecture and the costly, labor-intensive phenotyping. This study evaluated the potential of the normalized difference vegetation index (NDVI) to [...] Read more.

Alfalfa (Medicago sativa) is a globally important forage crop; however, improvements in its biomass yield have stagnated due to its complex genetic architecture and the costly, labor-intensive phenotyping. This study evaluated the potential of the normalized difference vegetation index (NDVI) to predict biomass yield and enhance selection efficiency in alfalfa breeding programs. Specifically, nineteen alfalfa experimental populations (AEXP 1–19) and one control cultivar (OS 66) were evaluated over two growing seasons in Croatia. NDVI was measured at four development stages using a GreenSeeker sensor and compared with forage yield, dry matter yield, and plant height. NDVI values varied significantly among genotypes, years, and growth stages, ranging from 0.23 to 0.87, and increased consistently from early to late vegetative phases. Strong positive correlations were observed between NDVI and forage yield (r = 0.543–0.843) and plant height (r = 0.537–0.738) at early vegetative, late vegetative, and early bud stages. Conversely, NDVI at the mid-vegetative stage correlated negatively with yield and height (r = –0.622 to –0.794). High-performing populations (AEXP 2, AEXP 15, AEXP 18) also exhibited the highest NDVI values. NDVI is a reliable, non-destructive indicator for early selection of high-yielding alfalfa genotypes, although multi-location validation is advised to confirm its broader applicability. Full article

(This article belongs to the Section Crop Breeding and Genetics)

22 pages, 1115 KB

Open AccessArticle

Oral Fluid Concentrations and Pharmacological Effects of Clephedrone and Methylone in Humans

by Lourdes Poyatos, Melani Núñez-Montero, Olga Hladun, Georgina De la Rosa, Soraya Martín, Sebastian Videla, Silvia Martínez-Couselo, Mireia Ventura, Nunzia La Maida, Annagiulia Di Trana, Francesco Paolo Busardò, Marta Torrens, Simona Pichini, Clara Pérez-Mañá, Magí Farré and Esther Papaseit

Int. J. Mol. Sci. 2026, 27(1), 89; https://doi.org/10.3390/ijms27010089 (registering DOI) - 21 Dec 2025

Abstract

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the [...] Read more.

Synthetic cathinones represent the second most frequently reported group of new psychoactive substances identified annually, according to the United Nations. It remains unknown whether specific derivatives differ in the onset of effects related to absorption kinetics. Clephedrone (4-chloromethcathinone, 4-CMC) has been among the most frequently seized cathinones in recent years; however, available data on its pharmacology and abuse potential remain scarce. A non-controlled, prospective, observational study was conducted involving eight healthy volunteers (six women) who self-administered a single oral dose of clephedrone (100 or 150 mg). Study variables were assessed at baseline and over a 5-h period following administration, including vital signs and subjective effects. Oral fluid concentrations of clephedrone and cortisol were determined. For comparison, this article also presents previously unpublished data from a pilot study in which 12 healthy male participants received 150 or 200 mg of methylone under comparable conditions to evaluate effects. Results indicated that both clephedrone and methylone produced stimulant-like subjective effects. However, clephedrone exhibited a delayed onset and peak of effects compared with methylone, indicating a clinically relevant pharmacokinetic difference. Both substances were detected in oral fluid, with peak concentrations occurring later following clephedrone administration, consistent with its delayed pharmacodynamic profile. Full article

(This article belongs to the Special Issue Molecular Advances in Forensic Toxicology: Innovative Approaches in Detection of New Psychoactive Substances)

20 pages, 1694 KB

Open AccessReview

The Impact of Air Pollution and Obesity on Cognitive Decline and Risk of Alzheimer’s Disease

by Zoe A. Keller, Katherine M. Eggers, Joshua P. Nixon and Tammy A. Butterick

Int. J. Mol. Sci. 2026, 27(1), 92; https://doi.org/10.3390/ijms27010092 (registering DOI) - 21 Dec 2025

Abstract

Obesity and air pollution are two pervasive and increasingly prevalent risk factors for neurodegenerative diseases, like Alzheimer’s disease. Both independently disrupt brain homeostasis through overlapping mechanisms, including chronic neuroinflammation, oxidative stress, and insulin resistance. Recent evidence highlights the Wnt/β-catenin signaling pathway as a [...] Read more.

Obesity and air pollution are two pervasive and increasingly prevalent risk factors for neurodegenerative diseases, like Alzheimer’s disease. Both independently disrupt brain homeostasis through overlapping mechanisms, including chronic neuroinflammation, oxidative stress, and insulin resistance. Recent evidence highlights the Wnt/β-catenin signaling pathway as a critical integrator of these insults, mediating neuroprotective processes such as synaptic plasticity, blood–brain barrier integrity, and neuronal survival. In this review, we synthesize emerging data on how obesity-driven metabolic dysfunction and air pollution-induced oxidative injury synergize to impair brain metabolism and accelerate cognitive decline. We describe the roles of pathways such as JAK-STAT, NF-κB, and TLR4 signaling cascades, as well as leptin and adiponectin imbalances, in modulating glial reactivity and neuroimmune signaling. Particular attention is given to the suppression of Wnt/β-catenin signaling in obese and pollution-exposed brains, and its consequences for Alzheimer’s disease pathology, including β-amyloid accumulation and tau hyperphosphorylation. Finally, we examine the translational implications, highlighting the Wnt pathway as a potential therapeutic target that offers neuroprotection in the context of dual metabolic and environmental stress. Together, these insights provide a mechanistic framework that links systemic dysfunction to central nervous system vulnerability, offering pathways for intervention in at-risk populations. Full article

(This article belongs to the Special Issue Wnt/β-Catenin Signaling in Health and Disease)

14 pages, 244 KB

Open AccessArticle

Split Fiction: Gaming, Authorship, and Corporate Extraction in the Age of AI

by Anastasia Salter and John T. Murray

Humanities 2026, 15(1), 2; https://doi.org/10.3390/h15010002 (registering DOI) - 21 Dec 2025

Abstract

This article examines Split Fiction, a cooperative video game that engages with themes of authorship, creativity, and artificial intelligence in the digital age. The game presents aspiring authors whose creative ideas are extracted by a corporate machine—a metaphor for contemporary generative AI [...] Read more.

This article examines Split Fiction, a cooperative video game that engages with themes of authorship, creativity, and artificial intelligence in the digital age. The game presents aspiring authors whose creative ideas are extracted by a corporate machine—a metaphor for contemporary generative AI systems. Through its mandatory two-player cooperative mechanics and genre-shifting gameplay, Split Fiction explores tensions between human creativity and automated generation, individual authorship and corporate extraction, and procedural rhetoric versus narrative meaning. We analyze how the game’s mechanical variety, intertextual references, and meta-narrative structure comment on the current landscape of AI in creative industries, particularly as director Josef Fares’s ambivalent statements about AI complicate straightforward readings of the work as purely anti-AI critique. The game ultimately offers a nuanced exploration of creative labor futures in an age where the boundaries between human and machine authorship grow increasingly uncertain. Full article

(This article belongs to the Special Issue Electronic Literature and Game Narratives)

24 pages, 9514 KB

Open AccessArticle

Nutritional, Functional, and Morphological Insights into a Heritage Durum Wheat of Campania

by Maria Chiara Di Meo, Ilva Licaj, Vittorio Maria Mandrone, Jessica Raffaella Madera, Romualdo Varricchio, Chiara Germinario, Mariapina Rocco, Romania Stilo, Pasquale Vito and Ettore Varricchio

Agronomy 2026, 16(1), 24; https://doi.org/10.3390/agronomy16010024 (registering DOI) - 21 Dec 2025

Abstract

Ancient wheat cultivars play a crucial role in human and animal nutrition and health, serving as rich sources of bioactive compounds, essential nutrients, and functional metabolites. This study investigated Triticum turgidum subsp. durum (cv. Saragolla), an ancient wheat variety from the Campania [...] Read more.

Ancient wheat cultivars play a crucial role in human and animal nutrition and health, serving as rich sources of bioactive compounds, essential nutrients, and functional metabolites. This study investigated Triticum turgidum subsp. durum (cv. Saragolla), an ancient wheat variety from the Campania region of Southern Italy, to comprehensively characterize its morphological, functional, and nutritional attributes in support of germplasm conservation and valorization. Standard AOAC methods, including HPLC profiling, antioxidant assays, and quantification of total polyphenols and flavonoids, were applied to characterize the grain’s composition. The results revealed a balanced distribution of proteins, lipids, dietary fibers, and carbohydrates, that defines the nutritional and functional quality of Saragolla grains. Microscopic investigation through SEM coupled with EDX analysis provided high-resolution visualization of caryopsis morphology, ultrastructure, and mineral distribution, confirming its distinct varietal characteristics. Additionally, SSR marker analysis revealed notable genetic diversity within the Saragolla germplasm, identifying loci associated with key agronomic traits, including kernel weight, grain number, and stress tolerance parameters essential for future breeding programs. Overall, this integrated assessment highlights Saragolla as a valuable heritage wheat and a strategic genetic resource for breeding durum cultivars with enhanced nutritional quality, technological performance, and resilience to environmental stress. Full article

(This article belongs to the Special Issue Energy Crops in Sustainable Agriculture)

18 pages, 4303 KB

Open AccessArticle

Characterization and Spectroscopic Studies of the Morin-Zinc Complex in Solution and in PMMA Solid Matrix

by Malgorzata Sypniewska, Beata Jędrzejewska, Marek Pietrzak, Marek Trzcinski, Robert Szczęsny, Mateusz Chorobinski and Lukasz Skowronski

Appl. Sci. 2026, 16(1), 91; https://doi.org/10.3390/app16010091 (registering DOI) - 21 Dec 2025

Abstract

Flavonoids, natural organic compounds from the polyphenolic group with broad bioactive and pharmaceutical properties, are strong ligands for many metal ions. This work describes the formation of the complex between Zn(II) and morin. The synthesized compound is characterized using three analytical techniques, i.e., [...] Read more.

Flavonoids, natural organic compounds from the polyphenolic group with broad bioactive and pharmaceutical properties, are strong ligands for many metal ions. This work describes the formation of the complex between Zn(II) and morin. The synthesized compound is characterized using three analytical techniques, i.e., ¹H NMR, IR, and thermal gravimetric analysis. Importantly, the complex was successfully obtained in the form of a solid, which enables its further physicochemical and structural characterization. Physicochemical characterization of the Morin-Zn complex was performed by steady-state and time-resolved spectroscopy. The absorption spectrum of the complex contains two main bands at ca. 407–415 nm and ca. 265 nm, and the complex emits yellow-green light with higher intensity than the free ligand. In the next step, morin and zinc complex were dispersed in a PMMA (poly (methyl methacrylate)) polymer matrix, and respective thin layers were produced. The studied thin films were deposited on silicon substrates by using the spin-coating method and characterized by X-ray photoelectron spectroscopy (XPS), Atomic Force Microscopy (AFM), Spectroscopic Ellipsometry (SE), UV-VIS spectroscopy, and photoluminescence (PL). The absorption of thin layers showed, similarly to solutions, the presence of two transitions: π→π* and n→π*, and a bathochromic shift for the morin-zinc complex compared to morin. The photoluminescence of the complex thin film showed two bands, the first in the range of 380–440 nm corresponding to PMMA, and the second with a maximum at 490 nm, derived from the synthesized compound. Full article

(This article belongs to the Special Issue Light-Emitting Materials and Devices: Design, Characterization, and Applications of Optoelectronics and Sensing)

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26 pages, 2447 KB

Open AccessReview

Engineering Polyampholytes for Energy Storage Devices: Conductivity, Selectivity, and Durability

by Madina Mussalimova, Nargiz Gizatullina, Gaukhargul Yelemessova, Anel Taubatyrova, Zhanserik Shynykul and Gaukhar Toleutay

Polymers 2026, 18(1), 18; https://doi.org/10.3390/polym18010018 (registering DOI) - 21 Dec 2025

Abstract

Polyampholytes combine cationic and anionic groups in one macromolecular platform and are emerging as versatile components for energy storage and conversion. This review synthesizes how their charge balance, hydration, and architecture can be engineered to address ionic transport, interfacial stability, and safety across [...] Read more.

Polyampholytes combine cationic and anionic groups in one macromolecular platform and are emerging as versatile components for energy storage and conversion. This review synthesizes how their charge balance, hydration, and architecture can be engineered to address ionic transport, interfacial stability, and safety across batteries, supercapacitors, solar cells, and fuel cells. We classify annealed, quenched, and zwitterionic systems, outline molecular design strategies that tune charge ratio, distribution, and crosslinking, and compare device roles as gel or solid electrolytes, eutectogels, ionogels, binders, separator coatings, and interlayers. Comparative tables summarize ionic conductivity, cation transference number, electrochemical window, mechanical robustness, and temperature tolerance. Across Li and Zn batteries, polyampholytes promote ion dissociation, homogenize interfacial fields, suppress dendrites, and stabilize interphases. In supercapacitors, antifreeze hydrogels and poly(ionic liquid) networks maintain conductivity and elasticity under strain and at subzero temperature. In solar cells, zwitterionic interlayers improve work function alignment and charge extraction, while ordered networks in fuel cell membranes enable selective ion transport with reduced crossover. Design rules emerge that couple charge neutrality with controlled hydration and dynamic crosslinking to balance conductivity and mechanics. Key gaps include brittleness, ion pairing with multivalent salts, and scale-up. Opportunities include soft segment copolymerization, ionic liquid and DES plasticization, side-chain engineering, and operando studies to guide translation. Full article

(This article belongs to the Special Issue Functional Gel and Their Multipurpose Applications)

15 pages, 9430 KB

Open AccessArticle

Structure–Property Relationship in Ultra-Thin Copper Foils: From Nanotwinned to Fine-Grained Microstructures

by Fu-Chian Chen, Dinh-Phuc Tran and Chih Chen

Materials 2026, 19(1), 36; https://doi.org/10.3390/ma19010036 (registering DOI) - 21 Dec 2025

Abstract

This study systematically investigates the thickness-dependent mechanical properties of electroplated copper foils with fine-grained (FG-Cu) and columnar nanotwinned (NT-Cu) microstructures. Tensile testing across a thickness range of 5–30 μm revealed that NT-Cu exhibits superior mechanical stability, with significantly lower reductions in both ultimate [...] Read more.

This study systematically investigates the thickness-dependent mechanical properties of electroplated copper foils with fine-grained (FG-Cu) and columnar nanotwinned (NT-Cu) microstructures. Tensile testing across a thickness range of 5–30 μm revealed that NT-Cu exhibits superior mechanical stability, with significantly lower reductions in both ultimate tensile strength (UTS) and yield strength (YS) compared to FG-Cu. The UTS of the 30 μm thick FG-Cu foil was measured at 651 MPa, increasing to 792 MPa at a thickness of 5 μm. In contrast, the UTS of NT-Cu foils only rose from 624 MPa at 30 μm to 663 MPa at 5 μm. A similar trend was observed for the YS. Microstructural analysis confirmed that NT-Cu maintains a stable columnar grain structure with minimal grain growth, contributing to its resistance to thickness-induced strength loss. These findings highlight NT-Cu as a promising candidate for applications requiring consistent mechanical performance across varying foil thicknesses. Full article

(This article belongs to the Special Issue Flexible Electronic Materials and Devices: Preparation and Application)

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13 pages, 814 KB

Open AccessArticle

Unveiling Bulk Modulus and Stretching Bond Force Constants of Cubic and Wurtzite Boron Nitride Structures: A DFT Study

by Melissa L. Casais-Molina, César A. Cab, Rubén A. Medina-Esquivel and Jorge A. Tapia

Condens. Matter 2026, 11(1), 1; https://doi.org/10.3390/condmat11010001 (registering DOI) - 21 Dec 2025

Abstract

The mechanical properties of cubic (c-BN) and wurtzite (w-BN) boron nitride structures were investigated and compared using density functional theory (DFT) with several exchange–correlation functionals. This research focuses on determining the bulk modulus (

B

) and, for the first time, the stretching [...] Read more.

The mechanical properties of cubic (c-BN) and wurtzite (w-BN) boron nitride structures were investigated and compared using density functional theory (DFT) with several exchange–correlation functionals. This research focuses on determining the bulk modulus (

B

) and, for the first time, the stretching bond force constants (

k_{r}

), two fundamental parameters that describe the intrinsic stiffness and elastic resistance of these BN structures. Despite their structural similarity with the same tetrahedral coordination between atoms, c-BN and w-BN exhibit subtle differences in bond strength and compressibility that have not been fully clarified at the atomistic level. By systematically analyzing the influence of hybrid and semi-local functionals, consistent relationship between structural configuration and the predicted

B

and

k_{r}

values of both c-BN and w-BN structures were established and compared. These findings not only validate DFT as a reliable approach for assessing the mechanical properties of BN polymorphs, but also offer key parameters for machine learning and advanced multiscale modeling. Therefore, this theoretical study contributes to understanding the origin of mechanical properties in BN structures and supports their design in applications where a particular hardness and stability are required. Full article

(This article belongs to the Section Physics of Materials)

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23 pages, 2953 KB

Open AccessArticle

Estimate Laplacian Spectral Properties of Large-Scale Networks by Random Walks and Graph Transformation

by Changlei Zhan, Xiangyu Li and Jie Chen

Mathematics 2026, 14(1), 26; https://doi.org/10.3390/math14010026 (registering DOI) - 21 Dec 2025

Abstract

For network graphs, numerous graph features are intimately linked to eigenvalues of the Laplacian matrix, such as connectivity and diameter. Thus, it is very important to solve eigenvalues of the Laplacian matrix for graphs. Similarly, for higher-order networks, eigenvalues of combinatorial Laplacian matrices [...] Read more.

For network graphs, numerous graph features are intimately linked to eigenvalues of the Laplacian matrix, such as connectivity and diameter. Thus, it is very important to solve eigenvalues of the Laplacian matrix for graphs. Similarly, for higher-order networks, eigenvalues of combinatorial Laplacian matrices are also important for invariants of graphs. However, for large-scale networks, it is difficult to calculate eigenvalues of the Laplacian matrix directly because it is either very difficult to obtain the whole network structure or requires a lot of computing resources. Therefore, this article makes the following contributions. Firstly, this paper proposes a random walk approach for estimating the bounds of the greatest eigenvalues of Laplacian matrices for large-scale networks. Considering the relationship between the spectral moments of the adjacency matrix and the closed paths in the network, we utilize the relationship between the adjacency matrix and the Laplacian matrix to establish the relationship between the Laplacian matrix and the closed paths. Then, we employ equiprobable random walks to sample the large graph to obtain the small graph. Through algebraic topology knowledge, we obtain the bounds of the largest eigenvalue of the Laplacian matrix of the large graph by using Laplacian spectral moments of the small graph. Secondly, for high-order networks, this paper proposes a method based on random walks and graph transformations. The graph transformation we propose mainly converts graphs with second-order simplices into ordinary weighted graphs, thereby transforming the problem of solving the spectral moments of the second-order combined Laplacian matrix into solving the spectral moments of the adjacency matrix. Then, we use the aforementioned random walk method to solve bounds of the greatest eigenvalue of the second-order combinatorial Laplacian matrix. Finally, by comparing the proposed method with existing algorithms in synthetic and real networks, its accuracy and superiority are demonstrated. Full article

(This article belongs to the Special Issue Dynamic Analysis and Decision-Making in Complex Networks)

15 pages, 2541 KB

Open AccessArticle

PathQC: Determining Molecular and Structural Integrity of Tissues from Histopathological Slides

by Ranjit Kumar Sinha, Anamika Yadav and Sanju Sinha

Bioengineering 2026, 13(1), 5; https://doi.org/10.3390/bioengineering13010005 (registering DOI) - 21 Dec 2025

Abstract

Quantifying tissue, molecular, and structural integrity is essential for biobank development. However, current assessment methods either involve destructive testing that depletes valuable biospecimens or rely on manual evaluations, which are not scalable and lead to interindividual variation. To overcome these challenges, we present [...] Read more.

Quantifying tissue, molecular, and structural integrity is essential for biobank development. However, current assessment methods either involve destructive testing that depletes valuable biospecimens or rely on manual evaluations, which are not scalable and lead to interindividual variation. To overcome these challenges, we present PathQC, a deep-learning framework that directly predicts the tissue RNA Integrity Number (RIN) and the extent of autolysis from hematoxylin and eosin (H & E)-stained whole-slide images of normal tissue biopsies. Advancing over prior QC methods focused on imaging quality control, PathQC provides sample-quality control through the direct quantification of molecular integrity (RIN) and structural degradation (autolysis). PathQC first extracts morphological features from the slide using a recently developed digital pathology foundation model (UNI), followed by a supervised model that learns to predict RNA Integrity Number and autolysis scores from these morphological features. PathQC is trained on and applied to the Genotype-Tissue Expression (GTEx) cohort, which comprises 25,306 non-diseased post-mortem samples across 29 tissues from 970 donors, when paired ground-truth RIN and autolysis scores were available. Here, PathQC predicted RIN with an average Pearson correlation of 0.47 and an autolysis score of 0.45, with notably high performance using adrenal gland tissue (R = 0.82) for RIN and colon tissue (R = 0.83) for autolysis. We provide a pan-tissue model for predicting RIN and autolysis scores for new slides from any tissue type (GitHub). Overall, PathQC enables a scalable assessment of tissue molecular and structural integrity from routine H & E images, enhancing biobank quality control and retrospective analyses across 29 tissues and multiple collection sites. Full article

(This article belongs to the Special Issue Machine Learning-Aided Medical Image Analysis)

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