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17 pages, 13332 KB  
Article
Weight-Adaptable Disturbance Observer for Continuous-Control-Set Model Predictive Control of NPC-3L-Fed PMSMs
by Zhenyan Liang, Jiang Wang, Yitong Wu and Zhen Zhang
Energies 2025, 18(21), 5864; https://doi.org/10.3390/en18215864 - 6 Nov 2025
Abstract
This paper presents a cascaded control strategy for neutral-point-clamped three-level (NPC-3L) inverter-fed permanent magnet synchronous motors (PMSMs), integrating continuous-control-set model-predictive control (CCS-MPC) with mid-point voltage regulation and an online Lyapunov-stable neural-network (NN) disturbance observer. The outer CCS-MPC loop optimizes voltage vector application for [...] Read more.
This paper presents a cascaded control strategy for neutral-point-clamped three-level (NPC-3L) inverter-fed permanent magnet synchronous motors (PMSMs), integrating continuous-control-set model-predictive control (CCS-MPC) with mid-point voltage regulation and an online Lyapunov-stable neural-network (NN) disturbance observer. The outer CCS-MPC loop optimizes voltage vector application for accurate current tracking and harmonic suppression, while the inner loop balances mid-point voltage by adjusting the dwell times of P/N small-voltage vectors (VVs). The NN-based disturbance observer compensates parameter mismatches in real time, reducing steady-state dq-axis current errors. To validate the effectiveness of the proposed strategy, experiments are conducted using a three-phase PMSM fed by three-phase NPC-3L inverters. Experimental results demonstrate substantial improvements in mid-point voltage balance, current quality, and robustness against model uncertainties. Full article
(This article belongs to the Collection State-of-the-Art of Electrical Power and Energy System in China)
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11 pages, 648 KB  
Article
Permeation of 2-Butoxyethanol Through Multiple Layers of a Disposable Nitrile Glove Material and a Single Layer of Microflex 93-260
by Eun Jin Song Kuramoto and Shane Que Hee
Materials 2025, 18(21), 5055; https://doi.org/10.3390/ma18215055 - 6 Nov 2025
Abstract
Double gloving of disposable gloves occurs in healthcare when extra protection is required against carcinogens, sensitizers, pathogens and sharps. Triple gloving is much rarer. The resistances of single, double and triple layers of disposable nitrile glove material against 2-butoxyethanol (2-BE) were compared with [...] Read more.
Double gloving of disposable gloves occurs in healthcare when extra protection is required against carcinogens, sensitizers, pathogens and sharps. Triple gloving is much rarer. The resistances of single, double and triple layers of disposable nitrile glove material against 2-butoxyethanol (2-BE) were compared with the resistance of a single layer of Microflex 93-260 (Microflex). Three 2.54 cm ASTM F739 permeation cells with closed-loop water collection without recirculation in a moving tray water bath at 35.0 ± 0.5 °C facilitated the permeation relative to a blank cell. Capillary gas chromatography/mass spectrometry allowed the determination of the standardized breakthrough time (SBT), steady state permeation rate (SSPR) and cumulated permeated mass/area (CPM/A) by 30 min. Two nitrile layers (267 ± 14 µm) were about the same thickness as the Microflex layer (249 ± 6 µm). Statistical analysis showed equivalence at p ≤ 0.05 of the multiple layers and the Microflex layer relative to average SBT and CPM/A by 30 min, all such comparisons with the single nitrile layer also being statistically different. The triple layer had an average SSPR or post-breakthrough permeation rate 8 times lower than its single layer, while that for the Microflex layer was 1.5 times lower. Thus, the Microflex layer in terms of CPM/A by 30 min at 210 ± 40 µg/cm2 appeared closer to two nitrile layers (520 ± 560 µg/cm2) than three (93 ± 93 µg/cm2). Full article
(This article belongs to the Section Advanced Materials Characterization)
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9 pages, 438 KB  
Article
Effect of Menstrual Cycle on Glycemic Outcomes and Insulin Requirements in Women with Type 1 Diabetes Who Are Users of Advanced Hybrid Closed-Loop Systems
by Marta Rosado-Fernández, Elisenda Climent, Mercè Fernández-Miró, Anna Garrido, Rosa Gaja, Verónica Amador, Gracia Natera, Andrea González, Gemma Llauradó, Juan José Chillarón and Juana A. Flores-Le Roux
Diabetology 2025, 6(11), 139; https://doi.org/10.3390/diabetology6110139 - 4 Nov 2025
Viewed by 117
Abstract
Purpose: It has been previously described that some women with type 1 diabetes (T1D) may experience changes in glucose levels in relation to their menstrual cycle. However, whether an advanced hybrid closed-loop system (AHCL) can mitigate these cycle-dependent changes is yet to be [...] Read more.
Purpose: It has been previously described that some women with type 1 diabetes (T1D) may experience changes in glucose levels in relation to their menstrual cycle. However, whether an advanced hybrid closed-loop system (AHCL) can mitigate these cycle-dependent changes is yet to be determined. Methods: This study is a prospective analysis of a cohort of premenopausal women with T1D with spontaneous menstrual cycles who are users of an AHCL system 780G Medtronic®. Three consecutive cycles were analyzed for each patient, and each cycle was divided into three phases (menstrual, luteal, and rest of cycle phase). Results: Fifteen subjects were included. Mean age was 38 ± 7.6 years, HbA1c was 7.12 ± 0.7%, and diabetes duration was 21 ± 13.7 years. Mean glucose was higher in the luteal phase compared to the menstrual period (p = 0.029 luteal vs. menstrual) and the rest of the cycle (p = 0.018 luteal vs. rest of cycle). The time in range (TIR) was lower in the luteal phase compared to the rest of cycle phase (p = 0.015 luteal vs. rest of cycle). The time below range (TBR) was significantly higher in the menstrual compared to the luteal phase (p = 0.007 luteal vs. menstrual). Daily insulin requirements were higher in luteal phase compared to rest of cycle (p = 0.017 luteal vs. rest of cycle). Conclusions: A higher mean glucose and lower TIR, despite a higher total insulin dose, was observed in the luteal phase. A higher TBR was observed in the menstrual phase. However, AHCL with 780G Medtronic® achieves a TIR of almost 70% in all cycle phases. Full article
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21 pages, 1232 KB  
Review
Gut Microbiome in Patients with Chronic Kidney Disease Stages 4 and 5: A Systematic Literature Review
by Ioana Livia Suliman, Florin Gabriel Panculescu, Dragos Fasie, Bogdan Cimpineanu, Andreea Alexandru, Nelisa Gafar, Stere Popescu, Teodor Stefan Nitu, Florin-Daniel Enache, Tatiana Chisnoiu, Georgeta Camelia Cozaru and Liliana-Ana Tuta
Int. J. Mol. Sci. 2025, 26(21), 10706; https://doi.org/10.3390/ijms262110706 - 3 Nov 2025
Viewed by 143
Abstract
This systematic review investigates the role of the gut microbiota in patients with advanced chronic kidney disease (CKD), specifically stages 4 and 5. Increasing evidence suggests that dysbiosis—an alteration in the normal balance of gut microbial populations—is not merely a secondary consequence of [...] Read more.
This systematic review investigates the role of the gut microbiota in patients with advanced chronic kidney disease (CKD), specifically stages 4 and 5. Increasing evidence suggests that dysbiosis—an alteration in the normal balance of gut microbial populations—is not merely a secondary consequence of renal decline but a significant driver of disease progression. Such microbial imbalances are closely linked to a range of CKD-associated complications, including systemic inflammation, accumulation of uremic toxins, and heightened cardiovascular risk. Using PRISMA 2020 guidelines, we analyzed 87 peer-reviewed studies published between 2019 and 2025. The review revealed a consistent decline in beneficial microbes such as short-chain fatty acid-producing bacteria were markedly reduced, while populations of uremic toxin-generating microbes were notably increased. This microbial imbalance was associated with elevated concentrations of indoxyl sulfate and p-cresyl sulfate, heightened systemic inflammation, and impaired intestinal barrier integrity. Five conceptual frameworks—including the gut—kidney axis and endotoxemia—inflammation loop—were discussed. Ten microbiome assessment tools were reviewed, including 16S rRNA sequencing and LC-MS/MS for uremic toxin detection. Although probiotics, prebiotics, and synbiotics are gaining attention as potential therapeutic options, questions remain regarding their long-term efficacy and incorporation into standard clinical practice. Increasing scientific evidence underscores the gut microbiome’s pivotal role in CKD progression and management, reinforcing the need for carefully designed, long-term interventions aimed at restoring a healthier microbial balance to support renal function. Full article
(This article belongs to the Special Issue Intestinal Diseases and Gut Microbiota)
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23 pages, 2919 KB  
Article
From Black Box to Transparency: The Impact of Multi-Level Visualization on User Trust in Autonomous Driving
by Mengniu Li, Ming Zhou, Yajun Li, Wentao Wei, Tianlu Zhu, Xun Xu, Linyan Ren, Nuowen Zhang, Renhan Xu and Jinye Li
Sensors 2025, 25(21), 6725; https://doi.org/10.3390/s25216725 - 3 Nov 2025
Viewed by 208
Abstract
Autonomous systems’ “black-box” nature impedes user trust and adoption. To investigate explainable visualizations’ impact on trust and cognitive states, we conducted a within-subjects study with 29 participants performing high-fidelity driving tasks across three transparency conditions: black-box, standard, and enhanced visualization. Multimodal data analysis [...] Read more.
Autonomous systems’ “black-box” nature impedes user trust and adoption. To investigate explainable visualizations’ impact on trust and cognitive states, we conducted a within-subjects study with 29 participants performing high-fidelity driving tasks across three transparency conditions: black-box, standard, and enhanced visualization. Multimodal data analysis revealed that enhanced visualization significantly increased perceived usefulness by 28.5% (p < 0.001), improved functional trust, and decreased average pupil diameter by 15.3% (p < 0.05), indicating lower cognitive load. The black-box condition elicited minimal visual exploration, lowest subjective ratings, and “out-of-the-loop” behaviors. Fixation duration showed no significant difference between standard and enhanced conditions. These findings demonstrate that well-designed visualizations enable balanced trust calibration and cognitive efficiency, advocating “meaningful transparency” as a core design principle for effective human–machine collaboration in autonomous vehicle interfaces. This study provides empirical evidence that transparency enhances user experience and system performance. Full article
(This article belongs to the Section Vehicular Sensing)
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16 pages, 788 KB  
Perspective
The Nallan–Nickel Effect: A Mechanistic Perspective on Burning Sensations and Lichenoid Reactions in Long-Serving Porcelain-Fused-to-Metal Restorations
by Nallan C. S. K. Chaitanya, Nada Tawfig Hashim, Vivek Padmanabhan, Md Sofiqul Islam, Rasha Babiker, Riham Mohammed and Muhammed Mustahsen Rahman
Dent. J. 2025, 13(11), 507; https://doi.org/10.3390/dj13110507 - 3 Nov 2025
Viewed by 223
Abstract
Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple [...] Read more.
Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple mechanical wear. This Perspective introduces the Nallan–Nickel Effect, a theoretical model proposing that a host- and environment-dependent threshold of bioavailable nickel ions (Ni2+), once exceeded, may trigger a neuro-immune cascade culminating in a burning phenotype. Within this framework, slow corrosion at exposed PFM interfaces releases Ni2+ into saliva and crevicular fluid, facilitating epithelial uptake and activation of innate immune sensors such as TLR4 and NLRP3. The resulting cytokine milieu (IL-1β, IL-6, TNF-α) drives NF-κB, mediated inflammation and T-cell activation, while neurogenic mediators—including nerve growth factor (NGF), substance P, and CGRP—sensitize TRPV1/TRPA1 nociceptors, establishing feedback loops of persistent burning and neurogenic inflammation. Modifying factors such as low salivary flow, acidic oral pH, mixed-metal galvanic coupling, and parafunctional stress can lower this threshold, whereas replacement with high-noble or all-ceramic materials may restore tolerance. The model generates testable predictions: elevated local free Ni2+ levels and increased expression of TLR4 and TRPV1 in symptomatic mucosa, along with clinical improvement following substitution of nickel-containing restorations. Conceptually, the Nallan–Nickel Effect reframes PFM-associated burning and lichenoid lesions as threshold-governed, neuro-immune phenomena rather than nonspecific irritations. By integrating corrosion chemistry, mucosal immunology, and sensory neurobiology, this hypothesis offers a coherent, testable framework for future translational research and patient-centered management of PFM-related complications. Full article
(This article belongs to the Section Dental Materials)
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10 pages, 1203 KB  
Brief Report
Engineering Linker-Enhanced OmpG Nanopores for Rapid Single-Molecule Protease Detection
by Minji Kim and Bach Pham
Sensors 2025, 25(21), 6681; https://doi.org/10.3390/s25216681 - 1 Nov 2025
Viewed by 222
Abstract
Single-molecule nanopore sensors have enabled real-time detection of enzymatic cleavage events, yet achieving sensitive and specific analysis of protease activity remains an important challenge for diagnostic applications. We engineered OmpG nanopore constructs incorporating thrombin recognition peptides into loop 6 with varied flexible and [...] Read more.
Single-molecule nanopore sensors have enabled real-time detection of enzymatic cleavage events, yet achieving sensitive and specific analysis of protease activity remains an important challenge for diagnostic applications. We engineered OmpG nanopore constructs incorporating thrombin recognition peptides into loop 6 with varied flexible and negatively charged linkers to optimize accessibility and cleavage. SDS-PAGE gel analysis showed that constructs with the recognition peptide placed after residue D225 and incorporating dual linkers achieved cleavage efficiencies up to 95%, whereas constructs without linkers showed limited cleavage. Single-channel recordings revealed that linker integration modulates pore conductance, with extended loops exhibiting intermediate open-state currents near 18 pA compared to 25 pA in wild-type OmpG. Upon thrombin addition, rapid and irreversible current drops confirmed real-time protease activity detection. These results demonstrate the critical role of linker design, particularly flexibility and charge, in optimizing nanopore protease sensors, providing a versatile platform for biomedical applications. Full article
(This article belongs to the Section Biosensors)
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20 pages, 3060 KB  
Article
Molecular Phylogenetics of Seven Cyprinidae Distant Hybrid Lineages: Genetic Variation, 2nNCRC Convergent Evolution, and Germplasm Implications
by Ziyi Wang, Yaxian Sun, Ting Liao, Hui Zhong, Qianhong Gu and Kaikun Luo
Biology 2025, 14(11), 1527; https://doi.org/10.3390/biology14111527 - 30 Oct 2025
Viewed by 312
Abstract
Distant hybridization is key to trait innovation and speciation, with Cyprinidae hybrid phylogeny helping to clarify diversification mechanisms. Yet, a major gap persists in Cyprinidae studies: the stabilization mechanisms of interspecific distant hybrid lineages. To address this, we systematically analyzed the molecular phylogeny [...] Read more.
Distant hybridization is key to trait innovation and speciation, with Cyprinidae hybrid phylogeny helping to clarify diversification mechanisms. Yet, a major gap persists in Cyprinidae studies: the stabilization mechanisms of interspecific distant hybrid lineages. To address this, we systematically analyzed the molecular phylogeny of seven Cyprinidae distant hybrid lineages and their parental species, using an integrative genetic framework encompassing four mitochondrial genes (Cytb, COI, 16S rRNA, D-loop) and five nuclear genes (EGR2b, IRBP2, RAG1, RAG2, RH2). Homologous sequences of 41 representative Cyprinidae species (85 samples) were retrieved from GenBank to supplement the dataset. Phylogenies were reconstructed from concatenated sequences, complemented by haplotype networks. Intra-/interspecific divergence was quantified using two mitochondrial genes (COI, Cytb) and two nuclear (RAG1, RH2). The results showed that these hybrid lineages exhibited variation patterns analogous to other Cyprinidae species. Both ML and BI trees reconstructed exhibited congruent topologies with high support (bootstrap/BPP > 80%), resolving genus/species-level relationships. While most hybrids clustered intermediately between their parental species, they typically displayed maternal affinity. A notable exception was the 2nNCRC (a homodiploid hybrid from Cyprinus carpio ♀ × Megalobrama amblycephala ♂), which displayed convergent evolution toward Carassius auratus. COI-based K2P genetic distance analysis revealed 2nNCRC had a much closer relationship with C. auratus (0.0119) than with its parents (0.1249 to C. carpio, 0.1552 to M. amblycephala). These nine genes elucidate the genetic relationships between Cyprinid hybrid lineages and progenitors, serving as pivotal molecular markers for parentage tracing and genetic dissection of distant hybridization mechanisms. The integrated mitochondrial–nuclear marker system in this study advances understanding of cytonuclear coadaptation and the stabilization of interspecific distant hybrid lineages in Cyprinidae. Specifically, it provides a precise tool for parentage tracing, Cyprinid germplasm conservation, and targeted regulation of hybrid breeding—laying a foundation for exploring hybrid speciation and developing elite aquaculture germplasms. Full article
(This article belongs to the Special Issue Genetics and Evolutionary Biology of Aquatic Organisms)
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18 pages, 4036 KB  
Article
Precise Control of Micropipette Flow Rate for Fluorescence Imaging in In Vivo Micromanipulation
by Ruimin Li, Shaojie Fu, Zijian Guo, Jinyu Qiu, Yuzhu Liu, Mengya Liu, Qili Zhao and Xin Zhao
Sensors 2025, 25(21), 6647; https://doi.org/10.3390/s25216647 - 30 Oct 2025
Viewed by 540
Abstract
Precise regulation of micropipette outlet flow is critical for fluorescence imaging in vivo micromanipulations. In such procedures, a micropipette with a micro-sized opening is driven by gas pressure to deliver internal solution into the in vivo environment. The outlet flow rate needs to [...] Read more.
Precise regulation of micropipette outlet flow is critical for fluorescence imaging in vivo micromanipulations. In such procedures, a micropipette with a micro-sized opening is driven by gas pressure to deliver internal solution into the in vivo environment. The outlet flow rate needs to be precisely regulated to ensure a uniform and stable fluorescence distribution. However, conventional manual pressure injection methods face inherent limitations, including insufficient precision and poor reproducibility. Existing commercial microinjection systems lack a quantitative relationship between pressure and flow rate. And existing calibration methods in the field of microfluidics suffer from a limited flow-rate measurement resolution, constraining the establishment of a precise pressure–flow quantitative relationship. To address these challenges, we developed a closed-loop pressure regulation system with 1 Pa-level control resolution and established a quantitative calibration of the pressure–flow relationship using a droplet-based method. The calibration revealed a linear relationship with a mean pressure–flow gain of 4.846 × 1017m3·s1·Pa1 (R2 > 0.99). Validation results demonstrated that the system achieved the target outlet flow rate with a flow control error less than 10 fL/s. Finally, the application results in brain-slice environment confirmed its capability to maintain stable fluorescence imaging, with fluorescence intensity fluctuations around 1.3%. These results demonstrated that the proposed approach provides stable, precise, and reproducible flow regulation under physiologically relevant conditions, thereby offering a valuable tool for in vivo micromanipulation and detection. Full article
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26 pages, 2876 KB  
Article
Blend Prediction Model for Vapor Pressure of Jet Fuel Range Hydrocarbons
by Randall C. Boehm, Robert Parker, Zhibin Yang, Stephen Dooley and Joshua S. Heyne
Sustainability 2025, 17(21), 9612; https://doi.org/10.3390/su17219612 - 29 Oct 2025
Viewed by 197
Abstract
The ability to predict the vapor pressure and vapor-phase composition of hydrocarbon mixtures (such as jet fuel, sustainable aviation fuel or its un-refined precursors) and partially vaporized hydrocarbon mixtures is important to simulations of processes that involve vaporization such as distillations, flash points, [...] Read more.
The ability to predict the vapor pressure and vapor-phase composition of hydrocarbon mixtures (such as jet fuel, sustainable aviation fuel or its un-refined precursors) and partially vaporized hydrocarbon mixtures is important to simulations of processes that involve vaporization such as distillations, flash points, combustion properties of partially vaporized fuels, etc. Raoult’s Law provides a simple algebraic formula relating liquid composition and temperature to vapor composition and pressure. However, Raoult’s Law is not accurate at low mole fractions, which is typical for complex mixtures such as fuels. A common approach to correcting Raoult’s Law is to apply a scale factor, a so-called activity coefficient. Numerous models exist for predicting activity coefficients. Here we benchmark against the UNIFAC model, which predicts activity coefficients based on mole fractions, group fractions, Van der Waals volume and surface area and temperature-dependent interaction terms between groups. While this approach is truly predictive, its accuracy at very low mole fractions has not been validated, and it is computationally intensive, particularly for simulations (especially optimizations) that require vapor composition or pressure within the inner-most loop. Here we present an alternative correction to Raoult’s law, where the vapor pressure of the ith component is represented by a modified form of the Clausius–Clapeyron equation. The reference temperature (Tref) is replaced by a simple algebraic function that converges to Tref as xi approaches 1 while smoothly increasing from this value as xi decreases. Simultaneously, the heat of vaporization (ΔHvap,i(T)) term is replaced by another simple algebraic expression that converges to ΔHvap,iT as xi approaches 1 while smoothly decreasing as xi decreases. In this model, the temperature-dependent heat of vaporization is tuned at each temperature such that the Clausius–Clapeyron equation reproduces the correct vapor pressure of the neat material, while the parameterized algebraic corrections are tuned to vapor pressure data of mixtures involving n-pentane, toluene, and dodecane, where the mole fractions of n-pentane and toluene are maintained below 10%mol. Validation of the resulting model is accomplished by comparing modeled vapor–liquid equilibrium systems with experimental measurements. This approach improves the accuracy and computational efficiency of volatility predictions, thereby supporting the development, certification, and adoption of sustainable aviation fuel. Full article
(This article belongs to the Section Energy Sustainability)
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48 pages, 5070 KB  
Article
Dual Inhibitory Potential of Conessine Against HIV and SARS-CoV-2: Structure-Guided Molecular Docking Analysis of Critical Viral Targets
by Ali Hazim Abdulkareem, Meena Thaar Alani, Sameer Ahmed Awad, Safaa Abed Latef Al-Meani, Mohammed Mukhles Ahmed, Elham Hazeim Abdulkareem and Zaid Mustafa Khaleel
Viruses 2025, 17(11), 1435; https://doi.org/10.3390/v17111435 - 29 Oct 2025
Viewed by 397
Abstract
Human immunodeficiency virus (HIV-1) and SARS-CoV-2 continue to co-burden global health, motivating discovery of broad-spectrum small molecules. Conessine, a steroidal alkaloid, has reported membrane-active and antimicrobial properties but remains underexplored as a dual antiviral chemotype. To interrogate conessine’s multi-target antiviral potential against key [...] Read more.
Human immunodeficiency virus (HIV-1) and SARS-CoV-2 continue to co-burden global health, motivating discovery of broad-spectrum small molecules. Conessine, a steroidal alkaloid, has reported membrane-active and antimicrobial properties but remains underexplored as a dual antiviral chemotype. To interrogate conessine’s multi-target antiviral potential against key enzymatic and entry determinants of HIV-1 and SARS-CoV-2 and to benchmark performance versus approved comparators. Eight targets were modeled: HIV-1 reverse transcriptase (RT, 3V81), protease (PR, 1HVR), integrase (IN, 3LPT), gp120–gp41 trimer (4NCO); and SARS-CoV-2 main protease (Mpro, 6LU7), papain-like protease (PLpro, 6W9C), RNA-dependent RNA polymerase (RdRp, 7BV2), spike RBD (6M0J). Ligands (conessine; positive controls: dolutegravir for HIV-1, nirmatrelvir for SARS-CoV-2) were prepared with standard protonation, minimized, and docked using AutoDock Vina v 1.2.0exhaustiveness 4; 20 poses). Binding modes were profiled in 2D/3D. Protocol robustness was verified by re-docking co-crystallized ligands (RMSD ≤ 2.0 Å). Atomistic MD (explicit TIP3P, OPLS4, 300 K/1 atm, NPT; 50–100 ns) assessed pose stability (RMSD/RMSF), pocket compaction (Rg, volume), and interaction persistence; MM/GBSA provided qualitative energy decomposition. ADMET was predicted in silico. Conessine showed coherent, hydrophobically anchored binding across both viral panels. Best docking scores (kcal·mol−1) were: HIV-1—PR −6.910, RT −6.672, IN −5.733; SARS-CoV-2—spike RBD −7.025, Mpro −5.745, RdRp −5.737, PLpro −5.024. Interaction maps were dominated by alkyl/π-alkyl packing to catalytic corridors (e.g., PR Ile50/Val82, RT Tyr181/Val106; Mpro His41/Met49; RBD L455/F486/Y489) with occasional carbon-/water-mediated H-bonds guiding orientation. MD sustained low ligand RMSD (typically ≤1.6–2.2 Å) and damped RMSF at catalytic loops, indicating pocket rigidification; MM/GBSA trends (≈ −30 to −40 kcal·mol−1, dispersion-driven) supported persistent nonpolar stabilization. Benchmarks behaved as expected: dolutegravir bound strongly to IN (−6.070) and PR (−7.319) with stable MD; nirmatrelvir was specific for Mpro and displayed weaker, discontinuous engagement at PLpro/RdRp/RBD under identical settings. ADMET suggested conessine has excellent permeability/BBB access (high logP), but liabilities include poor aqueous solubility, predicted hERG risk, and CYP2D6 substrate dependence.Conessine operates as a hydrophobic, multi-target wedge with the most favorable computed engagement at HIV-1 PR/RT and the SARS-CoV-2 spike RBD, while maintaining stable poses at Mpro and RdRp. The scaffold merits medicinal-chemistry optimization to improve solubility and de-risk cardiotoxicity/CYP interactions, followed by biochemical and cell-based validation against prioritized targets. Full article
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18 pages, 916 KB  
Article
Real-Time Electroencephalography-Guided Binaural Beat Audio Enhances Relaxation and Cognitive Performance: A Randomized, Double-Blind, Sham-Controlled Repeated-Measures Crossover Trial
by Chanaka N. Kahathuduwa, Jessica Blume, Chinnadurai Mani and Chathurika S. Dhanasekara
Physiologia 2025, 5(4), 44; https://doi.org/10.3390/physiologia5040044 - 24 Oct 2025
Viewed by 845
Abstract
Background/Objectives: Binaural beat audio has gained popularity as a non-invasive tool to promote relaxation and enhance cognitive performance, though empirical support has been inconsistent. We developed a novel algorithm integrating real-time electroencephalography (EEG) feedback to dynamically tailor binaural beats to induce relaxed brain [...] Read more.
Background/Objectives: Binaural beat audio has gained popularity as a non-invasive tool to promote relaxation and enhance cognitive performance, though empirical support has been inconsistent. We developed a novel algorithm integrating real-time electroencephalography (EEG) feedback to dynamically tailor binaural beats to induce relaxed brain states. This study aimed to examine the efficacy and feasibility of this algorithm in a clinical trial. Methods: In a randomized, double-blinded, sham-controlled crossover trial, 25 healthy adults completed two 30 min sessions (EEG-guided intervention versus sham). EEG (Fp1) was recorded using a consumer-grade single-electrode headset, with auditory stimulation adjusted in real time based on EEG data. Outcomes included EEG frequency profiles, stop signal reaction time (SSRT), and novelty encoding task performance. Results: The intervention rapidly reduced dominant EEG frequency in all participants, with 100% achieving <8 Hz and 96% achieving <4 Hz within median 7.4 and 9.0 min, respectively. Compared to the sham, the intervention was associated with an faster novelty encoding reaction time (p = 0.039, dz = −0.225) and trends towards improved SSRT (p = 0.098, dz = −0.209), increased boundary separation in stop trials (p = 0.065, dz = 0.350), and improved inhibitory drift rate (p = 0.067, dz = 0.452) within the limits of the exploratory nature of these findings. Twenty-four (96%) participants reached a target level of <4 Hz with the intervention, while none reached this level with the sham. Conclusions: Real-time EEG-guided binaural beats may rapidly induce low-frequency brain states while potentially preserving or enhancing aspects of executive function. These findings support the feasibility of personalized, closed-loop auditory entrainment for promoting “relaxed alertness.” The results are preliminary and hypothesis-generating, warranting larger, multi-channel EEG studies in ecologically valid contexts. Full article
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13 pages, 2313 KB  
Article
The Role of a Newly Synthesized Antimicrobial Peptide (KK)2-KWWW-NH2 in Modulating Phosphatidylinositol Monolayer Properties in the Presence of Ascorbic Acid
by Iwona Golonka, Aleksandra Sebastiańczyk, Izabela W. Łukasiewicz, Katarzyna E. Greber, Wiesław Sawicki and Witold Musiał
Int. J. Mol. Sci. 2025, 26(21), 10344; https://doi.org/10.3390/ijms262110344 - 23 Oct 2025
Viewed by 239
Abstract
Ascorbic acid (AA) and its derivatives (EAA), due to their antioxidant properties, may offer potential support in acne therapy. The aim of this study was to evaluate the effect of compound P6—(KK)2-KWWW-NH2—in the presence of AA or EAA on [...] Read more.
Ascorbic acid (AA) and its derivatives (EAA), due to their antioxidant properties, may offer potential support in acne therapy. The aim of this study was to evaluate the effect of compound P6—(KK)2-KWWW-NH2—in the presence of AA or EAA on the stability and organization of phosphatidylinositol (PI) monolayers. The conducted experiments showed that the monolayers were in the expanded liquid state (37.45–48.35 mN/m) or in the transitional phase between the expanded liquid and condensed states (51.06–56.82 mN/m). Compression and decompression isotherms indicated the highest flexibility for the PI + P6 system, with the compression reversibility coefficient (Rv) ranging from 87.34% to 97.77%, increasing with temperature in successive loops. The surface pressure vs. time dependence after compound injection into the subphase revealed a decrease in monolayer surface pressure followed by stabilization after approximately 300 s for the PI + P6 + AA and PI + P6 + EAA systems. In contrast, for the PI + P6 system at 35 °C, an increase in surface pressure was observed. Full article
(This article belongs to the Section Molecular Biology)
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19 pages, 3171 KB  
Article
Cardiac Circular RNAs CDR1as, Circ-RCAN2, Circ-C12orf29 Show Cell-Specific Hypoxia-Induced Dysregulation and Distinct In Vitro Effects
by Ena Hasimbegovic, Dominika Lukovic, Nina Kastner, Benedikt S. Hofer, Andreas Spannbauer, Denise Traxler, Julia Mester-Tonczar, Kevin Hamzaraj, Emilie Han, Martin Riesenhuber, Babette Maleiner, Katrin Müller-Zlabinger and Mariann Gyöngyösi
Int. J. Mol. Sci. 2025, 26(21), 10334; https://doi.org/10.3390/ijms262110334 - 23 Oct 2025
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Abstract
Circular RNAs (circRNAs) are looped RNA molecules with regulatory roles in myocardial infarction and post-infarction cascades. We aimed to (i) confirm the circularity of novel circRNAs (CDR1as, circ-RCAN2, circ-C12orf29) implicated in myocardial infarction, (ii) examine cell-specific regulation patterns under hypoxia, and (iii) assess [...] Read more.
Circular RNAs (circRNAs) are looped RNA molecules with regulatory roles in myocardial infarction and post-infarction cascades. We aimed to (i) confirm the circularity of novel circRNAs (CDR1as, circ-RCAN2, circ-C12orf29) implicated in myocardial infarction, (ii) examine cell-specific regulation patterns under hypoxia, and (iii) assess their effects on cell viability and downstream miRNA targets. Experiments were conducted on porcine cardiac progenitor cells (pCPCs), bone marrow mesenchymal stem cells (pMSCs) and cardiac fibroblasts (pCFs). Circularity was assessed by RNase R treatment, subsequent qPCR, gel electrophoresis and Sanger sequencing. Hypoxia experiments with/without serum deprivation mimicked ischemia. Effects on viability with/without hypoxia (MTT assay) and downstream miRNA targets were assessed via short interfering RNA (siRNA)-mediated knockdown of circ-RCAN2 and circ-C12orf29. Following RNase R treatment, qPCR product electrophoresis demonstrated amplification of singular products for all circRNAs, with backsplice junction amplification confirmed via Sanger sequencing. Serum deprivation and hypoxia resulted in cell-specific circRNA expression patterns, with an upregulation of all candidates in pCPCs across all intervals of hypoxia, an upregulation of circ-RCAN2 and circ-C12orf29 in pMSCs with prolonged hypoxia, and no detectable dysregulation in pCFs. siRNA knockdown of circ-RCAN2 reduced pCF- and increased pMSC-viability. circ-C12orf29 knockdown increased pCPC- and reduced pMSC-viability. circ-C12orf29 knockdown also upregulated ssc-miR-21-5p and ssc-miR-181c in pCPCs, with no detectable targets for circ-RCAN2. In conclusion, CDR1as, circ-RCAN2 and circ-C12orf29 are circular and dysregulated in a time- and cell-type-specific manner following hypoxia. circ-RCAN2 and circ-C12orf29 exhibit cell-type specific effects on viability, with circ-C12orf29 also targeting downstream miRNAs. Full article
(This article belongs to the Section Molecular Biology)
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Review
Visceral Obesity and Metabolic Dysfunction in IgA Nephropathy: Nutritional and Metabolic Perspectives on Disease Progression
by Agnieszka Skibicka and Sylwia Małgorzewicz
Nutrients 2025, 17(20), 3307; https://doi.org/10.3390/nu17203307 - 21 Oct 2025
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Abstract
Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. In addition to genetic and immunological factors, visceral obesity and metabolic syndrome (MetS) are the main determinants of disease progression. This review aims to critically assess the role of visceral [...] Read more.
Introduction: IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. In addition to genetic and immunological factors, visceral obesity and metabolic syndrome (MetS) are the main determinants of disease progression. This review aims to critically assess the role of visceral obesity and metabolic syndrome in driving the progression of IgA nephropathy (IgAN), with an emphasis on their underlying pathophysiological mechanisms and clinical implications. Methods: A systematic review was carried out in accordance with PRISMA guidelines. PubMed was searched (2015–2025) using terms related to IgA nephropathy, obesity, metabolic syndrome, and immunometabolic pathways. Only English-language observational and clinical studies in adults, excluding pediatric and animal studies, were included in the review. Additional sources were consulted to give context to the mechanistic aspects of obesity-related IgAN progression. Results: Visceral obesity and MetS accelerate IgAN progression through endocrine, inflammatory, and immune pathways, including cytokines derived from visceral adipose tissue, adipokines, intestinal dysbiosis, and BAFF/APRIL-mediated immune activation. MetS patients had higher proteinuria, a faster decrease in eGFR, and a higher risk of end-stage renal failure (23/65 vs. 15/60 endpoints, p < 0.001). Nutritional and metabolic interventions—including weight reduction, GLP-1 receptor agonists, dual GLP-1/GIP agonists, and bariatric/metabolic surgery—demonstrate renoprotective effects in obesity-related kidney disease and may have implications for IgAN. Conclusions: Obesity should be considered a chronic disease and a modifiable risk factor for IgAN. Nutrition-focused interventions targeting visceral obesity and metabolic dysfunction can slow the progression of the disease and should be included in renal guidelines. This review expands current knowledge by demonstrating that when sequential steps of IgAN pathophysiology are mapped with respect to endocrine and immunological effects of visceral adipose tissue, they converge on the same proinflammatory and immune pathways. This convergence suggests a bidirectional amplification loop in which obesity accelerates IgAN progression and increases the burden of complications. Full article
(This article belongs to the Section Nutrition and Obesity)
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