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13 pages, 3727 KB  
Article
Transcutaneous Electrical Nerve Stimulation Based on a Microneedle/Hydrogel Composite System
by Xiangyu Li, Donghao Li, Yuqi Wang, Peng Tian and Yunfeng Wang
Appl. Sci. 2026, 16(6), 2841; https://doi.org/10.3390/app16062841 - 16 Mar 2026
Abstract
Transcutaneous electrical nerve stimulation (TENS) is constrained by high skin impedance and unstable electrode contact. This study proposes a novel composite electrode system comprising a polyvinyl alcohol/silver (PVA/Ag) microneedle array and a highly conductive polyacrylamide/lithium chloride (PAAm/LiCl) hydrogel. The PVA/Ag microneedles (~365 µm [...] Read more.
Transcutaneous electrical nerve stimulation (TENS) is constrained by high skin impedance and unstable electrode contact. This study proposes a novel composite electrode system comprising a polyvinyl alcohol/silver (PVA/Ag) microneedle array and a highly conductive polyacrylamide/lithium chloride (PAAm/LiCl) hydrogel. The PVA/Ag microneedles (~365 µm in height, ~48 µm tip diameter) possess sufficient mechanical strength to penetrate the stratum corneum, establishing a low-resistance pathway. The complementary PAAm/LiCl hydrogel exhibits high conductivity (10.28 S/m) and mechanical flexibility, further optimizing the interface contact. The experimental results demonstrate that this composite system achieves low electrochemical impedance and induces stable, clear electromyographic responses in vivo. It effectively addresses the common issues of electrode detachment and signal attenuation associated with conventional electrodes, offering a promising hardware solution for efficient and comfortable wearable rehabilitation devices. Full article
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23 pages, 4110 KB  
Article
Mrgprb4-Lineage Neurons Participate in the Intervention of TENS Effects on Chronic Pain and Anxiety-like Symptoms in an Inflammatory Pain Mouse Model
by Longhua Du, Hongyi Cheng, Jiamian Zhang, Hang Sun, Xia Li, Shuya Wang, Yun Liu, Bing Zhu, Xinyan Gao and Kun Liu
Biomedicines 2026, 14(3), 670; https://doi.org/10.3390/biomedicines14030670 - 15 Mar 2026
Abstract
Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the [...] Read more.
Background: Mas-related G-protein-coupled receptor b4 (Mrgprb4)-lineage neurons in the peripheral nervous system are a type of C fibers in hairy skin. Our prior work demonstrated that these neurons respond to both noxious and innocuous mechanical and thermal stimuli. Ablating them eliminates the pleasant sensation elicited by gentle pressure on a mouse’s nape. However, their potential role in mitigating pain and pain-related negative emotions in response to somatic stimuli remains unclear. Methods: A CFA-induced chronic pain and anxiety comorbidity model was established in C57BL/6J mice. In vivo calcium imaging of dorsal root ganglia (DRG) neurons in Mrgprb4-GCaMP6s transgenic mice characterized neuronal responses to transcutaneous electrical nerve stimulation (TENS) at the Zusanli (ST36) acupoint. Optogenetic activation (Mrgprb4-ChR2 mice) and viral ablation of Mrgprb4-lineage neurons were employed to evaluate their role in mediating TENS effects on mechanical pain thresholds and anxiety-like behaviors. Results: In vivo calcium imaging revealed that 0.5 mA TENS preferentially activated Mrgprb4-lineage neurons compared to 2.0 mA TENS. In CFA model mice, 0.5 mA TENS at ST36 significantly increased mechanical pain thresholds and reduced anxiety-like behaviors in the open-field test. Optogenetic activation of Mrgprb4-lineage neurons at ST36 replicated these analgesic and anxiolytic effects, demonstrating the sufficiency of these neurons for therapeutic outcomes. Conversely, viral ablation of L3–L5 Mrgprb4-lineage neurons substantially attenuated the therapeutic effects of 0.5 mA TENS for both pain relief and anxiety reduction, indicating their necessity in mediating TENS efficacy. Conclusions: Mrgprb4-lineage neurons serve as critical peripheral mediators of TENS-induced analgesia and anxiolysis. These findings identify a specific neuronal population underlying the therapeutic effects of somatic stimulation at ST36, providing mechanistic insights that may guide optimization of TENS parameters for treating chronic pain and comorbid anxiety in clinical settings. Full article
(This article belongs to the Section Neurobiology and Clinical Neuroscience)
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30 pages, 3258 KB  
Review
The Role of GABA and Its Receptors in Temporal Lobe Epilepsy
by Günther Sperk and Susanne Pirker
Biomolecules 2026, 16(3), 422; https://doi.org/10.3390/biom16030422 - 12 Mar 2026
Viewed by 193
Abstract
Mesial temporal lobe epilepsy (TLE) is the most common and severe form of focal epilepsy. This review examines the diverse mechanisms by which the GABAergic system contributes both to seizure generation and to protective processes that limit epileptogenesis and seizure progression in TLE. [...] Read more.
Mesial temporal lobe epilepsy (TLE) is the most common and severe form of focal epilepsy. This review examines the diverse mechanisms by which the GABAergic system contributes both to seizure generation and to protective processes that limit epileptogenesis and seizure progression in TLE. We focus on findings from established animal models of TLE as well as studies of surgically resected tissue from patients who had undergone therapeutic intervention. Experimental models include sustained electrical stimulation of the perforant path, as well as the kainic acid (KA) and Li-pilocarpine models. Although these paradigms induce status epilepticus (SE) through distinct mechanisms, they ultimately converge on prolonged excitation of hippocampal CA3 pyramidal neurons and interconnected regions of the hippocampus and broader limbic network. In response to epileptic seizures, GABA synthesis is enhanced, as evidenced by the marked upregulation of the GABA-synthesizing enzymes GAD65 and GAD67, along with their ectopic expression in glutamatergic mossy fibers of the hippocampus. Shortly after acute seizures, a transient expression of the embryonic GAD67 splice variant, GAD25, is observed, although its functional significance remains unclear. At the receptor level, animal models of TLE show upregulation of GABAA receptor subunits α2, α4, β3, and γ2, accompanied by downregulation of α5 and δ subunits, suggesting reduced tonic inhibition. In contrast, hippocampal tissue from patients with TLE exhibits pronounced upregulation of α5 and δ subunits, indicative of enhanced extrasynaptic tonic inhibition. Similarly, whereas GABAA receptor subunits are mildly downregulated in animal models, they are consistently upregulated across hippocampal subfields in human TLE, pointing toward strengthened GABAergic inhibition. Conversely, genetic variants of GABAA receptor subunits and autoantibodies targeting these receptors can contribute to the etiology of epilepsy, often with onset in childhood. Moreover, degeneration or functional silencing of specific GABAergic interneuron populations—such as parvalbumin-positive neurons in the subiculum—can induce epilepsy in rodent models and is likewise associated with TLE in humans. Full article
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18 pages, 6345 KB  
Article
Shape Memory and Self-Healing Behavior of 4D-Printed Electroactive Polycaprolactone/Polylactic Acid/Graphene Nanocomposite: Structure-Properties Relations
by Rumiana Kotsilkova, Evgeni Ivanov, Vladimir Georgiev and Todor Batakliev
J. Compos. Sci. 2026, 10(3), 155; https://doi.org/10.3390/jcs10030155 - 12 Mar 2026
Viewed by 149
Abstract
The 4D printing of thermo-responsive shape-memory multicomponent polymer composites, which possess the ability to change shape by exposure to heat, has attracted much attention in recent years because of their scientific and technological significance. In the present study, we investigate shape memory performance [...] Read more.
The 4D printing of thermo-responsive shape-memory multicomponent polymer composites, which possess the ability to change shape by exposure to heat, has attracted much attention in recent years because of their scientific and technological significance. In the present study, we investigate shape memory performance of a polylactic acid-polycaprolactone-graphene nanocomposite activated directly by increasing the environmental temperature and indirectly, by Joule heating. The incorporation of graphene within the shape-memory biopolymer blend allowed formation of a programmable conduction path, whose electric properties are intimately coupled to thermo-mechanical processes. Advanced rheological, thermal, and thermo-mechanical properties were evaluated and related to the structure of nanocomposite. The electrically and thermally stimulated shape memory and self-healing behavior of the nanocomposite based on polycaprolactone/poly(lactic) acid blend reinforced with graphene nanoplatelets (PCL/PLA/GNP) were investigated. The shape memory tests revealed a good reversibility of 76% between the temporary and permanent states of the samples bent to 180 degrees and a high healing efficiency of 96% if stimulated by Joule heating. The highly electroactive nanocomposite demonstrated a great potential for 4D-printing of objects with complex structures, shapes, and electrically-stimulated shape-memory and self-healing functions. The nanocomposite is biodegradable, recyclable, and reusable, which may reduce the carbon footprint of the rapidly developing additive technology. Full article
(This article belongs to the Special Issue Advanced Additive Manufacturing of High-Performance Composites)
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32 pages, 5012 KB  
Review
A Review of Modelling, State of Charge Estimation and Management Methods of EV Lithium-Ion Batteries
by Moayad Albakri and Ahmed Darwish
Batteries 2026, 12(3), 92; https://doi.org/10.3390/batteries12030092 - 8 Mar 2026
Viewed by 270
Abstract
Electric Vehicles (EVs) can contribute significantly to reducing greenhouse gas emissions and addressing climate change problems. Modern EVs are primarily powered by electrochemical batteries such as lead-acid (Pb-acid), nickel-metal hydride (NiMH), sodium-ion (Na-ion), solid-state and lithium-ion (Li-ion) batteries. When compared to other battery [...] Read more.
Electric Vehicles (EVs) can contribute significantly to reducing greenhouse gas emissions and addressing climate change problems. Modern EVs are primarily powered by electrochemical batteries such as lead-acid (Pb-acid), nickel-metal hydride (NiMH), sodium-ion (Na-ion), solid-state and lithium-ion (Li-ion) batteries. When compared to other battery types, Li-ion batteries are the most suitable for EV applications due to their practical features such as their high energy density, high charging and discharging efficiency and extended lifetime. However, the main risk of Li-ion batteries is that they are exposed to thermal runaway phenomena, which raises severe concerns about the safety of EV propulsion systems. Thermal runaways should be considered carefully as they cannot be stopped once they start and can lead to battery explosion. One of the main reasons leading to this phenomenon is abusing the state of charge (SoC) of the battery. Therefore, the battery management system (BMS) plays a crucial role in mitigating the stimulation of the thermal runaway process by accurately estimating and properly managing the battery cells. To help researchers and designers with understanding this matter, this paper proposes a review of the most effective SoC estimation methods for EV Li-ion batteries and links these methods with practical energy management systems in the EV market. Full article
(This article belongs to the Special Issue Towards a Smarter Battery Management System: 3rd Edition)
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26 pages, 844 KB  
Systematic Review
The Role of Nuclear Energy in the Economic Transformation of Developing Countries: A Systematic Review of Evidence from Poland
by Marta Drosińska-Komor, Jerzy Głuch, Jędrzej Blaut, Aleksandra Szewieczek and Łukasz Breńkacz
Sustainability 2026, 18(5), 2604; https://doi.org/10.3390/su18052604 - 6 Mar 2026
Viewed by 158
Abstract
Growing electricity demand and decarbonisation requirements pose significant challenges for coal-dependent transition economies. This study examines whether nuclear deployment can support low-carbon economic transformation using Poland’s national nuclear programme as a case study. We conduct a structured document analysis that integrates a systematic [...] Read more.
Growing electricity demand and decarbonisation requirements pose significant challenges for coal-dependent transition economies. This study examines whether nuclear deployment can support low-carbon economic transformation using Poland’s national nuclear programme as a case study. We conduct a structured document analysis that integrates a systematic search and screening of peer-reviewed literature with an analysis of national policy and planning materials and a synthesis of publicly available project documentation for the Lubiatowo-Kopalino nuclear power plant, the Pątnów project, and the planned small modular reactor (SMR) deployments. Impacts on employment, infrastructure, technical education, technology transfer, and local supply chain participation are assessed and mapped to the sustainable development goals and the EU climate policy criteria. The analysis indicates that, if accompanied by early workforce development and supplier prequalification, nuclear investments can stimulate industrial upgrading, strengthen energy security, and deliver regional co-benefits beyond electricity generation. At the same time, scheduling slippage, governance uncertainty, and gaps in domestic capabilities in nuclear-specific components can limit these benefits. The article concludes with recommendations for national and local authorities on stakeholder engagement, local content strategy, and risk management that can be transferred to Central European economies with similar starting conditions. Full article
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12 pages, 578 KB  
Article
Novel Food Supplement Containing a Combination of Postbiotics and Plant-Derived Compounds Regulates Epithelial Barrier Integrity and Immune Response in Human Enterocytes
by Franca Oglio, Serena Coppola, Alessia Cadavere, Roberta Di Santillo, Vittoria Mauriello, Marco Michelini, Raffaele Federico Iorio, Erika Caldaria and Laura Carucci
Foods 2026, 15(5), 922; https://doi.org/10.3390/foods15050922 - 6 Mar 2026
Viewed by 191
Abstract
Background: Alterations of epithelial barrier integrity and immune response play a key role in the pathogenesis of allergic diseases and represent promising targets for nutritional interventions. Selected postbiotics and plant-derived compounds have been proposed as potential modulators of epithelial barrier and immune function. [...] Read more.
Background: Alterations of epithelial barrier integrity and immune response play a key role in the pathogenesis of allergic diseases and represent promising targets for nutritional interventions. Selected postbiotics and plant-derived compounds have been proposed as potential modulators of epithelial barrier and immune function. Methods: We investigated the effects of a novel food supplement combining heat-inactivated Lacticaseibacillus rhamnosus GG, butyrate, Quercetin, and Perilla frutescens extracts on epithelial barrier function and innate immunity in an experimental model of the human epithelial gut barrier. Results: Exposure to the food supplement resulted in epithelial barrier integrity enhancement, consisting of increased transepithelial electrical resistance, tight-junction protein expression, mucus production, and enterocyte differentiation. Moreover, the formulation markedly stimulated the expression of the innate immunity peptides β-defensin-2 and cathelecidin LL-37. Conclusions: The novel food supplement induces a beneficial modulation of the epithelial gut barrier and immune response. These findings support its potential use as a functional food strategy to restore mucosal homeostasis and to promote immune tolerance in allergic diseases. Full article
(This article belongs to the Section Nutraceuticals, Functional Foods, and Novel Foods)
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15 pages, 442 KB  
Article
Electrotherapy Plus Photobiostimulation for the Treatment of Mild Pelvic Organ Prolapse and Stress Urinary Incontinence
by Teresa Maria Manni, Desirèe De Vicari, Mariachiara Palucci, Alice Cola, Marta Barba and Matteo Frigerio
J. Clin. Med. 2026, 15(5), 2016; https://doi.org/10.3390/jcm15052016 - 6 Mar 2026
Viewed by 256
Abstract
Introduction: Pelvic floor disorders (PFDs) are a very widespread clinical phenomenon and are known to affect millions of women worldwide, significantly impairing their quality of life. New technologies and innovations such as electrotherapy and photobiostimulation are currently revolutionizing what concerns conservative treatment, allowing [...] Read more.
Introduction: Pelvic floor disorders (PFDs) are a very widespread clinical phenomenon and are known to affect millions of women worldwide, significantly impairing their quality of life. New technologies and innovations such as electrotherapy and photobiostimulation are currently revolutionizing what concerns conservative treatment, allowing clinicians to tailor therapy to every woman. The aim of this study was to evaluate the feasibility of use of electrotherapy and photobiostimulation in PFD management and the initial results of treatment in clinical practice. Methods: This prospective study (IRB code: GSM-RF 2025) aimed to analyze the impact of the innovative DAFNE system to treat PFDs through electrotherapy and photobiostimulation. We enrolled patients with mild pelvic organ prolapse and stress urinary incontinence who desired a conservative treatment for their conditions. The following validated scales were used for assessing baseline quality of life before and after treatment: Urinary Distress Inventory-6 (UDI-6), Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), Female Sexual Function Index-6 (FSFI-6), 0–100 VAS Scale, and Vaginal Health Index. Electrotherapy was delivered through 4 gold rings, providing Functional Electrical Stimulation (FES), Transcutaneous Electrical Nerve Stimulation (TENS) and/or Microcurrent Electrical Neuromuscular Stimulation (MENS). The photobiostimulation system consisted of 24 LEDs per wavelength (420 nm UVA; 630 nm RED; 870 nm NIR/INFRARED) positioned at 360° along the entire length of the handpiece for antimicrobial purposes, microcirculation improvement, and anti-inflammatory action. The cycle of treatment consisted of 3–5 sessions, according to necessity. Overall improvement was measured through the Patient Global Impression of Improvement (PGI-I). Statistical analysis was performed using Student’s t-Test. A value of p < 0.05 was considered as significant. Results: In the period of interest, 32 women were treated with the DAFNE system. The mean age was 57.0 ± 16.6 years. Indications for treatment were stress urinary incontinence (16/32), mild pelvic organ prolapse (14/32), or both (2/32). The mean number of treatments per patient was 4. Quality of life improved as a consequence of the treatment according to the considered scales. Specifically, 87.5% of patients considered themselves improved. Conclusions: The DAFNE system has been successful in managing mild pelvic organ prolapse and stress urinary incontinence, improving quality of life scores. Embracing new technologies such as electrotherapy and photobiostimulation appears to be successful in conservatively managing a variety of PFDs. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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30 pages, 2046 KB  
Article
Natural Extract Combination Modulates Intestinal Barrier and Hepatic Cholesterol via the Gut–Liver Axis In Vitro
by Francesca Uberti, Simone Mulè, Francesca Parini, Matteo Musu and Rebecca Galla
Pharmaceutics 2026, 18(3), 328; https://doi.org/10.3390/pharmaceutics18030328 - 5 Mar 2026
Viewed by 523
Abstract
Background/Objectives: The gut–liver axis plays a central role in cholesterol homeostasis, linking intestinal absorption, microbial metabolites, and hepatic lipid regulation. Dysregulation of this axis contributes to hypercholesterolemia and cardiometabolic risk, beyond classical cholesterol synthesis pathways. This study evaluated a novel multi-botanical formulation (MIX) [...] Read more.
Background/Objectives: The gut–liver axis plays a central role in cholesterol homeostasis, linking intestinal absorption, microbial metabolites, and hepatic lipid regulation. Dysregulation of this axis contributes to hypercholesterolemia and cardiometabolic risk, beyond classical cholesterol synthesis pathways. This study evaluated a novel multi-botanical formulation (MIX) that combines Gastrodia elata, Black Garlic, Primula veris, and Emblica officinalis (AMLA) to integrate modulation of cholesterol metabolism through intestinal and hepatic mechanisms. Methods: Individual extracts were chemically characterised for polyphenols, flavonoids, polysaccharides, S-allyl-L-cysteine (SAC), and tannins. Caco-2 cells were treated with varying doses to determine optimal concentrations and for viability, transepithelial electrical resistance, and permeability analysis. Supernatants post-intestinal passage were applied to HepG2 cells under high-glucose conditions to assess viability, oxidative stress, SRC/ERK-MAPK signalling, cholesterol synthesis (HMGR), LDL uptake, PCSK9–LDLR–SREBP-2 axis, and bile acid production. Results: MIX enhanced intestinal barrier integrity (TEER, tight junctions, permeability) and preserved cell viability compared with single extracts. In HepG2 cells, MIX demonstrated synergistic effects: it reduced HMGR expression by 83–90% relative to individual extracts, increased LDLR expression by 43–97%, suppressed PCSK9 by up to 92%, and lowered total cholesterol and LDL uptake more effectively than RYRF. MIX also amplified bile acid production and free cholesterol excretion, indicating improved hepatic clearance pathways. SRC and ERK-MAPK signalling were favourably modulated, supporting hepatocyte survival under metabolic stress. Conclusions: The multi-botanical formulation exerts complementary and synergistic effects on intestinal absorption and hepatic cholesterol regulation, integrating suppression of cholesterol synthesis, enhanced LDL clearance, and stimulated elimination via bile acids. These findings highlight the potential of the MIX formulation to modulate metabolically induced cholesterol dysregulation, supporting further in vivo and clinical investigation. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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16 pages, 1325 KB  
Article
Retrospective Analysis of Cardiovascular Effects of FES Cycling in People with Complete and Incomplete Spinal Cord Injury
by Mariann Mravcsik, Amelita Fodor, Balazs Radeleczki, Melinda Feher, Peter Cserhati, Andras Klauber, Jozsef Laczko and Lilla Botzheim
J. Clin. Med. 2026, 15(5), 1967; https://doi.org/10.3390/jcm15051967 - 4 Mar 2026
Viewed by 230
Abstract
Background: Globally, over 15 million people live with spinal cord injury (SCI), which often leads to permanent motor impairment. In these cases, functional electrical stimulation (FES) can generate muscle forces and active movements in affected body parts, enabling patients to perform cycling [...] Read more.
Background: Globally, over 15 million people live with spinal cord injury (SCI), which often leads to permanent motor impairment. In these cases, functional electrical stimulation (FES) can generate muscle forces and active movements in affected body parts, enabling patients to perform cycling tasks using their own paralyzed legs. Incomplete spinal cord injuries are more prevalent than complete injuries and FES cycling can be performed in both cases. However, differences in its effects between the two groups remain to be further investigated. Our objective is to compare the effects of FES-assisted cycling on blood pressure, heart rate, and power output in patients with incomplete (iSCI) versus complete (cSCI) spinal cord injuries. We aim to provide comparative data currently missing from existing research. Methods: Thirty-two patients (20 iSCI, 12 cSCI), completed at least ten FES cycling training sessions. Each session consisted of 30 min of cycling on a MOTOmed Viva2 cycle-ergometer (Reck GMBH, Betzenweiler, Germany) equipped with a multi-channel electrical stimulator. The outcome measures were assessed in each session four times: before and after the session, and approximately at the 10th and 20th minutes. Statistical analyses compared mean arterial pressure (MAP), heart rate (HR), average and peak power output between the two groups. Results: Regarding within session differences, the iSCI group maintained significantly higher MAP than the cSCI group at all measurement points. HR patterns also differed significantly, showing higher values in the iSCI group at the second and third measurement points. On the course of the sessions in iSCI patients, average and peak power output increased significantly from the first to the tenth session. In cSCI patients the average power output was nearly constant throughout the ten sessions. Conclusions: Patients with iSCI and cSCI show different cardiovascular adaptations, and increasing FES cycling power output indicates that patients with incomplete injuries can achieve greater improvements even after ten training sessions. Full article
(This article belongs to the Section Clinical Rehabilitation)
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19 pages, 1686 KB  
Article
Effect of Otago Exercise Program Combined with Neuromuscular Electrical Stimulation on Chronic Ankle Instability in Older Adults: A Pilot Randomized Controlled Trial
by Yunong Zhang, Min-Chul Shin, Ye Tao, Kexiang Yang and Shuting Liu
J. Clin. Med. 2026, 15(5), 1968; https://doi.org/10.3390/jcm15051968 - 4 Mar 2026
Viewed by 233
Abstract
Background: Chronic ankle instability (CAI) is a common functional disorder in older adults, affecting their balance and quality of life. Therefore, finding effective ways to enhance ankle stability and function under safe conditions remains a key issue for healthy aging. Objective: [...] Read more.
Background: Chronic ankle instability (CAI) is a common functional disorder in older adults, affecting their balance and quality of life. Therefore, finding effective ways to enhance ankle stability and function under safe conditions remains a key issue for healthy aging. Objective: This study aims to explore the effects of the Otago Exercise Program (OEP) combined with Neuromuscular Electrical Stimulation (NMES) on ankle stability, the pain index, and balance ability in older adults aged 60 and above with CAI. Methods: This study is a single-blind pilot randomized controlled trial, including 36 eligible older adults with CAI, with 34 completing the trial. Participants were randomly assigned to the OEP group, the combined group (OEP + NMES), and the control group. The intervention period lasted 8 weeks. Evaluation measures included the Cumberland Ankle Instability Tool (CAIT), Visual Analog Scale (VAS), Eyes-closed Single-Leg Stance Test (UST), and the Modified Star Excursion Balance Test (mSEBT), with assessments conducted before the intervention, at week 4, and at week 8. Result: After the intervention, all three groups showed significant improvements in CAIT, VAS, UST, and mSEBT scores (p < 0.05), with a large group × time effect observed for the primary outcome CAIT (partial η2 = 0.414). The combined group (OEP + NMES) demonstrated the most significant improvement in CAIT and UST scores (p < 0.05) and outperformed the other two groups in dynamic balance in the posteromedial and posterolateral directions. Conclusions: The combined intervention of OEP and NMES significantly improves ankle stability, both static and dynamic balance abilities, and alleviates pain in older adults with CAI. This combined approach offers a safe and effective rehabilitation strategy for the older adults, with promising clinical application prospects. Full article
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28 pages, 18564 KB  
Article
An Injectable Thermosensitive Chitosan/Astaxanthin/Ibuprofen Hydrogel Mitigates High-Voltage, Low-Current Electrical Burn Injury Through Inhibition of ROS–NF-κB Signaling-Mediated Inflammation
by Xiao Yang, Hui Wang, Wenjuan Zhang, Peng Gao, Xudong Yu, Weijia Qing, Ping Deng, Jingdian Li, Yan Luo, Li Tian, Jia Xie, Mengyan Chen, Zhengping Yu, Huifeng Pi, Ting Liu and Shenglin Luo
Pharmaceutics 2026, 18(3), 323; https://doi.org/10.3390/pharmaceutics18030323 - 3 Mar 2026
Viewed by 406
Abstract
Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive [...] Read more.
Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article
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18 pages, 1315 KB  
Review
Intensive Care Unit Acquired Weakness as a Modifiable Organ Dysfunction? A Narrative Review of Evolving Diagnostic and Therapeutic Concepts
by Moritz L. Schmidbauer and Konstantinos Dimitriadis
Nutrients 2026, 18(5), 820; https://doi.org/10.3390/nu18050820 - 3 Mar 2026
Viewed by 434
Abstract
Intensive Care Unit Acquired Weakness (ICUAW) is a highly prevalent neuromuscular complication affecting around 40% of critically ill patients, rising to over 80% in high-risk cohorts. It is independently associated with prolonged mechanical ventilation, increased intensive care unit (ICU) and hospital length of [...] Read more.
Intensive Care Unit Acquired Weakness (ICUAW) is a highly prevalent neuromuscular complication affecting around 40% of critically ill patients, rising to over 80% in high-risk cohorts. It is independently associated with prolonged mechanical ventilation, increased intensive care unit (ICU) and hospital length of stay, elevated mortality (in-hospital, 1-year, and 5-year), higher healthcare costs, and long-term functional impairment. ICUAW is clinically defined by symmetric flaccid tetraparesis, frequently involving respiratory muscles, and exhibits significant pathobiological heterogeneity. Further subclassification is based on neurotopographic patterns: Critical Illness Polyneuropathy (CIP), Myopathy (CIM), and Polyneuromyopathy (CIPNM). Diagnosis typically relies on the Medical Research Council (MRC) Sum Score, with a threshold of <48 indicating clinically relevant weakness. While adjunct modalities such as electromyography/nerve conduction studies support assessment, their utility may be limited by patient cooperation and availability. Preventive strategies center on modifiable metabolic factors. Caloric and protein deficits exacerbate catabolism, while overfeeding—linked to anabolic resistance and stress hyperglycemia—also impairs recovery. To date, pharmacologic interventions remain inconclusive. However, early mobilization and neuromuscular electrical stimulation are promising non-pharmacologic strategies. The multifactorial and heterogeneous pathophysiology of ICUAW highlights the need for a biologically refined definition that can guide future targeted therapeutic interventions. Comprehensive multimodal strategies, together with structured long-term follow-up in Post-Intensive Care Syndrome (PICS) clinics, are essential for improving outcomes in this prevalent complication of critical care. Full article
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51 pages, 66403 KB  
Review
Redefining Obstructive Sleep Apnea: Treatment in the Modern Era
by Jose Redondo, Kori B. Ascher and Alexandre R. Abreu
Pathophysiology 2026, 33(1), 20; https://doi.org/10.3390/pathophysiology33010020 - 2 Mar 2026
Viewed by 344
Abstract
Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous disorder associated with substantial cardiometabolic morbidity. Although continuous positive airway pressure (CPAP) remains first-line therapy, long-term effectiveness is frequently limited by suboptimal adherence. Advances in airway devices, surgical techniques, neuromodulation, and pharmacologic [...] Read more.
Background: Obstructive sleep apnea (OSA) is a highly prevalent and heterogeneous disorder associated with substantial cardiometabolic morbidity. Although continuous positive airway pressure (CPAP) remains first-line therapy, long-term effectiveness is frequently limited by suboptimal adherence. Advances in airway devices, surgical techniques, neuromodulation, and pharmacologic therapies have expanded the therapeutic landscape and created opportunities for individualized, mechanism-based treatment. Methods: We conducted a selective, narrative review with structured quantitative synthesis of randomized controlled trials, comparative cohorts, long-term follow-up studies, registries, and mechanistic investigations addressing OSA therapies beyond CPAP. Evidence spanning oral appliances, upper-airway and skeletal surgery, hypoglossal nerve stimulation, neuromuscular electrical stimulation, positional therapy, and pharmacologic interventions targeting metabolic and non-anatomical endotypes was integrated. Outcomes of interest included apnea–hypopnea index (AHI), oxygenation, blood pressure, patient-reported symptoms, durability, safety, and real-world adherence. Results: Mandibular advancement devices (MADs) consistently reduced AHI relative to placebo and produced symptom relief comparable to CPAP in mild-to-moderate OSA, largely due to superior adherence. Palatal surgery yielded meaningful short-term improvement in selected patients but demonstrated limited long-term durability. In contrast, maxillomandibular advancement (MMA) achieved the largest and most durable reductions in OSA severity, with efficacy comparable to CPAP and superior to other surgical modalities in appropriate skeletal phenotypes. Hypoglossal nerve stimulation (HNS) produced substantial, durable improvements in AHI and symptoms with high adherence, supported by randomized trials, long-term follow-up, and real-world registry data; newer bilateral and proximal stimulation systems may further broaden candidacy. Neuromuscular electrical stimulation and positional therapy provided modest, phenotype-dependent benefits, primarily as adjunctive or early-stage interventions. A major advance is the emergence of metabolic and endotype-targeted pharmacotherapy: longitudinal data demonstrate a dose-dependent relationship between weight change and OSA progression or regression, while randomized trials show that GLP-1-based therapies—particularly dual GLP-1/GIP agonism with tirzepatide—produce large, clinically meaningful reductions in AHI and cardiometabolic risk in obesity-associated OSA. Additional pharmacologic strategies targeting ventilatory loop gain and arousal threshold further support an endotype-driven treatment paradigm. Conclusions: Contemporary OSA management is shifting from a CPAP-centric model toward a precision-guided, multimodal framework that aligns therapy with dominant anatomic and physiological contributors to airway collapse. Integrating metabolic, neuromodulatory, and structural interventions—often in combination—offers the potential for durable disease control and improved patient-centered outcomes. Future priorities include head-to-head and combination trials, long-term cardiovascular outcomes, cost-effectiveness analyses, and pragmatic tools to operationalize personalized OSA therapy in routine clinical practice. Full article
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21 pages, 1458 KB  
Review
Microbial Metabolic Pathways for Synergistic Biomethane Augmentation and CO2 Sequestration in Coalbed Systems: A Mini-Review
by Yang Li, Longxi Shuai and Qian Zhang
Microorganisms 2026, 14(3), 566; https://doi.org/10.3390/microorganisms14030566 - 2 Mar 2026
Viewed by 210
Abstract
Natural gas represents a pivotal transitional clean energy resource, and biogenic coalbed methane (CBM) is ubiquitously distributed in coal reservoirs worldwide. In the context of carbon neutrality targets and the growing demand for large-scale commercial CBM exploitation, innovative technological solutions are urgently required. [...] Read more.
Natural gas represents a pivotal transitional clean energy resource, and biogenic coalbed methane (CBM) is ubiquitously distributed in coal reservoirs worldwide. In the context of carbon neutrality targets and the growing demand for large-scale commercial CBM exploitation, innovative technological solutions are urgently required. CBM bioengineering aims to substantially enhance CBM production by stimulating biomethane generation, promoting gas desorption, and improving reservoir permeability, while simultaneously enabling effective CO2 sequestration. The potential for biomethane generation is largely governed by the intrinsic physicochemical characteristics of coal, including aromatic structures, maceral composition, and pore–fracture architecture. In addition, hydrogeological conditions—such as geothermal gradients, pH variability, and redox potential—play critical roles in regulating microbial functional gene expression and metabolic enzyme synthesis. Core pretreatment strategies in coalbed gas bioengineering can be broadly classified into approaches that enhance coal bioconversion potential and those that optimize functional microbial consortia. Electric fields and conductive materials can influence microbial community structure by enriching electroactive microorganisms and facilitating interspecies electron transfer. In addition to engineered conductive interventions, reservoir environmental conditions also play an important role in shaping methanogenic community structure. Experimental observations under reservoir-relevant CO2 pressure and temperature conditions indicate that deep coalbed environments are associated with shifts in methanogenic community composition, including an increased relative abundance of hydrogenotrophic methanogens. These observations suggest that physicochemical conditions in deep coal seams may favor hydrogen-dependent CO2 reduction pathways, thereby supporting hydrogenotrophic methanogenesis and contributing to biomethane generation. The integration of supercritical CO2 with microbially acclimated stimulation fluids as an innovative reservoir fracturing strategy offers multiple advantages, including effective reservoir stimulation, permanent carbon sequestration, and sustainable biomethane generation. Future research should focus on modulating coal matrix bioavailability, optimizing microbial consortia, enhancing interspecies metabolic synergies, and advancing carbon fixation bioprocesses to facilitate the large-scale implementation of coalbed gas bioengineering systems. This review synthesizes recent advances in microbially mediated CBM enhancement and CO2 sequestration, with a particular focus on field-scale evidence and the key challenges that must be addressed for large-scale implementation. Full article
(This article belongs to the Section Microbial Biotechnology)
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