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23 pages, 53767 KB  
Article
BNIP3/BNIP3L-Dependent Mitophagy Protects Against Hippocampal Neuronal Damage and Apoptosis in a Model of Vascular Dementia
by Yujiao Wang, Daojun Xie, Shijia Ma, Yuhe Wang, Chengcheng Zhang and Zhuyue Chen
Cells 2026, 15(7), 585; https://doi.org/10.3390/cells15070585 (registering DOI) - 25 Mar 2026
Abstract
Mitophagy serves as an essential quality control mechanism that maintains mitochondrial homeostasis through selective autophagic clearance of damaged organelles. Vascular dementia (VD) has been increasingly associated with mitophagy dysregulation in recent studies. However, the precise molecular mechanisms underlying mitophagy’s involvement in VD pathogenesis [...] Read more.
Mitophagy serves as an essential quality control mechanism that maintains mitochondrial homeostasis through selective autophagic clearance of damaged organelles. Vascular dementia (VD) has been increasingly associated with mitophagy dysregulation in recent studies. However, the precise molecular mechanisms underlying mitophagy’s involvement in VD pathogenesis remain poorly characterized. To elucidate the role of mitophagy in VD, we systematically examined the expression of key mitophagy pathways in hippocampal neurons of bilateral common carotid artery occlusion (BCCAO) rats and in oxygen–glucose deprivation (OGD)-treated HT22 cells. Intriguingly, under autophagy-deficient conditions, both BNIP3 and BNIP3L were markedly downregulated, whereas FUNDC1 expression increased; PINK1/Parkin levels remained unaltered. To further dissect the functional contributions of BNIP3 and BNIP3L, we administered the mitochondrial fission inhibitor Mdivi-1 to BCCAO model rats. Histopathological analysis revealed pronounced neuronal damage and apoptosis in the hippocampal region, which was further exacerbated upon Mdivi-1 treatment. In vitro, BNIP3 silencing significantly compromised cell viability, elevated reactive oxygen species (ROS) accumulation, disrupted mitochondrial membrane potential (ΔΨm), suppressed mitophagy, and increased apoptotic rates. Conversely, BNIP3 overexpression reversed these detrimental effects. Notably, treatment with the autophagy inhibitor 3-methyladenine (3-MA) diminished LC3B-Tomm20 colocalization and intensified apoptosis, reinforcing the critical role of BNIP3-mediated mitophagy in neuronal survival. Similarly, BNIP3L overexpression enhanced cell viability, attenuated ROS production, restored ΔΨm, and mitigated apoptosis, while 3-MA treatment again impaired mitophagic flux and worsened cell death. Collectively, these findings underscore the critical and distinct roles of BNIP3 and BNIP3L in maintaining mitochondrial homeostasis and neuronal survival under ischemic conditions. Full article
(This article belongs to the Special Issue Autophagy-Related Proteins in Stress Responses)
22 pages, 8228 KB  
Article
Bridging Interfaces and Morphology: A Mesoscale Dynamics Framework for Predicting Percolation in Organic Solar Cells
by Estela Mayoral-Villa and Alfonso R. García-Márquez
Energies 2026, 19(7), 1624; https://doi.org/10.3390/en19071624 (registering DOI) - 25 Mar 2026
Abstract
The dynamic self-assembly and phase separation of donor–acceptor blends are processes that dictate the nanoscale morphology in organic solar cells. Here, we employ a fluidics-inspired framework, integrating dissipative particle dynamics simulations with percolation theory, to investigate the morphogenesis of two non-fullerene systems: P3HT-PPerAcr [...] Read more.
The dynamic self-assembly and phase separation of donor–acceptor blends are processes that dictate the nanoscale morphology in organic solar cells. Here, we employ a fluidics-inspired framework, integrating dissipative particle dynamics simulations with percolation theory, to investigate the morphogenesis of two non-fullerene systems: P3HT-PPerAcr and P3HT-PFTBT. We analyze monomeric and homopolymer blends, and copolymer macrostructures, focusing on how key parameters such as temperature and polymer chain flexibility govern the dynamic evolution towards percolating networks. Our simulations captured the fundamental fluidic behavior and universal scaling near the critical percolation threshold (χc). The critical exponent β revealed distinct universality classes dictated by system compatibility and flexibility: monomeric and flexible homopolymer blends below the critical temperature (Tc) exhibit mean field behavior (β ≈ 1). In contrast, monomeric systems above χc and flexible copolymers below χc display 3D percolation behavior (β ≈ 0.45). In the case of flexible copolymeric macromolecules, above percolation threshold a quasi-bidimensional behavior emerge with (β ≈ 0.1). Notably, semi-rigid and rigid homopolymeric and copolymeric linear architectures induce a dimensional crossover, yielding quasi-2D (β ≈ 0.14) and quasi-1D (β ≈ 0.0) morphologies. These findings establish a direct link between tunable fluidic interactions, chain dynamics, and the emergence of optimal bicontinuous percolation networks. Full article
(This article belongs to the Section A2: Solar Energy and Photovoltaic Systems)
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30 pages, 7155 KB  
Article
Antioxidant and Anticancer Potentials of Apple Peel and Fruit Extracts: A Combined Docking and Chemical Composition Study
by Ayla Hançer, Gülşen Güçlü, Ömer Kayır, Serkan Kapancık, Esra Uçar and Burak Tüzün
Curr. Issues Mol. Biol. 2026, 48(4), 343; https://doi.org/10.3390/cimb48040343 - 25 Mar 2026
Abstract
The apple (Malus domestica Borkh.) is one of the most widely consumed fruits worldwide due to its pleasant sensory properties and rich phytochemical composition. Therefore, the present study aimed to comprehensively investigate the chemical composition, antioxidant activity, anticancer effects, and molecular interactions [...] Read more.
The apple (Malus domestica Borkh.) is one of the most widely consumed fruits worldwide due to its pleasant sensory properties and rich phytochemical composition. Therefore, the present study aimed to comprehensively investigate the chemical composition, antioxidant activity, anticancer effects, and molecular interactions of peel and pulp extracts of the Hünkar apple cultivar collected from different locations, using a combined experimental and computational strategy. These factors had a big effect on the extracts’ phenolic composition and biological activity. Moreover, the anticancer results were corroborated by molecular docking analyses, which offered further understanding of the interactions between bioactive compounds and cancer-associated target proteins. This integrative approach underscores the impact of both biological and methodological variables on the antioxidant and anticancer properties of apple-derived extracts, reinforcing their potential as natural sources of bioactive compounds. Cytotoxic activity against HT-22 and C6 cell lines was evaluated using the MTT assay, showing dose- and time-dependent antiproliferative effects. Apple extracts exhibited anticancer effects that were dependent on dosage and duration. The activities of chemicals found in extracts of Hünkar apple samples collected from four different locations against brain cancer proteins (PDB ID: 2DME, 6YPE, 1RV1) were examined. ADME/T analysis was then performed on the three molecules with the highest activity. The quantum chemical properties of these three molecules were also examined using the Gaussian package program with B3LYP, HF, M062X level in 6–31g, 6–31++g, and 6–31++g(d,p) basis sets. Full article
(This article belongs to the Special Issue Advances in Phytochemicals: Biological Activities and Applications)
25 pages, 3739 KB  
Article
A Portable and Highly Selective Electrochemical Sensor Based on Copper–Nickel Oxide-Decorated Ordered Mesoporous Carbon for Serotonin Detection
by Thenmozhi Rajarathinam, Sivaguru Jayaraman, Jang-Hee Yoon and Seung-Cheol Chang
Biosensors 2026, 16(4), 185; https://doi.org/10.3390/bios16040185 - 24 Mar 2026
Abstract
Electrochemical sensors are user-friendly devices designed for the rapid and straightforward detection of target analytes. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter and neuromodulator that regulates diverse neuronal processes. Using a custom-designed screen-printed carbon electrode (SPCE) incorporating ordered mesoporous carbon–bimetal oxides of Cu [...] Read more.
Electrochemical sensors are user-friendly devices designed for the rapid and straightforward detection of target analytes. Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter and neuromodulator that regulates diverse neuronal processes. Using a custom-designed screen-printed carbon electrode (SPCE) incorporating ordered mesoporous carbon–bimetal oxides of Cu and Ni (CuO–NiO–OMC), rapid and real-time detection of 5-HT was achieved. The CuO–NiO–OMC structure featured highly active CuO and NiO catalytic sites that effectively promoted the irreversible oxidation of 5-HT (vs. Ag/AgCl reference electrode). The CuO–NiO–OMC/SPCE sensor, connected to a portable potentiostat, exhibited exceptional electrocatalytic performance for the oxidation of 5-HT, with a detection limit of 42.5 nM. The sensitivity was 1.56 A M−1 cm−2, and the linear dynamic range was 0.0–80.0 µM. The CuO–NiO–OMC/SPCE sensor also demonstrated outstanding selectivity in the presence of competing neurochemicals, including norepinephrine, epinephrine, dopamine, and glutamate, as well as high concentrations of tested biomolecules and inorganic ions. Furthermore, the practicality of the sensor was demonstrated using human serum and urine samples, with recovery percentages ranging from 91.1% to 98.3%. Thus, the CuO–NiO–OMC/SPCE sensor offers an effective approach for 5-HT sensing, thereby permitting molecular-level understanding of brain function. Full article
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17 pages, 4610 KB  
Article
Cytochrome P450 Genes Mediate High-Temperature Adaptation Under Diverging Humidity Conditions in Tuta absoluta
by Hina Gul, Guru-Pirasanna-Pandi Govindharaj, Ghulam Murtaza, Farman Ullah, Jun Huang, Wenchao Guo, Raul Narciso C. Guedes, Nicolas Desneux, Xiaowei Li and Yaobin Lu
Int. J. Mol. Sci. 2026, 27(7), 2935; https://doi.org/10.3390/ijms27072935 - 24 Mar 2026
Abstract
Temperature and humidity are critical abiotic factors shaping the survival and adaptation of insect pests. However, the molecular mechanisms underlying high-temperature tolerance under contrasting humidity conditions remain poorly understood, particularly in globally invasive species such as the tomato pinworm, Tuta absoluta. Previous studies [...] Read more.
Temperature and humidity are critical abiotic factors shaping the survival and adaptation of insect pests. However, the molecular mechanisms underlying high-temperature tolerance under contrasting humidity conditions remain poorly understood, particularly in globally invasive species such as the tomato pinworm, Tuta absoluta. Previous studies have examined individual stressors, leaving interactive thermo-hygrometric effects on gene expression and survival insufficiently resolved. Here, we assessed the contribution of cytochrome P450 genes to thermal adaptation under low- and high-humidity conditions using transcriptome profiling combined with nanocarrier-mediated RNA interference (RNAi). Third-instar larvae were exposed to high temperature under low humidity (HT-LH: 40 °C, 50% RH) or high humidity (HT-HH: 40 °C, 75% RH) for eight hours. Survival declined from 97.5% in the control to 74.16% under HT-LH and 68.33% under HT-HH conditions. Transcriptome analysis revealed extensive differential gene expression, with 464 genes upregulated and 565 downregulated in HT-LH, and 1145 upregulated and 1166 downregulated in HT-HH. Functional annotation highlighted pathways linked to metabolic regulation, proteostasis, and detoxification, including multiple cytochrome P450-associated processes. RT-qPCR confirmed the upregulation (3–5 fold) of four P450 genes (CYP6AB327, CYP6ABF1b, CYP6AE214, and CYP9A306c) under high temperature across both humidity regimes. RNAi-mediated silencing of these genes significantly reduced larval survival, demonstrating their functional role in thermal-hygrometric stress tolerance across. Cytochrome P450 genes underpin the adaptive capacity of the tomato pinworm to high-temperature stress across contrasting humidity conditions, highlighting RNAi-based disruption of P450 function as a promising avenue for sustainable pest management under climate change scenarios. Full article
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20 pages, 1453 KB  
Article
Prediction of Hazard Trees Based on Functional Groups, Succession, and Climate Zones
by Ming-Hsun Chan, Pei-Ju Chen and Jung-Tai Lee
Forests 2026, 17(4), 399; https://doi.org/10.3390/f17040399 - 24 Mar 2026
Abstract
Despite five years of hazard tree investigation and mitigation (Potential Hazard Tree monitoring and hazard tree removal) from 2020 to 2024, the incidence ratios of hazard trees (HTs) and Potential Hazard Trees (PHTs) along the Alishan Forest Railway corridor (spanning subtropical, warm temperate, [...] Read more.
Despite five years of hazard tree investigation and mitigation (Potential Hazard Tree monitoring and hazard tree removal) from 2020 to 2024, the incidence ratios of hazard trees (HTs) and Potential Hazard Trees (PHTs) along the Alishan Forest Railway corridor (spanning subtropical, warm temperate, and temperate zones) have not exhibited a significant downward trend. This study aims to investigate the impacts of climate zones, succession, and functional groups on hazard tree occurrence and to further predict the incidence ratios of hazard trees. We employed Generalized Linear Models (GLMs) and structural defect frequency to evaluate these interactions. The significance of the impacts is ranked as follows: functional group > succession regeneration > climate zone. Incidence was highest in subtropical (S) and warm temperate (W) zones (S ≈ W > T), and significantly greater for secondary succession (SS) areas compared to Planning Plantation (PP). Crucially, heliophilous species (H + P; small-to-medium pioneer and canopy heliophilous species) contributed significantly more to hazard incidence than non-heliophilous species (MT + T; mid-shade-tolerant and shade-tolerant species). Model predictions identified (H + P) + SS + S as the highest-incidence ecological combination, while (MT + T) + PP + T was the lowest. Structural defect relative frequency analysis revealed that the fast-growth strategy of H + P species fundamentally compromises their biomechanical stability, resulting in significantly higher defect frequencies compared to MT + T species. Furthermore, continuous corridor disturbances maintain a persistent light environment that perpetually recruits these H + P species via secondary succession. To effectively manage the incidence of HT and PHT, future mitigation measures must prioritize Planning Plantation (PP) using non-heliophilous (MT + T) species selected within their appropriate ecological amplitudes. Full article
(This article belongs to the Special Issue Forest Plants in Ecological Restoration and Disaster Mitigation)
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17 pages, 900 KB  
Article
Association of Serum Glucose/Potassium Ratio with Injury Severity and Transfusion Requirements in Traumatic Pelvic Fractures: A Retrospective Cohort Study
by Abdullah Alper Sahin, Yunus Emre Özbilen and Çağrı Akalın
Diagnostics 2026, 16(6), 939; https://doi.org/10.3390/diagnostics16060939 - 22 Mar 2026
Viewed by 139
Abstract
Background: We evaluated the association between admission serum glucose-to-potassium ratio (GPR) and injury severity as well as early transfusion requirements in patients with traumatic pelvic fractures. Methods: This single-center, retrospective cohort study included 84 adult patients with isolated or predominantly pelvic fractures admitted [...] Read more.
Background: We evaluated the association between admission serum glucose-to-potassium ratio (GPR) and injury severity as well as early transfusion requirements in patients with traumatic pelvic fractures. Methods: This single-center, retrospective cohort study included 84 adult patients with isolated or predominantly pelvic fractures admitted between January 2020 and December 2024. Patients with concomitant non-pelvic skeletal fractures were excluded to isolate the metabolic response attributable to pelvic injury. GPR was calculated from admission serum glucose and potassium levels. Higher transfusion requirement (HT) was defined as ≥4 units of packed red blood cells within 24 h. Receiver operating characteristic (ROC) analysis identified the optimal GPR cut-off using the Youden index. Internal validation was performed using bootstrap resampling (1000 iterations), and model calibration was assessed with the Hosmer–Lemeshow test. The incremental discriminatory value of GPR beyond the Injury Severity Score (ISS) was evaluated by comparing AUC values using the DeLong test, and reclassification metrics including the category-free net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. Sensitivity analyses were conducted using alternative transfusion thresholds (≥6 and ≥10 units). Results: The optimal GPR cut-off was 34 (area under the curve (AUC) = 0.730; 95% CI: 0.593–0.853; sensitivity 78.8%; specificity 59.0%). Patients with GPR ≥ 34 (n = 43) had significantly higher ISS values (median 25 [IQR: 16–34] vs. 9 [5–17]; p < 0.001), greater transfusion volumes (median 3 [0–6] vs. 0 [0–1] units; p < 0.001), and longer intensive care unit (ICU) stays (3 (0–6) vs. 0 (0–1) days; p < 0.001). In univariable logistic regression, GPR was significantly associated with HT (OR = 1.059 per unit increase; 95% CI: 1.015–1.104; p = 0.008); however, significance was not retained in the multivariable model after adjustment for ISS (p = 0.194). ISS remained the sole independent predictor (OR = 1.128; p < 0.001). The combined ISS + GPR model yielded an AUC of 0.857, representing a modest increment over ISS alone (AUC = 0.849; ΔAUC = 0.009; DeLong p = 0.566). Bootstrap-corrected AUCs confirmed minimal optimism (GPR alone: 0.726; ISS + GPR: 0.847). The Hosmer–Lemeshow test indicated adequate calibration for all models (p > 0.05). The category-free NRI was 0.627 (p = 0.009), whereas the IDI did not reach significance (0.017; p = 0.290). Sensitivity analysis at the ≥6-unit threshold yielded consistent results (GPR AUC = 0.709). Conclusions: Admission GPR is significantly associated with injury severity, hemorrhagic burden, and transfusion requirements in patients with traumatic pelvic fractures. Although GPR does not independently predict transfusion needs beyond ISS, it yields significant reclassification improvement and may serve as a practical, rapidly obtainable adjunct for early risk stratification in the acute trauma setting. Level of Evidence: III (retrospective prognostic study). Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 10516 KB  
Article
Autotaxin Induces S1P/S1PR1 Signaling to Affect Th17/Treg Cell Balance and Exacerbate Intestinal Inflammation in Colitis
by Siqi Xiao, Kaixin Peng, Congxin Li, Yuanyuan Long, Hongbing Yu, Suhong Xia, Qinghai Tan and Qin Yu
Int. J. Mol. Sci. 2026, 27(6), 2861; https://doi.org/10.3390/ijms27062861 - 21 Mar 2026
Viewed by 164
Abstract
Abnormal intestinal mucosal immunity plays a crucial role in ulcerative colitis (UC). Autotaxin (ATX) can promote T cell migration and was reported to have a regulatory effect on Th17 cells, while sphingosine-1-phosphate (S1P) and its receptors (S1PRs) modulate Th17/Treg balance and inflammation, with [...] Read more.
Abnormal intestinal mucosal immunity plays a crucial role in ulcerative colitis (UC). Autotaxin (ATX) can promote T cell migration and was reported to have a regulatory effect on Th17 cells, while sphingosine-1-phosphate (S1P) and its receptors (S1PRs) modulate Th17/Treg balance and inflammation, with S1PR modulators approved for UC. ATX can catalyze sphingosylphosphorylcholine (SPC) to produce S1P; however, the relationship between ATX and S1P/S1PRs in UC is unclear. Understanding the role of ATX-S1P/S1PRs in intestinal immunity can provide new treatment strategies for intestinal inflammatory diseases. Both UC patients and DSS-induced colitic mice showed significantly increased levels of ATX and S1P compared with healthy controls. ATX inhibitor PF8380 treatment led to reduced levels of S1P/S1PRs in colitic mice. Consistent with this, the S1PR antagonist etrasimod was able to alleviate ATX-induced intestinal inflammation, as well as partially restore ATX-induced Th17/Treg imbalance in MLNs and the spleen. In HT-29 and Raw246.7 cells, ATX treatment led to enhanced expression of S1P/S1PRs, with S1PR1 being the most significant. Furthermore, S1PR1 mediates the effect of ATX on Th17/Treg cell differentiation and function in vivo. Therefore, ATX affects the differentiation and function of Th17/Treg cells through S1P/S1PR1 signaling, increased ATX expression leading to Th17/Treg cell imbalance, intestinal mucosal immune dysfunction, and exacerbating intestinal inflammation. Full article
(This article belongs to the Section Molecular Immunology)
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14 pages, 3884 KB  
Article
Effective Energy Harvesting in Polymer Solar Cells Using NiS/Co as Nanocomposite Doping
by Jude N. Ike and Raymond Tichaona Taziwa
Micro 2026, 6(1), 22; https://doi.org/10.3390/micro6010022 - 21 Mar 2026
Viewed by 79
Abstract
Over the past two decades, organic semiconductors have attracted significant research interest due to their advantageous features, including low-cost fabrication, lightweight properties, and portability, for photonic device applications. In this study, nickel sulfide doped with cobalt [...] Read more.
Over the past two decades, organic semiconductors have attracted significant research interest due to their advantageous features, including low-cost fabrication, lightweight properties, and portability, for photonic device applications. In this study, nickel sulfide doped with cobalt (NiS/Co) nanocomposites were successfully synthesized via a wet-chemical processing technique and used as a dopant in the active layer of thin-film organic solar cells (TFOSCs). The poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) blend was used as the active layer in this investigation. The devices were fabricated with NiS/Co nanocomposites at 1 wt%, 2 wt%, and 3 wt% in the active layer to determine the optimal dopant concentration. However, the experimental evidence clearly showed that the solar cell’s performance depends on the concentration of the NiS/Co nanocomposites. As a result, the highest power conversion efficiency (PCE) recorded in this experimental work was 6.11% at a 1% doping concentration, compared with 2.48% for the pristine reference device under AM 1.5G illumination (100 mW/cm2) in ambient conditions. The optical and electrical properties of the active layers are found to be strongly influenced by the inclusion of NiS/Co nanocomposites in the medium. However, the device doped with 1 wt% NiS/Co nanocomposite exhibits the highest absorption intensity, consistent with the better performance observed in this study, which can be attributed to the localized surface plasmon resonance (LSPR) effect. The optical and morphological characteristics of the synthesized NiS/Co nanocomposites were comprehensively analyzed using high-resolution transmission electron microscopy (HRTEM), high-resolution scanning electron microscopy (HRSEM), and additional complementary techniques. Full article
(This article belongs to the Section Microscale Physics)
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19 pages, 3015 KB  
Article
The Role of Cholesterol at the CHOL2 Site and the Dimeric Interface in the Regulation of Serotonin Transporter Function and Dimerization
by Jian Yang, Chan Li, Xingyu Huang and Yuan-Wei Zhang
Biomolecules 2026, 16(3), 472; https://doi.org/10.3390/biom16030472 - 21 Mar 2026
Viewed by 112
Abstract
Serotonin transporter (SERT) precisely regulates serotonin (5–HT) signaling in the central nervous system and is a major target of antidepressants for the treatment of major depressive disorder. Despite significant progress in characterizing its structure and transport mechanism, the regulation of SERT function by [...] Read more.
Serotonin transporter (SERT) precisely regulates serotonin (5–HT) signaling in the central nervous system and is a major target of antidepressants for the treatment of major depressive disorder. Despite significant progress in characterizing its structure and transport mechanism, the regulation of SERT function by various modulators remains to be fully understood. In the present study, we focused on two potential cholesterol sites in human SERT to investigate cholesterol occupation at these sites and its functional relevance by biochemical approaches. Mutations of an intramolecular site (CHOL2) significantly decreased both specific transport activity and Km for 5–HT and stabilized the transporter in an inward-facing conformation. In addition, our NanoBiT luminescent assay for protein–protein proximity demonstrated that cholesterol mediated the protomer–protomer interactions by residing in a site at the dimeric interface. Mutations of the interfacial site remarkably reduced the interactions between SERT protomers and substantially impaired their transport activity. The structural analysis indicated that the residues participating in cholesterol residing in the interfacial site were conformationally sensitive. Thus, we have proposed that cholesterol at these sites could play a vital role in the regulation of SERT function by a conformational mechanism. Our study has provided new insights into the molecular mechanism by which cholesterol can regulate SERT function and dimerization. Full article
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11 pages, 614 KB  
Review
Beyond the Genomic Storm: Evaluating Tabernanthalog as a Potential Scaffold for Silent Neuroplasticity and Broad-Spectrum Therapy
by Ivan Anchesi, Ivana Raffaele, Maria Francesca Astorino, Maria Lui, Marco Calabrò and Giovanni Luca Cipriano
Int. J. Mol. Sci. 2026, 27(6), 2811; https://doi.org/10.3390/ijms27062811 - 20 Mar 2026
Viewed by 165
Abstract
The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or “psychoplastogens,” for psychiatric disorders. However, the widespread application of classical psychedelics—such as psilocybin and LSD—and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly [...] Read more.
The clinical renaissance of psychedelic medicine has highlighted the therapeutic potential of rapid-acting neuroplastogens, or “psychoplastogens,” for psychiatric disorders. However, the widespread application of classical psychedelics—such as psilocybin and LSD—and the atypical dissociative ibogaine is severely limited by their hallucinogenic properties and, particularly in the case of ibogaine, life-threatening cardiotoxicity. Addressing these limitations, Tabernanthalog (TBG) has emerged as a frontrunner in the field. This non-hallucinogenic analog of ibogaine was rationally designed to eliminate interactions with the human ether-à-go-go-related gene (hERG, KCNH2) potassium channel, thereby mitigating cardiotoxic risks. While initially characterized for its anti-addictive and antidepressant-like properties, recent data from 2024–2025 have significantly expanded its therapeutic horizon. TBG demonstrates robust efficacy in preclinical models of neuropathic and visceral pain, as well as in the rescue of cognitive deficits associated with cancer-related cognitive impairment (CRCI). TBG has shown efficacy in reversing cognitive impairments induced directly by the presence of a tumor in preclinical models, rather than by chemotherapy-specific neurotoxicity. Crucially, emerging evidence suggests that TBG’s mechanism extends beyond simple 5-HT2A receptor agonism. New findings point to a multi-target profile involving the inhibition of nicotinic acetylcholine receptors (nAChRs), positive modulation of NMDA receptors, and functional crosstalk with mGlu2 receptors. Furthermore, TBG appears to induce structural neuroplasticity without the widespread induction of immediate early genes (IEGs) seen with classical hallucinogens, suggesting a decoupling of therapeutic rewiring from the subjective psychedelic experience. This review synthesizes current preclinical evidence to discuss TBG as a promising chemical scaffold for next-generation neurotherapeutics targeting the intersection of psychiatry and neurology. Full article
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17 pages, 1501 KB  
Review
Review and Prospect of Key Technology for HTS Wind Generators of HPOSWP Integrated Systems
by Yujia Zhai, Shuai Liu, Liufei Shen, Long Chen, Wenjie Zhou, Cheng Zhang, Feiyue Shan, Xingzheng Wu and Siyu Duan
Energies 2026, 19(6), 1525; https://doi.org/10.3390/en19061525 - 19 Mar 2026
Viewed by 170
Abstract
As offshore wind power develops toward larger unit capacities and deeper offshore deployments, its inherent power intermittency poses increasing challenges to system stability and reliable grid integration. To address the issues of large-scale wind power fluctuation and efficient energy utilization, an integrated hydrogen [...] Read more.
As offshore wind power develops toward larger unit capacities and deeper offshore deployments, its inherent power intermittency poses increasing challenges to system stability and reliable grid integration. To address the issues of large-scale wind power fluctuation and efficient energy utilization, an integrated hydrogen production through offshore superconducting wind power (HPOSWP) system is investigated, which combines high-temperature superconducting (HTS) wind generators with water electrolysis. This paper reviews the operational characteristics of the HPOSWP system under wide power fluctuation conditions, specifically assessing the adaptability of high-power-density HTS wind generators and the feasibility of highly reliable liquid hydrogen (LH2) circulation cooling technologies from a qualitative perspective. This study provides valuable insights into the application of large-scale HPOSWP systems under fluctuating power conditions and establishes a solid theoretical foundation for subsequent system design and engineering implementation. Full article
(This article belongs to the Section F: Electrical Engineering)
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12 pages, 428 KB  
Article
Correlation Between Dosimetric Parameters and Hematologic Toxicity in Cervical Cancer Patients Undergoing Intensity-Modulated Pelvic Radiotherapy
by Shuang Zhao, Xi Yang, Lu Zhang, Duan Yang, Xuejiao Yang, Rui Wang, Shuangzheng Jia, Jusheng An and Manni Huang
Cancers 2026, 18(6), 992; https://doi.org/10.3390/cancers18060992 - 19 Mar 2026
Viewed by 107
Abstract
Objective: This study aimed to elucidate the association between hematologic toxicity (HT) and pelvic bone marrow (PBM) dosimetric parameters in patients with cervical cancer (CC) undergoing radiotherapy (RT) combined with artificial intelligence (AI)-assisted organ at risk (OAR) delineation (Software Copyright Registration Number 2023SR0150365). [...] Read more.
Objective: This study aimed to elucidate the association between hematologic toxicity (HT) and pelvic bone marrow (PBM) dosimetric parameters in patients with cervical cancer (CC) undergoing radiotherapy (RT) combined with artificial intelligence (AI)-assisted organ at risk (OAR) delineation (Software Copyright Registration Number 2023SR0150365). Accurate delineation of bone marrow (BM) regions and analysis of radiation doses may provide a theoretical foundation for the application of AI in predicting HT. Methods: This retrospective study included 141 patients with CC who received chemotherapy (sequential or concurrent) and/or pelvic volumetric modulated arc therapy (VMAT) at the Department of Gynecology, Cancer Hospital of the Chinese Academy of Medical Sciences, between March 2019 and December 2019. PBM and its subregions (ilium, lower pelvis, lumbosacral spine, and femoral heads) were delineated using AI-based automatic segmentation of CT images. The volumes receiving 10–40 Gy (V10, V20, V30, V40) were calculated, and baseline clinical characteristics were assessed. HT endpoints included grade ≥ 2 (HT2+) and grade ≥ 3 (HT3+) leukopenia, neutropenia, anemia, or thrombocytopenia. Associations between dosimetric parameters and HT were evaluated using logistic regression models. Results: Of the 141 patients, 107 (75.8%) developed HT2+ and 33 (23.4%) developed HT3+. Univariate analysis showed that chemotherapy and age were correlated with HT2+. Multivariate analysis identified femoral head V30, femoral head V40, and chemotherapy as independent predictors of HT3+. Conclusions: This study highlights the potential of AI-based OAR delineation for assessing PBM dosimetric parameters in patients with CC. Optimizing RT to minimize BM dose and volume may mitigate HT and enhance treatment tolerance. In our cohort, receipt of combined neoadjuvant and concurrent chemotherapy (NACT+CCRT) was a stronger predictor of HT than most BM dosimetric parameters, suggesting that the systemic effect of chemotherapy may dominate the hematologic toxicity profile in this setting. Consequently, patients receiving this combined modality treatment are at particularly high risk for HT and warrant close hematologic monitoring. Full article
(This article belongs to the Section Methods and Technologies Development)
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44 pages, 10334 KB  
Article
Yixin Yangshen Granules Target HIF−1 Signaling to Modulate the Neuroimmune Microenvironment in Alzheimer’s Disease: Insights from Integrative Multi-Omics and Deep Learning
by Zhihao Wang, Linshuang Wang, Yusheng Zhang, Sixia Yang, Bo Shi, Dasheng Liu, Han Zhang, Wan Xiao, Junying Zhang, Xuejie Han and Dongfeng Wei
Pharmaceuticals 2026, 19(3), 502; https://doi.org/10.3390/ph19030502 - 18 Mar 2026
Viewed by 164
Abstract
Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by [...] Read more.
Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ142-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia. Full article
22 pages, 6791 KB  
Article
Parabacteroides vesiculifaciens sp. nov., a Novel Immunomodulatory, Vesicle-Producing Gut Commensal Isolated from the Human Gut
by Andrei V. Chaplin, Irina V. Podoprigora, Victoria A. Shcherbakova, Natalya B. Zakharzhevskaya, Peter V. Evseev, Anna A. Vasilyeva, Filipp A. Koshkin, Dmitry A. Kardonsky, Elizaveta A. Vorobyeva, Daria A. Kashatnikova, Victoriia D. Kazakova and Boris A. Efimov
Int. J. Mol. Sci. 2026, 27(6), 2763; https://doi.org/10.3390/ijms27062763 - 18 Mar 2026
Viewed by 211
Abstract
The genus Parabacteroides comprises widespread gastrointestinal commensals, known to produce immunomodulatory molecules and extracellular vesicles, yet its full diversity is incompletely cataloged. This study describes strain ASD2025T, isolated from healthy child feces, using a polyphasic taxonomic approach including phenotypic profiling, chemotaxonomy, [...] Read more.
The genus Parabacteroides comprises widespread gastrointestinal commensals, known to produce immunomodulatory molecules and extracellular vesicles, yet its full diversity is incompletely cataloged. This study describes strain ASD2025T, isolated from healthy child feces, using a polyphasic taxonomic approach including phenotypic profiling, chemotaxonomy, and comparative genomics. Cells were non-motile, polymorphic rods that produced extracellular vesicles. Phylogenomic analysis placed ASD2025T within the genus Parabacteroides within a species complex consisting of P. acidifaciens, P. hominis, “P. massiliensis”, P. merdae, and P. johnsonii, with average nucleotide identities to the type strains of 85.5–89.9%. The large genome (5.16 Mbp, 46.2% GC content) contained integrative conjugative elements harboring antibiotic resistance genes and hankyphage-related prophage. The strain produced succinate as the major metabolic end product, and its major fatty acids were anteiso-C15:0, iso-C17:0 3-OH, and C15:0. Conditioned medium from ASD2025T antagonized the interleukin-8 response caused by E. coli lipopolysaccharide in HT29 cells. The majority of related metagenome-assembled genomes originate from mouse microbiomes. Based on these distinct characteristics, strain ASD2025T (=VKM B-3926T = JCM 37967T) represents a novel species of the genus Parabacteroides, for which the name Parabacteroides vesiculifaciens sp. nov. is proposed. Full article
(This article belongs to the Section Molecular Microbiology)
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