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Search Results (381)

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Keywords = selective growth restriction

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18 pages, 3523 KB  
Article
NIR-II Responsive Platinum-Engineered Vanadium Carbide MXene Endows Poly-L-Lactic Acid Bone Scaffold with Photothermal Antibacterial Property
by Lin Sun, Zihao Zhang, Bingxin Sun, Zhiheng Yu and Guoyong Wang
Polymers 2026, 18(3), 378; https://doi.org/10.3390/polym18030378 - 30 Jan 2026
Abstract
Vanadium carbide (V2C) MXene shows great potential for addressing challenging implant-associated infections in bone regeneration due to its strong photothermal conversion efficiency. However, its photothermal efficacy is restricted to the near-infrared I (NIR-I) region due to a limited absorption range. To [...] Read more.
Vanadium carbide (V2C) MXene shows great potential for addressing challenging implant-associated infections in bone regeneration due to its strong photothermal conversion efficiency. However, its photothermal efficacy is restricted to the near-infrared I (NIR-I) region due to a limited absorption range. To address this, we designed platinum nanoparticle-decorated V2C heterostructures (Pt@V2C) via an in situ growth method, leveraging Pt’s plasmonic and catalytic properties to extend the photoresponse to the NIR-II window. Subsequently, Pt@V2C was integrated into poly-L-lactic acid (PLLA) to fabricate PLLA-Pt@V2C scaffolds with photothermal antibacterial function by selective laser sintering. The optimized PLLA-Pt@V2C scaffold achieves a record photothermal conversion efficiency (56.03% at 1064 nm), triggering simultaneous hyperthermia (>52 °C) and catalytic ·OH radical generation. In vitro studies demonstrate exceptional antibacterial efficacy against Staphylococcus aureus and Escherichia coli, achieving over 99% killing rates upon 1064 nm near-infrared irradiation. Furthermore, the scaffold demonstrated significant inhibition of biofilm formation, achieving over 90% reduction in biofilm biomass. Moreover, the scaffold demonstrated high cell viability, confirming its dual functionality of potent bactericidal activity and biocompatibility that supports tissue regeneration. This work provides a feasible strategy for combating implant-associated infections. Full article
(This article belongs to the Special Issue Polymer Scaffold for Tissue Engineering Applications, 2nd Edition)
34 pages, 20136 KB  
Article
Comparative Study of the Underwater Soundscape in Natural and Artificial Environments in the Mediterranean
by Pedro Poveda-Martínez, Naeem Ullah, Jesús Carbajo, Carlos Valle, Aitor Forcada, Isabel Pérez-Arjona, Víctor Espinosa and Jaime Ramis-Soriano
J. Mar. Sci. Eng. 2026, 14(3), 241; https://doi.org/10.3390/jmse14030241 - 23 Jan 2026
Viewed by 165
Abstract
The recent growth of Blue Economy-related human activities has increased underwater noise pollution. Sound is a key factor in ensuring the well-being of marine animals as it allows them to communicate with each other and extract valuable information from the environment. Although the [...] Read more.
The recent growth of Blue Economy-related human activities has increased underwater noise pollution. Sound is a key factor in ensuring the well-being of marine animals as it allows them to communicate with each other and extract valuable information from the environment. Although the Marine Strategy Framework Directive requires monitoring programs to achieve good environmental status, there remains a significant deficit of information concerning three key domains: the characteristics of the underwater soundscape, its transformation due to anthropogenic activities, and the effects of noise on marine animals. This study aimed to evaluate the impact of anthropogenic activities on marine acoustic environments. Acoustic metrics and ecoacoustic indices were applied to characterise variability and assess daily, weekly, and seasonal patterns, as well as the effects of trawling restrictions. Three underwater soundscapes were compared in this study: two natural environments in the Mediterranean Sea and one artificial environment, a land-based fish farm tank. High anthropogenic noise levels were found, primarily due to fishing vessels near the selected locations. Similarly, the soundscape exhibited notable seasonal variations (annual and weekly), demonstrating a significant dependence on tourist activities. The results highlight the benefits of acoustic parameters as a tool for monitoring environmental conditions over time. Full article
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27 pages, 7708 KB  
Article
Effects of Substrate-Based Root Restriction on Tomato Growth, Fruit Quality, Yield, and Microbial Communities in a Simplified Automatic Soilless Cultivation System
by Yecheng Jin, Siqi Xia, Haili Zhang, Lingyu Wang, Ying Zhou, Jie Zhou, Xiaojian Xia, Nianqiao Shen and Zhenyu Qi
Agronomy 2026, 16(2), 212; https://doi.org/10.3390/agronomy16020212 - 15 Jan 2026
Viewed by 177
Abstract
Root restriction is an agronomic technique that influences plant morphology, physiology, and productivity. This study investigates the effects of root restriction on tomato growth, fruit quality, yield, and rhizosphere microbial communities using three distinct substrates: sand, soil, and peanut shell substrate (PSS), within [...] Read more.
Root restriction is an agronomic technique that influences plant morphology, physiology, and productivity. This study investigates the effects of root restriction on tomato growth, fruit quality, yield, and rhizosphere microbial communities using three distinct substrates: sand, soil, and peanut shell substrate (PSS), within a Simplified Automatic Soilless Culture System (SAS). Results demonstrated that root restriction at 8 cm height significantly enhanced fruit quality indicators: soluble sugar content increased by 69.01% (sand), 53.84% (soil), and 37.67% (PSS); soluble protein increased by 77.23%, 48.14%, and 66.51%; and lycopene increased by 100.03%, 62.33%, and 74.59%, respectively, compared to the 24 cm baseline. However, single-plant yield declined by 28.30% (sand), 64.28% (soil), and 22.06% (PSS). TOPSIS analysis (Technique for Order Preference by Similarity to Ideal Solution) identified PSS at 8 cm as the optimal combination for balancing quality and yield (Cj = 0.631). Microbial amplicon sequencing revealed higher rhizosphere microbial diversity in tomatoes grown in soil and peanut shell substrate compared to sand. These three types of growing media (soil, sand, and peanut shell substrate) establish the rhizosphere of bacterial and fungal communities by selecting specific microbial taxa. Changes in container height drive the reduction–oxidation functional divergence of bacterial communities, affecting the connectivity and complexity of microbial networks. Full article
(This article belongs to the Section Horticultural and Floricultural Crops)
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21 pages, 3882 KB  
Article
Construction of a Nocturnal Low-Temperature Tolerance Index for Strawberry and Its Correlation with Yield
by Hongbo Cui, Qingyan Han, Yanni Liu, Qian Zhang, Jun Liu, Jianfeng Wang and Huanyu Zhang
Horticulturae 2026, 12(1), 81; https://doi.org/10.3390/horticulturae12010081 - 9 Jan 2026
Viewed by 213
Abstract
Strawberry is widely cultivated due to its short growth cycle, high yield, and significant profits. In high-latitude cold regions, the planting area of overwintering strawberry has expanded rapidly in recent years. However, although daytime temperatures inside solar greenhouses rise quickly with solar radiation, [...] Read more.
Strawberry is widely cultivated due to its short growth cycle, high yield, and significant profits. In high-latitude cold regions, the planting area of overwintering strawberry has expanded rapidly in recent years. However, although daytime temperatures inside solar greenhouses rise quickly with solar radiation, plants are frequently subjected to persistent nocturnal low-temperature stress (nocturnal temperature below 10 °C). This stress restricts photosynthesis, delays growth, and markedly reduces yield. Therefore, accurately evaluating the tolerance of strawberry varieties to low nocturnal temperatures is crucial for unheated overwintering production in cold regions. This study selected Snow White, Benihoppe, and Kaorino as experimental materials for overwintering cultivation trials in a typical cold-region solar greenhouse. We measured and analyzed growth and development, photosynthetic characteristics, phenological traits, and fruit yield. Based on photosynthetic physiology and phenotypic traits, we constructed the Photosynthesis–Fluorescence Index (PFI), the Production–Phenotype Index (PPI), and the Nocturnal Cold Tolerance Index (NCTI). The results showed that Kaorino exhibited significantly higher values in all three indices compared with Benihoppe and Snow White. After exposure to low night temperatures, Kaorino exhibited rapid photosynthetic induction, strong maintenance of PSII activity, vigorous growth, early maturation, and high yield. Moreover, all three composite indices were strongly and positively correlated with total yield (R2 > 0.97), demonstrating their effectiveness in distinguishing the nocturnal low-temperature tolerance of strawberry cultivars. These composite indices provide a scientifically robust method for selecting suitable cultivars for unheated overwinter strawberry production in high-latitude cold regions. Full article
(This article belongs to the Section Vegetable Production Systems)
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15 pages, 2428 KB  
Article
Pituitary Neuroendocrine Tumors Extending Primarily Below the Sella and into the Clivus: A Distinct Growth Pattern with Specific Challenges
by Lennart W. Sannwald, Nina Kreße, Nadja Grübel, Andreas Knoll, Johannes Roßkopf, Michal Hlavac, Christian R. Wirtz and Andrej Pala
Curr. Oncol. 2026, 33(1), 36; https://doi.org/10.3390/curroncol33010036 - 8 Jan 2026
Viewed by 217
Abstract
Evaluation of pituitary neuroendocrine tumors remains complex depending on the exact growth pattern, involvement of critical neurovascular structures, pituitary function and endocrinological activity of the tumor. A predominant growth into the sphenoid sinus and clivus poses specific challenges. We reviewed 557 surgeries for [...] Read more.
Evaluation of pituitary neuroendocrine tumors remains complex depending on the exact growth pattern, involvement of critical neurovascular structures, pituitary function and endocrinological activity of the tumor. A predominant growth into the sphenoid sinus and clivus poses specific challenges. We reviewed 557 surgeries for pituitary neuroendocrine tumors in an endonasal endoscopic technique performed between 1 January 2015 and 31 August 2025 to identify 13 cases (2.3%). Clinical, radiological and surgical data were selected by chart review. Thirteen cases aged from 31 to 68 years with almost exclusively non-functioning or clinically silent tumors (92%) were identified. Clival infiltration was restricted to the dorsum sellae in 2/13 (15%), spread to the floor of the sphenoid in 6/13 (46%) and extended inferior to the sphenoid in 5/13 (38%) cases with a high rate of cavernous sinus (62%) and sphenoid sinus infiltration (69%). Complete resection was achieved in 31%, and the residual tumor was clival/sphenoidal in 5/13 cases or within the cavernous sinus in 6/13 cases. The diaphragma sellae was reported to be intact in 92% of cases, and postoperative transient arginine vasopressin deficiency did not occur. Pituitary neuroendocrine tumors predominantly growing below the sella and infiltrating the clivus and sphenoid present specific challenges with a high rate of preoperative pituitary insufficiency, frequent cavernous sinus infiltration and postoperative tumor residuals in the cavernous sinus, sphenoid bone and clivus which are sometimes difficult to delineate. The surgical approach must be tailored specifically to treat the clival infiltration zone to reduce the risk of recurrence. Full article
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12 pages, 4161 KB  
Article
Prenatal Amnioinfusion as a Diagnostic Tool in Severe Oligo- and Anhydramnios: A Retrospective Single-Center Experience with Descriptive Perinatal Outcomes
by Kristin Andresen, Christel Eckmann-Scholz, Andre Farrokh, Ulrich Pecks, Nicolai Maass, Veronika Günther, Ibrahim Alkatout and Johannes Ackermann
J. Clin. Med. 2026, 15(2), 511; https://doi.org/10.3390/jcm15020511 - 8 Jan 2026
Viewed by 236
Abstract
Objective: To evaluate the diagnostic utility of antepartum amnioinfusion in cases of severe oligo- and anhydramnios and to descriptively report perinatal outcomes. Methods: This retrospective single-center study analyzed all antepartum amnioinfusions performed between 2009 and 2024 in pregnancies between 16 + [...] Read more.
Objective: To evaluate the diagnostic utility of antepartum amnioinfusion in cases of severe oligo- and anhydramnios and to descriptively report perinatal outcomes. Methods: This retrospective single-center study analyzed all antepartum amnioinfusions performed between 2009 and 2024 in pregnancies between 16 + 0 and 34 + 0 weeks of gestation. The primary endpoint was diagnostic impact following amnioinfusion. Secondary endpoints were descriptive perinatal outcomes. No inferential statistical analyses were performed. Results: A total of 37 amnioinfusions were performed in 31 patients. Median gestational age at first amnioinfusion was 22 ± 4.3 weeks, with a mean infusion volume of 259 ± 59.4 mL. The most frequent etiologies were preterm prelabor rupture of membranes (PROM, 29%), fetal growth restriction (FGR, 25.8%), and urogenital malformations (22.6%). Amnioinfusion improved sonographic visualization and diagnostic assessment in the majority of cases. Pregnancy prolongation was observed in selected subgroups; however, causal inference regarding therapeutic efficacy cannot be drawn. Conclusions: Antepartum amnioinfusion represents a valuable adjunct for prenatal diagnostic evaluation in severe oligo- and anhydramnios. Observed perinatal outcomes should be interpreted descriptively. Further prospective, controlled studies are required to define the role of amnioinfusion beyond diagnostic feasibility. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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19 pages, 1618 KB  
Review
From Gut Dysbiosis to Skin Inflammation in Atopic Dermatitis: Probiotics and the Gut–Skin Axis—Clinical Outcomes and Microbiome Implications
by Adina Elena Micu, Ioana Adriana Popescu, Ioana Alina Halip, Mădălina Mocanu, Dan Vâță, Andreea Luana Hulubencu, Dragoș Florin Gheucă-Solovăstru and Laura Gheucă-Solovăstru
Int. J. Mol. Sci. 2026, 27(1), 365; https://doi.org/10.3390/ijms27010365 - 29 Dec 2025
Viewed by 924
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut–skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin disease in which barrier impairment, immune dysregulation, and gut–skin dysbiosis intersect, prompting growing interest in probiotics as microbiota-modulating adjuncts. We conducted a narrative review of peer-reviewed articles indexed in PubMed, Scopus, and Google Scholar, restricted to publications from 1 January 2018 to 31 October 2025 (searches last run in December 2025). Eligible evidence included randomized controlled trials (RCTs), observational studies, and mechanistic or conceptual reviews addressing microbiome alterations and microbiota-modulating interventions in AD. Most pediatric RCTs using multistrain, Lactobacillus-dominant formulations (often combined with Bifidobacterium) reported modest improvements in AD severity and pruritus and in selected barrier- and inflammation-related biomarkers. However, direct cutaneous microbiome “restoration” outcomes were reported in a minority of studies, and most clinical evidence relies on clinical endpoints and gut–skin axis plausibility rather than longitudinal skin microbiome readouts. Single-strain regimens showed inconsistent effects, and evidence in adolescents and adults remained heterogeneous. Mechanistically, probiotics may enhance short-chain fatty acid (SCFA) signaling, dampen toll-like receptor 2/4 (TLR2/4)-nuclear factor kappa B (NF-κB) activation, and promote interleukin-10 (IL-10)- and transforming growth factor-β (TGF-β)-driven tolerance. Probiotics are a biologically plausible adjunct targeting the gut–skin axis in AD and are generally well tolerated; however, heterogeneity across trials, limited follow-up, inconsistent adverse-event reporting, and scarce skin microbiome endpoints preclude firm clinical recommendations. Full article
(This article belongs to the Special Issue Skin Microbiome and Skin Health: Molecular Interactions)
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34 pages, 786 KB  
Review
Current State of the Neurotrophin-Based Pharmaceutics in the Treatment of Neurodegenerative Diseases and Neuroinflammation
by Tatiana A. Fedotcheva and Nikolay L. Shimanovsky
Med. Sci. 2026, 14(1), 15; https://doi.org/10.3390/medsci14010015 - 29 Dec 2025
Viewed by 691
Abstract
Background: The regulation of the synthesis of the nerve growth factor and other neurotrophins is one of the dynamically developing areas of pharmacotherapy of neurological and mental disorders. Despite a large number of studies of various ligands of neurotrophin receptors, only a few [...] Read more.
Background: The regulation of the synthesis of the nerve growth factor and other neurotrophins is one of the dynamically developing areas of pharmacotherapy of neurological and mental disorders. Despite a large number of studies of various ligands of neurotrophin receptors, only a few have reached clinical application and only for ocular diseases. The aim of this narrative review was to systematize the main progress on neurotrophin-based pharmaceutics; to perform a comparative critical analysis of various therapeutic strategies, elucidate the underlying causes of clinical trial failures, and identify the most promising avenues for future development. Methods: The literature search was conducted in PubMed, Google Scholar, Medline, and EBSCO, and the ClinicalTrials.gov database was used to track current clinical studies, along with the official websites of pharmaceutical companies. The search covered original studies published up to October 2025, with inclusion restricted to articles published in English. Articles describing specific pharmacological compounds that had reached the clinical trial stage were selected. Foundational biological research was referenced to contextually explain the mechanisms of action of the drugs and their therapeutic implications. Results: Recombinant neurotrophins and synthetic molecules, the agonists and antagonists of their receptors, and cell-based gene therapy are promising means for the prevention and rehabilitation of ischemic conditions, as well as the treatment of neuropathic pain and neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Some of these have undergone clinical trials, yet only neurotrophins for ocular diseases have been implemented in clinical practice: recombinant NGF—cenegermin and recombinant CNTF—Revakinagene taroretcel. The success of these eye drugs is likely attributable to their local administration, improved bioavailability, and low ocular immunoresistance. Conclusions: The study identified limitations and future prospects for neurotrophin-based pharmaceuticals. For future clinical trials, attention should be paid to the pharmacogenetic profiles of the patients and the evaluation of the inflammatory status of the disease. Novel plasma biomarkers of the effectiveness are needed as well as TSPO-PET imaging. Drug delivery systems remain insufficient; therefore, efforts should focus on inducing endogenous neurotrophin production and developing highly selective agonists and antagonists of neurotrophin receptors. It is crucial to establish a favorable premorbid background before neurotrophin therapy to minimize immunoresistance. Full article
(This article belongs to the Collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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15 pages, 2628 KB  
Article
Enhanced Cultivation of Actinomycetota Strains from Millipedes (Diplopoda) Using a Helper Strain-Assisted Method
by Yingying Shi, Eun-Young Seo, Jeffrey S. Owen, Zhaoyun He, Liufei Shi, Chang Yan, Wenhan Lin, Dawoon Jung and Shan He
Fermentation 2026, 12(1), 16; https://doi.org/10.3390/fermentation12010016 - 27 Dec 2025
Viewed by 520
Abstract
The limited cultivability of Actinomycetota strains restricts the exploration of their novel antibiotics, highlighting the need for improved isolation techniques. This study employed a helper strain-assisted cultivation method which utilizes culture supernatants from helper strains to isolate diverse members of the Actinomycetota from [...] Read more.
The limited cultivability of Actinomycetota strains restricts the exploration of their novel antibiotics, highlighting the need for improved isolation techniques. This study employed a helper strain-assisted cultivation method which utilizes culture supernatants from helper strains to isolate diverse members of the Actinomycetota from millipedes and compared its efficacy with a standard method. Using a preliminary dual-layer solid media assay and subsequent confirmation experiments, eight helper strains (M3, M9, M13, N3, N4, N6, N8, and N9) were identified, whose supernatants promoted the growth of Actinomycetota and other microbes. Application of this method to millipede samples established a novel cultivation strategy based on co-cultivation with helper strains. The new method enabled the isolation of 233 bacterial species in total, of which 143 were species of the phylum Actinomycetota, including 49 novel species. In contrast, the standard method yielded only 42 total bacterial species and 29 species of Actinomycetota, with merely 8 novel species. Comparative diversity analysis revealed that the helper strain-assisted method yielded Actinomycetota strains from 85 genera, which was 3.5 times higher than the standard method. This demonstrates that the helper strain-assisted approach is a highly effective strategy for accessing diverse and novel microbial majority. Among the isolated Actinomycetota strains, 75 strains predicted to have high biosynthetic gene clusters (BGCs) numbers or expected to be novel species were screened for antibacterial activity. Fourteen strains (17%) exhibited inhibitory effects against at least one indicator bacterium. One novel strain, Streptomyces sp. N8-31, was selected for whole-genome sequencing. AntiSMASH analysis predicted 40 biosynthetic gene clusters in N8-31, with 60% showing less than 70% similarity to known clusters; among these, 20 clusters showed less than 50% similarity. These findings indicate that strain N8-31 is a rich reservoir of novel genetic resources, and its broad-spectrum antibacterial activity is likely linked to these unique secondary metabolite gene clusters. Critically, this study confirms that helper strain-assisted cultivation is a powerful tool for unlocking the hidden biosynthetic potential of previously inaccessible Actinomycetota. Full article
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13 pages, 779 KB  
Article
Culture Growth Phase-Dependent Influence of Extracellular Vesicles Derived from Stem Cells from Human Exfoliated Deciduous Teeth on Oral Mucosa Cells Proliferation in Paracrine Co-Culture with Urethral Epithelium: Implication for Urethral Reconstruction
by Tsuyoshi Kawaharada, Daisuke Watanabe, Kazuki Yanagida, Kashia Goto, Ailing Hu, Yuhei Segawa, Madoka Higuchi, Masayuki Shinchi, Akio Horiguchi, Tatsuya Takagi and Akio Mizushima
Int. J. Mol. Sci. 2026, 27(1), 314; https://doi.org/10.3390/ijms27010314 - 27 Dec 2025
Viewed by 395
Abstract
Urethral stricture is a disease of fibrotic narrowing that compromises the urethral mucosa and spongiosum. Oral mucosal graft urethroplasty delivers excellent outcomes in complex cases, yet its procedural demands restrict availability beyond specialized centers. Endoscopic transplantation of oral mucosa has been proposed; while [...] Read more.
Urethral stricture is a disease of fibrotic narrowing that compromises the urethral mucosa and spongiosum. Oral mucosal graft urethroplasty delivers excellent outcomes in complex cases, yet its procedural demands restrict availability beyond specialized centers. Endoscopic transplantation of oral mucosa has been proposed; while feasibility is shown, clinical efficacy remains suboptimal. We asked whether extracellular vesicles from stem cells of human exfoliated deciduous teeth (SHED-EVs) promote oral mucosa fibroblast (OMF) growth under urethra-mimetic paracrine conditions and whether culture growth phase tunes EV function. SHED-EVs were collected during logarithmic (SHED-EV-L) or stationary (SHED-EV-S) phases under xeno-free conditions, isolated by a standardized workflow, and characterized by nanoparticle tracking analysis. miRNA cargo was profiled with a human miRNA microarray platform and normalized for comparative analyses. OMF proliferation was quantified in a horizontal indirect co-culture with urethral epithelial cells using incubator-based time-lapse imaging. SHED-EV-L produced a sustained pro-proliferative effect across 24–96 h, whereas SHED-EV-S showed a weaker early effect with a late catch-up; both exceeded vehicle at 96 h. Fibrosis-related miRNA heat maps showed culture growth phase-dependent patterns: SHED-EV-L displayed relatively higher signals for miR-31-3p, miR-146b-3p, several let-7 members, and selected miR-181 isoforms, whereas SHED-EV-S showed a marked relative increase of miR-486-3p; miR-21, miR-99/100, and miR-205 were broadly comparable between phases. These findings indicate that culture growth phase is a practical design lever that orients SHED-EV cargo and function, supporting phase-matched formulations for adjunctive transurethral applications and motivating in vivo validation and manufacturing-oriented quality controls. Full article
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17 pages, 609 KB  
Systematic Review
Natural Protein-Restricted Diets and Their Impact on Linear Growth in Patients with Propionic and Methylmalonic Acidemia: A Systematic Review
by Jessica Ramirez, María Jesús Leal-Witt, Juan Francisco Cabello and Verónica Cornejo
J. Pers. Med. 2026, 16(1), 4; https://doi.org/10.3390/jpm16010004 - 22 Dec 2025
Viewed by 417
Abstract
Background/Objectives: Propionic acidemia (PA) and methylmalonic acidemia (MMA) affect methionine, threonine, valine (Val), and isoleucine (Ile) (MTVI) metabolism, leading to the production of highly neurotoxic organic acids. Treatment involves a diet restricted in natural proteins and supplemented with a protein substitute (PS) with [...] Read more.
Background/Objectives: Propionic acidemia (PA) and methylmalonic acidemia (MMA) affect methionine, threonine, valine (Val), and isoleucine (Ile) (MTVI) metabolism, leading to the production of highly neurotoxic organic acids. Treatment involves a diet restricted in natural proteins and supplemented with a protein substitute (PS) with traces of MTVI. The aim was to analyze natural protein and PS intake in relation to linear growth impairment in individuals with PA and MMA. Methods: We followed the PRISMA protocol. We considered articles published between 1970 and 2025. We determined the eligibility criteria for selecting articles and evaluated the quality. Results: Thirteen studies were selected: two case reports, eight longitudinal, three cohorts, and one cross-sectional. Articles demonstrated that natural protein intake decreases with age, consistent with previous reports, underscoring the need for PS supplementation to meet protein requirements. Subjects with PA and non-responsive MMA had greater restriction of natural proteins, and the majority required PS; a higher PS intake was negatively correlated with a higher height-for-age (H/A) z-score. When analyzing the ratio of protein to energy (P:E), a negative correlation was found between the intake of natural proteins and energy, and a positive correlation with H/A z-score (p-value < 0.05). Supplementation with PS increased leucine levels, causing an imbalance with MTVI amino acids. This imbalance led to the paradoxical need to supplement L-Val and L-Ile, both propiogenic amino acids. As a result, a decrease in the H/A z-score was observed, particularly in PA and non-responsive MMA. Responsive MMA tolerated more natural proteins, received a lower intake of PS, and had a better H/A z-score. Conclusions: Restriction of natural proteins and PS is associated with a lower H/A z-score, primarily in subjects with PA and non-responsive MMA. Full article
(This article belongs to the Special Issue Inborn Errors of Metabolism: From Pathomechanisms to Treatment)
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22 pages, 4456 KB  
Article
Allosteric Conformational Locking of Sestrin2 by Leucine: An Integrated Computational Analysis of Branched-Chain Amino Acid Recognition and Specificity
by Muhammad Ammar Zahid, Abbas Khan, Mona A. Sawali, Osama Aboubakr Mohamed, Ahmed Mohammad Gharaibeh and Abdelali Agouni
Molecules 2025, 30(24), 4791; https://doi.org/10.3390/molecules30244791 - 16 Dec 2025
Viewed by 404
Abstract
Sestrin2 (SESN2) is a highly conserved stress-inducible protein that serves as a central hub for integrating cellular responses to nutrient availability, oxidative stress, and endoplasmic reticulum (ER) stress. A key function of SESN2 is its role as a direct sensor for the branched-chain [...] Read more.
Sestrin2 (SESN2) is a highly conserved stress-inducible protein that serves as a central hub for integrating cellular responses to nutrient availability, oxidative stress, and endoplasmic reticulum (ER) stress. A key function of SESN2 is its role as a direct sensor for the branched-chain amino acid (BCAA) leucine, which modulates the activity of the mechanistic target of rapamycin complex 1 (mTORC1), a master regulator of cell growth and metabolism. While the functional link between leucine and SESN2 is well-established, the precise molecular determinants that confer its high specificity for leucine over other BCAAs, such as isoleucine and valine, remain poorly understood. This study employs an integrated computational approach, spanning atomic interactions to global protein dynamics, combining molecular docking, extensive all-atom molecular dynamics (MD) simulations, and binding free energy calculations, to elucidate the structural and dynamic basis of BCAA-SESN2 recognition. Our thermodynamic analysis reveals a distinct binding affinity hierarchy (Leucine > Isoleucine > Valine), which is primarily driven by superior van der Waals interactions and the shape complementarity of leucine’s isobutyl side chain within the protein’s hydrophobic pocket. Critically, a quantitative analysis of the conformational ensemble reveals that leucine induces a dramatic collapse of the protein’s structural heterogeneity. This “conformational locking” mechanism funnels the flexible, high-entropy unbound protein—which samples 35 distinct conformations—into a sharply restricted ensemble of just 9 stable states. This four-fold reduction in conformational freedom is accompanied by a kinetic trapping effect, which significantly lowers the rate of transitions between states. This process of conformational selection stabilizes a well-defined, signaling-competent structure, providing a comprehensive, atom-to-global-scale model of SESN2’s function. In the context of these findings, this work provides a critical framework for understanding SESN2’s complex role in disease and offers a clear rationale for the design of next-generation allosteric therapeutics. Full article
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26 pages, 617 KB  
Review
Decoding Picky Eating in Children: A Temporary Phase or a Hidden Health Concern?
by Dorina Pjetraj, Amarildo Pjetraj, Dalia Sayed, Michele Severini, Ludovica Falcioni, Lucia Emanuela Svarca, Simona Gatti and Maria Elena Lionetti
Nutrients 2025, 17(24), 3884; https://doi.org/10.3390/nu17243884 - 12 Dec 2025
Viewed by 2070
Abstract
Background: Picky eating (PE), also termed food selectivity, is one of the most common feeding concerns in childhood. Although often a transient developmental stage, persistent or severe selectivity may lead to nutritional deficiencies, growth impairment, and psychosocial consequences. Methods: This narrative [...] Read more.
Background: Picky eating (PE), also termed food selectivity, is one of the most common feeding concerns in childhood. Although often a transient developmental stage, persistent or severe selectivity may lead to nutritional deficiencies, growth impairment, and psychosocial consequences. Methods: This narrative review is based on literature searches conducted in April 2025 across PubMed, Web of Science, Embase, Medline, and Google Scholar. Articles published between 2015 and 2025 were included if they addressed the epidemiology, etiology, assessment, or management of PE in children aged 0–18 years. Additional seminal references predating this period were also considered. Results: Prevalence estimates of PE vary widely (13–50%), with peak incidence between ages two and six. Contributing factors include genetic predisposition, sensory sensitivities, temperament, family feeding practices, environmental influences, and adverse feeding experiences. Distinction from avoidant/restrictive food intake disorder (ARFID) and pediatric feeding disorder (PFD) is essential, as these conditions carry greater risk of nutritional and psychosocial impairment. Assessment relies on caregiver-report instruments, clinical observation, growth monitoring, and targeted nutritional evaluation. Effective management integrates parental education, responsive feeding strategies, repeated exposure to novel foods, and, when indicated, nutritional supplementation or referral to multidisciplinary teams. Sensory-based therapies, behavioral interventions, and psychoeducational programs show particular benefit in persistent cases. Conclusions: While most children outgrow PE without adverse outcomes, a subset remains at risk of long-term nutritional compromise and psychosocial difficulties. Early recognition, family-centered guidance, and evidence-based interventions are essential. Future research should refine diagnostic criteria, develop culturally sensitive assessment tools, and evaluate innovative therapies to improve outcomes. Full article
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19 pages, 3511 KB  
Article
Enhancing CD8+ T Cells Infiltration Through the Protein Arginine Methyltransferase 5 (PRMT5)/CXCL10 Axis Restricts Cervical Cancer Progression
by Yongshuai Jiang, Yingying Wei, Ziyang Li, Zhenghang Huang, Junsheng Dong, Weijuan Gong and Li Qian
Biomolecules 2025, 15(12), 1717; https://doi.org/10.3390/biom15121717 - 10 Dec 2025
Viewed by 564
Abstract
PRMT5, a type II methyltransferase catalyzing symmetric dimethylation of arginine residues, has emerged as a promising therapeutic target in various cancers. However, the precise mechanism by which PRMT5 mediated the tumor immune microenvironment, particularly CD8+ T cell recruitment in cervical cancer remains [...] Read more.
PRMT5, a type II methyltransferase catalyzing symmetric dimethylation of arginine residues, has emerged as a promising therapeutic target in various cancers. However, the precise mechanism by which PRMT5 mediated the tumor immune microenvironment, particularly CD8+ T cell recruitment in cervical cancer remains elusive. Analysis of data from The Cancer Genome Atlas (TCGA) revealed elevated PRMT5 mRNA levels in cervical cancer tissues, which correlated with reduced immune cell infiltration and poorer patient prognosis. To further investigate the role of PRMT5 in tumor development, a CD8 knockout (KO) mouse tumor model was utilized. Significant inhibition of tumor growth was observed in cervical cancer using a mouse model lacking PRMT5. Notably, this antitumor effect was attenuated in CD8 KO mice lacking functional CD8+ T cells. Mechanistically, RNA sequencing (RNA-seq) analysis was conducted to explore how PRMT5 regulates immune cell recruitment. Disruption of PRMT5 was found to increase the secretion of chemokine CXCL10 by tumor cells. CXCL10 binds to its receptor CXCR3, thereby recruiting T cells to the tumor. Furthermore, in CXCR3 KO mice, PRMT5 knockdown failed to enhance T cell infiltration into tumors. These findings indicate that PRMT5 knockdown promotes CD8+ T cell recruitment to the tumor microenvironment via CXCL10 signaling. Furthermore, the therapeutic efficacy of the selective PRMT5 inhibitor EPZ015666 was evaluated in a cervical cancer xenograft mouse model. Treatment with EPZ015666 effectively suppressed tumor growth. In summary, these findings elucidate a novel mechanism whereby PRMT5 depletion in cervical cancer cells triggers a CXCL10-mediated chemotactic response, enhancing CD8+ T cell infiltration and restricting tumor progression. Thus, our study provides compelling evidence supporting the potential targeting of PRMT5 as a viable immunotherapeutic strategy for cervical cancer. Full article
(This article belongs to the Section Molecular Medicine)
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Article
Growth-Rate Related Quantitative Trait Locus Analysis of Monokaryotic Isolates of Grifola albicans f. huishuhua (Maitake)
by Panpan Zhang, Junling Wang, Guojie Li, Shangshang Xiao, Lei Sun, Xiao Li, Jinghua Tian, Ming Li and Shoumian Li
J. Fungi 2025, 11(12), 865; https://doi.org/10.3390/jof11120865 - 5 Dec 2025
Viewed by 582
Abstract
A genetic linkage map of Grifola albicans f. huishuhua (Maitake) is an important resource for chromosome analysis and the genetic basis of phenotypic variation determination. A total of 92 monokaryotic isolates were selected from the F1 generation of Q3-8 × Y1-18 in this [...] Read more.
A genetic linkage map of Grifola albicans f. huishuhua (Maitake) is an important resource for chromosome analysis and the genetic basis of phenotypic variation determination. A total of 92 monokaryotic isolates were selected from the F1 generation of Q3-8 × Y1-18 in this study. Restriction site-associated DNA sequencing, as well as identification of single nucleotide polymorphisms (SNPs), was performed, aiming to illustrate a high-density genetic linkage map. A total of 1122 high-quality SNP markers were located on a map with a length of 1473.60 centimorgan (cM) by screening 589534 SNPs. This map covers 12 linkage groups (LGs) with an average genetic distance of 122.80 cM. Three quantitative trait loci (QTLs) related to the growth rate of G. albicans f. huishuhua strains were identified using the composite interval mapping method. These QTLs were mapped to linkage groups (LGs) as follows: LG3 (qmgv), LG4 (qmb), LG5 (qmd), LG8 (qrdm1, qrdm2), and LG10 (qmgrc1, qmgrc2, qmgrc3). The genes associated with mycelial growth rate and biomass production of these strains were identified. This information could be used for molecular marker-assisted selective breeding in G. albicans f. huishuhua. Full article
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