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15 pages, 4562 KiB  
Article
DNA Methylation-Associated Epigenetic Changes in Thermotolerance of Bemisia tabaci During Biological Invasions
by Tianmei Dai, Yusheng Wang, Xiaona Shen, Zhichuang Lü, Fanghao Wan and Wanxue Liu
Int. J. Mol. Sci. 2025, 26(15), 7466; https://doi.org/10.3390/ijms26157466 (registering DOI) - 1 Aug 2025
Abstract
Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity [...] Read more.
Global warming and anthropogenic climate change are projected to expand the geographic distribution and population abundance of ectothermic species and exacerbate the biological invasion of exotic species. DNA methylation, as a reversible epigenetic modification, could provide a putative link between the phenotypic plasticity of invasive species and environmental temperature variations. We assessed and interpreted the epigenetic mechanisms of invasive and indigenous species’ differential tolerance to thermal stress through the invasive species Bemisia tabaci Mediterranean (MED) and the indigenous species Bemisia tabaci AsiaII3. We examine their thermal tolerance following exposure to heat and cold stress. We found that MED exhibits higher thermal resistance than AsiaII3 under heat stress. The fluorescence-labeled methylation-sensitive amplified polymorphism (F-MSAP) results proved that the increased thermal tolerance in MED is closely related to DNA methylation changes, other than genetic variation. Furthermore, the quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of DNA methyltransferases (Dnmts) suggested that increased expression of Dnmt3 regulates the higher thermal tolerance of female MED adults. A mechanism is revealed whereby DNA methylation enhances thermal tolerance in invasive species. Our results show that the Dnmt-mediated regulation mechanism is particularly significant for understanding invasive species’ successful invasion and rapid adaptation under global warming, providing new potential targets for controlling invasive species worldwide. Full article
(This article belongs to the Section Molecular Biology)
24 pages, 1396 KiB  
Article
Design of Experiments Leads to Scalable Analgesic Near-Infrared Fluorescent Coconut Nanoemulsions
by Amit Chandra Das, Gayathri Aparnasai Reddy, Shekh Md. Newaj, Smith Patel, Riddhi Vichare, Lu Liu and Jelena M. Janjic
Pharmaceutics 2025, 17(8), 1010; https://doi.org/10.3390/pharmaceutics17081010 (registering DOI) - 1 Aug 2025
Abstract
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription [...] Read more.
Background: Pain is a complex phenomenon characterized by unpleasant experiences with profound heterogeneity influenced by biological, psychological, and social factors. According to the National Health Interview Survey, 50.2 million U.S. adults (20.5%) experience pain on most days, with the annual cost of prescription medication for pain reaching approximately USD 17.8 billion. Theranostic pain nanomedicine therefore emerges as an attractive analgesic strategy with the potential for increased efficacy, reduced side-effects, and treatment personalization. Theranostic nanomedicine combines drug delivery and diagnostic features, allowing for real-time monitoring of analgesic efficacy in vivo using molecular imaging. However, clinical translation of these nanomedicines are challenging due to complex manufacturing methodologies, lack of standardized quality control, and potentially high costs. Quality by Design (QbD) can navigate these challenges and lead to the development of an optimal pain nanomedicine. Our lab previously reported a macrophage-targeted perfluorocarbon nanoemulsion (PFC NE) that demonstrated analgesic efficacy across multiple rodent pain models in both sexes. Here, we report PFC-free, biphasic nanoemulsions formulated with a biocompatible and non-immunogenic plant-based coconut oil loaded with a COX-2 inhibitor and a clinical-grade, indocyanine green (ICG) near-infrared fluorescent (NIRF) dye for parenteral theranostic analgesic nanomedicine. Methods: Critical process parameters and material attributes were identified through the FMECA (Failure, Modes, Effects, and Criticality Analysis) method and optimized using a 3 × 2 full-factorial design of experiments. We investigated the impact of the oil-to-surfactant ratio (w/w) with three different surfactant systems on the colloidal properties of NE. Small-scale (100 mL) batches were manufactured using sonication and microfluidization, and the final formulation was scaled up to 500 mL with microfluidization. The colloidal stability of NE was assessed using dynamic light scattering (DLS) and drug quantification was conducted through reverse-phase HPLC. An in vitro drug release study was conducted using the dialysis bag method, accompanied by HPLC quantification. The formulation was further evaluated for cell viability, cellular uptake, and COX-2 inhibition in the RAW 264.7 macrophage cell line. Results: Nanoemulsion droplet size increased with a higher oil-to-surfactant ratio (w/w) but was no significant impact by the type of surfactant system used. Thermal cycling and serum stability studies confirmed NE colloidal stability upon exposure to high and low temperatures and biological fluids. We also demonstrated the necessity of a solubilizer for long-term fluorescence stability of ICG. The nanoemulsion showed no cellular toxicity and effectively inhibited PGE2 in activated macrophages. Conclusions: To our knowledge, this is the first instance of a celecoxib-loaded theranostic platform developed using a plant-derived hydrocarbon oil, applying the QbD approach that demonstrated COX-2 inhibition. Full article
(This article belongs to the Special Issue Quality by Design in Pharmaceutical Manufacturing)
33 pages, 3764 KiB  
Article
Cu2+ and Zn2+ Ions Affecting Biochemical Paths and DNA Methylation of Rye (Secale cereale L.) Anther Culture Influencing Plant Regeneration Efficiency
by Wioletta Monika Dynkowska, Renata Orłowska, Piotr Waligórski and Piotr Tomasz Bednarek
Cells 2025, 14(15), 1167; https://doi.org/10.3390/cells14151167 - 29 Jul 2025
Viewed by 110
Abstract
Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu2+ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in [...] Read more.
Rye regeneration in anther cultures is problematic and affected by albino plants. DNA methylation changes linked to Cu2+ ions in the induction medium affect reprogramming microspores from gametophytic to sporophytic path. Alternations in S-adenosyl-L-methionine (SAM), glutathione (GSH), or β-glucans and changes in DNA methylation in regenerants obtained under different in vitro culture conditions suggest a crucial role of biochemical pathways. Thus, understanding epigenetic and biochemical changes arising from the action of Cu2+ and Zn2+ that participate in enzymatic complexes may stimulate progress in rye doubled haploid plant regeneration. The Methylation-Sensitive Amplified Fragment Length Polymorphism approach was implemented to identify markers related to DNA methylation and sequence changes following the quantification of variation types, including symmetric and asymmetric sequence contexts. Reverse-Phase High-Pressure Liquid Chromatography (RP-HPLC) connected with mass spectrometry was utilized to determine SAM, GSH, and glutathione disulfide, as well as phytohormones, and RP-HPLC with a fluorescence detector to study polyamines changes originating in rye regenerants due to Cu2+ or Zn2+ presence in the induction medium. Multivariate and regression analysis revealed that regenerants derived from two lines treated with Cu2+ and those treated with Zn2+ formed distinct groups based on DNA sequence and methylation markers. Zn2+ treated and control samples formed separate groups. Also, Cu2+ discriminated between controls and treated samples, but the separation was less apparent. Principal coordinate analysis explained 85% of the total variance based on sequence variation and 69% of the variance based on DNA methylation changes. Significant differences in DNA methylation characteristics were confirmed, with demethylation in the CG context explaining up to 89% of the variance across genotypes. Biochemical profiles also demonstrated differences between controls and treated samples. The changes had different effects on green and albino plant regeneration efficiency, with cadaverine (Cad) and SAM affecting regeneration parameters the most. Analyses of the enzymes depend on the Cu2+ or Zn2+ ions and are implemented in the synthesis of Cad, or SAM, which showed that some of them could be candidates for genome editing. Alternatively, manipulating SAM, GSH, and Cad may improve green plant regeneration efficiency in rye. Full article
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18 pages, 2600 KiB  
Article
Nintedanib Induces Mesenchymal-to-Epithelial Transition and Reduces Subretinal Fibrosis Through Metabolic Reprogramming
by David Hughes, Jüergen Prestle, Nina Zippel, Sarah McFetridge, Manon Szczepan, Heike Neubauer, Heping Xu and Mei Chen
Int. J. Mol. Sci. 2025, 26(15), 7131; https://doi.org/10.3390/ijms26157131 - 24 Jul 2025
Viewed by 297
Abstract
This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of [...] Read more.
This study aimed to investigate the tyrosine kinase inhibitor Nintedanib and its potential role in reversing epithelial–mesenchymal transition (EMT) induced by transforming growth factor beta 2 (TGF-β2) in retinal pigment epithelial (RPE) cells, along with its therapeutic potential using a mouse model of subretinal fibrosis. We hypothesized that the blockade of angiogenesis promoting and fibrosis inducing signaling using the receptor tyrosine kinase inhibitor Nintedanib (OfevTM) can prevent or reverse EMT both in vitro and in our in vivo model of subretinal fibrosis. Primary human retinal pigment epithelial cells (phRPE) and adult retinal pigment epithelial cell line (ARPE-19) cells were treated with TGF-β210 ng/mL for two days followed by four days of Nintedanib (1 µM) incubation. Epithelial and mesenchymal phenotypes were assessed by morphological examination, quantitative real-time polymerase chain reaction(qPCR) (ZO-1, Acta2, FN, and Vim), and immunocytochemistry (ZO-1, vimentin, fibronectin, and αSMA). Metabolites were measured using luciferase-based assays. Extracellular acidification and oxygen consumption rates were measured using the Seahorse XF system. Metabolic-related genes (GLUT1, HK2, PFKFB3, CS, LDHA, LDHB) were evaluated by qPCR. A model of subretinal fibrosis using the two-stage laser-induced method in C57BL/6J mice assessed Nintedanib’s therapeutic potential. Fibro-vascular lesions were examined 10 days later via fluorescence angiography and immunohistochemistry. Both primary and ARPE-19 RPE stimulated with TGF-β2 upregulated expression of fibronectin, αSMA, and vimentin, and downregulation of ZO-1, consistent with morphological changes (i.e., elongation). Glucose consumption, lactate production, and glycolytic reserve were significantly increased in TGF-β2-treated cells, with upregulation of glycolysis-related genes (GLUT1, HK2, PFKFB3, CS). Nintedanib treatment reversed TGF-β2-induced EMT signatures, down-regulated glycolytic-related genes, and normalized glycolysis. Nintedanib intravitreal injection significantly reduced collagen-1+ fibrotic lesion size and Isolectin B4+ neovascularization and reduced vascular leakage in the two-stage laser-induced model of subretinal fibrosis. Nintedanib can induce Mesenchymal-to-Epithelial Transition (MET) in RPE cells and reduce subretinal fibrosis through metabolic reprogramming. Nintedanib can therefore potentially be repurposed to treat retinal fibrosis. Full article
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12 pages, 11599 KiB  
Article
Dual pH- and Temperature-Responsive Fluorescent Hybrid Materials Based on Carbon Dot-Grafted Triamino-Tetraphenylethylene/N-Isopropylacrylamide Copolymers
by Huan Liu, Yuxin Ding, Longping Zhou, Shirui Xu and Bo Liao
C 2025, 11(3), 53; https://doi.org/10.3390/c11030053 - 22 Jul 2025
Viewed by 205
Abstract
Carbon dots (CDs), a class of carbon-based fluorescent nanomaterials, have garnered significant attention due to their tunable optical properties and functional versatility. In this study, we developed a hybrid material by grafting pH- and temperature-responsive copolymers onto CDs via reversible addition-fragmentation chain-transfer (RAFT) [...] Read more.
Carbon dots (CDs), a class of carbon-based fluorescent nanomaterials, have garnered significant attention due to their tunable optical properties and functional versatility. In this study, we developed a hybrid material by grafting pH- and temperature-responsive copolymers onto CDs via reversible addition-fragmentation chain-transfer (RAFT) polymerization. Triamino-tetraphenylethylene (ATPE) and N-isopropylacrylamide (NIPAM) were copolymerized at varying ratios and covalently linked to CDs, forming a dual-responsive system. Structural characterization using FTIR, 1H NMR, and TEM confirmed the successful grafting of the copolymers onto CDs. The hybrid material exhibited pH-dependent fluorescence changes in acidic aqueous solutions, with emission shifting from 450 nm (attributed to CDs) to 500 nm (aggregation-induced emission, AIE, from ATPE) above a critical pH threshold. Solid films of the hybrid material demonstrated reversible fluorescence quenching under HCl vapor and recovery/enhancement under NH3 vapor, showing excellent fatigue resistance over multiple cycles. Temperature responsiveness was attributed to the thermosensitive poly(NIPAM) segments, with fluorescence intensity increasing above 35 °C due to polymer chain collapse and ATPE aggregation. This work provides a strategy for designing multifunctional hybrid materials with potential applications in recyclable optical pH/temperature sensors. Full article
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19 pages, 47429 KiB  
Article
Overexpression of (P)RR in SHR and Renin-Induced HepG2 Cells Leads to Spontaneous Hypertension Combined with Metabolic Dysfunction-Associated Fatty Liver Disease
by Chen Gao, Xinyi Guo, Lingzhi Zhang, Xueman Lin and Hua Sun
Int. J. Mol. Sci. 2025, 26(13), 6541; https://doi.org/10.3390/ijms26136541 - 7 Jul 2025
Viewed by 494
Abstract
Hypertension and metabolic dysfunction-associated fatty liver disease (MAFLD) are both common chronic diseases globally. Nearly half of patients with hypertension are complicated by MAFLD. The mechanisms of the bidirectional promotion between the two remain unclear. The (pro) renin receptor ((P)RR) is one of [...] Read more.
Hypertension and metabolic dysfunction-associated fatty liver disease (MAFLD) are both common chronic diseases globally. Nearly half of patients with hypertension are complicated by MAFLD. The mechanisms of the bidirectional promotion between the two remain unclear. The (pro) renin receptor ((P)RR) is one of the classic members of the renin–angiotensin system (RAS) and serves as the receptor for prorenin. Although the role of (P)RR in the induction and progression of hypertension has been extensively studied, its role and underlying mechanisms in MAFLD remain underreported. In this study, we aim to investigate the role of (P)RR in the pathogenesis of hypertension combined with MAFLD. In this study, SHRs were used for the model for hypertension combined with MAFLD. Liver lipid content analysis, liver H&E staining, the detection of (P)RR, ERK and downstream proteins related to fatty acid synthesis and transport, and RNA sequencing and data analysis were performed. In the in vitro experiments, we activated (P)RR using renin and established the lipid deposition model of HepG2 cells induced by renin for the first time. (P)RR was specifically blocked using handle region peptide (HRP), and Nile red fluorescence staining, (P)RR/ERK/PPARγ protein expression analysis, and immunofluorescence were performed to further verify the role of (P)RR in the pathogenesis of hypertension combined with MAFLD. Our results demonstrate that (P)RR plays a role in the development and progression of hypertension combined with MAFLD. The hepatic TG and FFA levels in the SHRs were increased, and the protein expression of the (P)RR/ERK/PPARγ pathway and downstream proteins related to fatty acid synthesis and transport were upregulated. HRP reversed the activation of these proteins and reduced intracellular lipid accumulation. In conclusion, our study first reveals that (P)RR is a potential therapeutic target for hypertension combined with MAFLD. And we found the (P)RR/ERK/PPARγ axis for the first time, which plays an important role in the progression of spontaneous hypertension combined with MAFLD. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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15 pages, 3934 KiB  
Article
Methyl Viologen@β-Zeolite with Absorption/Fluorescence Dual-Mode and Photo/Chemical Synergistic Stimuli-Responsive Chromism
by Jingxuan Han, Shaoning Li, Huihui Li, Yu Li, Jiaqiao Qin, Fuxiang Wang and Qinhe Pan
Molecules 2025, 30(13), 2872; https://doi.org/10.3390/molecules30132872 - 6 Jul 2025
Viewed by 333
Abstract
In this work, methyl viologen (MV) was adsorbed into the nanopores of Si/Al H-β-zeolite via cation exchange. The resulting MV@β-zeolite possessed absorption/fluorescence dual-mode and photo/chemical synergistic stimuli-responsive chromism. Owing to the acidic surrounding provided by β-zeolite, the chromism of MV required the synergistic [...] Read more.
In this work, methyl viologen (MV) was adsorbed into the nanopores of Si/Al H-β-zeolite via cation exchange. The resulting MV@β-zeolite possessed absorption/fluorescence dual-mode and photo/chemical synergistic stimuli-responsive chromism. Owing to the acidic surrounding provided by β-zeolite, the chromism of MV required the synergistic stimuli of UV irradiation and a chemical reductant (such as Na2SO3). UV irradiation induced single electron transfer from the chemical reductant to MV@β-zeolite, leading to enhanced absorption at 610 nm together with a daylight color change from pale yellow to blue. Meanwhile, the nanopores of β-zeolite inhibited aggregation-caused quenching of MV, enabling MV to emit cyan fluorescence at 500 nm. After the single electron transfer of the chemical reductant under UV irradiation, the cyan fluorescence of MV@β-zeolite was quenched. Additionally, MV@β-zeolite exhibited a short stimulus response time (250 s) and good color change reversibility. These findings in this work provide valuable insights into the design of multi-mode and synergistic stimuli-responsive viologen-based chromic materials, particularly for applications in secure high-throughput information storage, high-level anti-counterfeiting and multi-target multi-mode sensing. Full article
(This article belongs to the Special Issue Novel Organic-Inorganic Hybrid Porous Photochromic Materials)
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13 pages, 2581 KiB  
Article
Triazine Calixarene as a Dual-Channel Chemosensor for the Reversible Detection of Cu2+ and I Ions via Water Content Modulation
by Fuyong Wu, Long Chen, Mei Yu, Liang Zhao, Lu Jiang, Tianzhu Shi, Ju Guo, Huayan Zheng, Ruixiao Wang and Mingrui Liao
Molecules 2025, 30(13), 2815; https://doi.org/10.3390/molecules30132815 - 30 Jun 2025
Viewed by 327
Abstract
Rationally designing and synthesizing chemosensors capable of simultaneously detecting both anions and cations via water content modulation is challenging. In this study, we synthesized and characterized a novel triazine calixarene derivative-based iodide and copper ion-selective fluorescent “turn-off” sensor. This dual-channeled fluorescent probe is [...] Read more.
Rationally designing and synthesizing chemosensors capable of simultaneously detecting both anions and cations via water content modulation is challenging. In this study, we synthesized and characterized a novel triazine calixarene derivative-based iodide and copper ion-selective fluorescent “turn-off” sensor. This dual-channeled fluorescent probe is able to recognize Cu2+ and I ions simultaneously in aqueous systems. The fluorescent sensor s4 was synthesized by displacement reaction of acridine with 1, 3-bis (dichloro-mono-triazinoxy) benzene in acetonitrile. Mass spectrometry (MS), UV-vis, and fluorescence spectra were acquired to characterize the fluorescence response of s4 to different cations and anions, while infrared (IR) spectroscopy and isothermal titration calorimetry (ITC) were employed to study the underlying selectivity mechanism of s4 to Cu2+ and I. In detail, s4 displayed extremely high sensitivity to Cu2+ with over 80% fluorescence decrement caused by the paramagnetic nature of Cu2+ in the aqueous media. The reversible fluorescence response to Cu2+ and the responses to Cu2+ in the solution of other potential interferent cations, such as Li+, Na+, K+, Ca2+, Cd2+, Zn2+, Sr2+, Ni2+, Co2+ were also investigated. Probe s4 also exhibited very good fluorescence selectivity to iodide ions under various anion (F, Cl, Br, NO3, HSO4, ClO4, PF6, AcO, H2PO4) interferences. In addition to the fluorescent response to I, s4 showed a highly selective naked-eye-detectable color change from colorless to yellow with the other tested anions. Full article
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17 pages, 8884 KiB  
Article
Pharmacological Preconditioning with Diazoxide Upregulates HCN4 Channels in the Sinoatrial Node of Adult Rat Cardiomyocytes
by Wilibaldo Orea, Elba D. Carrillo, Ascención Hernández, Rubén Moreno, María C. García and Jorge A. Sánchez
Int. J. Mol. Sci. 2025, 26(13), 6062; https://doi.org/10.3390/ijms26136062 - 24 Jun 2025
Viewed by 375
Abstract
Cardioprotection against ischemia is achieved using openers of mitochondrial ATP-sensitive K+ (mitoKATP) channels such as diazoxide (DZX), leading to pharmacological preconditioning (PPC). We previously reported that PPC decreases the abundance of ventricular Cav1.2 channels, but PPC’s effects on other channels remain largely [...] Read more.
Cardioprotection against ischemia is achieved using openers of mitochondrial ATP-sensitive K+ (mitoKATP) channels such as diazoxide (DZX), leading to pharmacological preconditioning (PPC). We previously reported that PPC decreases the abundance of ventricular Cav1.2 channels, but PPC’s effects on other channels remain largely unexplored. In this study, we hypothesized that DZX regulates the expression of hyperpolarization-activated cyclic nucleotide potassium channel 4 (HCN4) channels in sinoatrial node cells (SANCs), the specialized cardiomyocytes that generate the heartbeat. DZX increased the heart rate in intact adult rats. Patch-clamp experiments revealed an increase in the magnitude of ionic currents through HCN4 channels, which was abolished by the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC) and the selective mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD). Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blot assays showed that DZX increased HCN4 channel expression at the mRNA and protein levels. Immunofluorescence analyses revealed that PPC increased HCN4 fluorescence, which was abolished by NAC. DZX increased nuclear translocation of c-Fos and decreased protein abundance of RE1 silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), suggesting the involvement of these factors. Our results suggest that PPC increases the heart rate by upregulating HCN4 channel expression through a mechanism involving c-Fos, REST, and ROS. Full article
(This article belongs to the Special Issue Ion Channels as a Potential Target in Pharmaceutical Designs 2.0)
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13 pages, 3721 KiB  
Article
Effects of Sodium Hexametaphosphate on the Gel Properties and Structure of Glutaminase-Transaminase-Crosslinked Gelatin Gels
by Junliang Chen, Xia Ding, Weiwei Cao, Xinyu Wei, Xin Jin, Qing Chang, Yiming Li, Linlin Li, Wenchao Liu, Tongxiang Yang, Xu Duan and Guangyue Ren
Foods 2025, 14(13), 2175; https://doi.org/10.3390/foods14132175 - 21 Jun 2025
Viewed by 303
Abstract
Gelatin is a commonly used protein-based hydrogel. However, the thermo-reversible nature of gelatin makes it unstable at physiological and higher temperatures. Therefore, this study adopted phosphates and glutaminase transaminase (TG) to modify gelation and studied the effects of combining sodium hexametaphosphate (SHP) and [...] Read more.
Gelatin is a commonly used protein-based hydrogel. However, the thermo-reversible nature of gelatin makes it unstable at physiological and higher temperatures. Therefore, this study adopted phosphates and glutaminase transaminase (TG) to modify gelation and studied the effects of combining sodium hexametaphosphate (SHP) and TG on the structure and gel properties of TG-crosslinked gelatin. This study focused on the effects of different SHP concentrations (0, 0.4, 0.8, 1.2, 1.6, 2.0, 2.4, 2.8 mmol/L) on the water distribution, textural properties, rheological properties, and microstructure of the TG-crosslinked gelatin gels. Results showed that the free water content in the TG-crosslinked gelatin gel declined with the increasing SHP addition when the concentration of SHP was kept below 2.0 mmol/L. The gel of TG-crosslinked gelatin at the SHP concentration of 1.6 mmol/L exhibited the highest hardness (304.258 g), chewiness (366.916 g) and η50. All the TG-crosslinked gelatin gels with SHP modification were non-Newtonian pseudoplastic fluids. The G′ and G″ of TG-crosslinked gelatin increased before the SHP concentration reached 1.6 mmol/L, and the TG-crosslinked gelatin with 1.6 mmol/L SHP exhibited the largest G″ and G′. The fluorescence intensity of TG-crosslinked gelatin with SHP concentration above 1.6 mmol/L decreased with the increasing SHP concentration. SHP modified the secondary structure of TG-crosslinked gelatin gels. The gel of TG-crosslinked gelatin with the SHP concentration of 1.6 mmol/L exhibited a porous, smooth, and dense network structure. This research provides references for modifying gelatin and the application of gels in the encapsulation of bioactive ingredients and probiotics. Full article
(This article belongs to the Section Food Engineering and Technology)
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17 pages, 3825 KiB  
Article
Methionine Restriction Attenuates Scar Formation in Fibroblasts Derived from Patients with Post-Burn Hypertrophic Scar
by Hui Song Cui, Ya Xin Zheng, Yoon Soo Cho, Yu Mi Ro, In Suk Kwak, So Young Joo and Cheong Hoon Seo
Int. J. Mol. Sci. 2025, 26(12), 5876; https://doi.org/10.3390/ijms26125876 - 19 Jun 2025
Viewed by 364
Abstract
Methionine restriction (MetR) is a common adjuvant treatment for cancer. However, studies of MetR have paid little attention to its potential implications for fibrosis. Hypertrophic scarring (HTS) is an abnormal fibrotic response after burn trauma that results from the excessive activation of fibroblasts. [...] Read more.
Methionine restriction (MetR) is a common adjuvant treatment for cancer. However, studies of MetR have paid little attention to its potential implications for fibrosis. Hypertrophic scarring (HTS) is an abnormal fibrotic response after burn trauma that results from the excessive activation of fibroblasts. Because of the absence of a fully effective pharmacological treatment, HTS frequently causes great annoyance in patients as a common sequela of burns. To date, the effects of MetR on hypertrophic scar fibroblasts (HTSFs) remain unclear. This study aimed to investigate the anti-fibrotic effects of MetR and explore the associated alterations in signaling pathways in HTSFs. We isolated HTSFs from post-burn HTS tissues and cultured them in a specially prepared MetR medium. Cell and immunocytochemical staining images were captured using light and fluorescence microscopes, respectively. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. mRNA and protein expression levels were determined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. In HTSFs, MetR reduced cellular inflammation; downregulated multiple signaling pathways, including the TGF-β-SMAD, STAT, and AKT/mTOR pathways; and upregulated MAPKs. Furthermore, MetR arrested the cell cycle, promoted apoptosis, suppressed cell proliferation and migration, and reduced extracellular matrix protein secretion, thereby exerting multifaceted inhibitory effects on HTS. Our results demonstrated that MetR can inhibit scars’ formation and suggest that regulating methionine metabolism in the scar environment may help treat scars. Full article
(This article belongs to the Special Issue Molecular and Cellular Perspectives on Wound Healing)
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39 pages, 11795 KiB  
Review
Overview on the Thermally Activated Delayed Fluorescence and Mechanochromic Materials: Bridging Efficiency and Versatility in LECs and OLEDs
by Raheleh Ghahary, Marzieh Rabiei, Sohrab Nasiri, Juozas Padgurskas and Raimundas Rukuiza
Materials 2025, 18(12), 2714; https://doi.org/10.3390/ma18122714 - 9 Jun 2025
Viewed by 570
Abstract
Recent advancements in thermally activated delayed fluorescence (TADF) materials and mechanochromic materials have significantly enhanced the efficiency and versatility of light-emitting electrochemical cells (LECs) and organic light-emitting diodes (OLEDs). TADF materials have enabled efficiency improvements, achieving an internal quantum efficiency (IQE) of nearly [...] Read more.
Recent advancements in thermally activated delayed fluorescence (TADF) materials and mechanochromic materials have significantly enhanced the efficiency and versatility of light-emitting electrochemical cells (LECs) and organic light-emitting diodes (OLEDs). TADF materials have enabled efficiency improvements, achieving an internal quantum efficiency (IQE) of nearly 100% by utilizing both singlet and triplet excitons. Meanwhile, mechanochromic materials exhibit reversible optical changes upon mechanical stimuli, making them promising for stress sensing, encryption, and flexible electronics. The synergistic integration of TADF and mechanochromic materials in OLEDs and LECs has led to enhanced efficiency, stability, and multifunctionality in next-generation lighting and display technologies. This narrative review explores recent breakthroughs in devices that incorporate both TADF and mechanochromic materials as emitters. Particular attention is given to the molecular design that enable both TADF and mechanochromic properties, as well as optimal device structures and performance parameters. Moreover, this review discusses the only LEC fabricated so far using a TADF-mechanochromic emitter, highlighting its performance and potential. Finally, the report concludes with an outlook on the future commercial applications of these materials, particularly in wearable electronics and smart display technologies. Full article
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12 pages, 2769 KiB  
Article
5′ DREDGE: Direct Repeat-Enabled Downregulation of Gene Expression via the 5′ UTR of Target Genes
by Sagar J. Parikh, Heather M. Terron, Luke A. Burgard, Dylan D. Butler, Frank M. LaFerla, Shelley Lane and Malcolm A. Leissring
Cells 2025, 14(12), 866; https://doi.org/10.3390/cells14120866 - 8 Jun 2025
Viewed by 663
Abstract
Despite the availability of numerous methods for controlling gene expression, there remains a strong need for technologies that maximize two key properties: selectivity and reversibility. To this end, we developed a novel approach that exploits the highly sequence-specific nature of CRISPR-associated endoribonucleases (Cas [...] Read more.
Despite the availability of numerous methods for controlling gene expression, there remains a strong need for technologies that maximize two key properties: selectivity and reversibility. To this end, we developed a novel approach that exploits the highly sequence-specific nature of CRISPR-associated endoribonucleases (Cas RNases), which recognize and cleave short RNA sequences known as direct repeats (DRs). In this approach, referred to as DREDGE (direct repeat-enabled downregulation of gene expression), selective control of gene expression is enabled by introducing one or more DRs into the untranslated regions (UTRs) of target mRNAs, which can then be cleaved upon expression of the cognate Cas RNase. We previously demonstrated that the expression of target genes with DRs in their 3′ UTRs are efficiently controlled by the DNase-dead version of Cas12a (dCas12a) with a high degree of selectivity and complete reversibility. Here, we assess the feasibility of using DREDGE to regulate the expression of genes with DRs inserted in their 5′ UTRs. Among the five different Cas RNases tested, Csy4 was found to be the most efficient in this context, yielding robust downregulation with rapid onset in doxycycline-regulatable systems targeting either a stably expressed fluorescent protein or an endogenous gene, both in a fully reversible manner. Unexpectedly, dCas12a was also found to be modestly effective despite binding essentially irreversibly to the cut mRNA on its 5′ end and thereby boosting mRNA levels. Our results expand the utility of DREDGE as an attractive method for regulating gene expression in a targeted, highly selective, and fully reversible manner. Full article
(This article belongs to the Section Cell Methods)
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15 pages, 1924 KiB  
Article
A Rhodamine B-Based “Turn-On” Fluorescent Probe for Selective Fe3+ Ions Detection
by Md Foridul Islam, Abdulkadir Zakari Abdulkadir, Smaher M. Elbayomi and Pengfei Zhang
Sensors 2025, 25(11), 3477; https://doi.org/10.3390/s25113477 - 31 May 2025
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Abstract
Detecting heavy metal ions is essential for maintaining environmental safety, ensuring industrial quality control, and protecting public health. In this study, we have synthesized a novel Rhodamine B-based fluorescent probe, RhB-DCT, which is functionalized with 2,4-dichloro-1,3,5-triazine (DCT) to enhance selectivity and sensitivity for [...] Read more.
Detecting heavy metal ions is essential for maintaining environmental safety, ensuring industrial quality control, and protecting public health. In this study, we have synthesized a novel Rhodamine B-based fluorescent probe, RhB-DCT, which is functionalized with 2,4-dichloro-1,3,5-triazine (DCT) to enhance selectivity and sensitivity for metal ions detection. The probe functions through a “turn-on” fluorescence mechanism activated by the opening of the spiro-lactam ring induced by Fe3+ ions, resulting in a distinct color change from colorless to deep pink. The RhB-DCT probe demonstrated a rapid and robust fluorescence response within seconds, exhibited a broad pH stability from 4 to 13, showed excellent reversibility, and possessed a low detection limit of 0.0521 μM, surpassing numerous existing fluorescent probes. The RhB-DCT probe exhibited significant selectivity for Fe3+ than other competing metal ions. The integration of high sensitivity, rapid response, and strong stability positions RhB-DCT as a viable option for real-time detection of Fe3+ ions in aqueous settings. This study demonstrates the efficacy of the RhB-DCT probe in environmental monitoring, water quality assessment, and analytical sensing platforms, serving as an effective and dependable tool for detecting heavy metal ions. Full article
(This article belongs to the Special Issue Colorimetric and Fluorescent Sensors and Their Application)
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Article
Cinnamomum cassia Alleviates Neuropsychiatric Lupus in a Murine Experimental Model
by Georges Maalouly, Youakim Saliba, Joelle Hajal, Anna Zein-El-Din, Luana Fakhoury, Rouaa Najem, Viviane Smayra, Hussein Nassereddine and Nassim Fares
Nutrients 2025, 17(11), 1820; https://doi.org/10.3390/nu17111820 - 27 May 2025
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Abstract
Background: The pathogenesis of neuropsychiatric lupus erythematosus (NPSLE) is very complex and is associated with neuroinflammation and blood–brain barrier compromise. Experimental investigations of NPSLE have classically relied on spontaneous models. Recently, TLR7 agonist-induced lupus has been shown to exhibit similar neuropsychiatric manifestations to [...] Read more.
Background: The pathogenesis of neuropsychiatric lupus erythematosus (NPSLE) is very complex and is associated with neuroinflammation and blood–brain barrier compromise. Experimental investigations of NPSLE have classically relied on spontaneous models. Recently, TLR7 agonist-induced lupus has been shown to exhibit similar neuropsychiatric manifestations to spontaneous ones. Cinnamon is a widespread spice and natural flavoring agent. It has been proven to modulate vascular endothelial tight junctions, neuroinflammation, and autoimmunity pathways, but it has never been tested in relation to lupus. Hypothesis/Purpose: In this pilot study, we aimed to explore the disease-modifying effect of Cinnamomum cassia on NPSLE in a TLR7 agonist-induced model. Study Design: An experimental design was followed in this study. Methods: Lupus was induced in C57BL/6J female mice via the direct application of imiquimod, a TLR7 agonist (5% imiquimod cream, 1.25 mg three times weekly), to the skin. Mice were divided into five groups (n = 8 per group): a sham group (S), a sham group supplemented with cinnamon (SC), an imiquimod-treated group (L), an imiquimod-treated group supplemented with cinnamon starting from induction (LC), and an imiquimod-treated group supplemented with cinnamon beginning two weeks prior to induction (CLC). This protocol was followed for six consecutive weeks. Cinnamomum cassia powder was administered orally at 200 mg/kg, 5 days per week. Results: Behavioral alterations were significantly ameliorated in the CLC group compared to lupus mice. Neuronal shrinkage and nuclear chromatin condensation were visible in the hippocampal cornu ammonis and dentate gyrus zones of lupus mice, with an increased expression of TLR7 and NLRP3, versus significantly less neurodegeneration and TLR7 and NLRP3 expression in the CLC group. In addition, the expression of the blood–brain barrier endothelial cell tight junction proteins claudin-1, occludin, and ZO-1 was abnormally modified in lupus mice and was restored in the CLC group. Moreover, while the cell–cell border delocalization of claudin-1 was documented in cultured blood–brain barrier endothelial cells treated with the plasma of lupus mice to a punctate intracytoplasmic fluorescence pattern, only cells treated with the plasma of the CLC group exhibited a complete reversal of this redistribution of claudin-1. Finally, cinnamaldehyde seemed to interact with TLR7 at multiple sites. Conclusions:Cinnamomum cassia seems to alleviate the pathogenesis of NPSLE. Supplementation with Cinnamomum cassia could be of great interest to modulate the activity and severity of the disease. Full article
(This article belongs to the Section Nutritional Immunology)
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