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Search Results (2,093)

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9 pages, 2009 KB  
Article
Effect of Surface Morphology Formed by Additive Manufacturing on the Adhesion of Dental Cements to Zirconia
by Kumiko Yoshihara, Noriyuki Nagaoka, Sungho Lee, Yukinori Maruo, Fiona Spirrett, Soshu Kirihara, Yasuhiro Yoshida and Bart Van Meerbeek
Materials 2026, 19(3), 563; https://doi.org/10.3390/ma19030563 (registering DOI) - 31 Jan 2026
Abstract
Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs—(1) concave–convex hemispherical patterns, (2) concave [...] Read more.
Background: Durable bonding to zirconia remains difficult because its chemically inert surface resists acid etching. Additive manufacturing (AM) enables controlled surface morphology, which may enhance micromechanical retention without additional treatments. Methods: Zirconia specimens with three AM-derived surface designs—(1) concave–convex hemispherical patterns, (2) concave hemispherical patterns, and (3) as-printed surfaces—were fabricated using a slurry-based 3D printing system and sintered at 1500 °C. Zirconia specimens fabricated by subtractive manufacturing using CAD/CAM systems, polished with 15 µm diamond lapping film and with or without subsequent alumina sandblasting, served as controls. Surface morphology was analyzed by FE-SEM, and shear bond strength (SBS) was tested after cementation with a resin-based luting agent. Results: SEM revealed regular layered textures and designed hemispherical structures (~300 µm) in AM specimens, along with step-like irregularities (~40 µm) at layer boundaries. The concave–convex AM group showed significantly higher SBS than both sandblasted and polished subtractive-manufactured zirconia (p < 0.05). Vertically printed specimens demonstrated greater bonding strength than those printed parallel to the bonding surface, indicating that build orientation affects resin infiltration and interlocking. Conclusion: AM-derived zirconia surfaces can provide superior and reproducible micromechanical retention compared with conventional treatments. Further optimization of printing parameters and evaluation of long-term durability are needed for clinical application. Full article
(This article belongs to the Special Issue Advanced Dental Materials: From Design to Application, Third Edition)
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17 pages, 3345 KB  
Article
Covalently Immobilized Mitomycin C on Polypropylene Sutures Creates a Non-Releasing Bioactive Interface That Modulates Vascular Smooth Muscle Cell Fate and Prevents Intimal Hyperplasia
by Tzu-Yen Huang, Wei-Chieh Chiu, Ko-Shao Chen, Ya-Jyun Liang, Pin-Yuan Chen, Yao-Chang Wang and Feng-Huei Lin
Int. J. Mol. Sci. 2026, 27(3), 1328; https://doi.org/10.3390/ijms27031328 - 29 Jan 2026
Abstract
Intimal hyperplasia (IH) at vascular anastomosis sites arises from endothelial injury, thrombin activation, and the subsequent proliferation and phenotypic modulation of vascular smooth muscle cells (VSMCs). Existing clinically used systemic pharmacologic regimens (e.g., antiplatelet/anticoagulant therapy) and reported local material-based strategies in the literature [...] Read more.
Intimal hyperplasia (IH) at vascular anastomosis sites arises from endothelial injury, thrombin activation, and the subsequent proliferation and phenotypic modulation of vascular smooth muscle cells (VSMCs). Existing clinically used systemic pharmacologic regimens (e.g., antiplatelet/anticoagulant therapy) and reported local material-based strategies in the literature (e.g., drug-eluting sutures, hydrogels, or coatings) largely rely on drug release, which can result in burst kinetics, finite duration, and off-target/systemic exposure. We developed a covalently immobilized, non-releasing biointerface in which mitomycin C (MMC) is stably anchored onto polypropylene sutures via low-pressure, non-thermal acetic-acid plasma (AAP) activation. AAP functionalization introduced reactive oxygen-containing groups on polypropylene, enabling amide-bond immobilization of MMC while preserving suture mechanics. Anchored MMC exhibited potent contact-mediated regulation of VSMC fate, reducing metabolic activity to 81% of control, suppressing G2/M progression, and inducing a dominant sub-G1 apoptotic population (66.3%), consistent with MMC-induced DNA crosslinking, p21 upregulation, and cyclin B1–CDK1 inhibition. In vivo, in a rat infrarenal aortic anastomosis model (male Wistar rats, 10–12 weeks, 300–350 g), MMC-anchored sutures markedly reduced arterial wall thickening and α-SMA and PCNA accumulation at 4 and 12 weeks, without overt evidence of systemic toxicity. Notably, no measurable MMC release was detected under the tested conditions, supporting that the observed bioactivity is consistent with an interface-confined mechanism rather than bulk diffusion. This work establishes a non-releasing suture-based platform that delivers sustained molecular regulation of vascular healing through interface-confined control of VSMC behavior. Covalent drug anchoring transforms a clinically used suture into an active therapeutic interface, providing a promising strategy to prevent pathological vascular remodeling and anastomotic IH. Full article
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14 pages, 24295 KB  
Article
Rational Engineering of Cellobiose 2-Epimerase Through Flexible Loop Modulation and Structure-Guided Sequence Alignment for Enhanced Lactulose Synthesis
by Xinyan Mao, Hongbin Zhang, Chao Hu, Chunhui Ma, Xueqin Hu and Jingwen Yang
Biomolecules 2026, 16(2), 206; https://doi.org/10.3390/biom16020206 - 28 Jan 2026
Viewed by 34
Abstract
Lactulose, a valuable functional disaccharide with pharmaceutical and food applications, is efficiently synthesized via enzymatic isomerization of lactose. This study developed an integrated strategy combining protein engineering of cellobiose 2-epimerase (CsCE) from Caldicellulosiruptor saccharolyticus and process optimization to enhance lactulose production. A dual-track [...] Read more.
Lactulose, a valuable functional disaccharide with pharmaceutical and food applications, is efficiently synthesized via enzymatic isomerization of lactose. This study developed an integrated strategy combining protein engineering of cellobiose 2-epimerase (CsCE) from Caldicellulosiruptor saccharolyticus and process optimization to enhance lactulose production. A dual-track engineering approach—incorporating flexible loop modulation (residues 161–193) and structure-guided sequence alignment with N-acetyl-D-glucosamine-2-epimerase—enabled the creation of two superior mutants, R17Q/L184S and R17Q/S142T. The R17Q/L184S variant exhibited a 37% increase in crude enzyme activity, improved thermostability (half-life of 200 min at 80 °C), and enhanced substrate affinity (Km reduced by 23.2%). R17Q/S142T achieved a 21% higher specific activity (24.08 U/mg), the highest among all variants. Structural and molecular dynamics analyses revealed that L184S enriched hydrogen bonding and hydrophobic interactions, improving structural rigidity, while S142T introduced allosteric regulation that facilitated catalytic efficiency. Under optimized conditions (70 °C, pH 7.5, 40% lactose, 20 U/mL enzyme, 3 h), lactulose yield reached 75.6% with >95% purity. This work demonstrates the successful application of synergistic enzyme engineering and process intensification for high-efficiency lactulose biosynthesis, providing viable candidates and system solutions for industrial-scale production. Full article
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20 pages, 3020 KB  
Article
Structural, Swelling, and In Vitro Digestion Behavior of DEGDA-Crosslinked Semi-IPN Dextran/Inulin Hydrogels
by Tamara Erceg, Miloš Radosavljević, Ružica Tomičić, Vladimir Pavlović, Milorad Miljić, Aleksandra Cvetanović Kljakić and Aleksandra Torbica
Gels 2026, 12(2), 103; https://doi.org/10.3390/gels12020103 - 26 Jan 2026
Viewed by 134
Abstract
In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) [...] Read more.
In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) as a crosslinking agent at varying concentrations (5, 7.5, and 10 wt%), and their structural, thermal, and biological properties were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) confirmed successful crosslinking and physical incorporation of uracil through hydrogen bonding. Concurrently, differential scanning calorimetry (DSC) revealed an increase in glass transition temperature (Tg) with increasing crosslinking density (149, 153, and 156 °C, respectively). Swelling studies demonstrated relaxation-controlled, first-order swelling kinetics under physiological conditions (pH 7.4, 37 °C) and high gel fraction values (84.75, 91.34, and 94.90%, respectively), indicating stable network formation. SEM analysis revealed that the hydrogel morphology strongly depended on crosslinking density and drug incorporation, with increasing crosslinker content leading to a more compact and wrinkled structure. Uracil loading further modified the microstructure, promoting the formation of discrete crystalline domains within the semi-IPN hydrogels, indicative of physical drug entrapment. All formulations exhibited high encapsulation efficiencies (>86%), which increased with increasing crosslinker content, consistent with the observed gel fraction values. Simulated in vitro gastrointestinal digestion showed negligible drug release under gastric conditions and controlled release in the intestinal phase, primarily governed by crosslinking density. Antimicrobial assessment against Escherichia coli and Staphylococcus epidermidis, used as an initial or indirect indicator of cytotoxic potential, revealed no inhibitory activity, suggesting low biological reactivity at the screening level. Overall, the results indicate that DEGDA-crosslinked dextran/inulin semi-interpenetrating (semi-IPN) hydrogels represent promising carriers for colon-targeted antitumor drug delivery. Full article
(This article belongs to the Special Issue Biopolymer Hydrogels: Synthesis, Properties and Applications)
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12 pages, 5152 KB  
Article
An Initiator-Free Electrochemical Approach to Radical Thiol–Ene Coupling in a Microfluidic Reactor
by Kakeru Yamamoto and Kenta Arai
Molecules 2026, 31(3), 429; https://doi.org/10.3390/molecules31030429 - 26 Jan 2026
Viewed by 162
Abstract
The anti-Markovnikov addition of thiyl radicals, generated via one-electron oxidation of thiols, to C=C double bonds is a useful method for synthesizing unsymmetrical sulfides and has been widely applied in the preparation of pharmaceuticals and functional materials. However, conventional radical thiol–ene reactions require [...] Read more.
The anti-Markovnikov addition of thiyl radicals, generated via one-electron oxidation of thiols, to C=C double bonds is a useful method for synthesizing unsymmetrical sulfides and has been widely applied in the preparation of pharmaceuticals and functional materials. However, conventional radical thiol–ene reactions require metal-based photoinitiators or organic photosensitizers, raising concerns about product isolation and environmental impact. Herein, we demonstrate an initiator-free thiol–ene coupling via electrochemical oxidation of thiols. Using a microfluidic electrochemical reactor, the electrochemically generated thiyl radicals undergo rapid and selective addition to alkenes, affording thioethers in reasonable yields. Substrate scope studies involving 13 alkenes and 13 thiols indicate that thiol acidity (pKa), alkene electronic properties, and steric effects play key roles in determining reaction efficiency. Although further optimization is required to improve yields and broaden substrate scope, this electrochemical approach highlights the potential of thiol–ene coupling as a sustainable tool in green synthetic chemistry. Full article
(This article belongs to the Special Issue Recent Advances in Organochalcogen Chemistry)
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22 pages, 4772 KB  
Article
Deep Eutectic Solvent Ultrasonic-Assisted Extraction of Polysaccharides from Red Alga Asparagopsis taxiformis: Optimization, Characterization, Mechanism, and Immunological Activity in RAW264.7 Cells
by Kun Yang, Yuxin Wang, Wentao Zou, Qin Liu, Riming Huang, Qianwang Zheng and Saiyi Zhong
Foods 2026, 15(3), 438; https://doi.org/10.3390/foods15030438 - 25 Jan 2026
Viewed by 166
Abstract
Traditional polysaccharide extraction suffers from low efficiency and high energy consumption, while deep eutectic solvents (DESs) are promising sustainable solvents. This study used DES ChCl-LA (1:2) with ultrasonic assistance to extract polysaccharides from red alga A.taxiformis. Optimized via single-factor experiments and [...] Read more.
Traditional polysaccharide extraction suffers from low efficiency and high energy consumption, while deep eutectic solvents (DESs) are promising sustainable solvents. This study used DES ChCl-LA (1:2) with ultrasonic assistance to extract polysaccharides from red alga A.taxiformis. Optimized via single-factor experiments and response surface methodology (350 W, 1:30 g/mL, 75 °C), the yield reached 11.28% ± 0.50% (1.5 times higher than that obtained by water extraction). Structural characterization revealed that the DES extract was an acidic polysaccharide, mainly composed of galactose (89.2%), glucose (4.9%), xylose (4.9%), and glucuronic acid (1.0%), with a weight-average molecular weight of 99.88 kDa. Density functional theory and molecular dynamics simulations showed that ChCl-LA enhanced galactose solubility via stronger hydrogen bonding (−25.33 vs. −5.06 kcal/mol for water). Notably, the immunological activity of the DES-extracted polysaccharide was significantly compromised compared to the water-extracted counterpart (p < 0.05). At a concentration of 0.25 mg/mL, the water-extracted polysaccharide-treated group exhibited a 33.98% higher neutral red phagocytosis rate in macrophages, a nitric oxide (NO) secretion level of 34.14 μmol/L (94.98% higher) compared with the DES-extracted polysaccharide group, as well as significantly higher secretion levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The observed disparity in bioactivity is likely due to the distinct chemical profiles resulting from the two extraction methods, including the significantly reduced molecular weight and potential alterations of sulfation degree, monosaccharide composition, and protein content in the DES-extracted polysaccharide. This mechanistic perspective is supported by the relevant literature on the structure–activity relationships of polysaccharides. This study demonstrates the potential of ChCl-LA and elucidates the complex effects of extraction methods on polysaccharide’s structure and function, thereby informing the high-value utilization of A. taxiformis in functional foods. Full article
(This article belongs to the Section Food Engineering and Technology)
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19 pages, 2415 KB  
Article
Thermal–Electrical Fusion for Real-Time Condition Monitoring of IGBT Modules in Transportation Systems
by Man Cui, Yun Liu, Zhen Hu and Tao Shi
Micromachines 2026, 17(2), 154; https://doi.org/10.3390/mi17020154 - 25 Jan 2026
Viewed by 194
Abstract
The operational reliability of Insulated Gate Bipolar Transistor (IGBT) modules in demanding transportation applications, such as traction systems, is critically challenged by solder layer and bond wire failures under cyclic thermal stress. To address this, this paper proposes a novel health monitoring framework [...] Read more.
The operational reliability of Insulated Gate Bipolar Transistor (IGBT) modules in demanding transportation applications, such as traction systems, is critically challenged by solder layer and bond wire failures under cyclic thermal stress. To address this, this paper proposes a novel health monitoring framework that innovatively synergizes micro-scale spatial thermal analysis with microsecond electrical dynamics inversion. The method requires only non-invasive temperature measurements on the module baseplate and utilizes standard electrical signals (load current, duty cycle, switching frequency, DC-link voltage) readily available from the converter’s controller, enabling simultaneous diagnosis without dedicated voltage or high-bandwidth current sensors. First, a non-invasive assessment of solder layer fatigue is achieved by correlating the normalized thermal gradient (TP) on the baseplate with the underlying thermal impedance (ZJC). Second, for bond wire aging, a cost-effective inversion algorithm estimates the on-state voltage (Vce,on) by calculating the total power loss from temperature, isolating the conduction loss (Pcond) with the aid of a Foster-model-based junction temperature (TJ) estimate, and finally computing Vce,on at a unique current inflection point (IC,inf) to nullify TJ dependency. Third, the health states from both failure modes are fused for comprehensive condition evaluation. Experimental validation confirms the method’s accuracy in tracking both degradation modes. This work provides a practical and economical solution for online IGBT condition monitoring, enhancing the predictive maintenance and operational safety of transportation electrification systems. Full article
(This article belongs to the Special Issue Insulated Gate Bipolar Transistor (IGBT) Modules, 2nd Edition)
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16 pages, 1662 KB  
Article
Shear Bond Strength of Additively and Subtractively Manufactured CAD/CAM Restorative Materials After Different Surface Treatments and Adhesive Strategies: An In Vitro Study
by Sevim Atilan Yavuz, Ayse Tugba Erturk-Avunduk, Omer Sagsoz, Ebru Delikan and Ozcan Karatas
Polymers 2026, 18(2), 296; https://doi.org/10.3390/polym18020296 - 22 Jan 2026
Viewed by 130
Abstract
This study aims to evaluate the effects of different surface treatments and adhesive systems on the shear bond strength (SBS) of additively manufactured (AM) and subtractively manufactured (SM) restorative materials. A total 675 rectangular specimens of three AM (Saremco Crowntec/SC, VarseoSmile CrownPlus/VC, and [...] Read more.
This study aims to evaluate the effects of different surface treatments and adhesive systems on the shear bond strength (SBS) of additively manufactured (AM) and subtractively manufactured (SM) restorative materials. A total 675 rectangular specimens of three AM (Saremco Crowntec/SC, VarseoSmile CrownPlus/VC, and VarseoSmile TriniQ/VT) and two SM (Vita Enamic/VE and Cerasmart/CS) restorative materials were fabricated. Each material was randomly divided into three groups regarding surface treatments: control/C, sandblasting/S, and etching/E. Following surface treatments, each AM and SM restorative material was then divided into three subgroups (15 specimens/subgroup) on the basis of adhesive systems (etch-and-rinse, self-etch, and universal). All specimens were thermocycled at 10,000 cycles, 5–55 °C, 30 s dwell time, and tested under SBS until failure, and failure types were examined under a stereomicroscope. Representative specimens were examined by SEM to evaluate fracture morphology. Statistical analysis was set at p < 0.05. There were significant differences in bond strength according to the material, surface treatment, adhesives, and their interactions (p < 0.05). The highest SBS value was obtained with SC × sandblasting × etch-and-rinse (16.45 ± 0.93 MPa), while the lowest value was found in the CS × control × universal interaction (4.68 ± 1.1 MPa). Outcomes varied according to the materials, surface treatment, and adhesive strategy. Clinically, these findings indicate that SM materials may require various surface treatment to achieve reliable adhesion, whereas AM materials provide more similar bond strength performance with no surface treatment. Full article
(This article belongs to the Special Issue Additive Manufacturing of Polymer Based Materials)
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30 pages, 4217 KB  
Review
Overview of Platinum Group Minerals (PGM): A Statistical Perspective and Their Genetic Significance
by Federica Zaccarini, Giorgio Garuti, Maria Economou-Eliopoulos, John F. W. Bowles, Hannah S. R. Hughes, Jens C. Andersen and Saioa Suárez
Minerals 2026, 16(1), 108; https://doi.org/10.3390/min16010108 - 21 Jan 2026
Viewed by 142
Abstract
The six platinum group elements (PGE) are among the rarest elements in the upper continental crust of the earth. Higher values of PGE have been detected in the upper mantle and in chondrite meteorites. The PGE are siderophile and chalcophile elements and are [...] Read more.
The six platinum group elements (PGE) are among the rarest elements in the upper continental crust of the earth. Higher values of PGE have been detected in the upper mantle and in chondrite meteorites. The PGE are siderophile and chalcophile elements and are divided into the following: (1) the Ir subgroup (IPGE) = Os, Ir, and Ru and (2) the Pd subgroup (PPGE) = Rh, Pt, and Pd. The IPGE are more refractory and less chalcophile than the PPGE. High concentrations of PGE led, in rare cases, to the formation of mineral deposits. The PGE are carried in discrete phases, the platinum group minerals (PGM), and are included as trace elements into the structure of base metal sulphides (BM), such as pentlandite, chalcopyrite, pyrite, and pyrrhotite. Similarly to PGE, the PGM are also divided into two main groups, i.e., IPGM composed of Os, Ir, and Ru and PPGM containing Rh, Pt, and Pd. The PGM occur both in mafic and ultramafic rocks and are mainly hosted in stratiform reefs, sulphide-rich lenses, and placer deposits. Presently, there are only 169 valid PGM that represent about 2.7% of all 6176 minerals discovered so far. However, 496 PGM are listed among the valid species that have not yet been officially accepted, while a further 641 are considered as invalid or discredited species. The main reason for the incomplete characterization of PGM resides in their mode of occurrence, i.e., as grains in composite aggregates of a few microns in size, which makes it difficult to determine their crystallography. Among the PGM officially accepted by the IMA, only 13 (8%) were discovered before 1958, the year when the IMA was established. The highest number of PGM was discovered between 1970 and 1979, and 99 PGM have been accepted from 1980 until now. Of the 169 PGM accepted by the IMA, 44% are named in honour of a person, typically a scientist or geologist, and 31% are named after their discovery localities. The nomenclature of 25% of the PGM is based on their chemical composition and/or their physical properties. PGM have been discovered in 25 countries throughout the world, with 64 from Russia, 17 from Canada and South Africa (each), 15 from China, 12 from the USA, 8 from Brazil, 6 from Japan, 5 from Congo, 3 from Finland and Germany (each), 2 from the Dominican Republic, Greenland, Malaysia, and Papua New Guinea each, and only 1 from Argentine, Australia, Bulgaria, Colombia, Czech Republic, England, Ethiopia, Guyana, Mexico, Serbia, and Tanzania each. Most PGM phases contain Pd (82 phases, 48% of all accepted PGM), followed, in decreasing order of abundances, by those of Pt 35 phases (21%), Rh 23 phases (14%), Ir 18 phases (11%), Ru 7 phases (4%), and Os 4 phases (2%). The six PGE forming the PGM are bonded to other elements such as Fe, Ni, Cu, S, As, Te, Bi, Sb, Se, Sn, Hg, Ag, Zn, Si, Pb, Ge, In, Mo, and O. Thirty-two percent of the 169 valid PGM crystallize in the cubic system, 17% are orthorhombic, 16% hexagonal, 14% tetragonal, 11% trigonal, 3% monoclinic, and only 1% triclinic. Some PGM are members of a solid-solution series, which may be complete or contain a miscibility gap, providing information concerning the chemical and physical environment in which the mineral was formed. The refractory IPGM precipitate principally in primitive, high-temperature, mantle-hosted rocks such as podiform and layered chromitites. Being more chalcophile, PPGE are preferentially collected and concentrated in an immiscible sulphide liquid, and, under appropriate conditions, the PPGM can precipitate in a thermal range of about 900–300 °C in the presence of fluids and a progressive increase of oxygen fugacity (fO2). Thus, a great number of Pt and Pd minerals have been described in Ni-Cu sulphide deposits. Two main genetic models have been proposed for the formation of PGM nuggets: (1) Detrital PGM represent magmatic grains that were mechanically liberated from their primary source by weathering and erosion with or without minor alteration processes, and (2) PGM reprecipitated in the supergene environment through a complex process that comprises solubility, the leaching of PGE from the primary PGM, and variation in Eh-pH and microbial activity. These two models do not exclude each other, and alluvial deposits may contain contributions from both processes. Full article
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20 pages, 1579 KB  
Article
Phthalimide Derivatives as Anti-Inflammatory Agents: In Silico COX-2 Targeting and In Vitro Inhibition of PGE2 Production
by Héctor M. Heras Martínez, Blanca Sánchez-Ramírez, Linda-Lucila Landeros-Martínez, David Rodríguez-Guerrero, José C. Espinoza-Hicks, Gerardo Zaragoza-Galán, Alejandro Bugarin and David Chávez-Flores
Pharmaceutics 2026, 18(1), 129; https://doi.org/10.3390/pharmaceutics18010129 - 20 Jan 2026
Viewed by 251
Abstract
Background/Objectives: The development of specific inhibitors for cyclooxygenase-2 (COX-2) is a challenge for public health. A series of 17 N-phthalimide hybrids was evaluated using a functional M06 meta-GGA hybrid in combination with a polarized 6-311G (d, p) basis set. The top [...] Read more.
Background/Objectives: The development of specific inhibitors for cyclooxygenase-2 (COX-2) is a challenge for public health. A series of 17 N-phthalimide hybrids was evaluated using a functional M06 meta-GGA hybrid in combination with a polarized 6-311G (d, p) basis set. The top three candidates (6, 10, and 17) were synthesized and evaluated as selective COX-2 inhibitors of PGE-2 using an integrated in silico–in vitro approach. Methods: Molecular docking against COX-2 (PDB 5KIR) and COX-1 (PDB 6Y3C), supported by homology modeling and DFT geometry optimization (B3LYP/6-31G*), revealed that the phthalimide carbonyl groups and the 3,4,5-trimethoxyphenyl or geranyl-derived moieties establish key hydrogen bonds and hydrophobic contacts with Arg120, Tyr355, Tyr385, and Ser530 in the COX-2 active site, conferring predicted selectivity ΔGCOX−2 vs. COX−1 = −1.4 to −2.8 kcal/mol. Results: The compounds complied with Lipinski’s and Veber’s rules and displayed favorable ADMET profiles. In vitro assessment in LPS-stimulated J774A.1 murine macrophages confirmed potent inhibition of PGE2 production, 3.05 µg/mL, with compound 17 exhibiting the highest efficacy, 97.79 ± 5.02% inhibition at 50 µg/mL, and 10 showing 95.22 ± 6.03% inhibition at 50 µg/mL. Notably, all derivatives maintained >90% cell viability up to 250 µg/mL by resazurin assay and showed no evidence of cytotoxicity or mitosis potential in the tests at 24 h. Conclusions: These results demonstrate that strategic hybridization of phthalimide with natural and synthetic product-derived fragments yields highly potential PGE2 inhibitors. Therefore, compounds 6, 10, and 17 are promising lead candidates for the development of safer anti-inflammatory agents. Full article
(This article belongs to the Special Issue Natural Pharmaceuticals Focused on Anti-inflammatory Activities)
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20 pages, 6235 KB  
Article
Mutation-Induced Resistance of SARS-CoV-2 Mpro to WU-04 Revealed by Multi-Scale Modeling
by Mengting Liu, Derui Zhao, Hui Duan, Junyao Zhu, Liting Zheng, Nan Yuan, Yuanling Xia, Peng Sang and Liquan Yang
Int. J. Mol. Sci. 2026, 27(2), 1000; https://doi.org/10.3390/ijms27021000 - 19 Jan 2026
Viewed by 146
Abstract
The clinical durability of SARS-CoV-2 main protease (Mpro) inhibitors depends on their resilience to emerging resistance mutations. Recent genomic surveillance and functional reports have highlighted substitutions at positions 49, 165, and 301, raising questions about the robustness of the noncovalent inhibitor [...] Read more.
The clinical durability of SARS-CoV-2 main protease (Mpro) inhibitors depends on their resilience to emerging resistance mutations. Recent genomic surveillance and functional reports have highlighted substitutions at positions 49, 165, and 301, raising questions about the robustness of the noncovalent inhibitor WU-04 in variant backgrounds. Here, we combined μs-scale, triplicate molecular dynamics simulations with end-state binding free energy estimates and a network-rewiring inference (NRI) framework that maps long-range dynamical communication across the full protease dimer. We evaluated wild type (WT), single mutants M49K, M165V, S301P, and selected double mutants (M49K & M165V, M49K & S301P). Relative to WT, single substitutions produced reductions in computed binding affinity of up to ~12kcal/mol, accompanied by loss or reshaping of the S2 subsite and altered ligand burial. Notably, the M49K/S301P double mutant partially restored WU-04 engagement, narrowing the ΔΔGrestore gap to within ΔΔGrestore of WT and re-establishing key hydrophobic and hydrogen-bond contacts. NRI analysis revealed that distal residue 301 participates in a communication corridor linking the C-terminal helical domain to the active-site cleft; its substitution rewires inter-domain coupling that can compensate for local disruptions at residue 49. Together, these results identify structural hotspots and network pathways that may inform the design of next-generation Mpro inhibitors with improved mutation tolerance—specifically by strengthening interactions that do not rely solely on the mutable S2 pocket and by engaging conserved backbone features near the 165–166 region. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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17 pages, 3126 KB  
Article
A Multifunctional Peptide Linker Stably Anchors to Silica Spicules and Enables MMP-Responsive Release of Diverse Bioactive Cargos
by So-Hyung Lee, Suk-Hyun Kwon, Byung-Ho Song, In-Gyeong Yeo, Hyun-Seok Park, A-Ri Kim, Lee-Seul Kim, Ji-Min Noh, Hee-Jung Choi, Da-Jeoung Lim and Young-Wook Jo
Micromachines 2026, 17(1), 127; https://doi.org/10.3390/mi17010127 - 19 Jan 2026
Viewed by 178
Abstract
Silica spicules provide a natural transdermal conduit but require a linker that binds strongly under physiological conditions and releases payloads selectively in response to biological cues. Existing silane chemistries or polydopamine coatings lack enzyme responsiveness and show limited control over release. We created [...] Read more.
Silica spicules provide a natural transdermal conduit but require a linker that binds strongly under physiological conditions and releases payloads selectively in response to biological cues. Existing silane chemistries or polydopamine coatings lack enzyme responsiveness and show limited control over release. We created a 180-member peptide library with the motif L–X1–X2–[Y–F–Y]–A–L–G–P–H–C and screened for silica binding. Biophysical assays (circular dichroism, ζ-potential, quartz crystal microbalance, atomic force microscopy) and molecular dynamics identified high-affinity binders. The lead, P176, was tested for matrix metalloprotease (MMP)-responsive cleavage. Conjugation and release of Vitamin C and Stigmasterol were analyzed by HPLC and Franz diffusion cells. P176 showed high silica affinity (~55 µg mg−1), robust biophysical signals (Δf −35 to −38 Hz; rupture force ~154 pN; ζ shift −22 to−11.5 mV), and favorable adsorption energy (−48.5 kcal mol−1, contact 4.5 nm2, 8.5 H-bonds). The MMP gate displayed efficient kinetics (Vmax 117.9 RFU·min−1, Km 5.0 µM) with >90% cleavage at 60 min, reduced to 26% by inhibitor. Conjugation yields reached 87% (Vitamin C) and 77% (Stigmasterol). Franz diffusion showed MMP-dependent release (24 h: Vitamin C 90–96%, Stigmasterol 80–85%) with minimal basal leakage. Released Vitamin C enhanced collagen I to ~250% in fibroblasts, while Stigmasterol attenuated LPS-induced macrophage morphology; keratinocytes retained normal marker expression. This study demonstrates that a single amphipathic, sequence-programmed peptide can couple strong silica anchoring with protease-responsive release and broad payload compatibility, establishing a versatile platform for spicule-based transdermal and regenerative delivery. Full article
(This article belongs to the Section B5: Drug Delivery System)
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11 pages, 1626 KB  
Article
Effects and Mechanisms of Silicone Fertilizer on Salt Ion Activity in Saline–Alkaline Soils
by Furu Song, Dongxia Li, Liqiang Song, Ziku Cao, Zhipei Cao, Yafei Sang and Lianwei Kang
Polymers 2026, 18(2), 231; https://doi.org/10.3390/polym18020231 - 16 Jan 2026
Viewed by 152
Abstract
The high salt content in saline–alkali soil has a significant impact on plant nutrient absorption and water transport, severely inhibiting crop growth. Through esterification reactions, silicic acid is grafted onto humic acid to form an organic silicon fertilizer (OSiF). The unique Si-O-C bond [...] Read more.
The high salt content in saline–alkali soil has a significant impact on plant nutrient absorption and water transport, severely inhibiting crop growth. Through esterification reactions, silicic acid is grafted onto humic acid to form an organic silicon fertilizer (OSiF). The unique Si-O-C bond in the material endows this new type of organic silicon-based fertilizer with the ability to effectively alleviate the harm of high-salt soil to plants. In this study, a soil column experiment was designed to systematically evaluate and compare the effects of organic silicon fertilizers with different organic silicon contents (0%, 5%, and 10%) and traditional compound fertilizers on soil water characteristics, salt ion concentration, pH value, and electrical conductivity. The results showed that the addition of an appropriate amount of organic silicon fertilizer could significantly reduce the activity of salt ions in the soil solution. Experimental data indicated that the 5% and 10% organic silicon fertilizers had the most significant effect on the consumption of major salt ions such as sodium and chloride ions. X-ray photoelectron spectroscopy (XPS) analysis revealed that the reaction of Si-O-C bonds in the soil with Lewis bases led to a shift in the valence state of the 1S electrons of silicon atoms, providing a theoretical basis for the mechanism by which silicon fertilizers alleviate high-salt stress. Full article
(This article belongs to the Special Issue Advanced Polymer Composites and Foams)
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11 pages, 1910 KB  
Article
In Situ Growth of Metal–Organic Frameworks (MOFs) Within Porous Silicon Carbide (p-SiC) for Constructing Hierarchical Porous Composites
by Long Zhou, Guangzhi Liao, Tingting Lin, Wensong Huang, Jiawei Zhang, Ruiqi Fan, Yanghui Li, Xiaolin Zhang, Ziyun Cheng and Lizhi Xiao
Nanomaterials 2026, 16(2), 117; https://doi.org/10.3390/nano16020117 - 15 Jan 2026
Viewed by 255
Abstract
Metal–organic frameworks (MOFs) typically exist in the form of powders or dispersed crystals, which limits their direct application in practical engineering scenarios that require monolithic structures and processability. To address this issue, the present study successfully anchored MOF (zeolitic imidazolate framework-8, ZIF-8) nanocrystals [...] Read more.
Metal–organic frameworks (MOFs) typically exist in the form of powders or dispersed crystals, which limits their direct application in practical engineering scenarios that require monolithic structures and processability. To address this issue, the present study successfully anchored MOF (zeolitic imidazolate framework-8, ZIF-8) nanocrystals within a porous silicon carbide (p-SiC) substrate via a facile in situ growth strategy, achieving both stable macroscopic loading and intimate microscopic interfacial bonding. The resulting ZIF-8/p-SiC composite exhibits a hierarchical porous structure, with a specific surface area approximately 183 times higher than that of the raw p-SiC, alongside a substantially enhanced CO2 adsorption capacity. By utilizing a low-cost p-SiC support and mild ZIF-8 synthesis conditions, this work demonstrates excellent reproducibility and scalability, providing a facile and effective pathway for fabricating MOF/porous media composite systems that possess both superior mechanical properties and tailored pore structures. Additionally, the developed MOF/p-SiC composites can serve as controllable rock-analog porous media, offering new perspectives for investigating MOF-rock interfacial interactions and CO2 geological sequestration mechanisms, thereby establishing an organic link between fundamental materials science and geological engineering applications. Full article
(This article belongs to the Section Nanocomposite Materials)
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28 pages, 8828 KB  
Article
Oil-Water Biphasic Metal-Organic Supramolecular Gel for Lost Circulation Control: Formulation Optimization, Gelation Mechanism, and Plugging Performance
by Qingwang Li, Songlei Li, Ye Zhang, Chaogang Chen, Xiaochuan Wu, Menglai Li, Shubiao Pan and Junfei Peng
Gels 2026, 12(1), 74; https://doi.org/10.3390/gels12010074 - 15 Jan 2026
Viewed by 165
Abstract
Lost circulation in oil-based drilling fluids (OBDFs) remains difficult to mitigate because particulate lost circulation materials depend on bridging/packing and gel systems for aqueous media often lack OBDF compatibility and controllable in situ sealing. A dual-precursor oil–water biphasic metal–organic supramolecular gel enables rapid [...] Read more.
Lost circulation in oil-based drilling fluids (OBDFs) remains difficult to mitigate because particulate lost circulation materials depend on bridging/packing and gel systems for aqueous media often lack OBDF compatibility and controllable in situ sealing. A dual-precursor oil–water biphasic metal–organic supramolecular gel enables rapid in situ sealing in OBDF loss zones. The optimized formulation uses an oil-phase to aqueous gelling-solution volume ratio of 10:3, with 2.0 wt% Span 85, 12.5 wt% TXP-4, and 5.0 wt% NaAlO2. Apparent-viscosity measurements and ATR–FTIR analysis were used to evaluate the effects of temperature, time, pH, and shear on MOSG gelation. Furthermore, the structural characteristics and performances of MOSGs were systematically investigated by combining microstructural characterization, thermogravimetric analysis, rheological tests, simulated fracture-plugging experiments, and anti-shear evaluations. The results indicate that elevated temperatures (30–70 °C) and mildly alkaline conditions in the aqueous gelling solution (pH ≈ 8.10–8.30) promote P–O–Al coordination and strengthen hydrogen bonding, thereby facilitating the formation of a three-dimensional network. In contrast, strong shear disrupts the nascent network and delays gelation. The optimized MOSGs rapidly exhibit pronounced viscoelasticity and thermal resistance (~193 °C); under high shear (380 rpm), the viscosity retention exceeds 60% and the viscosity recovery exceeds 70%. In plugging tests, MOSG forms a dense sealing layer, achieving a pressure-bearing gradient of 2.27 MPa/m in simulated permeable formations and markedly improving the fracture pressure-bearing capacity in simulated fractured formations. Full article
(This article belongs to the Topic Advanced Technology for Oil and Nature Gas Exploration)
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