Search Results (1,146)

AlphaFold3, the latest release of AlphaFold developed by Google DeepMind and Isomorphic Labs, was designed to predict protein structures with remarkable accuracy. AlphaFold3 enhances our ability to model not only single protein structures but also complex biomolecular interactions, including protein–protein interactions, protein–ligand docking, and protein-nucleic acid complexes. Herein, we provide a detailed examination of AlphaFold3’s capabilities, emphasizing its applications across diverse biological fields and its effectiveness in complex biological systems. The strengths of the new AI model are also highlighted, including its ability to predict protein structures in dynamic systems, multi-chain assemblies, and complicated biomolecular complexes that were previously challenging to depict. We explore its role in advancing drug discovery, epitope prediction, and the study of disease-related mutations. Despite its significant improvements, the present review also addresses ongoing obstacles, particularly in modeling disordered regions, alternative protein folds, and multi-state conformations. The limitations and future directions of AlphaFold3 are discussed as well, with an emphasis on its potential integration with experimental techniques to further refine predictions. Lastly, the work underscores the transformative contribution of the new model to computational biology, providing new insights into molecular interactions and revolutionizing the fields of accelerated drug design and genomic research. Full article

Background: Ulcerative colitis (UC), a subtype of chronic inflammatory bowel disease (IBD), is primarily treated with oral medications to reduce inflammation and alleviate symptoms. Celecoxib (CXB) is an attractive candidate for UC; however, its limited solubility and low bioavailability pose significant challenges to its clinical application. Methods: We reported a novel chondroitin sulfate A–Celecoxib (CSA-CXB) polymeric nanoprodrug to address the limited solubility and low bioavailability of CXB. CXB was conjugated to chondroitin sulfate A (CSA) via succinic anhydride (SA) and ethylenediamine to prepare CSA-CXB polymers, which can self-assemble into nanoparticle structural prodrugs in aqueous condition. We investigated the stability, blood compatibility, and responsiveness of the nanoparticles. The ability of the nanoparticles to treat UC in vitro and in vivo was then evaluated. Results: The CSA-CXB nanoprodrug was spherical with a mean particle size of 188.4 ± 2.2 nm, a zeta potential of −22.9 ± 0.1 mV, and sustained drug release behavior. Furthermore, CSA-CXB exhibited remarkable antioxidant and anti-inflammatory effects, as it can significantly increase the free radical scavenging rate and reduce the expression level of ROS, TNF-α, IL-6, nitric oxide (NO), and COX-2 protein in vitro. In vivo results demonstrated that CSA-CXB targeted the mice’s colon efficiently mitigate UC symptoms by inhibiting the expression of inflammatory cytokine. Conclusions: The CSA-CXB nanoprodrug can improve the therapeutic impact of CXB, and has potential as a new preparation for a clinical UC treatment nanoprodrug. Full article

Background/Objectives: Cytomegalovirus (CMV) infection expands early endosomes (EEs) into tubular extensions that may contribute to the control of virus replication and virion assembly. Sequential recruitment of protein coats and sorting nexins (SNXs) creates membrane zones at the EEs that serve as scaffolds for membrane tubulation and retrieval of cargo proteins, including host cell signaling proteins and viral glycoproteins. This study aims to investigate whether the SNX3-dependent zone of EEs contributes to CMV replication and assembly. Methods: Protein localization was analyzed by confocal imaging and expression by Western blot. The contribution of SNX3 to murine CMV (MCMV) replication, assembly compartment (AC) formation, and virion release was analyzed by siRNA and shRNA depletion. The impact of other downstream SNXs that act in EE tubulation was investigated by combined siRNA knockdowns of SNX1, SNX2, SNX4, SNX17, and SNX27 on cell lines expressing shRNA for SNX3. Results: The SNX3-162 isoform acting at EEs was efficiently knocked down by siRNA and shRNA. The SNX3-dependent EE zone recruited SNX27 and contributed to Rab10-dependent tubulation within the pre-AC. SNX3 was not essential for MCMV replication but contributed to the SNX27-, SNX17- and SNX4-dependent release of virions. Silencing SNX3 further reduced the release of virions after silencing SNX27, SNX4, and SNX17, three SNXs that control recycling to the plasma membrane. Conclusions: SNX3 contributes to the formation of pre-AC and MCMV assembly. It acts sequentially with SNX27, SNX4, and SNX17 along the recycling pathway in the process of the production and release of infection virions, suggesting that multiple membrane sources may contribute to the secondary envelopment of MCMV virions. Full article

Amphiphilic block copolymers with complex topologies (e.g., star and brush topologies) have attracted significant attention in drug delivery owing to their superior performance over linear micelles. However, their precise synthesis and structure–property relationships require further investigation. In this study, hydroxylated polybutadiene with adjustable topology and hydroxyl group density was employed as a macroinitiator to synthesize well-defined amphiphilic poly (ethylene oxide)-b-poly(ε-caprolactone-ran-δ-valerolactone) (PEO-b-P(CL-ran-VL)) copolymers via ring-opening polymerization (ROP). A series of linear, star, linear–comb, and star–comb copolymers were prepared as curcumin-loaded micellar carriers for the study. The self-assembly behavior, drug encapsulation efficiency, and in vitro release profiles of these copolymers in aqueous environments were systematically investigated. The results demonstrated that increasing the branch length of star–comb copolymers effectively reduced micelle size from 143 to 96 nm and enhanced drug encapsulation efficiency from 27.3% to 39.8%. Notably, the star–comb architecture exhibited 1.2-fold higher curcumin encapsulation efficiency than the linear counterparts. Furthermore, the optimized star–comb nanoparticles displayed sustained release kinetics (73.38% release over 15 days), outperforming conventional linear micelles. This study establishes a quantitative structure–property relationship between copolymer topology and drug delivery performance, providing a molecular design platform for programmable nanocarriers tailored to diverse therapeutic requirements of various diseases. Full article

Research on nano-sustained-release factors for bone tissue scaffolds has significantly promoted the precision and efficiency of bone-defect repair by integrating biomaterials science, nanotechnology, and regenerative medicine. Current research focuses on developing multifunctional scaffold materials and intelligent controlled-release systems to optimize the spatiotemporal release characteristics of growth factors, drugs, and genes. Nano slow-release bone scaffolds integrate nano slow-release factors, which are loaded with growth factors, drugs, genes, etc., with bone scaffolds, which can significantly improve the efficiency of bone repair. In addition, these drug-loading systems have also been extended to the fields of anti-infection and anti-tumor. However, the problem of heterotopic ossification caused by high doses has led to a shift in research towards a low-dose multi-factor synergistic strategy. Multiple Phase II clinical trials are currently ongoing, evaluating the efficacy and safety of nano-hydroxyapatite scaffolds. Despite significant progress, this field still faces a series of challenges: the immunity risks of the long-term retention of nanomaterials, the precise matching of multi-factor release kinetics, and the limitations of the large-scale production of personalized scaffolds. Future development directions in this area include the development of responsive sustained-release systems, biomimetic sequential release design, the more precise regeneration of injury sites through a combination of gene-editing technology and self-assembled nanomaterials, and precise drug loading and sustained release through microfluidic and bioprinting technologies to reduce the manufacturing cost of bone scaffolds. The progress of these bone scaffolds has gradually changed bone repair from morphology-matched filling regeneration to functional recovery, making the clinical transformation of bone scaffolds safer and more universal. Full article

Natural hydrogels have attracted considerable attention due to advantages of moisturizing, biocompatibility, and plasticity. In this study, a dual-network oxidized peach gum polysaccharide–carboxymethyl chitosan (OPGC) hydrogels with ultrafast self-healing ability was constructed by self-assembly using oxidized peach gum polysaccharide (OPGP) and carboxymethyl chitosan (CMCS). After complete fracture, OPGC hydrogels rapidly self-healed within 30 s due to the dual-network structure formed by the hydrogen bonds between the OPGP molecules and the Schiff base bonds between them and the CMCS. Meanwhile, the hydrogels exhibited good injectability and biocompatibility. With the increase of CMCS from 0.5 wt% to 2.5 wt%, the gel formation time of OPGC hydrogels was drastically shortened from 12 min to 3 min, while the strength and water-holding capacity were enhanced. Furthermore, experimental in vitro and in vivo animal studies demonstrated excellent drug loading capacity of OPGC hydrogels, and the release rate of bactericide could be controlled by adjusting the content of CMCS. The OPGC hydrogels have outstanding properties for potential applications in the health and medical fields. Full article

The rapid evolution of micro- and nano-architectures is revolutionizing biomedical engineering, particularly in the fields of therapeutic and diagnostic micromechanics. This review explores the recent innovations in micro- and nanostructured materials and their transformative impact on healthcare applications, ranging from drug delivery and tissue engineering to biosensing and diagnostics. Key advances in fabrication techniques, such as lithography, 3D printing, and self-assembly, have enabled unprecedented control over material properties and functionalities at microscopic scales. These engineered architectures offer enhanced precision in targeting and controlled release in drug delivery, foster cellular interactions in tissue engineering, and improve sensitivity and specificity in diagnostic devices. We examine critical design parameters, including biocompatibility, mechanical resilience, and scalability, which influence their clinical efficacy and long-term stability. This review also highlights the translational potential and current limitations in bringing these materials from the laboratory research to practical applications. By providing a comprehensive overview of the current trends, challenges, and future perspectives, this article aims to inform and inspire further development in micro- and nano-architectures that hold promise for advancing personalized and precision medicine. Full article

An advanced, eco-friendly, and fully bio-based flame retardant (FR) system has been created and applied to the cellulose structure of the cotton fabric through a layer-by-layer coating method. This study examines the flame-retardant mechanism of protein-based and phosphorus-containing coatings to improve fire resistance. During combustion, the phosphate groups (−PO₄²⁻) in phosphorus containing flame retardant layers interact with the amino groups (–NH₂) of protein, forming ester bonds, which results in the generation of a crosslinked network between the amino groups and the phosphate groups. This structure greatly enhances the thermal stability of the residual char, hence improving fire resistance. Cone calorimeter and flammability tests show significant improvements in fire safety, including lower peak heat release rates, reduced smoke production, and higher char residue, all contributing to better flame-retardant performance. pHRR, THR, and TSP of the flame-retarded cotton fabric demonstrated 25, 54, and 72% reduction, respectively. These findings suggest that LbL-assembled protein–phosphorus-based coatings provide a promising, sustainable solution for creating efficient flame-retardant materials. Full article

In this study, novel fluorescent DNA biosensors for mercury (Hg²⁺) and silver (Ag⁺) ions were developed based on thymine (T)- and cytosine (C)-rich recognition elements in combination with exonuclease III and a mismatch-catalyzed hairpin assembly (MCHA)-based cascade isothermal signal-amplification strategy. In the presence of the respective target analytes, the recognition element terminals form so-called T-Hg²⁺-T or C-Ag⁺-C structures, resulting in cleavage by Exo III and the release of the trigger strand for MCHA. This binds to the H1 hairpin, which is fluorescently labeled with carboxyfluorescein (FAM) and tetramethylrhodamine (TAMRA), disrupting fluorescence resonance energy transfer between them and, thus, restoring FAM fluorescence, generating a strong signal at 520 nm. The linear range of the Hg²⁺ sensor is 0.5 to 3 pM, with a detection limit of 0.07 pM. The recovery range in actual spiked water samples is between 98.5% and 105.2%, with a relative standard deviation (RSD) ranging from 2.0% to 4.2%. The linear range of the Ag⁺ sensor is 10 to 90 pM, with a detection limit of 7.6 pM. The recovery range in actual spiked water samples is between 96.2% and 104.1%, with an RSD ranging from 3.2% to 6.3%. The cascade isothermal signal amplification strategy effectively enhances sensor sensitivity, while MCHA decreases the false-positive rate. The aptamer sensor exhibits high specificity, is resistant to interference, and can be used for the detection of Hg²⁺ and Ag⁺ in environmental water samples. Full article

The discovery of efficient and stable nanopesticides with improved water solubility and sustained release effects has become particularly important. Pyrimethanil (Pyr) as a low toxicity fungicide of an aniline pyrimidine group is widely used for the prevention and control of gray mold in crops and ornamental plants, however, poor water solubility hinders its further development. Herein, we use a supramolecular self-assembly process to encapsulate a pyrimethanil in a hydroxypropyl-gamma-cyclodextrin (HPγCD) via electrostatic interactions, thereby constructing the inclusion complex nanofibers. The HPγCD as an environmentally friendly carrier material for pesticide delivery is favorable for facilitating the control efficacy, water solubility, and thermostability with Pyr. The diameter of the prepared inclusion nanofiber is 426.6 ± 82.1 nm. Pyr/HPγCD inclusion complex nanofibers could be completely dissolved in water within 3 s. As predicted, the fungicidal activity of Pyr/HPγCD inclusion complex nanofibers is much higher than that of either Pyr, and the EC₅₀ value of Pyr/HPγCD inclusion nanofibers is 0.437 μg/mL, which is about half of that of Pyr (0.840 μg/mL). The inclusion strategy achieved by Pyr and HPγCD is important for improving the safety of nanopesticides. This work provides a versatile insight to promote the development of water-based pesticide dosage forms and reduce pesticide losses in agricultural production. Full article

Background: Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods: A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w/w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results: The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug (p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls (p < 0.001), leading to 58.7% tumor volume reduction (p < 0.001). Conclusions: The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy. Full article

Self-assembling amphiphilic polymers represent highly promising materials with emerging applications across various fields. In these polymers, the presence of hydrophilic and hydrophobic segments within their structure drives the self-assembly process in aqueous environments, leading to organized structures capable of incorporating lipophilic drugs. Their high chemical versatility enables the design of tailored structures to meet specific requirements, such as the active targeting ability, thereby broadening their potential applications. In this work, a polyethylene glycol-phospholipid conjugate was employed to form nanocarriers loaded with a lipophilic derivative of gemcitabine. To achieve nano-assemblies actively targeted towards cancer cells overexpressing the hyaluronic acid (HA) receptor CD44, a HA-phospholipid conjugate was co-formulated in various molar ratios (1%, 10%, and 20%). All formulations exhibited a mean diameter below 130 nm, a negative zeta potential (approximately −30 mV), and a high encapsulation efficiency (above 90%). These nano-assemblies demonstrated stability during storage and effectively released the encapsulated drug in a cell culture medium. Upon incubation with cancer cells, the nano-assemblies were internalized via a CD44 endocytosis-mediated mechanism, with the extent of internalization depending on the HA conjugate content. Consistently, cell viability studies revealed that the nanocarriers decorated with higher amounts of HA exerted a higher cytotoxicity, enabling a fine tuning of the nano-assembly properties. Full article

Marine biofouling is a major problem that contributes to the failure of man-made marine structures. Conventional marine antifouling coatings that release heavy metal ions for antimicrobial purposes are no longer in line with today’s environmental issues. In this paper, a layer-by-layer (LBL) self-assembled marine antifouling coating based on an addition reaction between polyvinylpyrrolidone (PVP) and phenols to anchor pyrogallic (PG) with an antimicrobial effect on stainless steel surfaces is presented. For this purpose, three phenolics were selected, and their antifouling effects were compared. Field emission scanning electron microscopy, contact angle measurement, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy analysis (FTIR) were used to thoroughly characterize the LBLPGs, and the results showed superior homogeneity of the coatings with no significant delamination. Simulated marine antifouling and friction tests showed that the coating inhibited Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Phaeodactylum tricornutum (P. tricornutum) by more than 90% and reduced the friction coefficient of the stainless steel surface from 0.38 to 0.24, demonstrating superior antifouling and friction resistance effects. Full article

Sesaminol is a natural functional compound of sesame with low bioaccessibility due to its high crystallinity. Here, a peptide-based self-assembly microgel was constructed to encapsulate sesaminol, reducing its crystallinity and improving its bioaccessibility. In this contribution, the peptide AcNH-Leu-Tyr-Tyr-CONH₂ (LYY) was shown to form a mesoporous three-dimensional (3D) microgel through microstructure characterization. Various characterization methods revealed that the LYY peptide self-assembled through β-folds and random coils, and the primary intermolecular interactions arose from hydrogen bonding and the π-π stacking effect. Subsequently, sesaminol was encapsulated within the microgel through co-assembly. The maximum encapsulation efficiency of sesaminol was 80.8 ± 0.9%, mainly in the form of nanoparticles encapsulated in microgel by morphology characterization. The XRD results indicated that sesaminol primarily existed in an amorphous state following encapsulation. The cumulative release indicated that sesaminol had a sustained release effect in the encapsulation system. Its bioaccessibility and antioxidant levels were increased. Molecular docking indicated that the main interactions between sesaminol and the self-assembled structure were hydrogen bonding and π-π interactions. Establishing sesaminol encapsulation provides valuable data and theoretical support for the research of sesaminol and the sesame processing industry. Full article

In this work, we developed 3D ionic liquid (IL) functionalized graphene assemblies (GAs) decorated by ultrafine RuCu alloy nanoparticles (RuCu-ANPs) via a one-step synthesis process, and integrated it into a microfluidic sensor chip for in situ electrochemical detection of NO released from living cells. Our findings have demonstrated that RuCu-ANPs on 3D IL-GA exhibit high density, uniform distribution, lattice-shaped arrangement of atoms, and extremely ultrafine size, and possess high electrocatalytic activity to NO oxidation on the electrode. Meanwhile, the 3D IL-GA with hierarchical porous structures can facilitate the efficient electron/mass transfer at the electrode/electrolyte interface and the cell culture. Moreover, the graft of IL molecules on GA endows it with high hydrophilicity for facile and well-controllable printing on the electrode. Consequently, the resultant electrochemical microfluidic sensor demonstrated excellent sensing performances including fast response time, high sensitivity, good anti-interference ability, high reproducibility, long-term stability, as well as good biocompatibility, which can be used as an on-chip sensing system for cell culture and real-time in situ electrochemical detection of NO released from living cells with accurate and stable characteristics in physiological conditions. Full article