Potential Scaffold Research Articles

Discovery of natural compounds as novel FMS-like tyrosine kinase-3 (FLT3) therapeutic inhibitors for the treatment of acute myeloid leukemia: An in-silico approach

FLT3 mutations, observed in approximately 30–35% of Acute Myeloid Leukemia (AML) cases, drive leukemic proliferation and survival pathways, presenting a significant challenge in clinical management. To address this therapeutic need, we employed a comprehensive computational approach integrating pharmacophore screening, molecular docking, ADMET analysis, and molecular dynamics simulations to identify potent inhibitors targeting FLT3. Utilizing ligand-based pharmacophore models generated from experimentally proven FLT3 inhibitors from BindingDB, we screened over 400,000 natural compounds from the COCONUT database. Hits identified through pharmacophore screening underwent further evaluation via Lipinski and Golden triangle criteria to ensure drug-like properties. Molecular docking against the FLT3 receptor, combined with ADMET analyses, facilitated the prioritization of lead compounds. Subsequently, three promising candidates were subjected to molecular dynamics simulations to assess binding stability. Our findings reveal three top-performing compounds, demonstrating robust and stable binding affinity and favorable ADMET characteristics. These compounds hold promise as potential scaffolds or leads for developing novel FLT3 inhibitors in AML therapy.

Harnessing computational and experimental approaches to identify potent hits against Leishmania donovani sterol C-24 methyltransferase from ChemBridge library

Leishmaniasis is a neglected tropical disease and is one of the major causes of mortality in poverty-stricken areas. A limited chemotherapeutics arsenal is available to tackle this deadly infection. Thus, identifying novel potent scaffolds using innovative strategies is the need of the hour. High-throughput screening (HTS) is a critical technique that can accelerate the process of drug discovery by evaluating millions of drug-like molecules using various automation tools and biological assays. In the present study, we have employed the HTS strategy to identify potent hits against Leishmania donovani sterol C-24 methyltransferase (LdSMT) from the in-house ChemBridge library. Firstly, a robust dataset was prepared with previously reported sterol C-24 methyltransferase inhibitors, belonging to diverse structural classes. Then, ligand-based virtual screening using similarity search was performed to screen the ChemBridge library having ∼20,000 molecules. This computational approach yielded 81 candidate compounds, which were selected for further molecular docking and biological evaluation. Anti-leishmanial assays revealed that out of 81 molecules, seven showed potential parasitic killing. Three molecules namely IIIM-CB-14, IIIM-CB-29, and IIIM-CB-45 were the most potent ones with 50 % inhibitory concentration (IC50) of 5.76, 8.08, and 10.64 µg/mL, respectively. SEM analyses suggest that these potent hits cause considerable morphological alterations. ADME studies of the potent hit molecules indicate that all the hits have considerable drug-likeness properties. Further, molecular dynamics studies were also performed to check the stable confirmation of LdSMT protein with the top two hits (IIIM-CB-14 and IIIM-CB-45). Thus, the present study harnesses computational and experimental approaches to unravel potent anti-leishmanial scaffolds.

Photo-responsive Carboxymethyl Chitosan/Laponite Hydrogel as a Potential Spinal Cord Injury Scaffold: Characterization and Cytocompatibility Study

Photo-responsive Carboxymethyl Chitosan/Laponite Hydrogel as a Potential Spinal Cord Injury Scaffold: Characterization and Cytocompatibility Study

Accelerated hit identification with target evaluation, deep learning and automated labs: prospective validation in IRAK1

BackgroundTarget identification and hit identification can be transformed through the application of biomedical knowledge analysis, AI-driven virtual screening and robotic cloud lab systems. However there are few prospective studies that evaluate the efficacy of such integrated approaches.ResultsWe synergistically integrate our in-house-developed target evaluation (SpectraView) and deep-learning-driven virtual screening (HydraScreen) tools with an automated robotic cloud lab designed explicitly for ultra-high-throughput screening, enabling us to validate these platforms experimentally. By employing our target evaluation tool to select IRAK1 as the focal point of our investigation, we prospectively validate our structure-based deep learning model. We can identify 23.8% of all IRAK1 hits within the top 1% of ranked compounds. The model outperforms traditional virtual screening techniques and offers advanced features such as ligand pose confidence scoring. Simultaneously, we identify three potent (nanomolar) scaffolds from our compound library, 2 of which represent novel candidates for IRAK1 and hold promise for future development.ConclusionThis study provides compelling evidence for SpectraView and HydraScreen to provide a significant acceleration in the processes of target identification and hit discovery. By leveraging Ro5’s HydraScreen and Strateos’ automated labs in hit identification for IRAK1, we show how AI-driven virtual screening with HydraScreen could offer high hit discovery rates and reduce experimental costs.Scientific contributionWe present an innovative platform that leverages Knowledge graph-based biomedical data analytics and AI-driven virtual screening integrated with robotic cloud labs. Through an unbiased, prospective evaluation we show the reliability and robustness of HydraScreen in virtual and high-throughput screening for hit identification in IRAK1. Our platforms and innovative tools can expedite the early stages of drug discovery.

Novel pyrrole based triazole moiety as therapeutic hybrid: synthesis, characterization and anti-Alzheimer potential with molecular mechanism of protein ligand profile

As a springboard to explore novel potent inhibitors of cholinesterase enzymes (AChE and BChE) responsible for causing Alzheimer disorder, the current study was conducted to synthesize pyrrole derived triazole based Schiff base scaffolds by facile synthetic route. These compounds were validated by 1HNMR, 13CNMR and HREI-MS. All these scaffolds (1–16) were examined for their inhibitory activity against AChE and BChE in contrast to Donepezil (10.20 ± 0.10 and 10.80 ± 0.20 µM) and Allanzanthone (12.40 ± 0.10 and 13.10 ± 0.10 µM). All pyrrole derived triazole based Schiff base scaffolds (1–16) showed varied range of inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes with lowest inhibition concentration values ranging from 5.10 ± 0.40–27.10 ± 0.10 µM (for AChE) and 5.60 ± 0.30–28.40 ± 0.30 µM (for BChE). SAR analysis of these derivatives revealed analog 7 as lead molecule against targeted enzyme, while analog 6 and 11 were ranked as second and third most potent scaffolds. Binding affinity and selectivity of potent molecules against targeted enzymes were examined by molecular docking and obtained results showed that potent molecule have versatile significant binding interactions with stated enzymes. Furthermore, safety profiles of potent analogues were predicted via ADMET protocols.Graphical

TMEM232 is required for the formation of sperm flagellum and male fertility in mice

Asthenoteratozoospermia is a major cause of male infertility. Thus far, the identified related genes can explain only a small share of asthenoteratozoospermia cases, suggesting the involvement of other genes. The transmembrane protein TMEM232 is highly expressed in mouse testes. In the present study, to determine its function of TMEM232 in testes, we constructed a Tmem232-null mouse model using CRISPR–Cas9 technology. Tmem232 knockout (KO) male mice was completely infertile, and their sperm were immotile, with morphological defects of the flagellum. Electron microscopy revealed an aberrant midpiece-principal junction and the loss of the fourth outer microtubule doublet in the sperm of Tmem232−/− mice. Sperm cells presented an 8 + 2 conformation and an irregular arrangement of the mitochondrial sheath. Proteomic analysis revealed altered expression of proteins related to flagellar motility, sperm capacitation, the integrity and stability of sperm structure, especially an upregulated expression of multiple ribosome components in TMEM232-deficient spermatids. Additionally, TMEM232 was observed to be involved in autophagy by interacting with autophagy-related proteins, such as ATG14, to regulate ribosome homeostasis during spermiogenesis. These results suggest that TMEM232, as a potential scaffold protein involving in the correct assembly, distribution, and stability maintenance of certain functional complexes by recruiting key intracellular proteins, is essential for the formation of a highly structured flagellum and plays an important role in the autophagic elimination of cytosolic ribosomes to provide energy for sperm motility.

New Ester‐Containing Azole Derivatives With Potent Anti‐Candida Effects: Synthesis, Antifungal Susceptibility, Cytotoxicity, and Molecular Modeling Studies

ABSTRACTMortalities due to mycoses have dramatically increased with the emergence of drug‐resistant strains and growing immune‐compromised populations globally. Azole antifungals have been the first choice against fungal infections of a wide spectrum and several azole derivatives with ester function were reported for their potentially promising and favorable activity against Candida spp. In this study, we designed and synthesized a series of 1‐(aryl)−2‐(1H‐imidazol‐1‐yl/1H‐1,2,4‐triazol‐1‐yl)ethyl esters, and tested them against seven reference Candida strains using EUCAST reference microdilution method. Among the series, 6a, 6d, and 6g proved highly potent in vitro compared to fluconazole; especially against Candida albicans and Candida tropicalis with minimum inhibitor concentration (MIC) values as low as 0.125 and 0.06 mg/L, respectively, although their activities against Candida krusei and Candida glabrata remained limited. The compounds also showed minimal toxicity to murine fibroblasts according to the in vitro cytotoxicity tests. Molecular modeling predicted 6g as an orally available druglike compound according to all parameters and CYP51 inhibition as the likely mechanism for their antifungal effects. The study underpins the promise of azoles with ester functionality as a potential scaffold for small‐molecule antifungal drug design.

Cellulose Acetate-Based Wound Dressings Loaded with Bioactive Agents: Potential Scaffolds for Wound Dressing and Skin Regeneration.

Wound healing and skin regeneration are major challenges in chronic wounds. Among the types of wound dressing products currently available in the market, each wound dressing material is designed for a specific wound type. Some of these products suffer from various shortcomings, such as poor antibacterial efficacy and mechanical performance, inability to provide a moist environment, poor permeability to oxygen and capability to induce cell migration and proliferation during the wound healing process. Hydrogels and nanofibers are widely reported wound dressings that have demonstrated promising capability to overcome these shortcomings. Cellulose acetate is a semisynthetic polymer that has attracted great attention in the fabrication of hydrogels and nanofibers. Loading bioactive agents such as antibiotics, essential oils, metallic nanoparticles, plant extracts, and honey into cellulose acetate-based nanofibers and hydrogels enhanced their biological effects, including antibacterial, antioxidant, and wound healing. This review reports cellulose acetate-based hydrogels and nanofibers loaded with bioactive agents for wound dressing and skin regeneration.

PlexinA1 (PLXNA1) as a novel scaffold protein for the engineering of extracellular vesicles.

Extracellular vesicles (EVs) had been described as a next-generation drug delivery system, due to the compelling evidence that they can facilitate the transfer of a variety of biomolecules between cells. The most frequently used strategy for loading protein cargoes is the endogenous engineering of EVs through genetic fusion of the protein of interest (POI) and scaffold proteins with high EV-sorting ability. However, the lack of scaffold proteins had become a major issue hindering the promotion of this technology. Herein, we proposed novel screening criteria that relax the inclusion requirement of candidate scaffold proteins and eventually identified a new scaffold protein, PLXNA1. The truncated PLXNA1 not only inherits the high EV-sorting ability of its full-length counterpart but also allows the fusion expression of POI in both outer surface and luminal areas, individually or simultaneously. In conclusion, our screening criteria expanded the range of potential scaffold proteins. The identified scaffold protein PLXNA1 showed great potential in developing therapeutic EVs.

Inhibitory Effects of Mangifera indica Secondary Metabolites and Their Synthetic Derivatives against SARS-CoV-2 Mpro and NS2B/NS3 (ZIKV and DENV-2).

Chemical studies of Mangifera indica twigs yielded two compounds, identified as taraxerol (1) and methyl gallate (2). The galloyl moiety was suggested as a potential scaffold that can interfere with proteases by previous biological investigations on SARS-CoV-2 main protease (Mpro) inhibitors in combination with docking studies. Therefore, a series of 13 gallate esters were prepared by treating gallic acid with natural and non-natural alcohols. Their inhibitory effects were evaluated against Mpro and NS2B/NS3 of Zika and Dengue viruses. Among the obtained compounds, 2e and 2i were the most potent against Mpro with IC50 values of 2.60 and 4.0 μM, respectively. Compounds 2f and 2g were more potent than others against ZIKV protease with IC50 values of 2.7 and 1.9 μM, respectively. The bioactivity profile against DENV NS2B/NS3 was different with 2e and 2f showing moderate inhibition with IC50 values of 66.0 and 59.29 μM, respectively. It was found that 2f and 2g inhibited ZIKV NS2B/NS3 via a noncompetitive mechanism. The study also showed that 2e and 2f could exert noncompetitive inhibition at the previously described allosteric pocket of flaviviral NS2B/NS3 proteases. Molecular docking revealed different types of interactions among the most prominent were hydrogen bonding with the galloyl moiety.

Alpha-calcium sulfate hemihydrate incorporated with tri-calcium phosphate and hydroxyapatite bioceramics as potential scaffold for bone regeneration

The development of artificial grafts, including biodegradable materials and non-biodegradable ones, for bone regeneration is a significant advance in the field of biomaterial science. Notably, bioceramics such as calcium sulfate hemihydrate and calcium phosphates have attracted extensive attention from researchers due to their natural bone-like composition. However, some requirements related to mechanical properties, resorption ability, osteoinduction and osteoconduction of each bioceramics have not been effectively controlled to make them ideal materials for bone regeneration applications. In this study, composites of β-tricalcium phosphate, hydroxyapatite, and α-calcium sulfate hemihydrate (β-TCP/HA/α-CSH) were synthesized using wet mixing method in order to create a template that degrades in sync with bone growth, offer sufficient mechanical strength during healing process, and has appropriate setting time for precise surgical application. The β-TCP/HA compositional phase with the ratio of 80/20 (% in weight) would be used for the entire study meanwhile the influence of α-CSH on the behaviour of β-TCP/HA/α-CSH composites would be investigated. The successful preparation of β-TCP/HA/α-CSH composite was evaluated by FTIR, XRD, and SEM. In vitro testing has further demonstrated the commendable biodegradability of β-TCP/HA/α-CSH composites and its ability for cell adhesion and migration, suggesting that β-TCP/HA/α-CSH composites would be a promising biomaterial for bone engineering.

Development of a P(L-D,L)LA Foam as a Dura Substitute and Its In Vitro Evaluation

Dura substitutes are used to reduce the risk of postoperative complications following neurosurgical interventions, and to facilitate the healing of dura damages or defects caused by injuries. Traditional tissue transplants have limitations like limited tissue availability, potential risk of immune rejection and disease transmission. The use of biomaterials composed of synthetic polymers as dura substitutes offers a promising approach to overcome these limitations to replace and treat damaged dura mater. Potential biocompatible porous scaffolds still need to be developed to minimize the risks of immune response and disease transmission, while also ensuring effective cell migration and cell ingrowth in three dimension. The aim of the present study was to develop a poly(L-lactide-co-D,L-lactide) (P(L-D,L)LA) foam with an optimal pore size for dura mater substitution, investigate its morphological characteristics, and evaluate its potential for dura mater regeneration by assessing the spreading and growth of meningeal cells within it through in vitro studies. Foams were produced by lyophilization using different concentrations of P(L-D,L)LA solution. A GMP-grade P(L-D,L)LA, suitable for medical device applications, was used in this study. Morphological analysis was performed using scanning electron microscopy, and porosity of the foams was studied with mercury porosimetry. In in vitro studies, meningeal cells were seeded onto the polymeric foams, and their behavior and proliferation in these scaffolds were investigated with cytoskeleton and nucleus staining, and colorimetric cell proliferation assay, respectively. Scanning electron microscopy results showed that the foams prepared with 2.5% and 3% polymer solutions displayed good structural integrity and convenient interconnectivity, with pore sizes ranging from 80 to 150 µm. However, the foams prepared with 2% and 4% polymer solution demonstrated poor structural integrity and low interconnectivity, respectively. In vitro studies showed that the foams prepared with 2.5% and 3% polymer solutions served effectively as scaffolds for meningeal cells, and the cells attached, spread and homogeneously distributed. In addition, the cells proliferated and increased in number over time within these polymeric scaffolds. These findings suggest that the foams produced with 2.5% and especially 3% P(L-D,L)LA polymer solutions could effectively serve as a suitable substitute for the dura mater, providing an appropriate environment for cell ingrowth and tissue integration. This indicates that the developed foam could be a promising treatment for dura mater damage or defects, with the potential approach to promote regeneration in future in vivo and clinical studies.

Novel purine derivatives as selective CDK2 inhibitors with potential anticancer activities: Design, synthesis and biological evaluation

Purine analogues were discovered to be inhibitors of CDK2, suggesting a potential therapeutic scaffold. This paper addresses the design, synthesis, and anticancer evaluation of purine analogues as kinase inhibitors. In the early stages of the investigation, the designed compounds demonstrated a promising docking score and greater protein–ligand stability in MD simulation than the standard, indicating a higher affinity against CDK2. Thus, we synthesised new purine analogues under simple and optimised reaction conditions. Among the studies under NCI-60, 5g and 5i were the most effective, with a percentage GI of 98.09 and 90 against OVCAR-4 and SNB-75, respectively, at a dose of 10 µM. Additionally, 5g and 5i demonstrated 7.80-fold and 1.54-fold greater cytotoxicity against PA-1 and MCF-7, with IC50s of 1.08 µM and 3.54 µM, respectively, compared to seliciclib (8.43 µM and 5.46 µM). In addition, 5g and 5i showed selective cytotoxicity against PA-1 and MCF-7 than normal cells, with selectivity indexes of 26.40 and 15.45, respectively, as compared to the standard (SI=3.83 and 5.91). In the kinase selectivity assay, both compounds demonstrated greater affinity against CDK2 than other kinases, with IC50 of 0.21 µM and 0.59 µM, in contrast to the standard (IC50 = 0.63 µM). Furthermore, 5g confirmed kinase inhibition in the western blot by lowering CDK2, cyclin A2, and other downstream substrates. Moreover, it triggered cell death by apoptosis and cell cycle arrest in G2/M. Taken together, 5g merits further investigation in PKPD research to discover a potential therapeutic candidate against cancer.

Digital annealing optimization for natural product structure elucidation.

The digital annealer (DA) leverages its computational capabilities of up to 100000 bits to address the complex nondeterministic polynomial-time (NP)-complete challenge inherent in elucidating complex structures of natural products. Conventional computational methods often face limitations with complex mixtures, as they struggle to manage the high dimensionality and intertwined relationships typical in natural products, resulting in inefficiencies and inaccuracies. This study reformulates the challenge into a Quadratic Unconstrained Binary Optimization framework, thereby harnessing the quantum-inspired computing power of the DA. Utilizing mass spectrometry data from three distinct herb species and various potential scaffolds, the DA proficiently locates optimal sidechain combinations that adhere to predefined target molecular weights. This methodology enhances the probability of selecting appropriate sidechains and substituted positions and ensures the generation of solutions within a reasonable 5-min window. The findings underscore the transformative potential of the DA in the realms of analytical chemistry and drug discovery, markedly improving both the precision and practicality of natural product structure elucidation.

Synergistic on engineering layered N-doped carbon/MXene heterostructure: A potential scaffold for simultaneous electrochemical detection of Cu2+ and Hg2+ ions

The presence of heavy metal ions (HMIs) like Cu2+ and Hg2+ in natural water and foods is a major health and environmental concern. Thus advanced electrochemical sensors are required to monitor these ions. Herein, we introduce a nitrogen-rich carbon-MXene composite (layered N-doped carbon/MXene) as an electrochemical sensor suitable for the simultaneous detection of Cu2+ and Hg2+. Synthesizing 2D/2D heterostructure interfaces using controlled thermal decomposition conditions with the incorporation of quaternary nitrogen from choline chloride and the formation of hydrogen bonds of urea within the MXene (Ti3C2Tx) provided active surfaces area that is suitable for the detection of Cu2+ and Hg2+. The intermediate structure of layered N-doped carbon/MXene, had a nitrogen content of ∼6 %, maximized sensitivity for Cu2+ and Hg2+. The layered N-doped carbon/MXene composite exhibited excellent electrochemical sensing for Cu2+ and Hg2+ in 0.1 M acetate buffer at low sensing potentials. The limits of detection (LODs) of layered N-doped carbon/MXene were 0.019 and 0.056 µM with a sensitivity of 114.54 and 64.317 µA µM−1 cm−2 for Cu2+ and Hg2+, respectively. Furthermore, the layered N-doped carbon/MXene heterostructure exhibited high selectivity for Cu2+ and Hg2+ in the presence of potentially interfering common metal ions. This study introduces a promising advanced material for rapid Cu2+ and Hg2+ detection in food and environmental applications.

Macroporous PEG-Alginate Hybrid Double-Network Cryogels with Tunable Degradation Rates Prepared via Radical-Free Cross-Linking for Cartilage Tissue Engineering.

Trauma or repeated damage to joints can result in focal cartilage defects, significantly elevating the risk of osteoarthritis. Damaged cartilage has an inherently limited self-healing capacity and remains an urgent unmet clinical need. Consequently, there is growing interest in biodegradable hydrogels as potential scaffolds for the repair or reconstruction of cartilage defects. Here, we developed a biodegradable and macroporous hybrid double-network (DN) cryogel by combining two independently cross-linked networks of multiarm polyethylene glycol (PEG) acrylate and alginate.Hybrid DN cryogels are formed using highly biocompatible click reactions for the PEG network and ionic bonding for the alginate network. By judicious selection of various structurally similar cross-linkers to form the PEG network, we can generate hybrid DN cryogels with customizable degradation kinetics. The resulting PEG-alginate hybrid DN cryogels have an interconnected macroporous structure, high mechanical strength, and rapid swelling kinetics. The interconnected macropores in the cryogels support efficient mesenchymal stem cell infiltration at a high density. Finally, we demonstrate that PEG-alginate hybrid DN cryogels allow sustained release of chondrogenic growth factors and support chondrogenic differentiation of mouse mesenchymal stem cells. This study provides a novel method to generate macroporous hybrid DN cryogels with customizable degradation rates and a potential scaffold for cartilage tissue engineering.

Hybrid scaffolds for bone tissue engineering: Integration of composites and bioactive hydrogels loaded with hDPSCs

Bone tissue regeneration remains a significant challenge in clinical settings due to the complexity of replicating the mechanical and biological properties of bone environment. This study addresses this challenge by proposing a hybrid scaffold designed to enhance both bioactivity and physical stability for bone tissue regeneration. This research is the fisrt to develop a rigid 3D structure composed of polycaprolactone (PCL) and hydroxyapatite nanoparticles (nHA) integrated with a bioink containing human dental pulp stem/stromal cells (hDPSCs), alginate, nHA and collagen (Col). The biofabricated constructs were extensively characterized through cytocompatibility tests, osteogenic differentiation assessment, and biocompatibility evaluation in a rat model. In vitro results demontrated that the hybrid scaffolds presented significantly higher cell viability after 168 h compared to the control group. Furthermore, the hybrid scaffolds showed increased osteogenic differentiation relative to other groups. In vivo evaluation indicated good biocompatibility, characterized by minimal inflammatory response and successful tissue integration. These findings highlight the scaffold's potential to support bone tissue regeneration by combining the mechanical strength of PCL and nHA with the biological activity of the alginate-nHA-Col and hDPSCs bioink. The current study provides a promising foundation for the development of biomaterials aimed at improving clinical outcomes in bone repair and regeneration, particulary for the treatment of critical-size bone defects, targeted drug administration, and three-dimensional models for bone tissue engineering.

Surface Heterogeneity at the Polymer-Food Interface Influences Ag Migration from Plastic Packaging Incorporating Ag-Exchanged Zeolites.

Silver-enabled polymers, with their antimicrobial properties, could prolong the shelf life and maintain quality in packaged foods. However, there is limited understanding about how the Ag form in the polymer, food chemistry, and other factors affect the transfer (migration) of Ag from the polymer to the food under the intended conditions of use. In this study, we investigated the release of Ag from polymer composites (PCs) incorporating two different Ag-exchanged zeolites (Ag-Y), which have been explored as potential scaffolds for loading high concentrations of Ag within common polymers. We manufactured two Ag-Y films based on low-density polyethylene (LDPE): one incorporating ionic Ag (Ag+) and one incorporating nanoparticulate Ag (AgNPs), each with similar initial Ag concentrations. Then, we assessed the migration of Ag out of these PCs into food simulants under accelerated room temperature storage conditions. In all simulants investigated, the Ag+-Y/LDPE film exhibited a higher migration of Ag compared to the AgNP-Y/LDPE film, suggesting a lower fraction of readily releasable Ag in the latter material. Total Ag migration from AgNP-Y/LDPE over 10 days at 40 °C was 11.10 ± 2.05 ng cm-2 of packaging surface area in water, 7.63 ± 1.59 ng cm-2 in a 9 wt % aqueous sucrose solution, and 21.29 ± 1.98 ng cm-2 in a commercial sweetened carbonated beverage (Squirt). In contrast, Ag migration from Ag+-Y/LDPE was measured at 49.61 ± 3.46, 57.48 ± 9.65, and 91.54 ± 5.58 ng cm-2 in water, sucrose solution, and Squirt drink, respectively. Surface characterization techniques, including atomic force microscopy (AFM), scanning electron microscopy (SEM), and conductivity measurements, revealed the presence of exposed zeolite particles at the surface of the films, suggesting that direct interactions between Ag-exchanged zeolites and food components at the simulant-polymer interface play an important role in determining Ag migration from Ag-Y/LDPE PCs.

Regenerated fat induced by a decellularized adipose matrix can survive long-term in vivo

Decellularized adipose matrix (DAM) is considered to be the most potential biological scaffold for soft tissue repair and reconstruction, as it is able to induce the regeneration of adipose tissue in situ in adulthood. But how does this adipose tissue regeneration happen and develop in vivo? Is it the same as the original autologous one? Temporary existence or long-term survival? These are the key questions that will determine the future applications of DAM. In this study, we investigated the composition, structure and biomechanical properties of DAM before implanting it into the subcutaneous back of immunodeficient mice. The entire regeneration process in vivo was closely monitored histologically from 3 days to 1 year after implantation, including fat regeneration, vascular growth, inflammatory responses, and matrix degradation and remodeling. Transcriptome sequencing was used to analyze the difference in gene expression between regenerated fat and autologous fat at different periods. The results showed that the DAM-induced regenerated fat first appeared at 1 w and remained stable over 6 m, indicating remarkable similarity to autologous fat at the later stages of implantation. And about (18.3 ± 29.3) % of the regenerated adipocytes were still viable after one year. The process of adipogenesis was enhanced by the decrease in inflammatory infiltration and proceeded in parallel with angiogenesis. Statement of significanceThe decellularized adipose matrix (DAM) is the only biological scaffold that can spontaneously generate adipocytes in vivo without the need to add exogenous cells. However, in the previous studies, the longest DAM-related animal experiments were about 3 months. The different stages and characteristics of DAM implantation cannot be fully captured. Comprehensive preclinical researches on the initiation, characteristics, and long-term outcomes of DAM-induced adipose tissue regeneration in adulthood is crucial.In this study, we closely observed various aspects of the entire process in vivo from 3 days to 1 year after implantation including fat regeneration, vascular growth, inflammatory reactions as well as matrix degradation and remodeling. The thorough research will contribute to the understanding of stability and dynamic remodeling of DAM regeneration models.

N-acyl-4-arylaminopiperidines: Design and synthesis of a potential antimicrobial scaffold

We report a concise synthesis of N-acylated piperidines through a Knoevenagel-Doebner condensation/amide construction/ amination sequence. The design of the piperidines considered the pharmacophoric features found in previously reported inhibitors of FabI, an enzyme implicated in bacterial fatty acid biosynthesis. After the microbiological evaluation at 50 μM, the analogs displayed moderate activity against some pathogens from the ESKAPE group, reaching up to 42 % of growth inhibition for MRSA, 54 % for K. pneumoniae, and 37 % for P. aeruginosa (multiresistant strains). Docking studies demonstrate that almost all of them docked satisfactorily into the catalytic domain of S. aureus FabI, maintaining a similar pose as other reported inhibitors. The results shown herein propose the N-acyl-4-arylaminopiperidines as the basis for the development of more active candidates.