Performance Enhancement of Polyurethane Acrylate Resin by Urushiol: Rheological and Kinetic Studies.

A natural extract, i.e., urushiol, was employed to effectively cross-link and modify commercial wet-cured polyurethane acrylic resin. Comprehensive characterization of the paint film was performed using techniques such as FTIR, SEM, and TGA. The results indicated that the incorporation of urushiol significantly increased the cross-linking density of the resin, which in turn enhanced the film-forming properties, mechanical strength, and thermal stability of the paint film. Additionally, the study discovered that under isothermal conditions, the dynamic moduli (G' and G″) of the paint film are related to the gel point frequency by a power law, aligning with the predictions of percolation theory. The application of the autocatalytic model has provided a novel approach to studying non-isothermal kinetic reactions, offering valuable insights for process optimization and further development of urushiol-based polyurethane.

High-Speed Countercurrent Chromatography Isolation of Active Components from Evodia Rutaecarpa and Affinity Ultrafiltration Screening for Their Acetylcholinesterase Inhibitor Activity.

Acetylcholinesterase inhibitors from Evodia rutaecarpa were screened, prepared, and evaluated. To screen the lipophilic alkaloid active constituents in E. rutaecarpa, we improved and optimized an ultrafiltration system. Three acetylcholinesterase (AChE) inhibitors, dehydroevodiamine, evodiamine, and rutecarpine, were screened. Addressing the limitations of the traditional response surface methodology (RSM) for multiobjective screening, we integrated RSM with the Non-dominated Sorting Genetic Algorithm III to achieve the optimal extraction of these active ingredients. High-speed countercurrent chromatography was used to isolate the active components using a two-phase solvent system: n-hexane/ethyl acetate/methanol/water (3.0:2.5:3.5:2.0, v/v/v/v) and ethyl acetate/methanol/water (3.0:1.0:4.0, v/v/v). The nuclear magnetic resonance spectroscopy confirmed the structures of the compounds, and molecular docking and dynamics simulations assessed the inhibitory effects of the chemical components on AChE, which were consistent with the findings of the ultrafiltration experiments. We also confirmed the neuroprotective properties of these compounds against glutamate-induced apoptosis in PC12 cells. Overall, we achieved the systematic optimization of multitarget compound extraction and lipophilic alkaloid ultrafiltration screening, as well as preparation and activity validation, laying the groundwork for the development of AChE inhibitors from lipophilic alkaloids.

Efficacy of vitamin D supplementation on depressive symptoms in older patients: a meta-analysis of randomized controlled trials.

Background: The relationship between vitamin D and depression has garnered significant attention in recent years. However, the efficacy of vitamin D in ameliorating depression among specific subgroups of older patients remains controversial. This study aimed to assess the impact of vitamin D supplementation on depressive symptoms and the prevalence of depression in older adults. Additionally, the study sought to examine potential moderating factors, including differences among population subgroups and various supplementation strategies. Methods: A systematic literature search was conducted in the databases PubMed, EMBASE, Web of Science, and the Cochrane Library up to March 2024. The RevMan 5.3 software was utilized to calculate the standardized mean difference (SMD) and to evaluate the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The objective was to determine the efficacy of vitamin D supplementation in alleviating depressive symptoms or treating depression in older adults. Results: This meta-analysis encompassed eleven studies, comprising a total of 21,561 participants. The findings did not indicate a statistically significant therapeutic benefit of vitamin D supplementation for depression in older patients [SMD: -0.10; 95% CI: (-1.19, 0.00); p = 0.05]. Subgroup analyses revealed that the efficacy of vitamin D intervention in geriatric depression correlated with several factors, including baseline serum 25(OH)D levels, the dosage of the intervention, gender, and the initial presence of depressive symptoms or a diagnosis of depression. Conclusion: The current evidence is insufficient to conclusively establish the significant efficacy of vitamin D supplementation in alleviating depressive symptoms among older patients. Consequently, additional randomized controlled trials are warranted to further validate the relationship between vitamin D supplementation and depression in the older adults.

High-performance ratiometric fluorescence detection and removal of tetracycline in milk based on CDs@ZSM-5:Eu3.

Exploring materials with the dual functionality of detecting and removing tetracycline (TC) residues is crucial because of the environmental and health risks posed by antibiotic overuse. This study introduces a dual-emissive luminescent probe, CDs@ZSM-5:Eu3+, created through a solvent-free method combined with subsequent Eu3+ion exchange. The nanocomposite's blue emission, originating from carbon dots (CDs), is quenched by TC via an internal filtering effect, while an antenna effect triggers a strong red fluorescence of a TC-Eu3+chelate. The ratiometric fluorescence changes in CDs@ZSM-5:Eu3+ endow a self-calibrated sensing mechanism for TC, offering a low detection limit of 5.04 nM and a broad detection range of 0.01-50 µM. Demonstrated in real milk samples, the probe exhibits high selectivity and accuracy in detecting TC. The nanocomposite also displayed an impressive TC removal capacity of 238.1 mg g-1 in water, ascribing to the enrichment and electrostatic attraction effects of ZSM-5 toward TC molecules. This research offers a facile strategy for constructing multifunctional zeolite-based hybrids for simultaneous TC detection and removal from aqueous solutions.

Bio-Based Epoxy Vitrimers with Excellent Properties of Self-Healing, Recyclability, and Welding.

The development of more recyclable materials is a key requirement for a transition towards a more circular economy. Thanks to exchange reactions, vitrimer, an attractive alternative for recyclable materials, is an innovative class of polymers that is able to change its topology without decreasing its connectivity. In this work, a bisphenol compound (VP) was prepared from saturated cardanol, i.e., 3-pentadecylphenol and vanillyl alcohol. Then, VP was epoxidized to obtain epoxide (VPGE). Finally, VPGE and citric acid (CA) were polymerized in the presence of catalyst TBD to prepare a fully bio-based vitrimer based on transesterification. The results from differential scanning calorimetry (DSC) showed that the VPGE/CA system could be crosslinked at around 163 °C. The cardanol-derived vitrimers had good network rearrangement properties. Meanwhile, because of the dynamic structural elements in the network, the material was endowed with excellent self-healing, welding, and recyclability.

Advances in crosslinking chemistry and proximity-enabled strategies: deciphering protein complexes and interactions.

Mass spectrometry, coupled with innovative crosslinking techniques to decode protein conformations and interactions through uninterrupted signal connections, has undergone remarkable progress in recent years. It is crucial to develop selective crosslinking reagents that minimally disrupt protein structure and dynamics, providing insights into protein network regulation and biological functions. Compared to traditional crosslinkers, new bifunctional chemical crosslinkers exhibit high selectivity and specificity in connecting proximal amino acid residues, resulting in stable molecular crosslinked products. The conjugation with specific amino acid residues like lysine, cysteine, arginine and tyrosine expands the XL-MS toolbox, enabling more precise modeling of target substrates and leading to improved data quality and reliability. Another emerging crosslinking method utilizes unnatural amino acids (UAAs) derived from proximity-enabled reactivity with specific amino acids or sulfur-fluoride exchange (SuFEx) reactions with nucleophilic residues. These UAAs are genetically encoded into proteins for the formation of specific covalent bonds. This technique combines the benefits of genetic encoding for live cell compatibility with chemical crosslinking, providing a valuable method for capturing transient and weak protein-protein interactions (PPIs) for mapping PPI coordinates and improving the pharmacological properties of proteins. With continued advancements in technology and applications, crosslinking mass spectrometry is poised to play an increasingly significant role in guiding our understanding of protein dynamics and function in the future.

Synergistic Etching and Hydrogen Bonding-Induced Self-Assembly of MXene/MOF Hybrid Aerogel for Flexible Room-Temperature Gas Sensing.

Limited by insufficient active sites and restricted mechanical strength, designing reliable and wearable gas sensors with high activity and ductility remains a challenge for detecting hazardous gases. In this work, a thermally induced and solvent-assisted oxyanion etching strategy was implemented for selective pore opening in a rigid microporous Cu-based metal-organic framework (referred to as CuM). A conductive CuM/MXene aerogel was then self-assembled through cooperative hydrogen bonding interactions between the carbonyl oxygen atom in PVP grafted on the surface of defect-rich Cu-BTC and the surface functional hydroxyl group on MXene. A flexible NO2 sensing performance using the CuM/MXene aerogel hybridized sodium alginate hydrogel is finally achieved, demonstrating extraordinary sensitivity (S = 52.47 toward 50 ppm of NO2), good selectivity, and rapid response/recovery time (0.9/4.5 s) at room temperature. Compared with commercial sensors, the relative error is less than 7.7%, thereby exhibiting significant potential for application in monitoring toxic and harmful gases. This work not only provides insights for guiding rational synthesis of ideal structure models from MOF composites but also inspires the development of high-performance flexible gas sensors for potential multiscenario applications.

Quaternity method for integrated screening, separation, extraction optimization, and bioactivity evaluation of acetylcholinesterase inhibitors from Sophora flavescens Aiton.

INTRODUCTION: Sophora flavescens Aiton (Fabaceae), a ubiquitous plant species in Asia, contains a wide range of pharmacologically active compounds, such as flavonoids, with potential anti-Alzheimer's disease (anti-AD) effects. OBJECTIVES: The objective of the study is to develop a quaternity method for the screening, isolation, extraction optimization, and activity evaluation of acetylcholinesterase (AChE)-inhibiting compounds from S. flavescens to realize high-throughput screening of active substances in traditional Chinese medicine and to provide experimental data for the development of anti-AD drugs. METHODS: With AChE as the target molecule, affinity ultrafiltration and liquid chromatography-mass spectrometry were applied to screen for potential inhibitors of the enzyme in S. flavescens. Orthogonal array experiments combined with the multi-objective Non-Dominated Sorting Genetic Algorithm III was used for the first time to optimize the process for extracting the active substances. Enzyme inhibition kinetics and molecular docking studies were performed to verify the potential anti-AD effects of the active compounds. RESULTS: Five AChE-inhibiting compounds were identified: kushenol I, kurarinone, sophoraflavanone G, isokurarinone, and kushenol E. These were successfully separated at purities of 72.88%, 98.55%, 96.86%, 96.74%, and 95.84%, respectively, using the n-hexane/ethyl acetate/methanol/water (4.0/5.0/4.0/5.0, v/v/v/v), n-hexane/ethyl acetate/methanol/water (5.0/5.0/6.0/4.0, v/v/v/v), and n-hexane/ethyl acetate/methanol/water (4.9/5.1/5.7/4.3, v/v/v/v) mobile phase systems. Enzyme inhibition kinetics revealed that kushenol E had the best inhibitory effect. CONCLUSION: This study elucidates the mechanism of action of five active AChE inhibitors in S. flavescens and provides a theoretical basis for the screening and development of anti-AD and other therapeutic drugs.

An Integrated Strategy Based on 10-DAB Extraction and In Situ Whole-Cell Biotransformation of Renewable Taxus Needles to Produce Baccatin III.

Baccatin III is a crucial precursor in the biosynthesis pathway of paclitaxel. Its main sources are extraction from Taxus or chemical synthesis using 10-deacetylbaccatin III (10-DAB) as substrate. However, these preparation approaches exhibit serious limitations, including the low content of baccatin III in Taxus and the complicated steps of chemical synthesis. Heterologous expression of 10-deacetylbaccatin III-10-O-acetyltransferase (TcDBAT) in microbial strains for biotransformation of 10-DAB is a promising alternative strategy for baccatin III production. Here, the promotion effects of glycerol supply and slightly acidic conditions with a low-temperature on the catalysis of recombinant TcDBAT strain were clarified using 10-DAB as substrate. Taxus needles is renewable and the content of 10-DAB is relatively high, it can be used as an effective source of the catalytic substrate 10-DAB. Baccatin III was synthesized by integrating the extraction of 10-DAB from renewable Taxus needles and in situ whole-cell catalysis in this study. 40 g/L needles were converted into 20.66 mg/L baccatin III by optimizing and establishing a whole-cell catalytic bioprocess. The method used in this study can shorten the production process of Taxus extraction for baccatin III synthesis and provide a reliable strategy for the efficient production of baccatin III by recombinant strains and the improvement of resource utilization rate of Taxus needles.

Highly Selective Electroreduction of Nitrobenzene to Aniline by Co-Doped 1T-MoS2.

The selective electrocatalytic reduction of nitrobenzene (NB) to aniline demands a desirable cathodic catalyst to overcome the challenges of the competing hydrogen evolution reaction (HER), a higher overpotential, and a lower selectivity. Here, we deposit Co-doped 1T MoS2 on Ti mesh by the solvothermal method with different doping percentages of Co as x % Co-MoS2 (where x = 3, 5, 8, 10, and 12%). Because of the lowest overpotential, lower charge-transfer resistance, strong suppression of the competing HER, and higher electrochemical surface area, 8% Co-MoS2 achieves 94% selectivity of aniline with 54% faradaic efficiency. The reduction process follows first-order dynamics with a reaction coefficient of 0.5 h-1. Besides, 8% Co-MoS2 is highly stable and retains 81% selectivity even after 8 cycles. Mechanistic studies showed that the selective and exothermic adsorption of the nitro group at x % Co-MoS2 leads to a higher rate of NB reduction and higher selectivity of aniline. The aniline product is successfully removed from the solution by polymerization at FTO. This study signifies the impact of doping metal atoms in tuning the electronic arrangement of 1T-MoS2 for the facilitation of organic transformations.

Incorporation of Ag in Co9S8-Ni3S2 for Predominantly Enhanced Electrocatalytic Activities for Oxygen Evolution Reaction: A Combined Experimental and DFT Study.

Electrodeposition of abundant metals to fabricate efficient and durable electrodes indicate a viable role in advancing renewable electrochemical energy tools. Herein, we deposit Co9S8-Ag-Ni3S2@NF on nickel foam (NF) to produce Co9S8-Ag-Ni3S2@NF as a exceedingly proficient electrode for oxygen evolution reaction (OER). The electrochemical investigation verifies that the Co9S8-Ag-Ni3S2@NF electrode reveals better electrocatalytic activity to OER because of its nanoflowers' open-pore morphology, reduced overpotential (η10=125 mV), smaller charge transfer resistance, long-term stability, and a synergistic effect between various components, which allows the reactants to be more easily absorbed and subsequently converted into gaseous products during the water electrolysis route. Density functional theory (DFT) calculation as well reveals the introduction of Ag (222) surface into the Co9S8 (440)-Ni3S2 (120) structure increases the electronic density of states (DOS) per unit cell of a system and increases the electrocatalytic activity of OER by considerably lowering the energy barriers of its intermediates. This study provides the innovation of employing trimetallic nanomaterials immobilized on a conductive, continuous porous three-dimensional network formed on a nickel foam (NF) substrate as a highly proficient catalyst for OER.

Effect of high-fat diet on cerebral pathological changes of cerebral small vessel disease in SHR/SP rats.

Cerebral small vessel diseases (CSVD) are neurological disorders associated with microvessels, manifested pathologically as white matter (WM) changes and cortical microbleeds, with hypertension as a risk factor. Additionally, a high-fat diet (HFD) can affect peripheral vessel health. Our study explored how HFD affects cerebral small vessels in normotensive WKY, hypertensive SHR, and SHR/SP rats. The MRI results revealed that HFD specifically increased WM hyperintensity in SHR/SP rats. Pathologically, it increased WM pallor and vacuolation in SHR and SHR/SP rats. Levels of blood-brain barrier (BBB) protein claudin 5 were decreased in SHR and SHR/SP compared to WKY, with HFD having minimal impact on these levels. Conversely, collagen IV levels remained consistent among the rat strains, which were increased by HFD. Consequently, HFD caused vessel leakage in all rat strains, particularly within the corpus callosum of SHR/SP rats. To understand the underlying mechanisms, we assessed the levels of hypoxia-inducible factor-1α (HIF-1α), Gp91-phox, and neuroinflammatory markers astrocytes, and microglia were increased in SHR and SHR/SP compared to WKY and were further elevated by HFD in all rat strains. Gp91-phox was also increased in SHR and SHR/SP compared to WKY, with HFD causing an increase in WKY but little effect in SHR and SHR/SP. In conclusion, our study demonstrates that HFD, in combined with hypertension, intensifies cerebral pathological alterations in CSVD rats. This exacerbation involves increased oxidative stress and HIF-1α in cerebral vessels, triggering neuroinflammation, vascular basement membrane remodeling, IgG leakage, and ultimately WM damage.

Integrated analysis and separation of 5-lipoxygenase inhibitors from triterpenes of Poria cocos using bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking and target-based multiple complex networks.

Poria cocos (Schw.) Wolf (P. cocos) has been widely used as medical plant in East Asia with remarkable anti-Alzheimer's disease (anti-AD) activity. However, the underlying mechanisms are still confused. In this study, based on the ß-Amyloid deposition hypothesis of AD, an integrated analysis was conducted to screen and separation 5-lipoxygenase (5-LOX) inhibitors from triterpenoids of P. cocos and investigate the anti-AD mechanisms, containing bioaffinity ultrafiltration UPLC-Q-Exactive, molecular docking, and multiple complex networks. Five triterpenoids were identified as potential 5-LOX inhibitors, including Tumulosic acid, Polyporenic acid C, 3-Epi-dehydrotumulosic acid, Pachymic acid and Dehydrotrametenolic acid. Five potential 5-LOX inhibitors were screened by ultrafiltration affinity assay in P. cocos. The molecular docking simulation results are consistent with the ultrafiltration experimental results, which further verifies the accuracy of the experiment. The commercial 5-LOX inhibitor that Zileuton was used as a positive control to evaluate the inhibitory effect of active ingredients on 5-LOX. Subsequently, the established separation method allowed the five active ingredients (Pachymic acid, 3-Epi-dehydrotumulosic acid, Dehydrotrametenolic acid, Tumulosic acid and Polyporenic acid C) with high purity to be isolated. Targeting network pharmacology analysis showed that five active ingredients correspond to a total of 286 targets. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that target cells were mainly enriched in Pathways in cancer, Lipid and atherosclerosis. Our results indicate that P. cocos extract has the potential to be used in the prevention and treatment of neurodegenerative diseases. This will help elucidate the mechanisms of action of various medicinal plants at the molecular level and provide more opportunities for the discovery and development of new potential treatments from health food resources.

The relationship of the tertiary lymphoid structures with the tumor-infiltrating lymphocytes and its prognostic value in gastric cancer.

Introduction: To explore the relationship between the tertiary lymphoid structures (TLSs) and tumor-infiltrating lymphocytes (TILs), and their distribution characteristics as well as the prognostic value in gastric cancer (GC). Material and methods: The TLSs and four subtypes of TILs were assessed by immunohistochemical (IHC) staining. The presence of MECA-79 positive high endothelial venules (HEVs) identified among the ectopic lymphocyte aggregation area in the GC tissue was defined as valid TLSs. The number of labeled TILs was observed in 5 fields of the most positive cells in the tumor center, invasive edge and within the TLSs, at a field of vision ×40. Results: The TLS distribution was significantly higher in the tumor invasive edge than the tumor center (p < 0.001). Similarly, the infiltrating density of CD8+ T cells and GrB+ T cells was statistically significantly higher in the tumor infiltrating edge than the tumor center. The total number of TILs and FOXP3+ T cells showed a contrary distribution. There was a positive correlation of the density of TLSs and TILs with both the location and the immune phenotype. A higher frequency of TILs and TLSs is often associated with favorable clinicopathologic parameters. Higher numbers of peri-TLSs (p = 0.007), peri-CD8+ (p = 0.019) and peri-GrB+TILs (p = 0.032) were significantly correlated with the favorable overall survival. Multivariate analysis revealed that the densities of TILs (p = 0.019) and TLSs (p = 0.037) were independent prognostic predictor for GC patients. Conclusions: We provide evidence that TLSs were positively associated with lymphocyte infiltration in GC. Thus, the formation of TLSs predicts advantageous immune system function and can be considered as a novel biomarker to stratify the overall survival risk of untreated GC patients.

Bromine-mediated strategy endows efficient electrochemical oxidation of amine to nitrile.

Conventional methods for nitrile synthesis bring inherent environmental risks due to their reliance on oxidants and harsh reaction conditions. Meanwhile, direct electrooxidation of amines to nitriles suffers from low current density. In this study, we propose an innovative indirect electrooxidation strategy for nitrile formation, mediated by Br-/Br2, utilizing a highly efficient CoS2/CoS@Graphite Felt (GF) electrode. Notably, the anodic nitrile generation can be synergistically coupled with the cathodic hydrogen evolution reaction (HER). Through meticulous optimization of reaction parameters, we achieve an impressive 98% selectivity for octanenitrile at a current density of 60 mA cm-2 with a remarkable faradaic efficiency (FE) of 87%. Furthermore, our approach demonstrates excellent versatility, as we successfully evaluate both aliphatic and aromatic primary amines, highlighting its promising potential for practical applications in the field.

Efficient and fast screening and separation based on computer-aided screening and complex chromatography methods for lipoxygenase inhibitors from Ganoderma lucidum.

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.

Correction: Shibly et al. Analysis of Cerebral Small Vessel Changes in AD Model Mice. Biomedicines 2023, 11, 50.

In the original publication [...].

Rapid screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Polyporus umbellatus and mechanism of action in the treatment of gout.

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.

Screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Poria Cum Radix Pini and mechanism of action in the treatment of gout disease.

Poria Cum Radix Pini is a rare medicinal fungus that contains several potential therapeutic ingredients. On this basis, a particle swarm mathematical model was used to optimize the extraction process of total triterpenes from P. Cum Radix Pini, and xanthine oxidase inhibitors were screened using affinity ultrafiltration mass spectrometry. Meanwhile, the accuracy of the ultrafiltration assay was verified by molecular docking experiments and molecular dynamics analysis, and the mechanism of action of the active compounds for the treatment of gout was analyzed by enzymatic reaction kinetics and network pharmacology. A high-speed countercurrent chromatography method combined with the consecutive injection and the economical two-phase solvent system preparation using functional activity coefficient of universal quasichemical model (UNIFAC) mathematical model was developed for increasing the yield of target compound. In addition, dehydropachymic acid and pachymic acid were used as competitive inhibitors, and 3-O-acetyl-16alpha-hydroxydehydrotrametenolic acid and dehydrotrametenolic acid were used as mixed inhibitors. Then, activity-oriented separation and purification were performed by high-speed countercurrent chromatography combined with semi-preparative high-performance liquid chromatography and the purity of the four compounds isolated was higher than 90%. It will help to provide more opportunities to discover and develop new potential therapeutic remedies from health care food resources.

Stabilized cyclic peptides as modulators of protein-protein interactions: promising strategies and biological evaluation.

Protein-protein interactions (PPIs) control many essential biological pathways which are often misregulated in disease. As such, selective PPI modulators are desirable to unravel complex functions of PPIs and thus expand the repertoire of therapeutic targets. However, the large size and relative flatness of PPI interfaces make them challenging molecular targets for conventional drug modalities, rendering most PPIs "undruggable". Therefore, there is a growing need to discover innovative molecules that are able to modulate crucial PPIs. Peptides are ideal candidates to deliver such therapeutics attributed to their ability to closely mimic structural features of protein interfaces. However, their inherently poor proteolysis resistance and cell permeability inevitably hamper their biomedical applications. The introduction of a constraint (i.e., peptide cyclization) to stabilize peptides' secondary structure is a promising strategy to address this problem as witnessed by the rapid development of cyclic peptide drugs in the past two decades. Here, we comprehensively review the recent progress on stabilized cyclic peptides in targeting challenging PPIs. Technological advancements and emerging chemical approaches for stabilizing active peptide conformations are categorized in terms of α-helix stapling, ß-hairpin mimetics and macrocyclization. To discover potent and selective ligands, cyclic peptide library technologies were updated based on genetic, biochemical or synthetic methodologies. Moreover, several advances to improve the permeability and oral bioavailability of biologically active cyclic peptides enable the de novo development of cyclic peptide ligands with pharmacological properties. In summary, the development of cyclic peptide-based PPI modulators carries tremendous promise for the next generation of therapeutic agents to target historically "intractable" PPI systems.