Erythrocyte Membrane Coating Alleviate Immune Response And Promoted Adipogenesis In Adipose Matrix.

Xenotransplantation of adipose extracellular matrix (AAM) has come to prominence as an intriguing option for soft tissue reconstruction. However, the presence of immunogenic antigens within AAM can trigger unfavorable immune reactions, leading to inadequate in vivo regeneration outcomes. Therefore, the development of advanced technology capable of modulating immune responses is crucial for the therapeutic implementation of AAM xenografts. In this work, a innovative technique is created to bypass the immune system by covering the surface of both AAM and RGD peptide-modified AAM xenografts with autologous red blood cell (RBC) membrane. The RBC membrane coating remained persistent and exhibited no significant decline even after 21 days. Moreover, it effectively reduced the expression of antigen MHC1 on the AAM surface. Following xenogeneic transplantation, the RBC coated xenografts demonstrated increased expression of the adipogenic factor PPAR-γ and higher numbers of adipocytes. Additionally, they exhibited decreased expression of immunological factors including IL-6, IL-2, IFN-γ and TNF-α, and fewer inflammatory cells. These findings indicate that RBC membrane coating successfully suppressed immune responses and promoted increased adipogenesis in AAM xenografts. Therefore, AAM camouflage coating with RBC has a lot of potential as a biomaterial for soft tissue reconstruction in clinical settings.

Functional Characterization of Double Mutations T929I/K1774N in the Voltage-Gated Sodium Channel of Megalurothrips usitatus (Bagnall) Related to Pyrethroid Resistance.

Megalurothrips usitatus (Bagnall), the main pest on legume vegetables, is controlled by pyrethroids in the field. Field strains of M. usitatus resistant to pyrethroids were collected from three areas in Hainan Province (Haikou, Ledong, and Sanya City), and two mutations, T929I and K1774N, were detected in the voltage-gated sodium channel. In this study, the sodium channel in M. usitatus was first subcloned and successfully expressed in Xenopus oocytes. The single mutation (T929I or K1774N) and double mutation (T929I/K1774N) shifted the voltage dependence of activation in the hyperpolarization direction. The three mutants all reduced the amplitude of tail currents induced by type I (permethrin and bifenthrin) and type II (deltamethrin and λ-cyhalothrin) pyrethroids. Homology modeling analysis of these two mutations shows that they may change the local hydrophobicity and positive charge of the sodium channel. Our data can be used to reveal the causes of the resistance of M. usitatus to pyrethroids and provide guidance for the comprehensive control of M. usitatus in the future.

Site specific redox properties in ligand differentiated di-nickel complexes inspired by the acetyl CoA synthase active site.

Bimetallic transition metal complexes with site-specific redox properties offer a versatile platform for understanding electron polarization, intramolecular electron transfer processes, and customizing electronic and magnetic properties that might impact reactivity and catalyst design. Inspired by the dissymmetric nickel sites in the Acetyl CoA Synthase (ACS) Active Site, three new bimetallic Ni(N2S2)-Ni(S2C2R2) complexes based on Ni(N2S2) metalloligand donor synthons, Nid, in mimicry of the nickel site distal to the redox-active iron sulfur cluster of ACS, and nickel dithiolene receiver units, designated as Nip, the nickel proximal to the 4Fe4S cluster, were combined to explore the influence of ligand environment on electronic structure and redox properties of each unit. The combination of synthons gave a matrix of three S-bridged dinickel complexes, characterized by X-ray crystallography, and appropriate spectroscopies. Computational modeling is connected to the electronic characteristics of the nickel donor and receiver units. This study demonstrated the intricacies of identifying sites of electrochemical redox processes, within multi-metallic systems containing non-innocent ligands.

Mutation V65I in the ß1 Subunit of the Nicotinic Acetylcholine Receptor Confers Neonicotinoid and Sulfoxaflor Resistance in Insects.

Neonicotinoids have been widely used to control pests with remarkable effectiveness. Excessive insecticides have led to serious insect resistance. Mutations of the nicotinic acetylcholine receptor (nAChR) are one of the reasons for neonicotinoid resistance conferred in various agricultural pests. Two mutations, V65I and V104I, were found in the nAChR ß1 subunit of two neonicotinoid-resistant aphid populations. However, the specific functions of the two mutations remain unclear. In this study, we cloned and identified four nAChR subunits (α1, α2, α8, and ß1) of thrips and found them to be highly homologous to the nAChR subunits of other insects. Subsequently, we successfully expressed two subtypes nAChR (α1/α2/α8/ß1 and α1/α8/ß1) by coinjecting three cofactors for the first time in thrips, and α1/α8/ß1 showed abundant current rapidly. Acetylcholine, neonicotinoids, and sulfoxaflor exhibited different activation capacities for the two subtypes of nAChRs. Finally, V65I was found to significantly reduce the binding ability of nAChR to neonicotinoids and sulfoxaflor through electrophysiology and computer simulations. V104I caused a decrease in agonist affinity (pEC50) but an increase in the efficacy (Imax) of nAChR against neonicotinoids and reduced the binding ability of nAChR to sulfoxaflor. This study provides theoretical and technical support for studying the molecular mechanisms of neonicotinoid resistance in pests.

Combined Use of Autologous Sustained-Release Scaffold of Adipokines and Acellular Adipose Matrix to Construct Vascularized Adipose Tissue.

BACKGROUND: Adipose tissue engineering plays a key role in the reconstruction of soft-tissue defects. The acellular adipose matrix (AAM) is a promising biomaterial for the construction of engineered adipose tissue. However, AAM lacks sufficient adipoinduction potency because of the abundant loss of matrix-bound adipokines during decellularization. METHODS: An adipose-derived extracellular matrix collagen scaffold, "adipose collagen fragment" (ACF), was prepared using a novel mechanical method that provides sustained release of adipokines. Here, the authors used label-free proteomics methods to detect the protein components in AAM and ACF. In vivo, ACF was incorporated into AAM or acellular dermal matrix and implanted into nude mice to evaluate adipogenesis. Neoadipocytes, neovessels, and corresponding gene expression were evaluated. The effects of ACF on adipogenic differentiation of human adipose-derived stem cells and tube formation by human umbilical vein endothelial cells were tested in vitro. RESULTS: Proteomics analysis showed that ACF contains diverse adipogenic and angiogenic proteins. ACF can release diverse adipokines and induce highly vascularized, mature adipose tissue in AAM, and even in nonadipogenic acellular dermal matrix. Higher expression of adipogenic markers peroxisome proliferator-activated receptor gamma and CCAAT/enhancer-binding protein alpha and greater numbers of tubule structures were observed in ACF-treated groups in vitro. CONCLUSION: The combination of ACF and AAM could serve as a novel and promising strategy to construct mature, vascularized adipose tissue for soft-tissue reconstruction. CLINICAL RELEVANCE STATEMENT: The combined use of AAM and ACF has been proven to induce a highly vascularized, mature, engineered adipose tissue in the nude mouse model, which may serve as a promising strategy for soft-tissue reconstruction.

Functional diversity of voltage-gated sodium channel in Drosophila suzukii (Matsumura).

BACKGROUND: The larvae of Drosophila suzukii Matsumura feed directly inside the fruit, causing catastrophic damage to orchards. The misuse of pyrethroid insecticides during the control period has led to increasing resistance of D. suzukii to pyrethroids acting on the voltage-gated sodium channel (VGSC). RESULTS: In this study, the sodium channel of D. suzukii was cloned (DsNav 5 GenBank number: OQ871532). The results of multiple-sequence alignment showed that the homology of sodium channel between D. suzukii and Drosophila melanogaster was as high as 95.3%. Analysis of transcripts from 62 variants of D. suzukii VGSC revealed a total of six alternative splicing sites (exons u, j, a, b, e, and h) and 33 RNA editing. Exons j, a, b, e, and h are conserved in D. melanogaster and other insects, whereas exon u has never been reported before. The number of A-to-I was distinctly more than that of U-to-C for RNA editing. All D. suzukii VGSC variants were expressed in Xenopus oocytes, but only one (type 5) was able to produce robust currents and nine produce weak currents. DsNav 5 with TipE of D. melanogaster co-expresses current better than its own TipE. Subsequently, tetrodotoxin was verified to be a blocker of VGSC, and the gating properties of DsNav 5 were investigated. CONCLUSION: These findings proved that the VGSC of D. suzukii has not only the basic gating properties, but also the diversity of gating properties. This study also laid a foundation for the study of pyrethroid resistance mechanism of VGSC in D. suzukii. © 2023 Society of Chemical Industry.

Pathological characteristics of breast nodules after large-volume fat grafting for breast augmentation.

BACKGROUND: The complications of large-volume fat grafting (LVFG) for breast augmentation remain unpredictable and include palpable breast nodules, oil cysts, and calcifications. AIMS: This study was aimed to provide an optimal treatment option for breast nodules after LVFG and evaluate their pathological characteristics. PATIENTS/METHODS: We effectively performed complete resection of breast nodules in 29 patients after LVFG using a minimal skin incision with the vacuum-assisted breast biopsy (VABB) system under ultrasound guidance. And we further carried on histologic examination of excised nodules and evaluated their pathological characteristics. RESULTS: The breast nodules were excised thoroughly with cosmetic effect satisfactorily. Interestingly, subsequent histologic examination showed that type I and VI collagens were strongly expressed in the fibrotic area and type IV collagen were positively expressed around the blood vessel. Furthermore, we found that the type VI collagen+ area appeared around mac2+ macrophages and α-SMA+ myofibroblasts. CONCLUSIONS: The VABB system may be the optimal treatment option for breast nodules after LVFG. And type VI collagens may serve as a biomarker of grafted adipose tissue fibrosis. The relationship between macrophages, fibroblasts, and collagen formation may be therapeutic targets for regulating fibrosis.

Corrigendum to 'Methoxy polyethylene glycol modification promotes adipogenesis by inducing the production of regulatory T cells in xenogeneic acellular adipose matrix' [Materials Today Bio 12 (2021) 100161].

[This corrects the article DOI: 10.1016/j.mtbio.2021.100161.].

Preliminary exploration of method for screening efficacy markers compatibility in TCM prescriptions based on Q-markers: Anti-inflammatory activity of Dachaihu decoction as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DD), a classic Chinese herbal prescription, is composed of radix of Bupleurum chinense DC. (Chaihu), radix of Scutellaria baicalensis Georgi (Huangqin), radix of Paeonia lactiflora Pall. (Baishao), rhizoma of Pinellia ternata (Thunb.) Breit. (Banxia), fructus of Citrus aurantium L. (Zhishi), rhizoma of Zingiber officinale Rosc. (Shengjiang), fructus of Ziziphus jujuba Mill. (Dazao) and rhizoma of Rheum officinale Baill. (Dahuang). DD has the traditional effects of soothing the liver, relieving depression and clearing heat from the stomach, and is mainly used to treat heat stagnation in the liver and stomach. AIM OF THE STUDY: Dachaihu decoction (DD), a classic prescription commonly used in clinical practice for the treatment of pancreatitis and cholecystitis. Although its pharmacological effects are clear, the efficacy components and mechanism of action remain intricate and difficult to clarify. MATERIALS AND METHODS: The action targets and components of the anti-inflammatory activity of DD were predicted by network pharmacology; the effective components and targets were verified by HPLC and qPCR; the efficacy markers of DD were further screened by in vitro experiments; the pharmacological value of DD and its components compatibility were evaluated by in vitro experiments. RESULTS: The key targets MMP9, JAK2, MAP2K1 and NR3C1 were screened by network pharmacology; HPLC analysis showed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were identified as potential efficacy markers of DD; molecular docking combined with qPCR verification suggested that baicalin, naringin, neohesperidin, hesperidin and baicalein and wogonoside had certain ability to regulate above targets; in vitro studies revealed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 could inhibit the release of NO, pancreatic lipase and α-glucosidase; after comprehensive comparison and analysis, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were selected as the efficacy markers of DD; in vivo studies indicated that DD and its efficacy markers (components compatibility) had definite therapeutic effects on guinea pigs with cholecystitis. CONCLUSIONS: The efficacy markers of DD including naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 can be used as components compatibility to exert anti-inflammatory activity. In addition, a method for obtaining the compatibility of efficacy markers by simplifying the prescription is initially established.

Recent Development of Self-Powered Tactile Sensors Based on Ionic Hydrogels.

Hydrogels are three-dimensional polymer networks with excellent flexibility. In recent years, ionic hydrogels have attracted extensive attention in the development of tactile sensors owing to their unique properties, such as ionic conductivity and mechanical properties. These features enable ionic hydrogel-based tactile sensors with exceptional performance in detecting human body movement and identifying external stimuli. Currently, there is a pressing demand for the development of self-powered tactile sensors that integrate ionic conductors and portable power sources into a single device for practical applications. In this paper, we introduce the basic properties of ionic hydrogels and highlight their application in self-powered sensors working in triboelectric, piezoionic, ionic diode, battery, and thermoelectric modes. We also summarize the current difficulty and prospect the future development of ionic hydrogel self-powered sensors.

Deciphering Adverse Detrapped Hole Transfer in Hot-Electron Photoelectric Conversion at Infrared Wavelengths.

Hot-carrier devices are promising alternatives for enabling path breaking photoelectric conversion. However, existing hot-carrier devices suffer from low efficiencies, particularly in the infrared region, and ambiguous physical mechanisms. In this work, the competitive interfacial transfer mechanisms of detrapped holes and hot electrons in hot-carrier devices are discovered. Through photocurrent polarity research and optical-pump-THz-probe (OPTP) spectroscopy, it is verified that detrapped hole transfer (DHT) and hot-electron transfer (HET) dominate the low- and high-density excitation responses, respectively. The photocurrent ratio assigned to DHT and HET increases from 6.6% to over 1133.3% as the illumination intensity decreases. DHT induces severe degeneration of the external quantum efficiency (EQE), especially at low illumination intensities. The EQE of a hot-electron device can theoretically increase by over two orders of magnitude at 10 mW cm-2 through DHT elimination. The OPTP results show that competitive transfer arises from the carrier oscillation type and carrier-density-related Coulomb screening. The screening intensity determines the excitation weight and hot-electron cooling scenes and thereby the transfer dynamics.

Functional Characterization of Knockdown Resistance Mutation L1014S in the German Cockroach, Blattella germanica (Linnaeus).

The effectiveness of pyrethroid insecticides is seriously threatened by knockdown resistance (kdr), which is induced in insects by inherited single-nucleotide polymorphisms in the voltage-gated sodium channel (VGSC) gene. VGSC's L1014F substitution results in the classic kdr mutation, which is found in many pest species. Other substitutions of the L1014 locus, such as L1014S, L1014C, L1014W, and L1014H, were also reported. In 2022, a new amino acid substitute L1014S of Blattella germanica was first discovered in China. We modified the BgNav1-1 sodium channel from cockroaches with the L1014S mutation to study how pyrethroid sensitivity and channel gating were affected in Xenopus oocytes. The L1014S mutation reduced the half-maximal activation voltage (V1/2,act) from -19.0 (wild type) to -15.5 mV while maintaining the voltage dependency of activation. Moreover, the voltage dependence of inactivation in the hyperpolarizing shifts from -48.3 (wild type) to -50.9 mV. However, compared with wild type, the mutation L1014S did not cause a significant shift in the half activation voltage (V1/2,act). Notably, the voltage dependency of activation was unaffected greatly by the L1014S mutation. Tail currents are induced by two types of pyrethroids (1 µM): type I (permethrin, bifenthrin) and type II (deltamethrin, λ-cyhalothrin). All four pyrethroids produced tail currents, and significant differences were found in the percentages of channel modifications between variants and wild types. Further computer modeling showed that the L1014S mutation allosterically modifies pyrethroid binding and action on B. germanica VGSC, with some residues playing a critical role in pyrethroid binding. This study elucidated the pyrethroid resistance mechanism of B. germanica and predicted the residues that may confer the risk of pyrethroid resistance, providing a molecular basis for understanding the resistance mechanisms conferred by mutations at the 1014 site in VGSC.

[Study on mechanism of Rehmanniae Radix Praeparata for treatment of osteoarthritis based on network pharmacology and molecular docking].

The mechanism of Rehmanniae Radix Praeparata against osteoarthritis was investigated based on network pharmacology, molecular docking, and in vitro experiments in the present study. Osteoclast models were established via receptor activator of nuclear factor-κB ligand(RANKL) and macrophage colony-stimulating factor(M-CSF) inducing RAW264.7 cells. Further, the influence of Rehmanniae Radix Praeparata on the activity of tartrate-resistant acid phosphatase(TRAP) was evaluated and the efficacy of Rehmanniae Radix Praeparata in the treatment of osteoarthritis was verified. The active components of Rehmanniae Radix Praeparata were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and literature, and the potential targets of the components were collected from SwissTargetPrediction. Osteoarthritis disease targets were searched in Online Mendelian Inheritance in Man(OMIM), Therapeutic Target Database(TTD), GeneCards, and DisGeNET. The intersection targets of Rehmanniae Radix Praeparata and osteoarthritis were obtained by Venny platform. The protein-protein interaction(PPI) network was constructed by Cytoscape 3.8.2, and key targets were obtained based on topology algorithm. The Database for Annotation, Visualization and Integrated Discovery(DAVID) was used to perform Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Finally, the mRNA expression of the key targets was determined by RT-qPCR and the binding activity between the components and key targets was validated by molecular docking. The results showed that Rehmanniae Radix Prae-parata inhibited the TRAP activity, thus inhibiting bone resorption by osteoclasts and treating osteoarthritis. By network pharmacology, 14 active components of Rehmanniae Radix Praeparata and 126 intersection targets were obtained. The network pharmacology enrichment results revealed 432 biological processes and 139 signaling pathways. Key targets such as proto-oncogene tyrosine-protein kinase Src(SRC), signal transducer and activator of transcription 3(STAT3) and transcription factor p65(RELA) were obtained according to the degree in topological analysis. SRC was highly expressed in osteoclasts, which accelerated the development of osteoarthritis. Therefore, SRC was selected for subsequent verification, and Rehmanniae Radix Praeparata decreased the gene expression level of SRC. The molecular docking showed that acteoside, isoacteoside, raffinose had good bonding activity with SRC, suggesting that they might be the critical components in treating osteoarthritis. In conclusion, Rehmanniae Radix Praeparata can inhibit bone resorption by osteoclasts and balance the metabolism of articular cartilage and subchondral bone via acting on SRC, thus playing a therapeutic role in osteoarthritis. In addition, Rehmanniae Radix Praeparata may exert overall efficacy on osteoarthritis through other targets such as STAT3 and RELA, and other related pathways such as PI3 K-AKT and IL-17 signaling pathways.

Adipose Collagen Fragment: A Novel Adipose-Derived Extracellular Matrix Concentrate for Skin Filling.

BACKGROUND: Skin filler is an option for treating skin aging and wrinkles; however, currently used fillers are limited by poor biocompatibility, rapid degradation, and possible hypersensitivity reactions. Autologous adipose tissue-derived products have been recognized as promising options for skin rejuvenation. OBJECTIVES: This study aimed to develop a novel adipose-derived product for skin filling. METHODS: Adipose collagen fragment (ACF) was prepared through pulverization, filtration, and centrifugation. The macrography, structure, types of collagen, and cell viability of ACF were evaluated by immunostaining, western blotting, and cell culture assays. ACF, nanofat, and phosphate-buffered saline (9 spots/side, 0.01 mL/spot) were intradermally injected in the dorsal skin of 36 female BALB/c nude mice; the skin filling capacity and the collagen remodeling process were then investigated. Twenty-one female patients with fine rhytides in the infraorbital areas were enrolled and received clinical applications of ACF treatment. Therapeutic effects and patients' satisfaction scores were recorded. RESULTS: The mean [standard deviation] yield of ACF from 50 mL of Coleman fat was 4.91 [0.25] mL. ACF contained nonviable cells and high levels of collagen I, collagen IV, and laminin. Fibroblasts and procollagen significantly increased in ACF and ACF-treated dermis (P < 0.05). Overall, 85.7% of patients were satisfied with the therapy results, and no infections, injection site nodules, or other unwanted side effects were observed. CONCLUSIONS: ACF significantly improved dermal thickness and collagen synthesis and may serve as a potential autologous skin filler.

Multi-target-based polypharmacology prediction (mTPP): An approach using virtual screening and machine learning for multi-target drug discovery.

Polypharmacology has become a new paradigm in drug discovery and plays an increasingly vital role in discovering multi-target drugs. In this context, multi-target drugs are a promising approach to treating polygenic diseases. Many in-silico prediction methods have been developed to screen active molecules acting on multiple targets. The relationship between the action of multiple targets and the drug's overall efficacy is significant for developing multi-target drugs. So, the prediction method for this relationship urgently needs to be developed. This paper introduces multi-target-based polypharmacology prediction (mTPP), an approach using virtual screening and machine learning to explore the relationship. To predict the activity of the potential hepatoprotective components, the data on the binding strength of a single ingredient with multiple targets and the proliferation rate of the compounds against acetaminophen (APAP)-induced injury L02 cells were all used to construct the mTPP model by Multi-layer Perceptron (MLP), Support Vactor Regression (SVR), Decision Tree Regressor (DTR), and Gradient Boost Regression (GBR) algorithms. Compared with MLP, SVR, and DTR algorithms, GBR algorithms showed the best performance with R2test = 0.73 and EVtest = 0.75. In addition, 20 candidates with potential effects against drug-induced liver injury (DILI) were predicted by the mTPP model. Furthermore, 2 of the 20 candidates, Chelerythrine and Biochanin A, were applied to evaluate the model's accuracy. The results showed that Chelerythrine and Biochanin A could improve the viability of APAP-induced injury cells. Thus, the mTPP model is hoped to help develop polypharmacology and discover multi-target drugs.

Macrophage-mediated extracellular matrix remodeling after fat grafting in nude mice.

Clinical unpredictability and variability following fat grafting remain non-negligible problems due to the unknown mechanism of grafted fat retention. The role of the extracellular matrix (ECM), which renders cells with structural and biochemical support, has been ignored. This study aimed to clarify the ECM remodeling process, related cellular events, and the spatiotemporal relationship between ECM remodeling and adipocyte survival and adipogenesis after fat grafting. Labeled Coleman fat by the matrix-tracing technique was grafted in nude mice. The ECM remodeling process and cellular events were assessed in vivo. The related cytokines were evaluated by qRT-PCR. An in vitro cell migration assay was performed to verify the chemotactic effect of M2-like macrophages on fibroblasts. The results demonstrated that in the periphery, most of the adipocytes of the graft survived or regenerated, and the graft-derived ECM was gradually replaced by the newly-formed ECM. In the central parts, most adipocytes in the grafts died shortly after, and a small part of the graft-derived and newly-formed ECM was expressed with irregular morphology. Adipose ECM remodeling is associated with increased infiltration of macrophages and fibroblasts, as well as up-regulated expression of cytokines in the adipose tissue. To sum up, our results describe the various preservation mode of fat grafts after transplantation and underscore the importance of macrophage-mediated ECM remodeling in graft preservation after fat grafting. The appreciation and manipulation of underlying mechanisms that are operant in this setting stand to explore new therapeutic approaches and improve clinical outcomes of fat grafting.

A Time-Division Position-Sensitive Detector Image System for High-Speed Multitarget Trajectory Tracking.

High-speed trajectory tracking with real-time processing capability is particularly important in the fields of pilotless automobiles, guidance systems, robotics, and filmmaking. The conventional optical approach to high-speed trajectory tracking involves charge coupled device (CCD) or complementary metal-oxide-semiconductor (CMOS) image sensors, which suffer from trade-offs between resolution and framerates, complexity of the system, and enormous data-analysis processes. Here, a high-speed trajectory tracking system is designed by using a time-division position-sensitive detector (TD-PSD) based on a graphene-silicon Schottky heterojunction. Benefiting from the high-speed optoelectronic response and sub-micrometer positional accuracy of the TD-PSD, multitarget real-time trajectory tracking is realized, with a maximum image output framerate of up to 62 000 frames per second. Moreover, multichannel trajectory tracking and image-distortion correction functionalities are realized by TD-PSD systems through frequency-related image preprocessing, which significantly improves the capacity of real-time information processing and image quality in complicated light environments.

Identification of a novel farnesoid X receptor agonist, kaempferol-7-O-rhamnoside, a compound ameliorating drug-induced liver injury based on virtual screening and in vitro validation.

Farnesoid X receptor (FXR), a bile acid receptor, plays an essential role in maintaining bile acid and liver homeostasis and has been recognized as an essential target for drug-induced liver injury (DILI). This study aimed to identify potential FXR agonists by virtual screening, molecular dynamics (MD) simulation, and biological assays. First, an in-house Traditional Chinese medicine compound database was screened using a virtual approach based on molecular docking to reveal potential FXR agonists. Secondly, MD was applied to analyze the process of agonist binding. Finally, the acetaminophen (APAP)-induced L02 cells model evaluated the pharmacodynamic activity of agonists treating DILI. Virtual screening results showed that kaempferol-7-O-rhamnoside was confirmed as the FXR agonist. MD results showed that kaempferol-7-O-rhamnoside could stably bind the FXR. In addition, in vitro cell-based assay showed that kaempferol-7-O-rhamnoside could promote the expression of the FXR gene and inhibit the Cyp7a1 gene expression in APAP-induced cells, significantly reducing the activities of AST, AKP and ROS, and enhancing the expression of GSH. The current study confirmed that kaempferol-7-O-rhamnoside might improve liver function by promoting proliferation, ameliorating oxidative stress, and regulating FXR target genes as observed in vitro. Therefore, in this study, discovering the FXR agonist, kaempferol-7-O-rhamnoside, provides valuable guidance for developing novel drugs against DILI.

Inflammation-mediated matrix remodeling of extracellular matrix-mimicking biomaterials in tissue engineering and regenerative medicine.

Extracellular matrix (ECM)-mimicking biomaterials are considered effective tissue-engineered scaffolds for regenerative medicine because of their biocompatibility, biodegradability, and bioactivity. ECM-mimicking biomaterials preserve natural microstructures and matrix-related bioactive components and undergo continuous matrix remodeling upon transplantation. The interaction between host immune cells and transplanted ECM-mimicking biomaterials has attracted considerable attention in recent years. Transplantation of biomaterials may initiate injuries and early pro-inflammation reactions characterized by infiltration of neutrophils and M1 macrophages. Pro-inflammation reactions may lead to degradation of the transplanted biomaterial and drive the matrix into a fetal-like state. ECM degradation leads to the release of matrix-related bioactive components that act as signals for cell migration, proliferation, and differentiation. In late stages, pro-inflammatory cells fade away, and anti-inflammatory cells emerge, which involves macrophage polarization to the M2 phenotype and leukocyte activation to T helper 2 (Th2) cells. These anti-inflammatory cells interact with each other to facilitate matrix deposition and tissue reconstruction. Deposited ECM molecules serve as vital components of the mature tissue and influence tissue homeostasis. However, dysregulation of matrix remodeling results in several pathological conditions, such as aggressive inflammation, difficult healing, and non-functional fibrosis. In this review, we summarize the characteristics of inflammatory responses in matrix remodeling after transplantation of ECM-mimicking biomaterials. Additionally, we discuss the intrinsic linkages between matrix remodeling and tissue regeneration. STATEMENT OF SIGNIFICANCE: Extracellular matrix (ECM)-mimicking biomaterials are effectively used as scaffolds in tissue engineering and regenerative medicine. However, dysregulation of matrix remodeling can cause various pathological conditions. Here, the review describes the characteristics of inflammatory responses in matrix remodeling after transplantation of ECM-mimicking biomaterials. Additionally, we discuss the intrinsic linkages between matrix remodeling and tissue regeneration. We believe that understanding host immune responses to matrix remodeling of transplanted biomaterials is important for directing effective tissue regeneration of ECM-mimicking biomaterials. Considering the close relationship between immune response and matrix remodeling results, we highlight the need for studies of the effects of clinical characteristics on matrix remodeling of transplanted biomaterials.