Mechanisms of Zhixiao Tang on Anti-Inflammatory Multiple Targets and Multiple Components: Metabonomics Combined with Database Mining Technology.

Purpose: Zhixiao Tang (ZXT), a traditional Chinese compound prescription, has been used clinically to treat pneumonia in China. However, the underlying mechanism of ZXT treatment in pneumonia is still unclear. The present study aimed to reveal the potential mechanism of ZXT in pneumonia using a strategy combining metabolomics and network pharmacology. Methods: Initially, the chemical compositions were identified by UPLC-QE-Orbitrap-MS, while the prediction of potential signal pathways was performed through network pharmacology. To assess the anti-inflammatory properties of ZXT in the context of pneumonia, models of 16HBE cells induced by LPS and zebrafish induced by CuSO4 were established to measure levels of inflammatory markers and apoptosis. Subsequently, the differential changes of endogenous metabolites in cells caused by ZXT were examined using metabolomics technology, and the molecular docking analysis of key targets was carried out using Autodock Vina software. Ultimately, the validation of the primary pathways and targets was conducted through quantitative RT-PCR and Western blot techniques. Results: A total of 75 compounds were identified through UPLC-QE-Orbitrap-MS analyses. Network pharmacological analysis shows that it plays an anti-inflammatory role in C-type lectin receptor signaling pathway. After ZXT intervention, the inflammatory factors and apoptosis in cells were significantly reduced. Metabonomics analysis showed that 18 metabolites changed significantly. Four key genes were identified, which exhibited partial compatibility with the findings of network pharmacology. Molecular docking analysis confirmed the substantial affinity of the primary targets for ZXT. Furthermore, ZXT exerted a suppressive effect on neutrophil migration, down-regulated the expression of pro-inflammatory cytokine genes, and inhibited the up-regulation of the Dectin-1/SYK/NF-κB signaling pathway. In vivo cell experiments also yielded consistent experimental outcomes. Conclusion: This study enhances comprehension of the pharmacological mechanism underlying ZXT's efficacy in pneumonia treatment, thereby establishing a scholarly basis for future research and clinical utilization of ZXT in pneumonia management.

Mechanisms and translational applications of regeneration in limbs: From renewable animals to humans.

BACKGROUND: The regenerative capacity of organisms declines throughout evolution, and mammals lack the ability to regenerate limbs after injury. Past approaches to achieving successful restoration through pharmacological intervention, tissue engineering, and cell therapies have faced significant challenges. OBJECTIVES: This review aims to provide an overview of the current understanding of the mechanisms behind animal limb regeneration and the successful translation of these mechanisms for human tissue regeneration. RESULTS: Particular attention was paid to the Mexican axolotl (Ambystoma mexicanum), the only adult tetrapod capable of limb regeneration. We will explore fundamental questions surrounding limb regeneration, such as how amputation initiates regeneration, how the limb knows when to stop and which parts to regenerate, and how these findings can apply to mammalian systems. CONCLUSIONS: Given the urgent need for regenerative therapies to treat conditions like diabetic foot ulcers and trauma survivors, this review provides valuable insights and ideas for researchers, clinicians, and biomedical engineers seeking to facilitate the regeneration process or elicit full regeneration from partial regeneration events.

Nonlinear Conductivity and Thermal Stability of Anti-Corona Epoxy Resin Nanocomposites.

The long-term operation of motors induces substantial alterations in the surface conductivity and nonlinear coefficient of anti-corona paint, diminishing its efficacy and jeopardizing the longevity of large motors. Hence, the development of high-performance anti-corona paint holds paramount importance in ensuring motor safety. In this study, we integrate two nano-fillers, namely silicon carbide (SiC) and organic montmorillonite (O-MMT), into a composite matrix comprising micron silicon carbide and epoxy resin (SiC/EP). Subsequently, three distinct types of anti-corona paint are formulated: SiC/EP, Nano-SiC/EP, and O-MMT/SiC/EP. Remarkably, O-MMT/SiC/EP exhibits a glass transition temperature about 25 °C higher than that of SiC/EP, underscoring its superior thermal properties. Moreover, the introduction of nano-fillers markedly augments the surface conductivity of the anti-corona paint. Aging tests, conducted across varying temperatures, unveil a notable reduction in the fluctuation range of surface conductivity post-aging. Initially, the nonlinear coefficients exhibit a declining trend, succeeded by an ascending trajectory. The O-MMT/SiC/EP composite displays a maximum nonlinearity coefficient of 1.465 and a minimum of 1.382. Furthermore, the incorporation of nanofillers amplifies the dielectric thermal stability of epoxy resin composites, with O-MMT/SiC/EP showcasing the pinnacle of thermal endurance. Overall, our findings elucidate the efficacy of nano-fillers in enhancing the performance and longevity of anti-corona paint, particularly highlighting the exceptional attributes of the O-MMT/SiC/EP composite in bolstering motor safety through improved thermal stability and electrical properties.

Osteoinductive micro-nano guided bone regeneration membrane for in situ bone defect repair.

BACKGROUND: Biomaterials used in bone tissue engineering must fulfill the requirements of osteoconduction, osteoinduction, and osseointegration. However, biomaterials with good osteoconductive properties face several challenges, including inadequate vascularization, limited osteoinduction and barrier ability, as well as the potential to trigger immune and inflammatory responses. Therefore, there is an urgent need to develop guided bone regeneration membranes as a crucial component of tissue engineering strategies for repairing bone defects. METHODS: The mZIF-8/PLA membrane was prepared using electrospinning technology and simulated body fluid external mineralization method. Its ability to induce biomimetic mineralization was evaluated through TEM, EDS, XRD, FT-IR, zeta potential, and wettability techniques. The biocompatibility, osteoinduction properties, and osteo-immunomodulatory effects of the mZIF-8/PLA membrane were comprehensively evaluated by examining cell behaviors of surface-seeded BMSCs and macrophages, as well as the regulation of cellular genes and protein levels using PCR and WB. In vivo, the mZIF-8/PLA membrane's potential to promote bone regeneration and angiogenesis was assessed through Micro-CT and immunohistochemical staining. RESULTS: The mineralized deposition enhances hydrophilicity and cell compatibility of mZIF-8/PLA membrane. mZIF-8/PLA membrane promotes up-regulation of osteogenesis and angiogenesis related factors in BMSCs. Moreover, it induces the polarization of macrophages towards the M2 phenotype and modulates the local immune microenvironment. After 4-weeks of implantation, the mZIF-8/PLA membrane successfully bridges critical bone defects and almost completely repairs the defect area after 12-weeks, while significantly improving the strength and vascularization of new bone. CONCLUSIONS: The mZIF-8/PLA membrane with dual osteoconductive and immunomodulatory abilities could pave new research paths for bone tissue engineering.

Salvianolic acid B protects against UVB-induced skin aging via activation of NRF2.

BACKGROUND: Prolonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored. METHODS: We conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting. RESULTS: Sal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts. CONCLUSION: In this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway.

Topical Application of TT-10 Ameliorates Impaired Wound Healing.

BACKGROUND: In recent decades, chronic wounds have become an increasingly significant clinical concern due to their increasing morbidity and socioeconomic toll. However, there is currently no product available on the market that specifically targets this intricate process. One clear indicator of delayed wound repair is the inhibition of re-epithelialization. Yes-associated protein (YAP), which is a potential focal point for tissue repair and regeneration, has been shown to be prominent in several studies. In this context, we have identified the pharmacological product TT-10, which is a YAP activator, as a potential candidate for the treatment of various forms of chronic wounds. METHODS: The role of TT-10 in regulating YAP activity and subcellular localization was determined by western blotting and immunofluorescence staining. The effect of TT-10 on the biological functions of keratinocytes was assessed by proliferation, wound healing, and apoptosis assays. The impairment of YAP activity in chronic wounds was measured in human and mouse tissues. The in vivo efficacy of TT-10 was examined by gross examination, H&E staining, and measuring wound areas and gaps in normal, diabetic, and ischemic wounds. RESULTS: Our findings suggest that TT-10 facilitates the nuclear transport of YAP, consequently increasing YAP activity, which in turn increases the proliferation and migration of keratinocytes. Moreover, we showed that intracutaneous injection of TT-10 along the wound periphery promoted re-epithelization via YAP activation in the epidermis, culminating in accelerated wound closure in several chronic wound healing models. CONCLUSIONS: Our research highlights the potential of TT-10 to treat chronic wounds, which is a persistent challenge in tissue repair.

Utilizing bioprinting to engineer spatially organized tissues from the bottom-up.

In response to the growing demand for organ substitutes, tissue engineering has evolved significantly. However, it is still challenging to create functional tissues and organs. Tissue engineering from the 'bottom-up' is promising on solving this problem due to its ability to construct tissues with physiological complexity. The workflow of this strategy involves two key steps: the creation of building blocks, and the subsequent assembly. There are many techniques developed for the two pivotal steps. Notably, bioprinting is versatile among these techniques and has been widely used in research. With its high level of automation, bioprinting has great capacity in engineering tissues with precision and holds promise to construct multi-material tissues. In this review, we summarize the techniques applied in fabrication and assembly of building blocks. We elaborate mechanisms and applications of bioprinting, particularly in the 'bottom-up' strategy. We state our perspectives on future trends of bottom-up tissue engineering, hoping to provide useful reference for researchers in this field.

NeuralRecon: Real-Time Coherent 3D Scene Reconstruction from Monocular Video.

We present a novel framework named NeuralRecon for real-time 3D scene reconstruction from a monocular video. Unlike previous methods that estimate single-view depth maps separately on each key-frame and fuse them later, we propose to directly reconstruct local surfaces represented as sparse TSDF volumes for each video fragment sequentially by a neural network. A learning-based TSDF fusion module based on gated recurrent units is used to guide the network to fuse features from previous fragments. This design allows the network to capture local smoothness prior and global shape prior of 3D surfaces when sequentially reconstructing the surfaces, resulting in accurate, coherent, and real-time surface reconstruction. The fused features can also be used to predict semantic labels, allowing our method to reconstruct and segment the 3D scene simultaneously. Furthermore, we purpose an efficient self-supervised fine-tuning scheme that refines scene geometry based on input images through differentiable volume rendering. This fine-tuning scheme improves reconstruction quality on the fine-tuned scenes as well as the generalization to similar test scenes. The experiments on ScanNet, 7-Scenes and Replica datasets show that our system outperforms state-of-the-art methods in terms of both accuracy and speed.

Synergistic large segmental bone repair by 3D printed bionic scaffolds and engineered ADSC nanovesicles: Towards an optimized regenerative microenvironment.

Achieving sufficient bone regeneration in large segmental defects is challenging, with the structure of bone repair scaffolds and their loaded bioactive substances crucial for modulating the local osteogenic microenvironment. This study utilized digital laser processing (DLP)-based 3D printing technology to successfully fabricate high-precision methacryloylated polycaprolactone (PCLMA) bionic bone scaffold structures. Adipose-derived stem cell-engineered nanovesicles (ADSC-ENs) were uniformly and stably modified onto the bionic scaffold surface using a perfusion device, constructing a conducive microenvironment for tissue regeneration and long bone defect repair through the scaffold's structural design and the vesicles' biological functions. Scanning electron microscopy (SEM) examination of the scaffold surface confirmed the efficient loading of ADSC-ENs. The material group loaded with vesicles (PCLMA-BAS-ENs) demonstrated good cell compatibility and osteogenic potential when analyzed for the adhesion and osteogenesis of primary rabbit bone marrow mesenchymal stem cells (BMSCs) on the material surface. Tested in a 15 mm critical rabbit radial defect model, the PCLMA-BAS-ENs scaffold facilitated near-complete bone defect repair after 12 weeks. Immunofluorescence and proteomic results indicated that the PCLMA-BAS-ENs scaffold significantly improved the osteogenic microenvironment at the defect site in vivo, promoted angiogenesis, and enhanced the polarization of macrophages towards M2 phenotype, and facilitated the recruitment of BMSCs. Thus, the PCLMA-BAS-ENs scaffold was proven to significantly promote the repair of large segmental bone defects. Overall, this strategy of combining engineered vesicles with highly biomimetic scaffolds to promote large-segment bone tissue regeneration holds great potential in orthopedic and other regenerative medicine applications.

Evaluating 3D Simulation Accuracy for Breast Augmentation Outcomes: A Volumetric and Surface Contour Analysis in Chinese Patients.

BACKGROUND: The use of three-dimensional imaging in breast augmentation with silicone implants has revolutionized the surgery planning process by providing detailed visualizations of expected post-surgical outcomes. This technology enhances the decision-making process, enabling patients to choose their implants with greater confidence and ultimately leading to higher satisfaction with the postoperative outcome. OBJECTIVE: This study aims to assess the accuracy of 3D imaging simulations using the Canfield Vectra XT 3D system in predicting breast augmentation outcomes in Chinese patients, focusing on volume, surface contour, breast anterior-posterior (AP) Projection, and breast internal angle. METHODS: Our study analyzed female patients who received breast augmentation, documenting their preoperative and three-month postoperative conditions with 3D Vectra XT system images. Exclusions were made for patients undergoing concurrent breast surgeries or those with tuberous or ptotic breasts, due to limitations of the imaging system. Implants used were either round textured or anatomically shaped cohesive silicone gel, inserted subpectorally through trans-axillary or inframammary incisions, based on personalized evaluations. A detailed comparison between preoperative simulations and actual postoperative outcomes was conducted, focusing on volume, surface contour, AP projection, and internal angle variations. Statistical significance was determined through paired T tests, P < 0.05. RESULTS: In the analysis of preoperative simulations for determining postoperative outcomes in breast surgery, our study involving 42 Chinese patients, a total of 84 breasts, was conducted. The results indicated a mean volumetric discrepancy of 21.5 ± 10.3 (SD) cubic centimeters between the simulated and actual postoperative outcomes, achieving an accuracy rate of 91.9%. The root mean square deviation for the breast surface geometry was calculated to be 4.5 ± 1.1 (SD) millimeters (mm), demonstrating a low variance between the predicted and observed outcomes. The investigation found no significant variations across any specific areas of the breast surface, highlighting the uniform accuracy of the simulations across the entire breast. Additionally, the mean differences in Anterior-Posterior (AP) projection and internal angle were determined to be 8.82 ± 5.64 mm and 0.48 ± 1.91 (SD) degrees, respectively. These findings collectively attest to the efficacy of preoperative simulations in accurately predicting the postoperative physical appearance of breasts, thereby providing a valuable tool for surgical planning and improving the consultation process for patients. CONCLUSIONS: The Canfield Vectra XT 3D system has proven to be remarkably accurate in predicting the volumetric outcomes of breast augmentation surgery, with an accuracy rate exceeding 91.9%. It stands as a valuable tool for surgeons and patients alike, enhancing the preoperative planning process by offering a realistic preview of surgical results. This advancement not only facilitates a deeper understanding and setting of realistic expectations for patients but also strengthens the communication between patients and surgeons, ultimately leading to higher satisfaction rates with the surgical outcomes. It also emphasizes the significance of detailed documentation and consent processes in protecting against legal repercussions. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Clay Sculpture-Inspired 3D Printed Microcage Module Using Bioadhesion Assembly for Specific-Shaped Tissue Vascularization and Regeneration.

3D bioprinting techniques have enabled the fabrication of irregular large-sized tissue engineering scaffolds. However, complicated customized designs increase the medical burden. Meanwhile, the integrated printing process hinders the cellular uniform distribution and local angiogenesis. A novel approach is introduced to the construction of sizable tissue engineering grafts by employing hydrogel 3D printing for modular bioadhesion assembly, and a poly (ethylene glycol) diacrylate (PEGDA)-gelatin-dopamine (PGD) hydrogel, photosensitive and adhesive, enabling fine microcage module fabrication via DLP 3D printing is developed. The PGD hydrogel printed micocages are flexible, allowing various shapes and cell/tissue fillings for repairing diverse irregular tissue defects. In vivo experiments demonstrate robust vascularization and superior graft survival in nude mice. This assembly strategy based on scalable 3D printed hydrogel microcage module could simplify the construction of tissue with large volume and complex components, offering promise for diverse large tissue defect repairs.

Integrated cell metabolomics and network pharmacology approach deciphers the anti-testosterone deficiency mechanisms of Bushen Zhuanggu Tang.

Testicular dysfunction is distinguished by a deficiency in testosterone levels, which can be attributed to the occurrence of oxidative stress injury in Leydig cells. The empirical prescription known as Bushen Zhuanggu Tang, developed by a highly experienced traditional Chinese medicine practitioner with six decades of clinical expertize, aligns with the traditional Chinese medicine principle of "kidney governing bone". Researchers have demonstrated that the administration of BSZGT can effectively enhance testosterone production. The objective of this study is to investigate the potential anti-testicular dysfunction effects of BSZGT and elucidate its underlying mechanism in an in vitro setting. Specifically, the impact of oxidative stress induced by H2O2 on the activity and testosterone levels of Leydig cells (TM3) was examined. Furthermore, the utilization of UPLC-QE-Qrbitrap-MS enabled the identification of the involvement of BSZGT in various metabolic pathways, including arginine biosynthesis, amino acyl-tRNA biosynthesis, Alanine, aspartate and glutamine metabolism, and Citrate Cycle, through the modulation of 25 distinct metabolites. Additionally, a network pharmacological analysis was conducted to investigate the pivotal protein targets associated with the therapeutic effects of BSZGT. The findings demonstrate the identification of six key proteins (CYP19A1, CYP1B1, ALOX5, ARG1, XDH, and MPO) that play a significant role in augmenting testicular function through their involvement in the ovarian steroid production pathway. In summary, our study presents a comprehensive research methodology that combines cell metabonomics and network pharmacology to enhance the discovery of new therapeutic agents for TD.

Study of the Mechanism of Astragali Radix in Treating Type 2 Diabetes Mellitus and Its Renal Protection Based on Enzyme Activity, Network Pharmacology, and Experimental Verification.

Astragali Radix (AR) is a common Chinese medicine and food. This article aims to reveal the active role of AR in treating Type 2 diabetes mellitus (T2DM) and its renal protective mechanism. The hypoglycemic active fraction was screened by α-glucosidase and identified by UPLC-QE-Orbitrap-MS spectrometry. The targets and KEGG pathway were determined through the application of network pharmacology methodology. Molecular docking and molecular dynamics simulation technology were used for virtual verification. Subsequently, a mouse model of T2DM was established, and the blood glucose and renal function indexes of the mice after administration were analyzed to further prove the pharmacodynamic effect and mechanism of AR in the treatment of T2DM. HA was determined as the best hypoglycemic active fraction by the α-glucosidase method, with a total of 23 compounds identified. The main active components, such as calycoside-7-O-ß-D-glucoside, methylnisoline, and formononetin, were revealed by network pharmacology. In addition, the core targets and the pathway have also been determined. Molecular docking and molecular dynamics simulation techniques have verified that components and targets can be well combined. In vivo studies have shown that AR can reduce blood sugar levels in model mice, enhance the anti-inflammatory and antioxidant activities of kidney tissue, and alleviate kidney damage in mice. And it also has regulatory effects on proteins such as RAGE, PI3K, and AKT. AR has a good therapeutic effect on T2DM and can repair disease-induced renal injury by regulating the RAGE/PI3K/Akt signaling pathway. This study provides ideas for the development of new drugs or dietary interventions for the treatment of T2DM.

Exploring Asthma Mechanism of Belamcanda Chinensis by "Dose-effect Weighted Coefficient" Network Pharmacology and Experiment Validation.

BACKGROUND: Asthma is a chronic inflammatory disease of the airways that seriously endangers human health. Belamcanda chinensis (BC), a traditional Chinese medicine, has been used to counteract asthma as it has been shown to possess anti-inflammatory and regulatory immunity properties. OBJECTIVE: The study aimed to investigate the mechanisms of action of BC in the treatment of asthma; a "dose-effect weighted coefficient" network pharmacology method was established to predict potential active compounds. METHODS: Information on the components and content of BC was obtained by UPLC-QEOrbitrap- MS spectrometry. Based on BC content, oral bioavailability, and molecular docking binding energy, dose-effect weighting coefficients were constructed. With the degree greater than average as the index, a protein-protein interaction (PPI) database was used to obtain the core key targets for asthma under dose-effect weighting. GO function and KEGG pathway analyses of the core targets were performed using DAVID software. Finally, MTT and ELISA assays were used to assess the effects of active components on 16HBE cell proliferation. RESULTS: The experimental results using the 16HBE model demonstrated BC to have a potential protective effect on asthma. Network pharmacology showed SYK, AKT1, and ALOX5 to be the main key targets, and Fc epsilon RI as the promising signaling pathway. Eight components, such as tectoridin, mangiferin, luteolin, and isovitexin were the main active compounds, Finally, we analyzed the LPS-induced 16HBE proliferation of each active ingredient. Based on the activity verification study, all five predicted components promoted the proliferation of 16HBE cells. These five compounds can be used as potential quality markers for asthma. CONCLUSION: This study provides a virtual and practical method for the simple and rapid screening of active ingredients in natural products.

Mechanism of action of Huangbaichen Sanwei formulation in treating T2DM based on network pharmacology and molecular docking.

Huangbaichen Sanwei formulation (HBCS) has been reported to have a good hypoglycemic effect, but its pharmacological mechanism of action remains unclear. We used network pharmacology and molecular docking to explore the potential mechanism of action of HBCS against type-2 diabetes mellitus (T2DM). Fifty-five active components from HBCS interfered with T2DM. Twenty-five core targets, such as AKT1, INS, INSR, MAPK1 were identified. Enrichment analyses showed that HBCS was involved mainly including insulin receptor signaling pathway, extracellular region, and insulin-like growth factor receptor binding and other biological processes; common targets had roles in treating T2DM by regulating diabetic cardiomyopathy and insulin resistance. Molecular docking verified that components combined with core targets. HBCS play a part in treating T2DM through multiple components and targets at the molecular level, which lays a theoretical foundation for research using HBCS to treat T2DM. The components, predicted targets, and T2DM targets of HBCS were searched through databases, and common targets were determined. Further screening of the core targets was conducted through the establishment of a protein -protein interaction network. The core targets were analyzed by Gene Ontology (GO) annotation utilizing the DAVID platform. And the enrichment of signaling pathways was explored by employing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Cytoscape 3.9.1 was employed to construct a "TCM-components-core target-pathway" network. Autodock Vina was used to dock molecules to compare the binding activity of active molecules with targets.

An ultra-thin and highly efficient electromagnetic interference shielding composite paper with hydrophobic and antibacterial properties.

Facing the increasing electromagnetic interference (EMI) pollution in the living environment, it is a new trend to explore an efficient EMI shielding material with facile fabrication and a wide range of application scenarios. A hydrophobic composite paper composed of silver nanowires (AgNWs) and kapok microfibers cellulose (MFC) was modified by methyl trimethoxy silane (MTMS) through a simple method. As a result, the composite paper has a good EMI shielding effectiveness (EMI SE) of 61.7 dB with electrical conductivity of 695.41 S/cm. The modification of MTMS improved the thermal stability performance of composite paper, which also increased its water contact angle to 113°. The free silver ions (Ag+) released from AgNWs can kill surrounding microbial bacteria, endowing the composite paper with good antibacterial property. Water resistance and antibacterial property enable MTMS/AgNWs/MFC composite paper to cope with complex application environments.

ZIF-8 induced hydroxyapatite-like crystals enabled superior osteogenic ability of MEW printing PCL scaffolds.

ZIF-8 may experience ion-responsive degradation in ionic solutions, which will change its initial architecture and restrict its direct biological use. Herein, we report an abnormal phenomenon in which ZIF-8 induces large hydroxyapatite-like crystals when soaked directly in simulated body fluid. These crystals grew rapidly continuously for two weeks, with the volume increasing by over 10 folds. According to Zn2+ release and novel XRD diffraction peak presence, ZIF-8 particles can probably show gradual collapse and became congregate through re-nucleation and competitive coordination. The phenomenon could be found on ZIF-8/PCL composite surface and printed ZIF-8/PCL scaffold surface. ZIF-8 enhanced PCL roughness through changing the surface topography, while obviously improving the in-vivo and in-vitro osteoinductivity and biocompatibility. The pro-biomineralization property can make ZIF-8 also applicable in polylactic acid-based biomaterials. In summary, this study demonstrates that ZIF-8 may play the role of a bioactive additive enabling the surface modification of synthetic polymers, indicating that it can be applied in in-situ bone regeneration.

Matrix stiffness-induced α-tubulin acetylation is required for skin fibrosis formation through activation of Yes-associated protein.

Skin fibrosis, a pathological process featured by fibroblast activation and extracellular matrix (ECM) deposition, makes a significant contribution to morbidity. Studies have identified biomechanics as the central element in the complex network of fibrogenesis that drives the profibrotic feedback loop. In this study, we found that the acetylation of α-tubulin at lysine 40 (K40) was augmented in fibrotic skin tissues. Further analysis showed that α-tubulin acetylation is required for fibroblast activation, including contraction, migration, and ECM deposition. More importantly, we revealed that biomechanics-induced upregulation of K40 acetylation promotes fibrosis by mediating mechanosensitive Yes-associated protein S127 dephosphorylation and its cytoplasm nucleus shuttle. Furthermore, we demonstrated that the knockdown of α-tubulin acetyltransferase 1 could rescue the K40 acetylation upregulation caused by increased matrix rigidity and ameliorate skin fibrosis both in vivo and in vitro. Herein, we highlight the critical role of α-tubulin acetylation in matrix stiffness-induced skin fibrosis and clarify a possible molecular mechanism. Our research suggests α-tubulin acetylation as a potential target for drug design and therapeutic intervention.

Reconfigurable Magnetic Liquid Building Blocks for Constructing Artificial Spinal Column Tissues.

All-liquid molding can be used to transform a liquid into free-form solid constructs, while maintaining internal fluidity. Traditional biological scaffolds, such as cured pre-gels, are normally processed in solid state, sacrificing flowability and permeability. However, it is essential to maintain the fluidity of the scaffold to truly mimic the complexity and heterogeneity of natural human tissues. Here, this work molds an aqueous biomaterial ink into liquid building blocks with rigid shapes while preserving internal fluidity. The molded ink blocks for bone-like vertebrae and cartilaginous-intervertebral-disc shapes, are magnetically manipulated to assemble into hierarchical structures as a scaffold for subsequent spinal column tissue growth. It is also possible to join separate ink blocks by interfacial coalescence, different from bridging solid blocks by interfacial fixation. Generally, aqueous biomaterial inks are molded into shapes with high fidelity by the interfacial jamming of alginate surfactants. The molded liquid blocks can be reconfigured using induced magnetic dipoles, that dictated the magnetic assembly behavior of liquid blocks. The implanted spinal column tissue exhibits a biocompatibility based on in vitro seeding and in vivo cultivating results, showing potential physiological function such as bending of the spinal column.

A transcriptomics and network pharmacology approach to elucidate the mechanism of action of geniposide on carbon tetrachloride-induced liver injury in rats.

Geniposide, the main active component of Fructus Gardeniae (FG), is known to confer protection against liver diseases. Herein we explored the hepatoprotective effects of geniposide and elucidated its molecular mechanism by transcriptome RNA-seq and network pharmacology. Liver injury was modeled by intraperitoneally injecting CCl4 (0.15% prepared with refined peanut oil) at a dose of 1.5 mL/kg thrice a week; from the second week, rats were administered geniposide (20 mg/kg or 40 mg/kg) by gavage for 6 weeks. Serum and liver samples were then collected to assess liver function indicators and inflammatory factors and to observe pathological changes in the liver. The Illumina HiSeq 4000 platform was used to obtain transcriptome data from the liver tissue of rats after geniposide administration. Core targets and pathways related to the liver protection mechanism of geniposide were further analyzed by integrating transcriptomics and network pharmacology. Differentially expressed genes (DEGs), core targets, and signaling pathways were identified by methods such as q-PCR, molecular docking, and Western blotting. We found that after geniposide administration, the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and inflammatory factors decreased in the model group, and liver injury cells be effectively repaired. RNA-seq data analysis showed that compared to control group, the model group reversed 1,451 DEGs; further, compared to model group, geniposide reversed 511 DEGs. Eight key targets, including PIK3R1, ACOX3, and EGF, were found through further analyses. Geniposide was determined to mainly regulate the PPAR signaling pathway, apoptosis signaling pathway, and MAPK signaling pathway in liver tissues. To summarize, the protective and restorative effects of geniposide on rat liver may seem to be related to its efficacy in inhibiting the activation of inflammatory pathways, thereby reducing cell apoptosis. Our findings should serve as the basis for the development of functional foods or drugs to prevent and treat liver diseases.