Tunable Fast Relaxation in Imine-Based Nanofibrillar Hydrogels Stimulates Cell Response through TRPV4 Activation.

As a key mechanical signal of natural extracellular matrix (ECM), stress relaxation plays an essential role in cell fate decision. However, the biomimetic matrix with fast stress relaxation and its cellular response mechanism have received little attention. Meanwhile, the nanofibrillar architecture which is conductive to mechanical transduction has invariably been ignored in the previous viscoelastic matrix design. Herein, by introducing a dynamic covalent imine bond into a physically cross-linked collagen hydrogel, we prepared bionic fast-relaxing nanofibrillar hydrogels with relaxation time less than 10 s. Through a single control of imine bond content, we realized fine-tuning of the relaxation rate while maintaining a constant initial modulus and fiber density. Using MC3T3-E1 cells as a model, we then proved that the nanofibrillar matrix with fast relaxation mechanics can effectively promote cell spreading and differentiation. In particular, TRPV4 as a molecular sensor of matrix viscoelasticity was demonstrated to regulate cell fate on the nanofibrillar hydrogels by mediating calcium influx. It is expected that the material design principle combining both nanofibrillar structure and tunable fast-relaxation can provide a more broadly adaptable materials platform for simulating natural ECM mechanical cues, and the investigation of the TRPV4 ion channel mediated cellular response will facilitate discovery of more fundamental mechanisms in tissue growth and development.

The systematic review and meta-analysis of X-ray detective rate of Kashin-Beck disease from 1992 to 2016.

BACKGROUND: Kashin-Beck disease (KBD) is a serious human endemic chronic osteochondral disease. However, quantitative syntheses of X-ray detective rate studies for KBD are rare. We performed an initial systematic review and meta-analysis to assess the X-ray detective rate of KBD in China. METHODS: For this systematic review and meta-analysis, we searched five databases (PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), WanFang Data and the China Science and Technology Journal Database (VIP))using a comprehensive search strategy to identify studies of KBD X-ray detective rate in China that were published from database inception to January 13, 2018. The X-ray detective rate of KBD was determined via an analysis of published studies using a random effect meta-analysis with the proportions approach. Subgroup analysis and meta-regression were used to explore heterogeneity, and study quality was assessed using the risk of bias tool. RESULTS: A total of 53 studies involving 14,039 samples with X-ray detective rate in 163,340 observations in total were included in this meta-analysis. These studies were geographically diverse (3 endemic areas). The pooled overall X-ray detective rate for KBD was 11% (95%CI,8-15%;Z = 13.14; p < 0.001). The pooled X-ray detective rate estimates were 11% (95%CI, 6-17%; Z = 7.06; p < 0.001) for northeast endemic areas, 13% (95%CI, 7-20%; Z = 7.45; p < 0.001) for northwest endemic areas, and 8% (95%CI, 5-12%; Z = 7.90; p < 0.001) for southwest endemic areas. There was a significant relationship between the survey year and the X-ray detective rate of KBD. CONCLUSIONS: Our systematic review found that the summary estimate of the X-ray detective rate of KBD was 11% and, that KBD X-ray positive rate ranged from 8.00 to 15.00% depending on the study. Further research is required to identify effective strategies for preventing and treating KBD.

Increased miR-16 expression induced by hepatitis C virus infection promotes liver fibrosis through downregulation of hepatocyte growth factor and Smad7.

Hepatitis C virus (HCV) is involved in the initiation and progression of liver fibrosis by regulating genes encoding host proteins. However, the underlying mechanism of HCV-induced liver fibrosis is still to be determined. Reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed to investigate the effect of HCV infection on the expression of the cellular microRNA miR-16 and its target genes encoding hepatocyte growth factor (HGF) and Smad7 in patients infected with HCV and in a liver cell line, QSG-7701, transfected with Ad-HCV, a recombinant adenovirus construct for expression of the HCV core protein. Regulation of HGF and Smad7 expression by miR-16 was assessed using luciferase reporter construct assays and miR-16 mimic transfection. Interferon-α (IFN-α) was used to verify the alteration of gene expression induced by HCV in QSG-7701 cells. Here, we found that miR-16 levels were increased in patients with HCV infection and were correlated with HGF and Smad7 expression levels in patients with HCV infection. Furthermore, HGF and Smad7 were predicted by bioinformatics analysis to be targets of miR-16. Upregulation of miR-16 and decreased HGF and Smad7 expression were still shown in QSG-7701 cells infected with Ad-HCV. Additionally, interferon-α (IFN-α) could reverse the changes in gene expression induced by HCV infection. These results suggest that the upregulation of miR-16 expression induced by HCV infection is a novel mechanism that contributes to downregulation of HGF and Smad7 in the development of liver fibrosis.

Proteasome inhibitors FHND6091 enhance the ability of NK cells to kill tumor cells through multiple mechanisms.

The immune system has a strong connection to tumors. When a tumor cell is recognized as an abnormal cell by the immune system, the immune system may initiate an immune response to kill the tumor cell. In this study, RNA sequencing was performed on multiple myeloma (MM) cells treated with the proteasome inhibitor FHND6091. The transcriptional changes induced by FHND6091 in RPMI8226 cells aligned notably with immune response activation and results indicated upregulation of cGAS-STING pathway-related genes in the FHND6091-treated group. In vivo and in vitro experiments had demonstrated that FHND6091 stimulated the immunoreaction of MM cells via activation of the cyclic guanosine monophosphate-adenosine synthase/stimulator of interferon genes (cGAS-STING) pathway. This activation resulted in the generation of type-I interferons and the mobilization of natural killer (NK) cells. Notably, FHND6091 upregulated the levels of calreticulin and the protein ligands UL16-binding protein 2/5/6, MHC class I chain-related A (MICA), and MICB on the surface of MM cells. Subsequently, upon engaging with the surface activation receptors of NK cells, these ligands triggered NK cell activation, leading to the subsequent elimination of tumor cells. Thus, our findings elucidated the mechanism whereby FHND6091 exerted its immunotherapeutic activity as a STING agonist, enhancing the killing ability of NK cells against tumor cells.

Molecular characterization of a feruloyl-CoA 6'-hydroxylase involved in coumarin biosynthesis in Clematis terniflora DC.

Coumarin is an important secondary metabolite that affects plant physiology. It is a lactone of cis-o-hydroxycinnamic acid and widely exists in medicinal plants. Clematis terniflora DC. is a plant belonging to Ranunculaceae and is rich in variety of coumarins. Feruloyl-CoA 6'-hydroxylase has been reported as a key enzyme in the formation of coumarin basic skeleton only in some common plants, however, its evidence in other species is still lacking especially for the biosynthesis of coumarins in C. terniflora. In the present study, we identified a feruloyl-CoA 6'-hydroxylase CtF6'H in C. terniflora, and functional characterization indicated that CtF6'H could hydroxylate feruloyl-CoA to 6-hydroxyferuloyl-CoA. Furthermore, the expression level of CtF6'H was differed among different tissues in C. terniflora, while under UV-B radiation, the level of CtF6'H was increased in the leaves. Biochemical characteristics and subcellular location showed that CtF6'H was mainly present in the cytosol. The crystal structure of CtF6'H was simulated by homology modeling to predict the potential residues affecting enzyme activity. This study provides the additional evidence of feruloyl-CoA 6'-hydroxylase in different plant species and enriches our understanding of biosynthetic mechanism of coumarin in C. terniflora.

Integrative Proteomic and Phosphoproteomic Analyses Revealed the Regulatory Mechanism of the Response to Ultraviolet B Stress in Clematis terniflora DC.

Clematis terniflora DC. (C. terniflora) has been used as an ancient Chinese traditional herbal medicine. The active substances in C. terniflora have been confirmed to be effective in treating diseases such as prostatitis. UV light radiation is a common environmental factor that damages plants and influences primary and secondary metabolism. Previous studies showed that ultraviolet B (UV-B) radiation followed by dark stress resulted in the accumulation of secondary metabolites in C. terniflora leaves. An in-depth understanding of how C. terniflora leaves respond to UV-B stress is crucial for improving C. terniflora value. Here, we conducted label-free proteomic and phosphoproteomic analyses to explore the protein changes under UV-B and UV-B combined with dark treatment. A total of 2839 proteins and 1638 phosphorylated proteins were identified. Integrative omics revealed that the photosynthetic system and carbohydrate balance were modulated under both stresses. The phosphoproteomic data indicated that the mitogen-activated protein kinase signaling pathway was triggered, while the abundance of phosphorylated proteins related to osmotic stress was increased under UV-B stress. Differentially abundant phosphoproteins from UV-B followed by dark treatment were mainly enriched in response to stimulus including calcium-mediated proteins. This study provides new insight into the impact of UV-B stress on C. terniflora and plant molecular resistance mechanisms through proteomic and phosphoproteomic analyses.

Integrative Omic Analysis Reveals the Dynamic Change in Phenylpropanoid Metabolism in Morus alba under Different Stress.

Morus alba is used as a traditional Chinese medicine due to its various biological activities. Phenylpropanoid metabolism is one of the most important pathways in Morus alba to produce secondary metabolites and response to stress. From the general phenylpropanoid pathway, there are two metabolic branches in M. alba, including flavonoid and lignin biosynthesis, which also play roles in response to stress. However, the dynamic changes between flavonoid and lignin biosynthesis under Botrytis cinerea infection and UV-B stress in M. alba were unclear. To explore the different regulation mode of flavonoid and lignin biosynthesis in M. alba leaves' response to biotic and abiotic stress, a combined proteomic and metabolomic study of M. alba leaves under UV-B stress and B. cinerea infection was performed. The results showed that most of the proteins involved in the lignin and flavonoid biosynthesis pathway were increased under either UV-B stress or B. cinerea infection in M. alba. This was also confirmed by enzyme assays and metabolomics analysis. Additionally, the abundance of proteins involved in the biosynthesis of jasmonic acid was increased after B. cinerea infection. This suggests that both flavonoid and lignin biosynthesis participate in the responses to abiotic and biotic stress in M. alba, but they might be regulated by different hormone signaling.

Co-delivery of immunochemotherapeutic by classified targeting based on chitosan and cyclodextrin derivatives.

Herein, a cyclodextrin derivative (R6RGD-CMßCD) with tumor target and a carboxymethyl chitosan derivative (M2pep-CMCS) with tumor-associated macrophages 2 (TAM2) target were successfully synthesized, respectively. DOX-loaded nanoparticles (R6RGD-CMßCD@DOX NPs, RCNPDOX) and R848-loaded nanoparticles (M2pep-CMCS@R848 NPs, MCNPR848) were prepared. Furthermore, the RCNPDOX and MCNPR848 exhibited good DOX and R848 absorption. Meanwhile, the synergetic cell toxicity of RCNPDOX and MCNPR848 was found. Additionally, RCNPDOX + MCNPR848 nanoparticles greatly promoted the expression levels of cleaved Caspase3, which indicated that the nanoparticles could induce cell apoptosis. At the same time, the immunohistochemical images exhibited that RCNPDOX + MCNPR848 group could effectively transform the phenotype of tumor-associated macrophages. Importantly, in vivo experiments revealed that RCNPDOX + MCNPR848 NPs exerted excellent anticancer effects in tumor-bearing mice. To summarize, RCNPDOX + MCNPR848 NPs are effective anticancer treatment combining chemotherapy and immunotherapy, M2pep-CMCS and R6RGD-CMßCD are good delivery materials.

A degradable membrane based on lignin-containing cellulose for high-energy lithium-ion batteries.

Traditional polyolefin separator has the defects of non-degradation and poor wettability with the electrolyte. In this paper, we have designed the porous membrane based on the lignin-containing cellulose nanofibers (LCNFs) from the unbleached pulp by a facile method. In the designed membrane, the amorphous lignin can effectively adjust the dispersion of the cellulose to form a uniform mesoporous structure. And the abundant oxygen-containing functional groups both in cellulose and lignin can promote the affinity of the membrane with the electrolyte. Finally, the prepared the LCNF porous membrane shows a high electrolyte uptake of 276 % and high ionic conductivity of 1.86 mS cm-1. As the separator for LIBs, the batteries with high-voltage Li3V2(PO4)3 as cathode (up to 4.8 V), the batteries displayed 183 mAh g-1 with the energy density of 669 Wh kg-1, indicating the good application potential in high-energy LIBs. More importantly, the LCNF membrane made from the unbleached pulp has low cost and it can degraded in soil only after 16 days, which can largely reduce environment pollution of the LIBs. This research provided an efficient and low-cost method to fabricate a membrane with good biodegradability and high electrochemical performance for LIBs.

SWATH-based quantitative proteomic analysis of Morus alba L. leaves after exposure to ultraviolet-B radiation and incubation in the dark.

Morus alba is a woody shrub of the family Moraceae and used as traditional Chinese medicine for a long history. Ultraviolet-B (UV-B) radiation, as a kind of abiotic stress factor, affected the growth and secondary metabolism in M. alba. Previous studies indicated that the contents of several secondary metabolites such as moracin N, chalcomaricin were significantly increased under high level UV-B radiation and dark incubation in M. alba leaves. To reveal the response mechanism under UV-B radiation and dark incubation in M. alba leaves, SWATH-based quantitative proteomic analysis was performed. Totally, 716 proteins were identified and quantified in the control, UVB, and UVD groups. Among them, 123 proteins and 96 proteins were identified as differentially abundant proteins in UVB group and UVD groups, respectively. Proteins related to photosynthesis, amino acid biosynthesis, and tocopherol biosynthesis were significantly altered in UVB group, while proteins related to the biosynthesis of phenolic compounds were significantly altered in UVD group. In addition, the abundances of proteins involved in the ubiquitin-proteasome system (UPS) were significantly increased in both UVB and UVD groups, indicating that UPS combined with secondary mechanism participated in the resistance to UV-B radiation and dark incubation. The obtained results provide novel insight into the effects of high level UV-B radiation on M. alba leaves and on the strategies used for maximizing the chemical constituents and the medicinal value of the M. alba leaves.

A porous carbon based on the surface and structural regulation of wasted lignin for long-cycle lithium-ion battery.

Lignin, as the second most abundant source in nature, is considered as a good precursor for hard carbon. However, direct carbonization of pure lignin leads to low surface area and porosity. Herein we develop a method to prepare lignin-based porous carbon by a self-template method assisted with surface modification. The oxygen-containing functional groups are introduced to regulate the surface chemistry of lignin. And the metal ions are chosen to coordinate with the oxygen-containing group in the lignin, which can form the carbonates to act as the self template to regulate the pores structure. The aromatic skeleton of lignin can also disperse the metal ions to bring uniform pore-forming sites. The results show that the carbonized lignin modified by chloroacetic acid (CCL) shows mesopores with surface area of 233.4384 m2 g-1. As anode for lithium-ion batteries (LIBs), the CCL shows a specific capacity of 500 mAh g-1 at 50 mA g-1. The capacity retention was 99 % after 1000 cycles at 1000 mA g-1, which are superior to most reported carbon anode. This work proposes a low-cost anode for LIBs and put forward a regulation strategy for bio-mass carbon. Besides, it would reduce the discard of lignin and alleviate the pollution.

Mitochondrial proteomic analysis reveals the regulation of energy metabolism and reactive oxygen species production in Clematis terniflora DC. leaves under high-level UV-B radiation followed by dark treatment.

Clematis terniflora DC. is an important medicinal plant from the family Ranunculaceae. A previous study has shown that active ingredients in C. terniflora, such as flavonoids and coumarins, are increased under ultraviolet B radiation (UV-B) and dark treatment and that the numbers of genes related to the tricarboxylic acid cycle and mitochondrial electron transport chain (mETC) are changed. To uncover the mechanism of the response to UV-B radiation and dark treatment in C. terniflora, mitochondrial proteomics was performed. The results showed that proteins related to photorespiration, mitochondrial membrane permeability, the tricarboxylic acid cycle, and the mETC mainly showed differential expression profiles. Moreover, the increase in alternative oxidase indicated that another oxygen-consuming respiratory pathway in plant mitochondria was induced to minimize mitochondrial reactive oxygen species production. These results suggested that respiration and mitochondrial membrane permeability were deeply influenced to avoid energy consumption and maintain energy balance under UV-B radiation and dark treatment in C. terniflora leaf mitochondria. Furthermore, oxidative phosphorylation was able to regulate intracellular oxygen balance to resist oxidative stress. This study improves understanding of the function of mitochondria in response to UV-B radiation and dark treatment in C. terniflora. SIGNIFICANCE: C. terniflora was an important traditional Chinese medicine for anti-inflammatory. Previous study showed that the contents of coumarins which were the main active ingredient in C. terniflora were induced by UV-B radiation and dark treatment. In the present study, to uncover the regulatory mechanism of metabolic changes in C. terniflora, mitochondrial proteomics analysis of leaves was performed. The results showed that photorespiration and oxidative phosphorylation pathways were influenced under UV-B radiation and dark treatment. Mitochondria in C. terniflora leaf played a crucial role in energy mechanism and regulation of cellular oxidation-reduction to maintain cell homeostasis under UV-B radiation followed with dark treatment.

Proteomic and Metabolomic Revealed Differences in the Distribution and Synthesis Mechanism of Aroma Precursors in Yunyan 87 Tobacco Leaf, Stem, and Root at the Seedling Stage.

Tobacco, as an important cash crop and model plant, has been the subject of various types of research. The quality of flue-cured tobacco products depends on the compound collection of tobacco leaves, including pigments, carbohydrates, amino acids, polyphenols, and alkaloid aroma precursors. The present study investigates tobacco seedling organs (leaf, stem, and root) with the assistance of label-free proteomic technology and untargeted metabonomic technology. We analyzed 4992 proteins and 298 metabolites obtained in the leaf, stem, and root groups and found that there were significant differences in both primary and secondary metabolism processes involved in aroma precursor biosynthesis, such as carbohydrate metabolism, energy metabolism, and amino acid biosynthesis, and phenylpropanoid, flavonoid, and alkaloid biosynthesis. The findings showed that the contents of alkaloid metabolites such as nornicotine, anatabine, anatalline, and myosmine were significantly higher in tobacco roots than in leaves and stems at the seedling stage.

Metabolomics and proteomics revealed the synthesis difference of aroma precursors in tobacco leaves at various growth stages.

Tobacco has a high economic value as the largest cash crop worldwide. The quality of flue-cured tobacco is closely related to the overall status of compounds in fresh tobacco leaves, and the aroma precursor plays a key role in the aroma quality of flue-cured tobacco. The untargeted metabolomics and label-free quantitative proteomics analysis of tobacco leaves in three growth stages (root stretching, prosperous growth, and maturation) retrieved 243 metabolites and 4313 proteins (944 differentially expressed proteins), which showed that carbohydrate, amino acid, and fatty acid metabolism varies among the three growth stages. Also, the most of amino acids, organic acids, fatty acids, and polyphenols reduced in the vegetative growth stage, while increased in the reproductive growth stage. On the other hand, alkaloids such as nicotine, nornicotine, and anatabine increased continuously in tobacco leaves during the three growth stages. This study helps us understand the growth and development characteristics of Yun87 flue-cured tobacco in the field before harvest, and it provides a certain omics basis for the industrial crop flue-cured tobacco.

Preclinical Pharmacokinetics, Tissue Distribution and in vitro Metabolism of FHND6091, a Novel Oral Proteasome Inhibitor.

Introduction: FHND6091, a novel N-capped dipeptidyl boronic acid proteasome inhibitor with promising pharmacological properties, entirely converted into active form FHND6081 under physiological conditions. The proteasome, a key component of the ubiquitin-proteasome pathway (UPP), has emerged as a validated target of multiple myeloma (MM) therapeutics. FHND6091 is a selective oral proteasome inhibitor that binds irreversibly to the ß5 submit of the 20S proteasome and exerts anti-cancer roles. Methods: In this study, we investigated the metabolic stability, metabolite production, metabolic pathways and plasma protein binding (PPB) of FHND6081 along with its absorption, tissue distribution, excretion (ADME) and pharmacokinetics (PK) in animals. Results: Ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) identified a total of nine new metabolites after co-incubation with FHND6091 in hepatocytes from different species. A hypothetical CYP450-metabolic pathway including dehydrogenation, N-dealkylation plus mono-oxygenation and other was proposed. In addition, FHND6081 was highly bound to plasma proteins (>99%); nevertheless, it preferred to partition to red blood cells (B/P ratio: 4.91). The results of microsomal metabolic stability corroborated that FHND6081 was a moderate-clearance compound. In Caco-2 cell experiments, the compound displayed modest permeability suggesting that it may show limited bioavailability via oral routes. Furthermore, FHND6081 was extensively distributed in rats and the highest exposure was achieved in the stomach followed by the small intestine and adrenal gland. Pharmacokinetic studies were done by using Sprague-Dawley (SD) rats, oral absorption was fast and plasma exposure was dose-dependent and oral bioavailability were low. At the same dose, FHND6081 exposure was severalfold higher in whole blood than in plasma, which was consistent with blood cell partitioning. Moreover, only a small fraction of the parent compound was excreted via feces and urine and oxidative metabolites were detected in feces and plasma. Conclusion: The overall preclinical pharmacokinetic profile supported the selection and development of FHND6091 as a clinical candidate.

Combined ultraviolet and darkness regulation of medicinal metabolites in Mahonia bealei revealed by proteomics and metabolomics.

Roots of Mahonia bealei have been used as traditional Chinese medicine with antibacterial, antioxidant and anti-inflammatory properties due to its high alkaloid content. Previously, we reported that alkaloid and flavonoid contents in the M. bealei leaves could be increased by the combined ultraviolet B and dark treatment (UV+D). To explore the underlying metabolic pathways and networks, proteomic and metabolomic analyses of the M. bealei leaves were conducted. Proteins related to tricarboxylic acid cycle, transport and signaling varied greatly under the UV + D. Among them, calmodulin involved in calcium signaling and ATP-binding cassette transporter involved in transport of berberine were increased. Significantly changed metabolites were overrepresented in phenylalanine metabolism, nitrogen metabolism, phenylpropanoid, flavonoid and alkaloid biosynthesis. In addition, the levels of salicylic acid and gibberellin decreased in the UV group and increased in the UV + D group. These results indicate that multi-hormone crosstalk may regulate the biosynthesis of flavonoids and alkaloids to alleviate oxidative stress caused by the UV + D treatment. Furthermore, protoberberine alkaloids may be induced through calcium signaling crosstalk with reaction oxygen species and transported to leaves. SIGNIFICANCE: Mahonia bealei root and stem, not leaf, were used as traditional medicine for a long history because of the high contents of active components. In the present study, UV-B combined with dark treatments induced the production of alkaloids and flavonoids in the M. bealei leaf, especially protoberberine alkaloids such as berberine. Multi-omics analyses indicated that multi-hormone crosstalk, enhanced tricarboxylic acid cycle and active calcium signaling were involved. The study informs a strategy for utilization of the leaves, and improves understanding of the functions of secondary metabolites in M. bealei.

Static-Dynamic Profited Viscoelastic Hydrogels for Motor-Clutch-Regulated Neurogenesis.

Viscoelasticity, a time-scale mechanical feature of the native extracellular matrix (ECM), is reported to play crucial roles in plentiful cellular behaviors, whereas its effects on neuronal behavior and the underlying molecular mechanism still remain obscure. Challenges are faced in the biocompatible synthesis of neural ECM-mimicked scaffolds solely controlled with viscoelasticity and due to the lack of suitable models for neurons-viscoelastic matrix interaction. Herein, we report difunctional hyaluronan-collagen hydrogels prepared by a static-dynamic strategy. The hydrogels show aldehyde concentration-dependent viscoelasticity and similar initial elastic modulus, fibrillar morphology, swelling as well as degradability. Utilizing the resulting hydrogels, for the first time, we demonstrate matrix viscoelasticity-dependent neuronal responses, including neurite elongation and expression of neurogenic proteins. Then, a motor-clutch model modified with a tension dissipation component is developed to account for the molecular mechanism for viscoelasticity-sensitive neuronal responses. Moreover, we prove enhanced recovery of rat spinal cord injury by implanting cell-free viscoelastic grafts. As a pioneer finding on neurons-viscoelastic matrix interaction both in vitro and in vivo, this work provides intriguing insights not only into nerve repair but also into neuroscience and tissue engineering.

Magnetoelectric Nanoparticles Incorporated Biomimetic Matrix for Wireless Electrical Stimulation and Nerve Regeneration.

Electrical stimulation is regarded pivotal to promote repair of nerve injuries, however, failed to get extensive application in vivo due to the challenges in noninvasive electrical loading accompanying with construction of biomimetic cell niche. Herein, a new concept of magneto responsive electric 3D matrix for remote and wireless electrical stimulation is demonstrated. By the preparation of magnetoelectric core/shell structured Fe3 O4 @BaTiO3 NPs-loaded hyaluronan/collagen hydrogels, which recapitulate considerable magneto-electricity and vital features of native neural extracellular matrix, the enhancement of neurogenesis both in cellular level and spinal cord injury in vivo with external pulsed magnetic field applied is proved. The findings pave the way for a novel class of remote controlling and delivering electricity through extracellular niches-mimicked hydrogel network, arising prospects not only in neurogenesis but also in human-computer interaction with higher resolution.

Tissue engineered artificial liver model based on viscoelastic hyaluronan-collagen hydrogel and the effect of EGCG intervention on ALD.

In alcoholic liver disease (ALD) research, animal models, as one of the most popular methods to explore pathology and therapeutic drug screening, show the limitations of expensive cost and ethic, as well as long modeling time. To minimize the use of animal models in ALD research, an artificial liver model has been developed by incorporating HepG2 cells into hydrogel matrix based on difunctional hyaluronan and collagen. And on this basis an alcohol-induced ALD model in vitro by adding alcohol in the engineering process has been established. Results showed that the construct exhibited a simulated synthetic and metabolic liver function thanks to the bionic fibrillar and viscoelastic characteristics of hydrogels. And the in vitro alcohol-induced ALD model was also proved to be successfully established, even presenting equal results with ALD mice. Furthermore, epigallocatechin gallate (EGCG) as an intervention on ALD was confirmed in both in vitro and in vivo model. The findings indicate our simple artificial liver model is not only highly predictive but also easy to apply to drug screening and implantation studies, suggesting a promising alternative to animal models. Moreover, as the main active ingredient of tea, EGCG's effective intervention and reversal effect on fatty liver provides support for the theory that green tea could prevent alcoholic fatty liver.

Phosphoproteomics Reveals Regulation of Secondary Metabolites in Mahonia bealei Exposed to Ultraviolet-B Radiation.

Mahonia bealei (M. bealei) is a traditional Chinese medicine containing a high alkaloid content used to treat various diseases. Generally, only dried root and stem are used as medicines, considering that the alkaloid content in M. bealei leaves is lower than in the stems and roots. Some previous research found that alkaloid and flavonoid contents in the M. bealei leaves may increase when exposed to ultraviolet B (UV-B) radiation. However, the underlying mechanism of action is still unclear. In this study, we used titanium dioxide material enrichment and mass-based label-free quantitative proteomics techniques to explore the effect and mechanism of M. bealei leaves when exposed to UV-B treatment. Our data suggest that UV-B radiation increases the ATP content, photosynthetic pigment content, and some enzymatic/nonenzymatic indicators in the leaves of M. bealei. Moreover, phosphoproteomics suggests phosphoproteins related to mitogen-activated protein kinase (MAPK) signal transduction and the plant hormone brassinosteroid signaling pathway as well as phosphoproteins related to photosynthesis, glycolysis, the tricarboxylic acid cycle, and the amino acid synthesis/metabolism pathway are all affected by UV-B radiation. These results suggest that the UV-B radiation activates the oxidative stress response, MAPK signal transduction pathway, and photosynthetic energy metabolism pathway, which may lead to the accumulation of secondary metabolites in M. bealei leaves.