Study on the anti-skin aging effect and mechanism of Sijunzi Tang based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si Jun Zi Tang (SJZT) is a famous traditional Chinese medicine formula composing of 4 herbal medicines (Ginseng Radix et Rhizoma, Atractylodis macrocephalae Rhizoma, Poria, and Glycyrrhizae Radix et Rhizoma) with tonifying spleen and anti-aging effects. It is also known that SJZT can be used to tone, nourish the skin and accelerate wound healing. However, due to the complexity of the formulation, the anti-aging especially anti-skin aging mechanisms as well as the key components of SJZT have not been fully investigated. Therefore, further in vitro and in vivo experimental studies are particularly needed to investigate the anti-skin ageing efficacy of SJZT. AIM OF THE STUDY: The purpose of this article was to explore the therapeutic effect and possible pharmacological mechanism of SJZT in the treatment of skin aging by topical application using network pharmacology and to validate the findings using in vitro and in vivo tests. MATERIALS AND METHODS: Network pharmacology method was applied to predict the underlying biological function and mechanism involved in the anti-skin aging effect of SJZT. Molecular docking was used to preliminarily predict the active components of SJZT-Skin Aging. UPLC QTOF MS/MS was carried out to analyze the chemical compounds. Finally, to confirm the anti-skin aging effort of SJZT, a mouse skin-aging model and UVB-induced EpiSCs (epidermal stem cells) senescence model were established. RESULTS: PPI network analysis and KEGG studies indicated that TP53, CDKN2A, TNF, IL6, and IL1B might be parts of the core targets associated with EpiSCs senescence. Furthermore, molecular docking suggested the top active components, glycyrrhizin, ginsenoside Rg5, ginsenoside Rh2, liquiritin, polyporenic acid C and atractylenolide II showed strong affinity to the key proteins involved in cellular senescence signaling. UPLC QTOF MS/MS analysis of SJZT confirmed the presence of these key components. In-vivo experiments revealed that SJZT could improve UVB-induced skin thickening, increase the number of collagen fibers, strengthen the structure of elastin fibers, and decrease the expression of MDA, as well as increase the expression of CAT and T-SOD in the skin tissue of mouse. And, in-vitro experiments indicated that SJZT could reduce ROS generation and oxidative stress, increase mitochondrial membrane potential, and upregulate the expression of stem cell markers. Moreover, SJZT could suppress the expression of p53, p-p53 and p21, downregulated p38 phosphorylation. Furthermore, the anti-cellular senescence effect of SJZT on EpiSCs disappeared after treatment with the p38 inhibitor adesmapimod. Taken all together, the regulation of senescence signaling in EpiSCs is an important mechanism of SJZT in combating skin aging. CONCLUSION: The research results indicate that SJZT has anti-skin aging effects on UVB-induced skin-aging model, possibly by mediating p38/p53 signaling pathway. These findings strongly demonstrate the great potential of SJZT as an active composite for anti-skin aging and cosmeceutical applications.

Photothermal-responsive lignin-based polyurethane with mechanically robust, fast self-healing, solid-state plasticity and shape-memory performance.

In light of the depletion of petrochemical resources and increase in environmental pollution, there has been a significant focus on utilizing natural biomass, specifically lignin, to develop sustainable and functional materials. This research presents the development of a lignin-based polyurethane (DLPU) with photothermal-responsiveness by incorporating lignin and oxime-carbamate bonds into polyurethane network. The abundant hydrogen bonds between lignin and the polyurethane matrix, along with its cross-linked structure, contribute to DLPU's excellent mechanical strength (30.2 MPa) and toughness (118.7 MJ·m-3). Moreover, the excellent photothermal conversion ability of DLPU (54.4 %) activates dynamic reversible behavior of oxime-carbamate bonds and hydrogen bonds, thereby endowing DLPU with exceptional self-healing performance. After 15 min of near-infrared irradiation, DLPU achieves self-healing efficiencies of 96.0 % for tensile strength and 96.3 % for elongation at break. Additionally, DLPU exhibits photocontrolled solid-state plasticity as well as an excellent phototriggered shape-memory effect (70 s), with shape fixity and recovery ratios reaching 98.8 % and 95.3 %, respectively. By exploiting the spatial controllability and photothermal-responsiveness of DLPU, we demonstrate multi-dimensional responsive materials with self-healing and shape-shifting properties. This work not only promotes the development of multi-functional polyurethanes but also provides a pathway for the high-value utilization of lignin.

Legumain-deficient macrophages regulate inflammation and lipid metabolism in adipose tissues to protect against diet-induced obesity.

Adipose tissue macrophages (ATMs) are key players in the development of obesity and associated metabolic inflammation, which contributes to systemic metabolic dysfunction, and understanding the interaction between macrophages and adipocytes is crucial for developing novel macrophage-based strategies against obesity. Here, we found that Legumain (Lgmn), a well-known lysosomal cysteine protease, is expressed mainly in the ATMs of obese mice. To further define the potential role of Lgmn-expressing macrophages in the generation of an aberrant metabolic state, LgmnF/F; LysMCre mice, which do not express Lgmn in macrophages, were maintained on a high-fat diet (HFD), and metabolic parameters were assessed. Macrophage-specific Lgmn deficiency protects mice against HFD-induced obesity, diminishes the quantity of proinflammatory macrophages in obese adipose tissues, and alleviates hepatic steatosis and insulin resistance. By analysing the transcriptome and proteome of murine visceral white adipose tissue (vWAT) after HFD feeding, we determined that macrophage Lgmn deficiency causes changes in lipid metabolism and the inflammatory response. Furthermore, the reciprocity of macrophage-derived Lgmn with integrin α5ß1 in adipocytes was tested via colocalization analyses. It is further demonstrated in macrophage and adipocyte coculture system that macrophage derived Lgmn bound to integrin α5ß1 in adipocytes, therefore attenuating PKA activation, downregulating lipolysis-related proteins and eventually exacerbating obesity development. Overall, our study identified Lgmn as a previously unrecognized regulator involved in the interaction between ATMs and adipocytes contributing to diet-induced obesity and suggested that Lgmn is a potential target for treating metabolic disorders.

Inhalation of hydrogen-rich gas before acute exercise alleviates exercise fatigue.

Hydrogen, as an antioxidant, may have the potential to mitigate fatigue and improve selected oxidative stress markers induced by strenuous exercise. This study focused on previously unexplored approach of pre-exercise inhalation of hydrogen-rich gas (HRG). Twenty-four healthy adult men first completed prelaboratories to determine maximum cycling power (Wmax) and maximum cycling time (Tmax). Then they were subjected to ride Tmax at 80% Wmax on cycle ergometers after inhaled HRG or placebo gas (air) for 60-minute in a double-blind, counterbalanced, randomized, and crossover design. The cycling frequency in the fatigue modelling process and the rating of perceived exertion (RPE) at the beginning and end of the ride were recorded. Before gas inhalation and after fatigue modeling, visual analog scale (VAS) for fatigue and counter-movement jump (CMJ) were tested, and blood samples were obtained. The results showed that compared to placebo, HRG inhalation induced significant improvement in VAS, RPE, the cycling frequency in the last 30 seconds, the ability to inhibit hydroxyl radicals, and serum lactate after exercise (p < 0.028), but not in CMJ height and glutathione peroxidase activit. In conclusions, HRG inhalation prior to acute exercise can alleviate exercise-induced fatigue, maintain functional performance, and improve hydroxyl radical and lactate levels.

Transcriptional Expression of Histone Acetyltransferases and Deacetylases During the Recovery of Acute Exercise in Mouse Hippocampus.

Protein acetylation, which is dynamically maintained by histone acetyltransferases (HATs) and deacetylases (HDACs), might play essential roles in hippocampal exercise physiology. However, whether HATs/HDACs are imbalanced during the recovery phase following acute exercise has not been determined. Groups of exercised mice with different recovery periods after acute exercise (0 h, 0.5 h, 1 h, 4 h, 7 h, and 24 h) were constructed, and a group of sham-exercised mice was used as the control. The mRNA levels of HATs and HDACs were detected via real-time quantitative polymerase chain reaction. Lysine acetylation on the total proteins and some specific locations on histones were detected via western blotting, as were various acylation modifications on the total proteins. Except for four unaffected genes (Hdac4, Ncoa1, Ncoa2, and Sirt1), the mRNA expression trajectories of 21 other HATs or HDACs affected by exercise could be categorized into three clusters. The genes in Cluster 1 increased quickly following exercise, with a peak at 0.5 h and/or 1 h, and remained at high levels until 24 h. Cluster 2 genes presented a gradual increase with a delayed peak at 4 h or 7 h postexercise before returning to baseline. The expression of Cluster 3 genes decreased at 0.5 h and/or 1 h, with some returning to overexpression (Hdac1 and Sirt3). Although most HATs were upregulated and half of the affected HDACs were downregulated at 0.5 h postexercise, the global or residue-specific histone acetylation levels were unchanged. In contrast, the levels of several metabolism-related acylation products of total proteins, including acetylation, succinylation, 2-hydroxyisobutyryllysine, ß-hydroxybutyryllysine, and lactylation, decreased and mainly occurred on nonhistones immediately after exercise. During the 24-h recovery phase after acute exercise, the transcriptional trajectory of HATs or the same class of HDACs in the hippocampus exhibited heterogeneity. Although acute exercise did not affect the selected sites on histone lysine residues, it possibly incurred changes in acetylation and other acylation on nonhistone proteins.

Regulation by distinct MYB transcription factors defines the roles of OsCYP86A9 in anther development and root suberin deposition.

Cytochrome P450 proteins (CYPs) play critical roles in plant development and adaptation to fluctuating environments. Previous reports have shown that CYP86A proteins are involved in the biosynthesis of suberin and cutin in Arabidopsis. However, the functions of these proteins in rice remain obscure. In this study, a rice mutant with incomplete male sterility was identified. Cytological analyses revealed that this mutant was defective in anther development. Cloning of the mutant gene indicated that the responsible mutation was on OsCYP86A9. OsMYB80 is a core transcription factor in the regulation of rice anther development. The expression of OsCYP86A9 was abolished in the anther of osmyb80 mutant. In vivo and in vitro experiments showed that OsMYB80 binds to the MYB-binding motifs in OsCYP86A9 promoter region and regulates its expression. Furthermore, the oscyp86a9 mutant exhibited an impaired suberin deposition in the root, and was more susceptible to drought stress. Interestingly, genetic and biochemical analyses revealed that OsCYP86A9 expression was regulated in the root by certain MYB transcription factors other than OsMYB80. Moreover, mutations in the MYB genes that regulate OsCYP86A9 expression in the root did not impair the male fertility of the plant. Taken together, these findings revealed the critical roles of OsCYP86A9 in plant development and proposed that OsCYP86A9 functions in anther development and root suberin formation via two distinct tissue-specific regulatory pathways.

Inorganic Halide Perovskite Nanowires/Conjugated Polymer Heterojunction-Based Optoelectronic Synaptic Transistors for Dynamic Machine Vision.

Inspired by the retina, artificial optoelectronic synapses have groundbreaking potential for machine vision. The field-effect transistor is a crucial platform for optoelectronic synapses that is highly sensitive to external stimuli and can modulate conductivity. On the basis of the decent optical absorption, perovskite materials have been widely employed for constructing optoelectronic synaptic transistors. However, the reported optoelectronic synaptic transistors focus on the static processing of independent stimuli at different moments, while the natural visual information consists of temporal signals. Here, we report CsPbBrI2 nanowire-based optoelectronic synaptic transistors to study the dynamic responses of artificial synaptic transistors to time-varying visual information for the first time. Moreover, on the basis of the dynamic synaptic behavior, a hardware system with an accuracy of 85% is built to the trajectory of moving objects. This work offers a new way to develop artificial optoelectronic synapses for the construction of dynamic machine vision systems.

Construction of a Female Sterility Maintaining System Based on a Novel Mutation of the MEL2 Gene.

BACKGROUND: Hybrid rice has significant yield advantage and stress tolerance compared with inbred rice. However, production of hybrid rice seeds requires extensive manual labors. Currently, hybrid rice seeds are produced by crosspollination of male sterile lines by fertile paternal lines. Because seeds from paternal lines can contaminate the hybrid seeds, mechanized production by mixed-seeding and mixed-harvesting is difficult. This problem can be solved if the paternal line is female sterile. RESULTS: Here we identified a female infertile mutant named h569 carrying a novel mutation (A1106G) in the MEL2 gene that was previously reported to regulate meiosis entry both in male and female organs. h569 mutant is female infertile but male normal, suggesting that MEL2 regulates meiosis entry in male and female organs through distinct pathways. The MEL2 gene and h569 mutant gave us tools to construct female sterility maintaining systems that can be used for propagation of female sterile lines. We connected the wild-type MEL2 gene with pollen-killer gene ZmAA1 and seed-marker gene DsRed2 in one T-DNA cassette and transformed it into ZZH1607, a widely used restorer line. Transgenic line carrying a single transgene inserted in an intergenic region was selected to cross with h569 mutant. F2 progeny carrying homozygous A1106G mutation and hemizygous transgene displayed 1:1 segregation of fertile and infertile pollen grains and 1:1 segregation of fluorescent and non-fluorescent seeds upon self-fertilization. All of the non-fluorescent seeds generated female infertile plants, while the fluorescent seeds generated fertile plants that reproduced in the way as their previous generation. CONCLUSIONS: These results indicated that the female sterility maintaining system constructed in the study can be used to breed and propagate paternal lines that are female infertile. The application of this system will enable mechanized production of hybrid rice seed by using the mixed-seeding and mixed harvesting approach, which will significantly reduce the cost in hybrid rice seed production.

Aberrant accumulation of ceramides in mitochondria triggers cell death by inducing autophagy in Arabidopsis.

Sphingolipids are membrane lipids and play critical roles in signal transduction. Ceramides are central components of sphingolipid metabolism that are involved in cell death. However, the mechanism of ceramides regulating cell death in plants remains unclear. Here, we found that ceramides accumulated in mitochondria of accelerated cell death 5 mutant (acd5), and expression of mitochondrion-localized ceramide kinase (ACD5) suppressed mitochondrial ceramide accumulation and the acd5 cell death phenotype. Using immuno-electron microscopy, we observed hyperaccumulation of ceramides in acer acd5 double mutants, which are characterized by mutations in both ACER (alkaline ceramidase) and ACD5 genes. The results confirmed that plants with specific ceramide accumulation exhibited localization of ceramides to mitochondria, resulting in an increase in mitochondrial reactive oxygen species production. Interestingly, when compared with the wild type, autophagy-deficient mutants showed stronger resistance to ceramide-induced cell death. Lipid profiling analysis demonstrated that plants with ceramide accumulation exhibited a significant increase in phosphatidylethanolamine levels. Furthermore, exogenous ceramide treatment or endogenous ceramide accumulation induces autophagy. When exposed to exogenous ceramides, an increase in the level of the autophagy-specific ubiquitin-like protein, ATG8e, associated with mitochondria, where it directly bound to ceramides. Taken together, we propose that the accumulation of ceramides in mitochondria can induce cell death by regulating autophagy.

Construction of a dual-component hydrogel matrix for 3D biomimetic skin based on photo-crosslinked chondroitin sulfate/collagen.

The main challenge in the field of 3D biomimetic skin is to search for a suitable hydrogel matrix with good biocompatibility, appropriate mechanical property and inner porosity that can support the adhesion and proliferation of skin cells. In this study, photocurable chondroitin sulfate methacrylate (CSMA) and collagen methacrylate (CoLMA) synthesized from chondroitin sulfate (CS) and type I collagen I (CoL) in the dermal matrix were used to construct a photo-crosslinked dual-component CSMA-CoLMA hydrogel matrix. Due to the toughening effect of the dual-component, the CSMA-CoLMA hydrogel improved the intrinsic brittleness of the single-component CSMA hydrogel, presented good mechanical tunability. The average storage and elasticity modulus could reach 3.3 KPa and 30.3 KPa, respectively, which were close to those of natural skin. The CSMA-CoLMA hydrogel with a ratio of 8/6 showed suitable porous structure and good biocompatibility, supporting the adhesion and proliferation of skin cells. Furthermore, the expression of characteristic marker proteins was detected in the epidermal and dermal bi-layered models constructed with the hydrogel containing keratinocytes and fibroblasts. These results suggest that the dual-component CSMA-CoLMA hydrogel has promising potential as a matrix to construct 3D biomimetic skin.

The lncRNA MEG3/miRNA-21/P38MAPK axis inhibits coxsackievirus 3 replication in acute viral myocarditis.

Evidence is emerging on the roles of long noncoding RNAs (lncRNAs) as regulatory factors in a variety of viral infection processes, but the mechanisms underlying their functions in coxsackievirus group B type3 (CVB3)-induced acute viral myocarditis have not been explicitly delineated. We previously demonstrated that CVB3 infection decreases miRNA-21 expression; however, lncRNAs that regulate the miRNA-21-dependent CVB3 disease process have yet to be identified. To evaluate lncRNAs upstream of miRNA-21, differentially expressed lncRNAs in CVB3-infected mouse hearts were identified by microarray analysis and lncRNA/miRNA-21 interactions were predicted bioinformatically. MEG3 was identified as a candidate miRNA-21-interacting lncRNA upregulated in CVB3-infected mouse hearts. MEG3 expression was verified to be upregulated in HeLa cells 48 h post CVB3 infection and to act as a competitive endogenous RNA of miRNA-21. MEG3 knockdown resulted in the upregulation of miRNA-21, which inhibited CVB3 replication by attenuating P38-MAPK signaling in vitro and in vivo. Knockdown of MEG3 expression before CVB3 infection inhibited viral replication in mouse hearts and alleviated cardiac injury, which improved survival. Furthermore, the knockdown of CREB5, which was predicted bioinformatically to function upstream of MEG3, was demonstrated to decrease MEG3 expression and CVB3 viral replication. This study identifies the function of the lncRNA MEG3/miRNA-21/P38 MAPK axis in the process of CVB3 replication, for which CREB5 could serve as an upstream modulator.

Establishment and Advances of Third-Generation Hybrid Rice Technology: A Review.

Rice (Oryza sativa L.) is one of the most important food crops worldwide. The utilisation of heterosis (hybrid vigour) has played a significant role in increasing rice yield and ensuring food supply. Over the past 50 years, the first-generation three-line system based on cytoplasmic male sterility, and the second-generation two-line system based on environment-sensitive genic male sterility (EGMS), have been widely applied in hybrid rice production. However, the three-line system is restricted by the matching relationship among the three parental lines and allows only ~ 2-5% of germplasms to be explored for elite combinations. The environmental sensitivity of EGMS lines has posed serious risks to the production of hybrid seeds. These factors have hindered the development and applications of hybrid rice. Third-generation hybrid rice technology (TGHRT) is based on environment-insensitive genic male sterility, which can effectively overcome the intrinsic problems of the three-line and two-line systems. Since the establishment of TGHRT, numerous findings and innovations have been reported. This paper gives a brief review of traditional hybrid rice technologies and discusses the establishment of TGHRT, technical innovations in TGHRT, and future research that is necessary to promote the wide application of TGHRT in rice production.

The ribosomal protein P0A is required for embryo development in rice.

BACKGROUND: The P-stalk is a conserved and vital structural element of ribosome. The eukaryotic P-stalk exists as a P0-(P1-P2)2 pentameric complex, in which P0 function as a base structure for incorporating the stalk onto 60S pre-ribosome. Prior studies have suggested that P0 genes are indispensable for survival in yeast and animals. However, the functions of P0 genes in plants remain elusive. RESULTS: In the present study, we show that rice has three P0 genes predicted to encode highly conserved proteins OsP0A, OsP0B and OsP0C. All of these P0 proteins were localized both in cytoplasm and nucleus, and all interacted with OsP1. Intriguingly, the transcripts of OsP0A presented more than 90% of the total P0 transcripts. Moreover, knockout of OsP0A led to embryo lethality, while single or double knockout of OsP0B and OsP0C did not show any visible defects in rice. The genomic DNA of OsP0A could well complement the lethal phenotypes of osp0a mutant. Finally, sequence and syntenic analyses revealed that OsP0C evolved from OsP0A, and that duplication of genomic fragment harboring OsP0C further gave birth to OsP0B, and both of these duplication events might happen prior to the differentiation of indica and japonica subspecies in rice ancestor. CONCLUSION: These data suggested that OsP0A functions as the predominant P0 gene, playing an essential role in embryo development in rice. Our findings highlighted the importance of P0 genes in plant development.

Identification of novel circulating miRNAs biomarkers for healthy obese and lean children.

BACKGROUND: The prevalence of childhood obesity and overweight has risen globally, leading to increased rates of metabolic disorders. Various factors, including genetic, epigenetic, and environmental influences such as diet and physical activity, contribute to pediatric obesity. This study aimed to identify specific circulating miRNAs as potential biomarkers for assessing obesity in children. METHODS: Thirty children, including 15 obese and 15 extremely thin individuals, were selected for this study. MiRNA expression in circulating plasma was assessed using miRNA microarrays. The reliability of differential miRNA expression was confirmed using TaqMan qPCR. The correlation between miRNAs and obesity was analyzed through multiple linear regression, receiver operator characteristic (ROC) curve analysis, and odds ratio (OR) calculations. Bioinformatics tools were utilized to identify target genes for the selected miRNAs, and a functional network map was constructed. RESULTS: A total of 36 differentially expressed miRNAs were identified through gene chip analysis, and TaqMan qPCR validation confirmed the upregulation of seven miRNAs: hsa-miR-126-3p, hsa-miR-15b-5p, hsa-miR-199a-3p, hsa-miR-20a-5p, hsa-miR-223-3p, hsa-miR-23a-3p, and hsa-miR-24-3p. Among these, hsa-miR-15b-5p and hsa-miR-223-3p exhibited a statistically significant difference except for hsa-miR-23a-3p. These two miRNAs showed more predicted target genes related to obesity than others. Multiple linear regression analysis revealed an association between obesity and hsa-miR-15b-5p and hsa-miR-223-3p [10.529 (4.974-16.084), -10.225 (-17.852~ -2.657)]. Even after adjusting for age and sex, these two miRNAs remained associated with obesity [8.936 (3.572-14.301), -8.449(-15.634~ -1.303)]. The area under the ROC curve (AUC) reached values of 0.816, 0.711, and 0.929, respectively. Odds ratio analysis demonstrated a significant correlation between obesity and hsa-miR-15b-5p (OR = 143, 95% CI 5.80 to 56,313, p = 0.024) and between obesity and hsa-miR-223-3p (OR = 0.01, 95% CI 0.00 to 0.23, p = 0.037). Importantly, hsa-miR-15b-5p was found to have numerous target genes associated with the FoxO, insulin, Ras, and AMPK signaling pathways. CONCLUSIONS: Differential miRNA expression profiles in the circulation of obese children compared to controls suggest underlying metabolic abnormalities. Hsa-miR-15b-5p and hsa-miR-223-3p may be considered as molecular markers for the screening of obese children and populations at risk of developing metabolic syndrome.

Reallocation of time between preschoolers' 24-h movement behaviours and executive functions: A compositional data analysis.

The objectives of the survey were to explored the associations of the 24-h movement behaviours (MB) with executive functions (EFs) and quantified the predicted changes in EFs following allocation of time among behaviours. In the cross-sectional survey, 135 preschoolers (3 ~ 5 years) were enrolled. Physical activity (PA) and sedentary (SED) time were objectively measured employing an ActiGraph GT9X. Sleep time was reported by parents. EFs were assessed using the iPad-based Early Years Toolbox which is a collection of computerized tasks consisting of brief tasks assessed from games administered and scored according to protocol. To explore the associations of the 24-h MB with EFs, compositional multiple linear regression was employed. To quantify the predicted changes in EFs following allocation of time among behaviours, compositional isotemporal substitution was used. Moderate-to-vigorous physical activity (MVPA) was positively related to cognitive flexibility. Replacing sleep or SED with MVPA was associated with positive changes in cognitive flexibility. When MVPA was replaced with sleep or SED, the predicted detriments to cognitive flexibility were larger than predicted benefits of replacing sleep or SED with MVPA. The findings highlight the key role of intensity of PA for preschoolers' EFs and the importance of meeting recommended levels of MVPA.

Role and mechanism of FLT4 in high-fat diet-induced obesity in mice.

The FLT4 gene plays an important role in the onset and progression of obesity and is involved in the structure and function of lymphatic vessels. By inducing a mouse obesity model with a high-fat diet and knocking out the FLT4 gene, which is associated with lymphatic vessel growth in mice, FLT4+/- mice were found to be susceptible to high-fat diet-induced obesity, with significant accumulation of visceral fat. BODIPY™ FL C16 imaging revealed dilated and branched mesenteric lymphatic vessels in FLT4+/- mice. Immunofluorescence staining showed that FLT4+/- exacerbated the morphological abnormalities of lymphatic vessels and submucosal lymphatic vessels in visceral adipose tissue of obese mice, accompanied by macrophage infiltration around lymphatic vessels. In addition, FLT4 knock down increased the proportion of M1-type macrophages in the adipose tissue of the epididymis, indicating significant chronic inflammation in FLT4+/- obese mice. These findings provide new evidence for the involvement of lymphatic vessel morphological abnormalities in the onset and progression of obesity and highlight the importance of further investigation of FLT4 to better understand the mechanism of HFD-induced obesity and to develop related treatments.

Construction and mechanism study of lignin-based polyurethane with high strength and high self-healing properties.

Lignin is a natural polymer with abundant functional groups with great application prospects in lignin-based polyurethane elastomers with self-healing abilities. In this study, a lignin self-healing polyurethane (PUDA-L) was specially designed using lignin as the raw material of polyurethane, combining lignin with Diels-Alder (DA) bond and hydrogen bonds. The experimental results showed that PUDA-L was prepared with good thermal stability, fatigue resistance, shape memory effect, excellent mechanical strength, and self-healing ability by partially replacing the crosslinking agents with bio-based lignin and hydroxylated modified lignin to increase the hydroxyl content. Polyurethane has a tensile strength of up to 29 MPa and an elongation at break of up to 500 %. The excellent self-healing ability of PUDA-L originates from the internal DA bonds and cross-linked hydrogen bonds. After the dumbbell sample was fused and heated at 130 °C for 4 h, the elastomer could be completely healed, the tensile strength was restored to 29 MPa, and the self-healing efficiency was up to 100 %. The developed PUDA-L elastomer has promising applications in sensors and smart skins.

Multi-omics analysis explores the effect of chronic exercise on liver metabolic reprogramming in mice.

Background: The effect of exercise on human metabolism is obvious. However, the effect of chronic exercise on liver metabolism in mice is less well described. Methods: The healthy adult mice running for 6 weeks as exercise model and sedentary mice as control were used to perform transcriptomic, proteomic, acetyl-proteomics, and metabolomics analysis. In addition, correlation analysis between transcriptome and proteome, and proteome and metabolome was conducted as well. Results: In total, 88 mRNAs and 25 proteins were differentially regulated by chronic exercise. In particular, two proteins (Cyp4a10 and Cyp4a14) showed consistent trends (upregulated) at transcription and protein levels. KEGG enrichment analysis indicated that Cyp4a10 and Cyp4a14 are mainly involved in fatty acid degradation, retinol metabolism, arachidonic acid metabolism and PPAR signaling pathway. For acetyl-proteomics analysis, 185 differentially acetylated proteins and 207 differentially acetylated sites were identified. Then, 693 metabolites in positive mode and 537 metabolites in negative mode were identified, which were involved in metabolic pathways such as fatty acid metabolism, citrate cycle and glycolysis/gluconeogenesis. Conclusion: Based on the results of transcriptomic, proteomics, acetyl-proteomics and metabolomics analysis, chronic moderate intensity exercise has certain effects on liver metabolism and protein synthesis in mice. Chronic moderate intensity exercise may participate in liver energy metabolism by influencing the expression of Cyp4a14, Cyp4a10, arachidonic acid and acetyl coenzyme A and regulating fatty acid degradation, arachidonic acid metabolism, fatty acyl metabolism and subsequent acetylation.

An injectable MB/BG@LG sustained release lipid gel with antibacterial and osteogenic properties for efficient treatment of chronic periodontitis in rats.

Periodontitis is a chronic inflammatory disease characterized by the colonization of pathogenic microorganisms and the loss of periodontal supporting tissue. However, the existing local drug delivery system for periodontitis has some problems including subpar antibacterial impact, easy loss, and unsatisfactory periodontal regeneration. In this study, a multi-functional and sustained release drug delivery system (MB/BG@LG) was developed by encapsulating methylene blue (MB) and bioactive glass (BG) into the lipid gel (LG) precursor by Macrosol technology. The properties of MB/BG@LG were characterized using a scanning electron microscope, a dynamic shear rotation rheometer, and a release curve. The results showed that MB/BG@LG could not only sustained release for 16 days, but also quickly fill the irregular bone defect caused by periodontitis through in situ hydration. Under 660 â€‹nm light irradiation, methylene blue-produced reactive oxygen species (ROS) can reduce local inflammatory response by inhibiting bacterial growth. In addition, in vitro and vivo experiments have shown that MB/BG@LG can effectively promote periodontal tissue regeneration by reducing inflammatory response, promoting cell proliferation and osteogenic differentiation. In summary, MB/BG@LG exhibited excellent adhesion properties, self-assembly properties, and superior drug release control capabilities, which improved the clinical feasibility of its application in complex oral environments.