Mesenchymal stem cell-derived exosomes (MSC-exos), with its inherent capacity to modulate cellular behavior, are emerging as a novel cell-free therapy for bone regeneration. Herein, focusing on ...practical applying problems, the osteoinductivity of MSC-exos produced by different stem cell sources (rBMSCs/rASCs) and culture conditions (osteoinductive/common) were systematically compared to screen out an optimized osteogenic exosome (BMSC-OI-exo). Via bioinformatic analyses by miRNA microarray and in vitro pathway verification by gene silencing and miRNA transfection, we first revealed that the osteoinductivity of BMSC-OI-exo was attributed to multi-component exosomal miRNAs (let-7a-5p, let-7c-5p, miR-328a-5p and miR-31a-5p). These miRNAs targeted Acvr2b/Acvr1 and regulated the competitive balance of Bmpr2/Acvr2b toward Bmpr-elicited Smad1/5/9 phosphorylation. On these bases, lyophilized delivery of BMSC-OI-exo on hierarchical mesoporous bioactive glass (MBG) scaffold was developed to realize bioactivity maintenance and sustained release by entrapment in the surface microporosity of the scaffold. In a rat cranial defect model, the loading of BMSC-OI-exo efficiently enhanced the bone forming capacity of the scaffold and induced rapid initiation of bone regeneration. This paper could provide empirical bases of MSC-exo-based therapy for bone regeneration and theoretical bases of MSC-exo-induced osteogenesis mechanism. The BMSC-OI-exo-loaded MBG scaffold developed here represented a promising bone repairing strategy for future clinical application.
Osteoporosis is a highly prevalent disorder characterized by low bone mineral density and an increased risk of fracture, termed osteoporotic fracture. Notably, bone mineral density, osteoporosis and ...osteoporotic fracture are highly heritable; however, determining the genetic architecture, and especially the underlying genomic and molecular mechanisms, of osteoporosis in vivo in humans is still challenging. In addition to susceptibility loci identified in genome-wide association studies, advances in various omics technologies, including genomics, transcriptomics, epigenomics, proteomics and metabolomics, have all been applied to dissect the pathogenesis of osteoporosis. However, each technology individually cannot capture the entire view of the disease pathology and thus fails to comprehensively identify the underlying pathological molecular mechanisms, especially the regulatory and signalling mechanisms. A change to the status quo calls for integrative multi-omics and inter-omics analyses with approaches in 'systems genetics and genomics'. In this Review, we highlight findings from genome-wide association studies and studies using various omics technologies individually to identify mechanisms of osteoporosis. Furthermore, we summarize current studies of data integration to understand, diagnose and inform the treatment of osteoporosis. The integration of multiple technologies will provide a road map to illuminate the complex pathogenesis of osteoporosis, especially from molecular functional aspects, in vivo in humans.
Background
Little is known about the microbiota and upper gastrointestinal tumors. Esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) occur in adjacent organs, co‐occur ...geographically, and share many risk factors despite being of different tissue types.
Methods
This study characterized the microbial communities of paired tumor and nontumor samples from 67 patients with ESCC and 36 patients with GCA in Henan, China. DNA was extracted with the MoBio PowerSoil kit. The V4 region of the 16S ribosomal RNA gene was sequenced with MiniSeq and was processed with Quantitative Insights Into Microbial Ecology 1. The linear discriminant analysis effect size method was used to identify differentially abundant microbes, the Wilcoxon rank‐sum test was used to test α diversity differences, and permutational multivariate analysis of variance was used to test for differences in β diversity.
Results
The microbial environments of ESCC and GCA tissues were all composed primarily of Firmicutes, Bacteroidetes, and Proteobacteria. ESCC tumor tissues contained more Fusobacterium (3.2% vs 1.3%) and less Streptococcus (12.0% vs 30.2%) than nontumor tissues. GCA nontumor tissues had a greater abundance of Helicobacter (60.5% vs 11.8%), which may have been linked to the lower α diversity (58.0 vs 102.5; P = .0012) in comparison with tumor tissues. A comparison of ESCC and GCA nontumor tissues showed that the microbial composition (P = .0040) and the α diversity (87.0 vs 58.0; P = .00052) were significantly different. No significant differences were detected for α diversity within ESCC and GCA tumor tissues.
Conclusions
This study showed differences in the microbial compositions of paired ESCC and GCA tumor and nontumor tissues and differences by organ site. Large‐scale, prospective cohort studies are needed to confirm these findings.
This is the first study to investigate the microbial composition of esophageal squamous cell carcinoma tumor and nontumor tissues through 16S ribosomal RNA gene sequencing and the differences between esophageal squamous cell carcinoma and gastric cardia adenocarcinoma tissues. The levels of Fusobacterium increase in esophageal squamous cell carcinoma tumor tissues, and there is a large decrease in the relative levels of Helicobacter in gastric cardia adenocarcinoma tumor tissues in comparison with nontumor tissues.
Xyloglucan endotransglucosylase/hydrolase genes (XTHs) are a multigene family and play key roles in regulating cell wall extensibility in plant growth and development. Brassica rapa and Brassica ...oleracea contain XTHs, but detailed identification and characterization of the XTH family in these species, and analysis of their tissue expression profiles, have not previously been carried out.
In this study, 53 and 38 XTH genes were identified in B. rapa and B. oleracea respectively, which contained some novel members not observed in previous studies. All XTHs of B. rapa, B. oleracea and Arabidopsis thaliana could be classified into three groups, Group I/II, III and the Early diverging group, based on phylogenetic relationships. Gene structures and motif patterns were similar within each group. All XTHs in this study contained two characteristic conserved domains (Glyco_hydro and XET_C). XTHs are located mainly in the cell wall but some are also located in the cytoplasm. Analyses of the mechanisms of gene family expansion revealed that whole-genome triplication (WGT) events and tandem duplication (TD) may have been the major mechanisms accounting for the expansion of the XTH gene family. Interestingly, TD genes all belonged to Group I/II, suggesting that TD was the main reason for the largest number of genes being in these groups. B. oleracea had lost more of the XTH genes, the conserved domain XET_C and the conserved active-site motif EXDXE compared with B. rapa, consistent with asymmetrical evolution between the two Brassica genomes. A majority of XTH genes exhibited different tissue-specific expression patterns based on RNA-seq data analyses. Moreover, there was differential expression of duplicated XTH genes in the two species, indicating that their functional differentiation occurred after B. rapa and B. oleracea diverged from a common ancestor.
We carried out the first systematic analysis of XTH gene families in B. rapa and B. oleracea. The results of this investigation can be used for reference in further studies on the functions of XTH genes and the evolution of this multigene family.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract In East Asia, the climate variability in boreal winter is dominated by the East Asian winter monsoon, one of the most energetic monsoon systems that can lead to disasters. The key variable, ...the East Asian winter surface air temperature (SAT), has significantly changed over the past century and has substantially impacted agriculture, ecosystems, economics, and public health. However, its projections are limited by considerable uncertainties. Here, we identify the first leading mode that explains almost 29.6% of the inter-model spread in future SAT change. Our research delves into the evolution of present-day biases under future scenarios and their consequential impact on the SAT. Models with stronger western currents’ heat transport in the North Pacific exhibit a warmer North Pacific at mid-latitudes during historical periods. Additionally, these models consistently demonstrate stronger western currents in the future, contributing to the amplified warming of the western North Pacific, thereby warming Eurasia via the weakened trough and subtropical jet through barotropic responses to the warm North Pacific. Incorporating observational sea surface temperature constraints reduces uncertainties by 9.40%, revealing a more reliable SAT change pattern by the end of the 21st century.
Strontium incorporation activated Erk1/2 MAPK and PI3K/AKT pathways for vascularized bone regeneration.
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•Strontium incorporation promoted osteogenesis coupled with ...angiogenesis.•Strontium incorporation activated Erk1/2 MAPK and PI3K/AKT pathways for vascularized bone regeneration.•Strontium incorporation mediated crosstalk between bone marrow mesenchymal stem cell and umbilical vein endothelial cells.
Angiogenesis, well-coupled with osteogenesis, plays an indispensable and vital role in modulating hard tissue regeneration. Thus, simultaneously promoting osteogenesis and angiogenesis in bone reconstruction process is important. Essential trace elements have shown great potential in enhancing osteogenesis and angiogenesis, providing an effective strategy to design grafts for vascularized bone regeneration. In this study, four types of bioactive bioceramic, including hydroxyapatite (HA), strontium (Sr)-incorporated hydroxyapatite (Sr5-HA, Sr10-HA, Sr20-HA) with Sr ions concentrations of 0, 5, 10 and 20%, were investigated for their osteogenic and angiogenic properties. The in vitro results showed that Sr-HA could enhance the proliferation and osteogenic differentiation of BMSCs via Erk1/2 MAPK and PI3K/AKT signaling pathways, and promote the proliferation and angiogenic gene expression of HUVECs via PI3K/AKT pathways. Moreover, HUVECs conditioned medium could apparently promote the osteogenesis of BMSCs, and BMSCs conditioned medium could enhance the angiogenic capacity of HUVECs. Furthermore, in vivo angiogenesis evaluation and bone formation estimation indicated that enhanced newly-formed vessels and new bone formation were observed in Sr-HA porous scaffolds compared to pure HA scaffold. Thus, this study suggests that Sr-incorporation is a promising modification strategy for bone implants to achieve enhanced angiogenic and osteogenic capacities.
As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising ...therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects.
ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro.
We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process.
Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.
•Mesoproterozoic Xiamaling carbonate concretions were formed in early diagenesis.•Non-zero I/(Ca + Mg) values of the concretions suggest oxygenated porewater.•Atmospheric oxygen level was estimated ...>6–9% of the present atmospheric level.
Oxygen availability is crucial for the evolution of eukaryotes in geological history. However, the evolution of mid-Proterozoic oceanic–atmospheric redox conditions remains heavily debated, e.g., O2 <0.1–1% PAL vs. >4–8% PAL (present atmospheric level). In order to further constrain the surface oxygen levels during Mesoproterozoic, an investigation on the I/(Ca + Mg) ratios of deep-water (>100 m) early diagenetic carbonate concretions from the shale-predominated Member IV of the Xiamaling Formation (~1.4 Ga) in three sections of the North China Platform was conducted. The results show that more than half (36/47) of the I/(Ca + Mg) values obtained from the concretions are higher than 0.5 μmol/mol (avg. 0.68), indicating non-negligible iodate retained in the porewaters where the concretions were formed. Compared with the iodine redox cycle and oxygen transportation pathway from bottom seawater to surface sediments in modern oceans, the oxygen concentration of the bottom seawater was estimated to be higher than 16–22 μM, and the minimal atmospheric oxygen level should be higher than 6–9% PAL. This result differs from the previous estimation that the atmospheric oxygen level is lower than 0.1–1% PAL, but is consistent with the estimation of >4–8% PAL at ~1.4 Ga.
Detection of pavement diseases is crucial for road maintenance. Traditional methods are costly, time-consuming, and less accurate. This paper introduces an enhanced pavement disease recognition ...algorithm, MS-YOLOv8, which modifies the YOLOv8 model by incorporating three novel mechanisms to improve detection accuracy and adaptability to varied pavement conditions. The Deformable Large Kernel Attention (DLKA) mechanism adjusts convolution kernels dynamically, adapting to multi-scale targets. The Large Separable Kernel Attention (LSKA) enhances the SPPF feature extractor, boosting multi-scale feature extraction capabilities. Additionally, Multi-Scale Dilated Attention in the network’s neck performs Spatially Weighted Dilated Convolution (SWDA) across different dilatation rates, enhancing background distinction and detection precision. Experimental results show that MS-YOLOv8 increases background classification accuracy by 6%, overall precision by 1.9%, and mAP by 1.4%, with specific disease detection mAP up by 2.9%. Our model maintains comparable detection speeds. This method offers a significant reference for automatic road defect detection.
Liposomes are the earliest and most widely used nanoparticles for targeted drug delivery. Exosomes are nanosized membrane-bound particles and important mediators of intercellular communication. ...Combining liposomes and exosomes using various membrane fusion methods gives rise to a novel potential drug delivery system called membrane fusion-based hybrid exosomes (MFHE). These novel MFHEs not only exhibit potential advantageous features, such as high drug loading rate and targeted cellular uptake
via
surface modification, but are also endowed with high biocompatibility and low immunogenicity. Here, we provide an overview of MFHEs’ various preparation methods, characterization strategies, and their applications for disease treatment and scientific research.
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