3D-printed porous zinc scaffold combined with bioactive serum exosomes promotes bone defect repair in rabbit radius.

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

Integrative analysis of cellular autophagy-related genes in steroid-induced osteonecrosis of the femoral head.

OBJECTIVE: This study aimed to identify and evaluate genes associated with cellular autophagy in steroid hormonal femoral head necrosis. METHODS: Autophagy-related differentially expressed genes (ARDEGs) in steroid-induced osteonecrosis of the femoral head (SONFH) were identified by obtaining the intersection of differentially expressed genes (DEGs) and autophagy-related genes in a SONFH Gene Expression Omnibus dataset. The ARDEGs were screened, and correlations between gene expression and immune cell infiltration were evaluated. Finally, the validation of hub genes was undertaken through quantitative real-time-PCR. RESULTS: A comparison of peripheral blood samples from patients with and without SONFH revealed 189 DEGs. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analyses showed that the DEGs were related to various biologic processes (e.g., neutrophil activation) and pathways (e.g., hematopoietic cell lineage). The expression levels of these genes were correlated with the infiltration of multiple immune cell types. Among the 189 putative autophagy-related genes associated with SONFH, three genes, RPL6, RPL9, and RPL23, were identified as candidate biomarkers or therapeutic targets based on network analysis and their correlations with immune cell subtypes. The quantitative real-time polymerase chain reaction results confirmed our prediction regarding the mRNA expression of RPL9 and RPS6. CONCLUSION: In this study, we identified 189 putative autophagy-related genes associated with SONFH, and the prediction of down-regulated genes RPL9 and RPS6 was validated using PCR, thereby expanding our understanding of the contribution of autophagy to SONFH.

Preparation of Monotrimethoxylsilylethyl-Terminated Polysiloxane Fluids and Their Application in Thermal Interface Materials.

In this study, α-Trimethylsilylmethyl-ω-dimethylsilyl-terminated polydimethylsiloxane, polydiethylsiloxane and poly[2,2,2-trifluoropropyl(methyl)siloxane] are synthesized using an anion catalyzed nonequilibrium polymerization reaction with trimethylsilylmethyl lithium as the initiator; hexamethylcyclotrisiloxane, hexaethylcyclotrisiloxane or 1,3,5-trimethyl-1,3,5-trifluoropropylcyclotrisiloxane as the monomer; and dimethylchlorosilane as an end-capping agent. Three kinds of α-trimethylsilylmethyl-ω-trimethoxylsilylethyl-terminated polysiloxanes are further prepared by hydrosilylation reaction of α-trimethylsilylmethyl-ω-dimethylsilyl-terminated polysiloxanes with vinyltrimethoxysilane using Karstedt's catalyst. These α-trimethylsilylmethyl-ω-trimethoxylsilylethyl-terminated polysiloxanes are functionalized as in situ surface treatment agents for AlN particles. The effects of the structure of these polysiloxanes on the dispersion of AlN in the polysiloxane matrix and on the heat transfer performance of silicone pastes and silicone rubbers are investigated. A possible mechanism of surface treatment of AlN fillers by these novel silicone fluids is also discussed.

Prognostic analysis and validation of diagnostic marker genes in patients with osteoporosis.

Backgrounds: As a systemic skeletal dysfunction, osteoporosis (OP) is characterized by low bone mass and bone microarchitectural damage. The global incidences of OP are high. Methods: Data were retrieved from databases like Gene Expression Omnibus (GEO), GeneCards, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Gene Expression Profiling Interactive Analysis (GEPIA2), and other databases. R software (version 4.1.1) was used to identify differentially expressed genes (DEGs) and perform functional analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression and random forest algorithm were combined and used for screening diagnostic markers for OP. The diagnostic value was assessed by the receiver operating characteristic (ROC) curve. Molecular signature subtypes were identified using a consensus clustering approach, and prognostic analysis was performed. The level of immune cell infiltration was assessed by the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm. The hub gene was identified using the CytoHubba algorithm. Real-time fluorescence quantitative PCR (RT-qPCR) was performed on the plasma of osteoporosis patients and control samples. The interaction network was constructed between the hub genes and miRNAs, transcription factors, RNA binding proteins, and drugs. Results: A total of 40 DEGs, eight OP-related differential genes, six OP diagnostic marker genes, four OP key diagnostic marker genes, and ten hub genes (TNF, RARRES2, FLNA, STXBP2, EGR2, MAP4K2, NFKBIA, JUNB, SPI1, CTSD) were identified. RT-qPCR results revealed a total of eight genes had significant differential expression between osteoporosis patients and control samples. Enrichment analysis showed these genes were mainly related to MAPK signaling pathways, TNF signaling pathway, apoptosis, and Salmonella infection. RT-qPCR also revealed that the MAPK signaling pathway (p38, TRAF6) and NF-kappa B signaling pathway (c-FLIP, MIP1ß) were significantly different between osteoporosis patients and control samples. The analysis of immune cell infiltration revealed that monocytes, activated CD4 memory T cells, and memory and naïve B cells may be related to the occurrence and development of OP. Conclusions: We identified six novel OP diagnostic marker genes and ten OP-hub genes. These genes can be used to improve the prognostic of OP and to identify potential relationships between the immune microenvironment and OP. Our research will provide insights into the potential therapeutic targets and pathogenesis of osteoporosis.

[Research progress of in-situ three dimensional bio-printing technology for repairing bone and cartilage injuries].

Objective: To review the research progress of in-situ three dimensional (3D) bio-printing technology in the repair of bone and cartilage injuries. Methods: Literature on the application of in-situ 3D bio-printing technology to repair bone and cartilage injuries at home and abroad in recent years was reviewed, analyzed, and summarized. Results: As a new tissue engineering technology, in-situ 3D bio-printing technology is mainly applied to repair bone, cartilage, and skin tissue injuries. By combining biomaterials, bioactive substances, and cells, tissue is printed directly at the site of injury or defect. At present, the research on the technology mainly focuses on printing mode, bio-ink, and printing technology; the application research in the field of bone and cartilage mainly focuses on pre-vascularization, adjusting the composition of bio-ink, improving scaffold structure, printing technology, loading drugs, cells, and bioactive factors, so as to promote tissue injury repair. Conclusion: Multiple animal experiments have confirmed that in-situ 3D bio-printing technology can construct bone and cartilage tissue grafts in a real-time, rapid, and minimally invasive manner. In the future, it is necessary to continue to develop bio-inks suitable for specific tissue grafts, as well as combine with robotics, fusion imaging, and computer-aided medicine to improve printing efficiency.

[Comparisons of endocrine hormones levels between Tibetan antelope and Tibetan sheep].

The Tibetan antelope, a prototype mammal, has developed a unique adaptation to extreme high altitude-associated hypoxia. To investigate the role of the endocrine system in adaptation to high altitude in the Tibetan antelope, comparisons of endocrine hormones levels between Tibetan antelope (n = 9) and Tibetan sheep (n = 10) were performed. Both two kinds of animals were captured at an altitude of 4 300 m and then transported to experimental base at 2 800 m altitude. The blood samples were drawn from right external jugular vein in the next morning, and the 20 hormones in hypothalamus-adenohypophysis-peripheral hormonal axis were measured with radioimmunoassay or enzyme-linked immunosorbent assay. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean pulmonary arterial pressure (mPAP) were recorded using catheterization. Moreover, hemoglobin (Hb) content was measured by blood analyser. The results showed that, the levels of FT(3), FT(4) and Ang II in Tibetan antelope were significantly lower than those in Tibetan sheep, whereas TRH, CRH, GHRH, F, E(2), Ald, ACTH and CGRP levels were significantly greater in Tibetan antelope than those in the Tibetan sheep. Compared with Tibetan sheep, Tibetan antelope showed lower HR, mPAP, SBP, DBP and Hb content. In Tibetan antelope and Tibetan sheep, both Hb and Ang II were correlated positively with respective mPAP. In Tibetan antelope, FT(3) level was correlated positively with GH and negatively with ACTH. These results suggest that the endocrine system of Tibetan antelope is characterized by low energy expenditure and high stress, which may be one of the mechanisms underlying the Tibetan antelope adaptation to chronic hypoxia.