Accurate identification of bacteriophages from metagenomic data using Transformer.

MOTIVATION: Bacteriophages are viruses infecting bacteria. Being key players in microbial communities, they can regulate the composition/function of microbiome by infecting their bacterial hosts and mediating gene transfer. Recently, metagenomic sequencing, which can sequence all genetic materials from various microbiome, has become a popular means for new phage discovery. However, accurate and comprehensive detection of phages from the metagenomic data remains difficult. High diversity/abundance, and limited reference genomes pose major challenges for recruiting phage fragments from metagenomic data. Existing alignment-based or learning-based models have either low recall or precision on metagenomic data. RESULTS: In this work, we adopt the state-of-the-art language model, Transformer, to conduct contextual embedding for phage contigs. By constructing a protein-cluster vocabulary, we can feed both the protein composition and the proteins' positions from each contig into the Transformer. The Transformer can learn the protein organization and associations using the self-attention mechanism and predicts the label for test contigs. We rigorously tested our developed tool named PhaMer on multiple datasets with increasing difficulty, including quality RefSeq genomes, short contigs, simulated metagenomic data, mock metagenomic data and the public IMG/VR dataset. All the experimental results show that PhaMer outperforms the state-of-the-art tools. In the real metagenomic data experiment, PhaMer improves the F1-score of phage detection by 27%.

Potential Use of Extracellular Vesicles in the Treatment of Intervertebral Disc Degeneration.

Intervertebral disc degeneration (IVDD) is a major cause of low back pain, and several studies have evaluated the efficacy of extracellular vesicles (EVs) in the treatment of IVDD. The databases PubMed, Embase, and Cochrane Library were systematically searched from inception to the end of 2022 to identify studies investigating the therapeutic potential of cell-derived EVs for IVDD treatment. The following outcome measures were utilized: magnetic resonance imaging (MRI) Pfirrmann grading system, disc height index (DHI), histological grading, and apoptosis rate. A comprehensive meta-analysis was conducted, including a total of 13 articles comprising 19 studies involving 218 experimental animals. Comparative analysis between normal cell-derived EVs and placebo revealed significant reductions in MRI grade, increased DHI values, decreased nucleus pulposus cell apoptosis rates, and improved tissue grades. These findings collectively demonstrate the effective inhibition of IVDD through the application of EVs derived from cells. In conclusion, this study provides an updated synthesis of evidence supporting the efficacy of EVs as a promising therapeutic approach for IVDD treatment.

Hypoxic preconditioning-engineered bone marrow mesenchymal stem cell-derived exosomes promote muscle satellite cell activation and skeletal muscle regeneration via the miR-210-3p/KLF7 mechanism.

Sarcopenia is a gradual and widespread decline in muscle mass and function in skeletal muscle, leading to significant implications for individuals and society. Currently, there is a lack of effective treatment methods for sarcopenia. Muscle satellite cells(SCs) play a crucial role in the occurrence and development of sarcopenia, and their proliferation and differentiation abilities are closely related to the progression of disease. This study evaluated the effects of exosomes derived from hypoxic preconditioning bone marrow mesenchymal stem cells (BMSCs) on the proliferation of SCs and skeletal muscle regeneration. We found that the capacity for the proliferation and differentiation of SCs in elderly rats was notably diminished, leading us to create a sarcopenia model in elderly rats. By separating and extracting exosomes from BMSCs treated with normoxic (N-Exos) and hypoxic (H-Exos) conditions, in vivo and in vitro studies showed that both N-Exos and H-Exos can regulate the proliferation and differentiation of SCs in elderly rats, and promote skeletal muscle regeneration and functional recovery. The beneficial effects of H-Exos were also more significant than those of the N-Exos group. In vitro studies demonstrated that H-Exos could influence the expression of the KLF7 gene and protein in SCs by delivering miR-210-3P. This, in turn, impacted the phosphorylation of the PI3K/AKT signaling pathway and contributed to the function of SCs. H-Exos stimulated SCs and promoted skeletal muscle regeneration during sarcopenia by delivering miR-210-3P to target the KLF7/PI3K/AKT signaling pathway. This may serve as a possible treatment option for sarcopenia.

Micro-RNA let-7a-5p Derived From Mesenchymal Stem Cell-Derived Extracellular Vesicles Promotes the Regrowth of Neurons in Spinal-Cord-Injured Rats by Targeting the HMGA2/SMAD2 Axis.

Spinal cord injury (SCI) often causes neuronal and axonal damage, resulting in permanent neurological impairments. Mesenchymal stem cells (MSCs) and extracellular vesicles (EVs) are promising treatments for SCI. However, the underlying mechanisms remain unclear. Herein, we demonstrated that EVs from bone marrow-derived MSCs promoted the differentiation of neural stem cells (NSCs) into the neurons and outgrowth of neurites that are extending into astrocytic scars in SCI rats. Further study found that let-7a-5p exerted a similar biological effect as MSC-EVs in regulating the differentiation of NSCs and leading to neurological improvement in SCI rats. Moreover, these MSC-EV-induced effects were attenuated by let-7a-5p inhibitors/antagomirs. When investigating the mechanism, bioinformatics predictions combined with western blot and RT-PCR analyses showed that both MSC-EVs and let-7a-5p were able to downregulate the expression of SMAD2 by inhibiting HMGA2. In conclusion, MSC-EV-secreted let-7a-5p promoted the regrowth of neurons and improved neurological recovery in SCI rats by targeting the HMGA2/SMAD2 axis.