TRNA-derived small RNAs (tsRNAs) are non-coding small RNAs produced by specific endonucleases following the processing and splicing of precursor or mature tRNAs upon starvation, oxidative stress, hypoxia, and other adverse conditions. tRNAs are classified into two major categories, tRNA fragments (tRFs) and tRNA-derived stress-induced small RNAs (tiRNAs), based on differences in splice sites. With the development of high-throughput sequencing technologies in recent years, tsRNAs have been found to have important biological functions, including inhibition of apoptosis, epigenetic regulation, cell–cell communication, translation, and regulation of gene expression. Additionally, these molecules have been found to be aberrantly expressed in various diseases and to be involved in several pathological processes. In this article, the classification and nomenclature, biological functions, and potential use of tsRNAs as diagnostic biomarkers and therapeutic targets in non-neoplastic diseases are reviewed. Although tsRNA research is at its infancy, their potential in the treatment of non-tumor diseases warrants further investigation.

Medical education is widely known to be a demanding process that may cause various mental health problems, such as burnout, which can lead to lowered levels of life satisfaction among medical students. Research shows that empathy is negatively correlated with burnout, but there are few studies on the relationship among empathy, burnout and life satisfaction in medical students. The objective of the present study is to explore the correlations of empathy and burnout with life satisfaction and the associated socio-demographic factors among Chinese undergraduate medical students. In this cross-sectional study, 1271 undergraduate medical students (age 19.42 ± 1.34 years, 36% male) from 1st to 4th grades completed questionnaires including the Interpersonal Reactivity Index Chinese version (IRI-C), the Maslach Burnout Inventory Modified Chinese version (MBI-MC), the Satisfaction With Life Scale (SWLS) and socio-demographic characteristics. Statistical analyses included Student’s t-test, one-way ANOVA, post hoc Bonferroni tests, hierarchical linear regression analysis and general linear model-univariate full factorial model. Over four academic years, medical students’ empathy levels declined, but their burnout levels almost plateaued and their life satisfaction levels witnessed an initial fall before a rebound. Empathy was correlated with students’ age and grade, and burnout was associated with students’ maternal education. Significant differences in life satisfaction were detected with regard to medical students’ age, academic year, the number of children in the family, place of residence and parents’ educational levels. Empathy explained 0.6% of the variance in life satisfaction in contrast to 13.7% of the variance explained by burnout in life satisfaction. Although empathy did not have a main effect on life satisfaction, there was an interaction effect of empathy and burnout on life satisfaction among students of high and low empathy and burnout levels. Students with high levels of empathy and low levels of burnout were most satisfied with life. Medical institutions and related authorities need to find effective measures to enhance students’ empathy levels and reduce burnout to improve their life satisfaction.

Developing bioactive materials for bone implants to enhance bone healing and bone growth has for years been the focus of clinical research. Barium titanate (BT) is an electroactive material that can generate electrical signals in response to applied mechanical forces. In this study, a BT piezoelectric ceramic coating was synthesized on the surface of a TC4 titanium alloy, forming a BT/TC4 material, and low-intensity pulsed ultrasound (LIPUS) was then applied as a mechanical stimulus. The combined effects on the biological responses of MC3T3-E1 cells were investigated. Results of scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray diffraction showed that an uniform nanospheres -shaped BT coating was formed on TC4 substrate. Piezoelectric behaviors were observed using piezoelectric force microscopy with the piezoelectric coefficient d₃₃ of 0.42 pC/N. Electrochemical measures indicated that LIPUS-stimulated BT/TC4 materials could produce a microcurrent of approximately 10 μA/cm². In vitro, the greatest osteogenesis (cell adhesion, proliferation, and osteogenic differentiation) was found in MC3T3-E1 cells when BT/TC4 was stimulated using LIPUS. Furthermore, the intracellular calcium ion concentration increased in these cells, possibly because opening of the L-type calcium ion channels was promoted and expression of the Ca_V1.2 protein was increased. Therefore, the piezoelectric BT/TC4 material with LIPUS loading synergistically promoted osteogenesis, rending it a potential treatment for early stage formation of reliable bone-implant contact.

Mesenchymal stem cells (MSCs) are multifunctional stem cells that exist in almost all human tissues. In addition to their self-renewal and multidirectional differentiation potential, they also have valuable immunomodulatory abilities. Bone marrow mesenchymal stem cells (BMMSCs) are the first discovered MSCs and are the most widely studied. Stem cells from the apical papilla (SCAP) are derived from the apical papilla of incompletely developed teeth and play an important role in the formation and development of tooth root. Recent studies have shown that mesenchymal stem cell-derived exosomes (MSC-exo) have similar biological functions as MSCs. Moreover, increasing evidence has highlighted the functional relationship between noncoding regulatory RNAs, especially microRNAs, and MSC-exo. However, few studies have addressed the role of PIWI-interacting RNAs (piRNAs) in MSC-exo. To develop a better understanding of the biological functions of SCAP and BMMSCs, we compared and analyzed the piRNA expression profiles of the exosomes derived from human SCAP (SCAP-exo) and the exosomes of BMMSCs (BMMSC-exo). A total of 593 and 920 known piRNAs were identified from SCAP-exo and BMMSC-exo, respectively, and 21 piRNAs were found to be differentially expressed. In addition, we predicted the target genes of the differentially expressed piRNAs, and the target genes were subjected to the Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analysis, revealing the possible biological functions of these differentially expressed piRNAs. We found that the target genes of the differentially expressed piRNAs mainly involved in biological regulation, cellular processes, metabolic processes, binding, and catalytic activity, which are closely related to the biological functions of MSCs. In conclusion, this study confirmed the differential expression profiles of piRNAs in SCAP-exo and BMMSC-exo and provided useful insights for further study of their functions.

Currently, cancer-related competing endogenous RNA (ceRNA) networks are attracting significant interest. As long noncoding RNA ZEB1-AS1 has been reported to function as an oncogene due to sponging microRNAs (miRNAs) in several cancers, we hypothesized that it could interact with specific miRNAs to form regulatory networks and facilitate the growth of gastric cancer (GC). MiRNAs interacting with ZEB1-AS1 were screened for and selected by bioinformatics analysis. Overexpression or repression of ZEB1-AS1 was performed to determine whether it could regulate selected miRNAs. Quantitative real-time polymerase chain reactions (qPCR) validated the expression profiles of ZEB1-AS1 and miR-149-3p in GC cell lines and tissue. Statistical analysis determined the clinical significance of ZEB1-AS1 in relation to miR-149-3p. Cell counting, wound healing and transwell assays were performed to assess cell proliferation, migration and invasion. A luciferase reporter assay was utilized to confirm the putative miR-149-3p-binding sites in ZEB1-AS1. Briefly, bioinformatics analysis inferred that ZEB1-AS1 interacts with miR-204, miR-610, and miR-149. Gain- or loss-of function assays suggested that ZEB1-AS1 negatively regulates miR-149-3p, miR-204-5p and miR-610 in GC cells. Validated by qPCR, ZEB1-AS1 was up-regulated and miR-149-3p down-regulated in GC cells and tissue. Data analyses indicated that ZEB1-AS1 and miR-149-3p are associated with the independent diagnosis and prognosis of GC. Functional assays support the theory that miR-149-3p hinders GC proliferation, migration and invasion, whereas its overexpression abrogates the corresponding effects induced by ZEB1-AS1. Lastly, dissection of the molecular mechanisms involved indicated that ZEB1-AS1 can regulate GC partly via a ZEB1-AS1/miR-149-3p axis. ZEB1-AS1 can interact with specific miRNAs, forming a miRNA-mediated ceRNA network and promoting GC progress, partly through a ZEB1-AS1/miR-149-3p axis.

Bone defects caused by various causes remain a major problem in orthopedic clinics. A number of different treatments have been developed and proposed, but until now, none has proven to be completely satisfactory. For 26 patients with bone defects but limited autologous bone source or allogeneic bone graft failure, we used individual tissue-engineered bones (iTEBs) for repairing, which were constructed by autologous bone marrow mesenchymal stem cells and allogenic decalcified bone matrix (DBM) scaffolds. The clinical outcomes, including efficacy and safety, were evaluated by radiological examinations, postoperative function recovery score and laboratory tests. Twenty-six patients, including 18 men and 8 women, were followed up for an average of 10 years to analyze the long-term outcome. The mean healing time for patients with lacunar bone defects was 3.87 ± 2.01 months (range, 2–9 months) and that for structural bone defects was longer than 12 months. The Musculoskeletal Tumor Society functional evaluation system and the Barthel Index scores were significantly improved during the long-term follow-up. The white blood cell, erythrocyte sedimentation rate, C reactive protein, complement, immunoglobulins, and liver and renal functions were not significantly affected by bone grafting. One patient with bone cyst relapsed at 3 years postoperatively and achieved bone healing after re-transplantation. No tumorigenesis, tumor metastasis, or blood transmissible disease was found in the whole process. The results demonstrated that iTEBs were effective and safe for repairing bone defects in the long period, especially for those with lacunar bone defects and limited autograft source. Impact statement: Currently, controversies exist about the long-term safety and effectiveness of the clinical application of tissue-engineered bones (TEBs) due to potential tumorigenesis, immune rejection, disease transmission, and others. In this study, we show that individual TEBs constructed by autologous MSCs and allogenic decalcified bone matrix are reliable for repairing bone defects in regard to its long-term safety and effectiveness. Our study provides experience and basis about the clinical application of TEBs in the treatment of bone defects.