Adipose mesenchymal stem cells-derived exosomes attenuated hyperoxia-induced lung injury in neonatal rats via inhibiting the NF-κB signaling pathway.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common chronic morbidity in extremely preterm infants. Mesenchymal stem cells-derived exosomes (MSC-Exos) therapies have shown prospects in animal models of BPD. Our study aimed to evaluate the effect of adipose mesenchymal stem cells-derived exosomes (AMSC-Exos) on BPD and the role of the NF-κB signaling pathway in this process. METHODS: The AMSCs were extracted and AMSC-Exos were isolated by ultracentrifugation method. Newborn rats were exposed to hyperoxia (90% O2) continuously for 7 days to establish a BPD model. The rats were treated with AMSC-Exos by intratracheal administration on postnatal day 4 (P4). Pulmonary morphology, pulmonary vasculature, inflammatory factors, and NF-κB were assessed. Hyperoxia-induced primary type II alveolar epithelial cells (AECIIs) and AMSC-Exos treatment with or without a pan-NF-κB inhibitor (PDTC) were established to explore the potential mechanism. RESULTS: Hyperoxia-exposed rats showed alveolar simplification with decreased radial alveolar count and increased mean linear intercept, low CD31, and vascular endothelial growth factor expression, reduced microvessel density, increased the expression of TNF-α, IL-1ß, and IL-6 and decreased the expression of IL-10, and induced NF-κB phosphorylation. AMSC-Exos protected the neonatal lung from the hyperoxia-induced arrest of alveolar and vascular development, alleviated inflammation, and inhibited NF-κB phosphorylation. Hyperoxia decreased viability, increased apoptosis, enhanced inflammation, and induced NF-κB phosphorylation of AECIIs but improved by AMSC-Exos, PDTC, or AMSC-Exos+PDTC. The effect of AMSC-Exos+PDTC in AECIIs was the same as AMSC-Exos, but more notable than PDTC alone. CONCLUSION: AMSC-Exos attenuated the hyperoxia-induced lung injury in neonatal rats by inhibiting the NF-κB signaling pathway partly.

Activating and Stabilizing a Reversible four Electron Redox Reaction of I-/I+ for Aqueous Zn-Iodine Battery.

Low capacity and poor cycle stability greatly inhibit the development of zinc-iodine batteries. Herein, a high-performance Zn-iodine battery has been reached by designing and optimizing both electrode and electrolyte. The Br- is introduced as the activator to trigger I+, and coupled with I+ forming interhalogen to stabilize I+ to achieve a four-electron reaction, which greatly promotes the capacity. And the Ni-Fe-I LDH nanoflowers serve as the confinement host to enable the reactions of I-/I+ occurring in the layer due to the spacious and stable interlayer spacing of Ni-Fe-I LDH, which effectively suppresses the iodine-species shuttle ensuring high cycling stability. As a result, the electrochemical performance is greatly enhanced, especially in specific capacity (as high as 350 mAh g-1 at 1 A g-1 far higher than two-electron transfer Zn-iodine batteries) and cycling performance (94.6 % capacity retention after 10000 cycles). This strategy provides a new way to realize high capacity and long-term stability of Zn-iodine batteries.

Effects of different supplemental levels of protease DE200 on the production performance, egg quality, and cecum microflora of laying hens.

This study aimed to investigate the effects of different levels of the protease DE200 on the performance, egg quality, organ index, and cecum microflora of Hy-line W36 laying hens. In this experiment, a total of 180 laying hens aged 300 d were randomly divided into three treatment groups and fed diets containing 0, 100, or 200 g/t DE200. The experimental period was 8 wk, including 2 wk of prefeeding and 6 wk of the formal experiment. Regular feeding was performed thrice a day and eggs were collected twice daily, and the feed intake and the egg quality were recorded. The results showed that in terms of production performance, dietary supplementation with different levels of DE200 significantly increased egg production (EP; P < 0.05) and significantly decreased the feed conversion ratio (FCR; P < 0.05) and average daily feed intake (ADFI; P < 0.05) without affecting egg weight (EW). In addition, the addition of DE200 significantly reduced the egg breakage rate (P < 0.05) and tended to increase the Haugh unit and decrease the water content of the yolk (P > 0.05). In the cecal microflora, the addition of DE200 increased the proportions of Bacteroidetes and Firmicutes at the phylum level while reducing the proportion of Fusobacteria. Furthermore, at the genus level, the addition of DE200 increased the proportions of Bacteroides and Faecalibacterium and reduced the proportion of Megamonas. This study suggested that the protease DE200 can be used as a feed supplement to improve the production performance of laying hens.

In the production of laying hens, improving the efficiency of dietary protein utilization is important. The aim of this study was to investigate the effects of the protease DE200 on the performance, egg quality and cecal microflora of Hyline white laying hens. A total of 180 laying hens aged 300 d were randomly divided into three treatment groups and fed diets containing 0, 100, or 200 g/t DE200 for 56 d. The results showed that supplementation with 100 or 200 g/t DE200 in the basal diet improved the production performance and egg quality of laying hens. DE200 (100 g/t) improved the balance of the cecal microflora, and DE200 (200 g/t) increased the richness and diversity of the cecal microflora of laying hens. Dietary supplementation with DE200 can improve the intestinal health and nutrient utilization efficiency of laying hens by improving the intestinal flora.

Atherosclerotic three-layer nanomatrix vascular sheets for high-throughput therapeutic evaluation.

In vitro atherosclerosis models are essential to evaluate therapeutics before in vivo and clinical studies, but significant limitations remain, such as the lack of three-layer vascular architecture and limited atherosclerotic features. Moreover, no scalable 3D atherosclerosis model is available for making high-throughput assays for therapeutic evaluation. Herein, we report an in vitro 3D three-layer nanomatrix vascular sheet with critical atherosclerosis multi-features (VSA), including endothelial dysfunction, monocyte recruitment, macrophages, extracellular matrix remodeling, smooth muscle cell phenotype transition, inflammatory cytokine secretion, foam cells, and calcification initiation. Notably, we present the creation of high-throughput functional assays with VSAs and the use of these assays for evaluating therapeutics for atherosclerosis treatment. The therapeutics include conventional drugs (statin and sirolimus), candidates for treating atherosclerosis (curcumin and colchicine), and potential gene therapy (miR-146a-loaded liposomes). The high efficiency and flexibility of the scalable VSA functional assays should facilitate drug discovery and development for atherosclerosis.

Outcome of chairside CAD/CAM ceramic restorations on endodontically treated posterior teeth: a prospective study.

OBJECTIVE: The aim of this study was to evaluate the outcome and risk factors for chairside CAD/CAM full cusp coverage restorations on endodontically treated posterior teeth after 3 years of follow-up. METHODS: A total of 245 endodontically treated posterior teeth of 224 patients were included and restored with CAD/CAM full cusp coverage all-ceramic restorations according to a standardized protocol. Patients were recalled after treatments 1 to 3 years and underwent clinical and radiological examinations. At recall, modified FDI criteria were used to determine treatment outcomes by 2 evaluators. Success was determined when FDI scores were 1-2, and failure was indicated when FDI scores were 5. Logistic regression analysis was performed to evaluate potential risk factors. RESULTS: A total of 183 patients presented at recall, and the clinical outcomes of 201 teeth were analyzed with a recall rate of 82.0% for teeth and 81.7% for patients after 1-3 years of follow-up.185 of 201 teeth were found to have FDI scores of 1-2, and the success rate was 92%. No teeth were extracted during the follow-up period. Fourteen failed cases with an FDI score of 5 presented restoration dislocation, fracture of restoration or/and tooth. Logistic regression analysis revealed that oral parafunction (OR 2.281, 95% CI 2.2 ~ 47.5, P value 0.01) was a risk factor for success rate. CONCLUSION: Chairside CAD/CAM all-ceramic full cusp coverage restoration was (could be) a promising alternative for restoring endodontically treated posterior teeth.

Excessive apoptosis of Rip1-deficient T cells leads to premature aging.

In mammals, the most remarkable T cell variations with aging are the shrinking of the naïve T cell pool and the enlargement of the memory T cell pool, which are partially caused by thymic involution. However, the mechanism underlying the relationship between T-cell changes and aging remains unclear. In this study, we find that T-cell-specific Rip1 KO mice show similar age-related T cell changes and exhibit signs of accelerated aging-like phenotypes, including inflammation, multiple age-related diseases, and a shorter lifespan. Mechanistically, Rip1-deficient T cells undergo excessive apoptosis and promote chronic inflammation. Consistent with this, blocking apoptosis by co-deletion of Fadd in Rip1-deficient T cells significantly rescues lymphopenia, the imbalance between naïve and memory T cells, and aging-like phenotypes, and prolongs life span in T-cell-specific Rip1 KO mice. These results suggest that the reduction and hyperactivation of T cells can have a significant impact on organismal health and lifespan, underscoring the importance of maintaining T cell homeostasis for healthy aging and prevention or treatment of age-related diseases.

Selective Mitochondrial Respiratory Complex I Subunit Deficiency Causes Tumor Immunogenicity.

Targeting of specific metabolic pathways in tumor cells has the potential to sensitize them to immune-mediated attack. Here we provide evidence for a specific means of mitochondrial respiratory Complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of the CI subunits Ndufs4 and Ndufs6 , but not other subunits, induces an immune-dependent tumor growth attenuation in mouse melanoma models. We show that deletion of Ndufs4 induces expression of the transcription factor Nlrc5 and genes in the MHC class I antigen presentation and processing pathway. This induction of MHC-related genes is driven by an accumulation of pyruvate dehydrogenase-dependent mitochondrial acetyl-CoA downstream of CI subunit deletion. This work provides a novel functional modality by which selective CI inhibition restricts tumor growth, suggesting that specific targeting of Ndufs4 , or related CI subunits, increases T-cell mediated immunity and sensitivity to ICB.

Adipose Stem Cells Derived Exosomes Alleviate Bronchopulmonary Dysplasia and Regulate Autophagy in Neonatal Rats.

BACKGROUND: Mesenchymal stem cell-derived exosomes (MSC-Exos) therapies have shown prospects in preclinical models of pathologies relevant to neonatal medicine, such as bronchopulmonary dysplasia (BPD). Adipose-derived stem cells (ADSCs) have been recognized as one of the most promising stem cell sources. Autophagy plays a key role in regulating intracellular conditions, maintaining cell growth and development, and participating in the pathogenesis of BPD. OBJECTIVES: To investigate the potential therapeutic role of ADSC-Exos on BPD and to illustrate the role of autophagy in this process. METHOD: ADSC-Exos was isolated from media conditioned of ADSCs by ultracentrifugation and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting (WB). Newborn rats were exposed to hyperoxia (90% O2) to mimic BPD, treated with ADSC-Exos by intratracheal or intravenous administration on postnatal day 4 (P4) and returned to room air on P7 until P14. Treated animals and appropriate controls were harvested on P7 and P14 for assessment of pulmonary parameters. RESULTS: Hyperoxia-exposed rats were presented with pronounced alveolar simplification with decreased radial alveolar count (RAC) and increased mean linear intercept (MLI), impaired vascular development with low vascular endothelial growth factor (VEGF) and CD31 expression, and stimulated inflammation with increased expression of TNF-α, IL-1ß, and IL-6, and decreased expression of IL-10. Meanwhile, the rats with hyperoxia exposure blocked autophagic flux with lower levels of Beclin1, LC3B, LC3BII/I ratio and higher levels of p62. ADSC-Exos administration protected the neonatal lung tissues from the hyperoxia-induced arrest of alveolar and vascular development, reduced inflammation, and facilitated autophagy. Intratracheal administration was more efficacious than intravenous administration. CONCLUSION: The intratracheal administration of ADSC-Exos significantly improved alveolarization and pulmonary vascularization arrest in hyperoxia-induced BPD, which was associated with facilitating autophagy in part.

Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikes.

SARS-CoV-2 spike protein (S) is structurally dynamic and has been observed by cryo-EM to adopt a variety of prefusion conformations that can be categorized as locked, closed, and open. S-trimers adopting locked conformations are tightly packed featuring structural elements incompatible with RBD in the "up" position. For SARS-CoV-2 S, it has been shown that the locked conformations are transient under neutral pH. Probably because of their transience, locked conformations remain largely uncharacterized for SARS-CoV-1 S. In this study, we introduced x1, x2, and x3 disulfides into SARS-CoV-1 S. Some of these disulfides have been shown to preserve rare locked conformations when introduced to SARS-CoV-2 S. Introduction of these disulfides allowed us to image a variety of locked and other rare conformations for SARS-CoV-1 S by cryo-EM. We identified bound cofactors and structural features that are associated with SARS-CoV-1 S locked conformations. We compare newly determined structures with other available spike structures of SARS-related CoVs to identify conserved features and discuss their possible functions.

Structures of sperm flagellar doublet microtubules expand the genetic spectrum of male infertility.

Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.

Coverage of 13-Valent Pneumococcal Conjugate Vaccine Among Children 0-15 Months of Age - 9 Provinces, China, 2019-2021.

What is already known on this topic?: Limited data exist regarding the coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) in China. A lack of official statistics, coupled with an insufficient body of published literature, hinders the accurate depiction of the current situation. What is added by this report?: This study investigated the utilization of PCV13 and estimated its coverage in nine provinces across eastern, central, and western China between 2019 and 2021. Despite an annual increase in PCV13 usage during this period, the overall coverage remained suboptimal. What are the implications for public health practice?: Consideration should be given to incorporating vaccines into the Expanded Program of Immunization, reducing vaccine prices, and addressing the vaccination coverage gap between eastern and western regions when there is an adequate supply of PCV13, particularly with domestic vaccines.

Serum lactate dehydrogenase concentration after transcatheter renal artery embolization correlates with reduction in renal angiomyolipoma volume.

BACKGROUND: The extent of renal angiomyolipoma (AML) volume reduction after renal transcatheter arterial embolization (TAE) varies between patients, with no predictive measure available. PURPOSE: To determine whether the serum lactate dehydrogenase (LDH) concentration shortly after TAE correlates with the extent of tumor shrinkage. MATERIAL AND METHODS: In a cohort of 36 patients undergoing prophylactic renal TAE for unruptured renal AML, we retrospectively acquired data from patient medical records, including serum LDH before and within 7 days after TAE and the tumor volume before and 12-36 months after TAE. The relationship between the serum level of LDH and reduction in tumor volume was evaluated using Spearman correlation analysis. RESULTS: The median LDH concentration was significantly higher after TAE than before (909.0 U/L vs. 186.5 U/L). This early post-TAE serum LDH level and LDH index (post-TAE LDH / pre-TAE LDH) correlated significantly and positively with the absolute decrease in tumor volume (both P < 0.0001). We observed no significant correlation between the relative tumor volume reduction and serum LDH level or LDH index. CONCLUSION: Serum LDH elevation occurs shortly after TAE and correlates with the extent of absolute decrease in AML volume at 12-36 months after TAE. Further large-scale studies are warranted to confirm the predictive role of post-TAE serum LDH level and LDH index in tumor shrinkage in patients with unruptured renal AML.

Long-term volume reduction in renal angiomyolipomas embolized by gelatin sponge particles with or without supplementary microcoil embolization.

OBJECTIVE: To examine the effect of supplementary microcoil embolization on the long-term progression of angiomyolipomas embolized using gelatin sponge particles (GSPs). METHODS: This retrospective study included 29 unruptured angiomyolipomas in 25 patients, treated by complete embolization and radiological follow-up for ≥3 years. Embolization was performed using GSPs and supplementary microcoils. Supplementary microcoil embolization affecting >90% of the tumor vasculature was defined as microcoil embolization. Tumor volumes pre- and post-embolization were measured by computed tomography or magnetic resonance imaging. RESULTS: Eleven tumors received supplementary microcoil embolization and 18 tumors did not. Relative tumor reduction at >3 years post-embolization was significantly greater in tumors with supplementary microcoil embolization compared with tumors without microcoil embolization (81% ± 8% vs. 55% ± 29%). Fourteen tumors tended to show volume regrowth and the volumes of the remaining 15 tumors continued to decline. Tumors without supplementary microcoil embolization were more likely to show volume regrowth during follow-up than tumors with supplementary microcoil embolization (78% vs. 0%, respectively). CONCLUSIONS: When using a combination of GSPs and microcoils, supplementary microcoil embolization should be carried out to ensure maximum long-term reduction in tumor volume in patients with angiomyolipomas.

Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-Secreted Cytokines.

Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I)-bound peptides, but this selection pressure favors outgrowth of MHC-I-deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I-deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I-deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified proapoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I-deficient tumor cells were efficiently cross-presented by dendritic cells, resulting in heightened tumor infiltration by IFNγ-and TNFα-producing T cells. Tumors with a substantial population of MHC-I-deficient cancer cells could be controlled by T cells when both pathways were targeted using genetic or pharmacologic approaches. SIGNIFICANCE: Tumor heterogeneity is a major barrier to immunotherapy. We show that MHC-I-deficient tumor cells are forced into apoptosis by T cell-derived cytokines when TNF signaling and autophagy pathways are targeted. This approach enables T cell-mediated elimination of tumors with a substantial population of resistant, MHC-I-deficient tumor cells. This article is highlighted in the In This Issue feature, p. 1027.

Variants of a putative baseplate wedge protein extend the host range of Pseudomonas phage K8.

BACKGROUND: Narrow host range is a major limitation for phage applications, but phages can evolve expanded host range through adaptations in the receptor-binding proteins. RESULTS: Here, we report that Pseudomonas phage K8 can evolve broader host range and higher killing efficiency at the cost of virion stability. Phage K8 host range mutant K8-T239A carries a mutant version of the putative baseplate wedge protein GP075, termed GP075m. While phage K8 adsorbs to hosts via the O-specific antigen of bacterial LPS, phage K8-T239A uses GP075m to also bind the bacterial core oligosaccharide, enabling infection of bacterial strains resistant to K8 infection due to modified O-specific antigens. This mutation in GP075 also alters inter-protein interactions among phage proteins, and reduces the stability of phage particles to environmental stressors like heat, acidity, and alkalinity. We find that a variety of mutations in gp075 are widespread in K8 populations, and that the gp075-like genes are widely distributed among the domains of life. CONCLUSION: Our data show that a typical life history tradeoff occurs between the stability and the host range in the evolution of phage K8. Reservoirs of viral gene variants may be widely present in phage communities, allowing phages to rapidly adapt to any emerging environmental stressors. Video Abstract.

MiR-146a encapsulated liposomes reduce vascular inflammatory responses through decrease of ICAM-1 expression, macrophage activation, and foam cell formation.

Vascular insults can create an inflammatory cascade involving endothelial cell, smooth muscle cell, and macrophage activation which can eventually lead to vascular disease such as atherosclerosis. Several studies have identified microRNA 146a's (miR-146a) anti-inflammatory potential based on its role in regulating the nuclear factor kappa beta (NF-κß) pathway. Therefore, in this study, we introduced exogenous miR-146a encapsulated by liposomes to lipopolysaccharide (LPS) stimulated vascular cells and macrophages to reduce inflammatory responses. First, the miR-146a encapsulated liposomes showed uniform size (radius 96.4 ± 4.22 nm) and round shape, long term stability (at least two months), high encapsulation efficiency (69.73 ± 0.07%), and were well transfected to human aortic endothelial cells (HAECs), human aortic smooth muscle cells (SMCs), and human differentiated monocytes (U937 cells). In addition, we demonstrated that miR-146a encapsulated liposomes reduced vascular inflammation responses in HAECs and SMCs through inhibition of ICAM-1 expression and decreased monocyte adhesion. In macrophages, miR-146a liposome treatment demonstrated decreased production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), as well as reduced oxidized low-density lipoprotein (ox-LDL) uptake and foam cell formation. Thus, based on these results, miR-146a encapsulated liposomes may be promising for reducing vascular inflammation by targeting its multiple associated mediators.

Effects of Silage Diet on Meat Quality through Shaping Gut Microbiota in Finishing Pigs.

With increasing demand for high-quality pork, development of green and healthy feed for finishing pigs is urgently needed. In this study, the effects and mechanisms of mulberry and paper mulberry silages on growth performance, meat quality, and intestinal health of finishing pigs were explored. Intestinal microbiota were profiled, and microbially produced short-chain fatty acids (SCFAs) were measured. The average daily gain (ADG) and feed conversion rate (FCR) with mulberry and paper mulberry silages were not significantly different from those of the control. Meat quality as measured by pork marbling and fatty acids in the longissimus dorsi was better with mulberry silage. The highest concentration of SCFAs was also with mulberry silage. According to 16S rRNA sequencing, Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae, which are important in SCFA production, were biomarkers of mulberry silage. PICRUSt functional analysis of intestinal microbes indicated that galactose metabolism, starch and sucrose metabolism, and carbohydrate digestion and absorption decreased significantly in silage treatments but increased in the control. Correlations between intestinal microbes and SCFAs and fatty acids indicated Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA and fatty acid contents. The results indicated that mulberry silage could increase SCFA content through shaping intestinal microbes to affect the deposition of fatty acids, which laid a solid theoretical foundation for improving pork quality. IMPORTANCE To avoid competition between people and animals for food, it is essential to develop nontraditional feeds. In this study, the effects of the silages of the unconventional feed resources mulberry and paper mulberry on meat quality of finishing pigs were examined. With mulberry silage in the diet, meat quality improved as indicated by meat color, marbling score, and beneficial fatty acids in the longissimus dorsi muscle. Pigs fed mulberry silage had the highest concentrations of short-chain fatty acids (SCFAs), and 16S rRNA sequencing identified Clostridium_sensu_stricto_1, Terrisporobacter, and Lachnospiraceae as biomarkers, which are important in SCFA production. Functions of intestinal microbes in the two silage groups primarily involved amino acid metabolism and SCFA production. Correlations between intestinal microbes and SCFAs and fatty acids indicated that Clostridium_sensu_stricto-1, Terrisporobacter, and Lachnospiraceae were closely associated with SCFA contents in the intestine and fatty acids in the longissimus dorsi.

Transfer RNA-derived small RNAs (tsRNAs) sequencing revealed a differential expression landscape of tsRNAs between glioblastoma and low-grade glioma.

BACKGROUND: Glioblastomas (GBMs) are the most lethal brain cancer with a median survival rate of fewer than 15 months. Both clinical and biological features of GBMs are largely different from those of low-grade gliomas (LGs), but the reasons for this intratumoral heterogeneity are not entirely clear. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) were derived from tRNA precursors and mature tRNA, referring to the specific cleavage of tRNAs by dicer and angiogenin (ANG) in particular cells or tissues or under certain conditions such as stress and hypoxia. With the characteristics of wide expression and high stability, tsRNAs could be used as favorable biomarkers for diagnosis, treatment, and prognosis prediction of the tumor, viral infection, neurological as well as other systemic diseases. In this study, we have compared the differential expressed tsRNAs between GBMs and LGs, so as to investigate the possible pathogenic molecules and provide references for discovering novel nucleic acid drugs in future studies. METHODS: Fresh tumor tissues of patients that were diagnosed as GBMs (4 cases) and LGs (5 cases) at the First Affiliated Hospital of Wenzhou Medical University from 2019.05 to 2021.01 were collected. The tsRNAs' levels were analyzed and compared through high-throughput sequencing, candidate tsRNAs were chosen according to the expression level, and the expression of the candidate tsRNAs was validated through qPCR. Finally, the potential targets were imputed using the Miranda and TargetScan databases, and possible biological functions of the differentially expressed (DE) tsRNAs' targets were enriched based on GO and KEGG databases. RESULTS: A total of 4 GBMs and 5 LGs patients were enrolled in the current study. High-throughput sequencing showed that 186 tsRNAs were expressed in two groups, over them, 43 tsRNAs were unique to GBMs, and 24 tsRNAs were unique to LGs. A total of 9 tsRNAs were selected as candidate tsRNAs according to the tsRNA expression level, among which 6 tsRNAs were highly expressed in GBMs and 3 tsRNAs were low expressed in GBMs. qPCR verification further demonstrated that 5 tsRNAs were significantly up-regulated and 1 tsRNA was significantly down-regulated in GBMs: tRF-1-32-chrM.Lys-TTT (p=0.00118), tiRNA-1-33-Gly-GCC-1 (p=0.00203), tiRNA-1-33-Gly-CCC-1 (p=0.00460), tRF-1-31-His-GTG-1 (p=0.00819), tiRNA-1-33-Gly-GCC-2-M3 (p=0.01032), and tiRNA-1-34-Lys-CTT-1-M2 (p=0.03569). Enrichment analysis of the qPCR verified DE tsRNAs showed that the 5 up-regulated tsRNAs seemed to be associated with axon guidance, pluripotent stem cells regulation, nucleotide excision repair, Hippo signaling pathway, and cancer-related pathways, while the down-regulated tsRNA (tRF-1-32-chrM.Lys-TTT) was associated with oocyte meiosis and renin secretion. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs.