Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior.

Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response. Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region-specific, particularly involving the corticolimbic system, including the ventral tegmental area, nucleus accumbens, prefrontal cortex, amygdala, and hippocampus. Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology. In this review, we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression. We focused on associated molecular pathways and neural circuits, with special attention to the brain-derived neurotrophic factor-tropomyosin receptor kinase B signaling pathway and the ventral tegmental area-nucleus accumbens dopamine circuit. We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature, severity, and duration of stress, especially in the above-mentioned brain regions of the corticolimbic system. Therefore, BDNF might be a biological indicator regulating stress-related processes in various brain regions.

Circular RNA Circ_0122396 Regulates Human Lens Epithelial Cell Progression by Regulating miR-23a-3p and MMP16 in Age-Related Cataract.

BACKGROUND: CircRNA plays a regulatory role in multiple life processes. Circ_0122396 could participate in the regulation of age-related cataract (ARC) progression. However, the precise molecular mechanisms of circ_0122396 In ARC remain enigmatic. METHODS: Circ_0122396, microRNA (miR)-23a-3p, and matrix metalloprotease (MMP)-16 (MMP16) expression levels were detected via quantitative real-time polymerase chain reaction. Western blot was used to detect the levels of MMP16 and apoptosis-related proteins. Cell counting kit-8 analysis and 5-ethynyl-2'-deoxyuridine assay were used to assess human lens epithelial cells (HLECs) proliferation. Flow cytometry was performed to determine cell apoptosis. Levels of malondialdehyde (MDA) and glutathione peroxidase (GSH-PX) were measured using commercial kits. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay were used to examine the interaction among circ_0122396, miR-23a-3p, and MMP16. RESULTS: Circ_0122396 and MMP16 were down-regulated while miR-23a-3p was up-regulated in ARC. H2O2 constrained proliferation and GSH-PX level, promotes apoptosis and MDA level in HLECs, and overexpression of circ_0122396 attenuated these effects. miR-23a-3p was a direct target of circ_0122396, and MMP16 was a direct target of miR-23a-3p. The effect of circ_0122396 overexpression on H2O2-induced HLECs was reversed by miR-23a-3p, and MMP16 elevation overturned the impacts of miR-23a-3p in H2O2-induced HLECs. CONCLUSIONS: Circ_0122396 may regulate the progression of ARC via the miR-23a-3p/MMP16 pathway in H2O2-stimulated HLECs, which may serve as a potentially valuable biomarker and novel therapeutic target for ARC.

Evidence of Spin Density Waves in La_{3}Ni_{2}O_{7-δ}.

The recently discovered superconductivity with critical temperature T_{c} up to 80 K in the double-layer Nickelate La_{3}Ni_{2}O_{7-δ} under pressure has drawn great attention. Here, we report the positive muon spin relaxation (µ^{+}SR) study of polycrystalline La_{3}Ni_{2}O_{6.92} under ambient pressure. Zero-field µ^{+}SR experiments reveal the existence of magnetic order in La_{3}Ni_{2}O_{6.92} with T_{N}=154 K. The weak transverse field µ^{+}SR measurements reveal the bulk nature of magnetism. In addition, a small quantity of oxygen deficiencies can greatly broaden the internal magnetic field distribution sensed by muons.

Infection­associated bile acid disturbance contributes to macrophage activation in patients with cirrhosis.

Cirrhosis impairs macrophage function and disrupts bile acid homeostasis. Although bile acids affect macrophage function in patients with sepsis, whether and how the bile acid profile is changed by infection in patients with cirrhosis to modulate macrophage function remains unclear. The present study aimed to investigate the changes in the bile acid profile of patients with cirrhosis and infection and their effects on macrophage function. Serum was collected from 20 healthy subjects, 18 patients with cirrhosis and 39 patients with cirrhosis and infection. Bile acid profiles were detected using high­performance liquid chromatography­triple time­of­flight mass spectrometer. The association between bile acid changes and infection was analysed using receiver operating characteristic (ROC) curves. Infection­altered bile acids were used in combination with lipopolysaccharides (LPS) to stimulate RAW264.7/THP­1 cells in vitro. The migratory capacity was evaluated using wound healing and Transwell migration assays. The expression of Arg­1, iNOS, IκBα, phosphorylated (p­)IκBα and p65 was examined with western blotting and immunofluorescence, Tnfα, Il1b and Il6 mRNA was examined with RT­qPCR, and CD86, CD163 and phagocytosis was measured with flow cytometry. The ROC curves showed that decreased hyodeoxycholic acid (HDCA) and deoxycholic acid (DCA) levels were associated with infection. HDCA or DCA combined with LPS enhanced the phagocytic and migratory ability of macrophages, accompanied by upregulation of iNOS and CD86 protein expression as well as Tnfα, Il1b, and Il6 mRNA expression. However, neither HDCA nor DCA alone showed an effect on these phenotypes. In addition, DCA and HDCA acted synergistically with LPS to increase the expression of p­IκBα and the intranuclear migration of p65. Infection changed the bile acid profile in patients with cirrhosis, among which the reduction of DCA and HDCA associated most strongly with infection. HDCA and DCA enhanced the sensitivity of macrophage function loss to LPS stimulation. These findings suggested a potential role for monitoring the bile acid profile that could help manage patients with cirrhosis and infection.

Long-term survival outcomes of endoscopic therapy vs. surgical resection in patients with cardia gastrointestinal stromal tumor.

The ideal surgical approach for treating cardia gastrointestinal stromal tumor (GIST) is not clearly established. This study aimed to assess the long-term survival results among patients who received endoscopic therapy (ET) or surgical resection (SR) for cardia GIST. Cardia GIST patients from 2000 to 2019 were selected from the surveillance, epidemiology, and end result (SEER) database. Multiple imputation (MI) was applied to handle missing data, and propensity score matching (PSM) was carried out to mitigate selection bias during comparisons. Demographic and clinical characteristics' effects on overall survival (OS) and cancer-specific survival (CSS) were assessed using Kaplan-Meier analyses and multivariate Cox proportional hazard models. A total of 330 patients with cardia GIST were enrolled, including 47 (14.2%) patients with ET and 283 (85.8%) patients with SR. The 5-year OS and CSS rates in the ET and SR groups were comparable [before PSM, (OS) (76.1% vs. 81.2%, P = 0.722), (CSS) (95.0% vs. 89.3%, P = 0.186); after PSM, (OS) (75.4% vs. 85.4%, P = 0.540), (CSS) (94.9% vs. 92.0%, P = 0.099)]. Moreover, there was no significant difference between ET and SR in terms of long-term OS (hazard ratio [HR] 0.735, 95% confidence interval [CI] 0.422-1.282) and CSS (HR 1.560, 95% CI 0.543-4.481). Our study found no significant disparity in long-term survival outcomes between ET and SR in cardia GIST patients, implying that ET could be a valid surgical strategy for treating cardia GIST.

Pathogenicity studies and molecular characterization of DPV infection in ducklings.

In the spring of 2023, 10 to 21-day-old chicks in a broiler duck farm in Shandong Province, China, developed swelling of the head and neck, moist eyes with mucous discharge, difficulty in walking, shrinking of the neck, and loose and disorganized coat. Anatomical observation revealed hemorrhages in the esophageal mucosa, myocardium, and liver, and severe hemorrhages in the trachea with copious inflammatory secretions. Soon after, similar symptoms appeared in a large number of ducks in the flock, which eventually led to the elimination of all the 20,000-odd newly introduced ducklings on the farm, resulting in huge economic losses. We detected duck plague virus in the tissues of liver, spleen and lungs of diseased and dead ducks, and successfully isolated the pathogenic strain, named SD423, by inoculating duck embryos and inoculating duck embryo fibroblasts. We successfully conducted animal regression experiments with the isolated strain, and the experimental animals in the 1 d of age group showed symptoms of swollen eyes and tearing, shrinking of the neck, crouching, and hemorrhage in organs such as the liver and intestines successively from the 3rd d. We sequenced the whole genome of the isolated duck plague strain, and by comparing the homology with the published duck plague virus whole sequences in Genbank, the virus strain obtained in this study had the highest homology with the Chinese virulent strain SD (MN518864.1), with nucleotide (nt) homology of about 99.90% and amino acid (aa) homology of about 99.75%, which indicated that the isolate is a virulent strain. Previously, it was reported that the natural infection of duck plague virus mainly occurs above 30 d of age, but the duck plague virus found in this study can naturally infect ducklings up to 20 d of age, and the mortality rate is as high as 100%. In this study, the pathogenicity test and whole genome sequence analysis of this isolate provided data support and theoretical basis for further research on pathogenicity and virulence-related gene analysis of duck plague virus.

Genomic variation of 363 diverse tea accessions unveils the genetic diversity, domestication, and structural variations associated with tea adaptation.

Domestication has shaped the population structure and agronomic traits of tea plants, yet the complexity of tea population structure and genetic variation that determines these traits remains unclear. We here investigated the resequencing data of 363 diverse tea accessions collected extensively from almost all tea distributions and found that the population structure of tea plants was divided into eight subgroups, which were basically consistent with their geographical distributions. The genetic diversity of tea plants in China decreased from southwest to east as latitude increased. Results also indicated that Camellia sinensis var. assamica (CSA) illustrated divergent selection signatures with Camellia sinensis var. sinensis (CSS). The domesticated genes of CSA were mainly involved in leaf development, flavonoid and alkaloid biosynthesis, while the domesticated genes in CSS mainly participated in amino acid metabolism, aroma compounds biosynthesis, and cold stress. Comparative population genomics further identified ~730 Mb novel sequences, generating 6,058 full-length protein-encoding genes, significantly expanding the gene pool of tea plants. We also discovered 217,376 large-scale structural variations and 56,583 presence and absence variations (PAVs) across diverse tea accessions, some of which were associated with tea quality and stress resistance. Functional experiments demonstrated that two PAV genes (CSS0049975 and CSS0006599) were likely to drive trait diversification in cold tolerance between CSA and CSS tea plants. The overall findings not only revealed the genetic diversity and domestication of tea plants, but also underscored the vital role of structural variations in the diversification of tea plant traits.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m2, End Stage Kidney Disease diagnosis, dialysis, or transplant.

Joint Optimization of Age of Information and Energy Consumption in NR-V2X System Based on Deep Reinforcement Learning.

As autonomous driving may be the most important application scenario of the next generation, the development of wireless access technologies enabling reliable and low-latency vehicle communication becomes crucial. To address this, 3GPP has developed Vehicle-to-Everything (V2X) specifications based on 5G New Radio (NR) technology, where Mode 2 Side-Link (SL) communication resembles Mode 4 in LTE-V2X, allowing direct communication between vehicles. This supplements SL communication in LTE-V2X and represents the latest advancements in cellular V2X (C-V2X) with the improved performance of NR-V2X. However, in NR-V2X Mode 2, resource collisions still occur and thus degrade the age of information (AOI). Therefore, an interference cancellation method is employed to mitigate this impact by combining NR-V2X with Non-Orthogonal multiple access (NOMA) technology. In NR-V2X, when vehicles select smaller resource reservation intervals (RRIs), higher-frequency transmissions use more energy to reduce AoI. Hence, it is important to jointly considerAoI and communication energy consumption based on NR-V2X communication. Then, we formulate such an optimization problem and employ the Deep Reinforcement Learning (DRL) algorithm to compute the optimal transmission RRI and transmission power for each transmitting vehicle to reduce the energy consumption of each transmitting vehicle and the AoI of each receiving vehicle. Extensive simulations demonstrate the performance of our proposed algorithm.

Genome-wide association study identified candidate genes for egg production traits in the Longyan Shan-ma duck.

Egg production is an important economic trait in layer ducks and understanding the genetics basis is important for their breeding. In this study, a genome-wide association study (GWAS) for egg production traits in 303 female Longyan Shan-ma ducks was performed based on a genotyping-by-sequencing strategy. Sixty-two single nucleotide polymorphisms (SNPs) associated with egg weight traits were identified (P < 9.48 × 10-5), including 8 SNPs at 5% linkage disequilibrium (LD)-based Bonferroni-corrected genome-wide significance level (P < 4.74 × 10-6). One hundred and nineteen SNPs were associated with egg number traits (P < 9.48 × 10-5), including 13 SNPs with 5% LD-based Bonferroni-corrected genome-wide significance (P < 4.74 × 10-6). These SNPs annotated 146 target genes which contained known candidate genes for egg production traits, such as prolactin and prolactin releasing hormone receptor. This study identified that these associated genes were significantly enriched in egg production-related pathways (P < 0.05), such as the oxytocin signaling, MAPK signaling, and calcium signaling pathways. It was notable that 18 genes were differentially expressed in ovarian tissues between higher and lower egg production in Shan-ma ducks. The identified potential candidate genes and pathways provide insight into the genetic basis underlying the egg production trait of layer ducks.

Assessment of cardiorespiratory fitness in Chinese patients with early to mid-stage Parkinson's disease.

PURPOSE: To evaluate cardiorespiratory fitness in patients with early to mid-stage Parkinson's disease by cardiopulmonary exercise test (CPET) on a stationary cycle ergometer. METHODS: To compare the differences in each index of the cardiopulmonary exercise test between the two groups of subjects; general data such as disease duration, medication use and exercise habits were also collected. RESULTS: (1) Finally, 36 Parkinson's disease patients and 12 healthy controls successfully completed the cardiopulmonary exercise test without any adverse events. (2) The V'O2peak, Metspeak, RERpeak, MVVpeak, Wpeak, HRpeak, HRpeak/pre, percentage of HRR-1 min decay > 12 bpm, SBPpeak in the Parkinson's disease group were lower than those in the control group (p < .05, each). Detailed data: V'O2peak (15.7 ± 4.5vs21.5 ± 3.6 ml/kg/min, p < .01), Metspeak (4.5 ± 1.3 vs 6.1 ± 1.0, p < .01), RERpeak (1.04 ± 0.10 vs 1.15 ± 0.10, p = .001), MVVpeak (37.22 ± 11.58 vs 53.00 ± 16.85L/min, p = .009), Wpeak (49.17 ± 29.72 vs 49.17 ± 29.72W, p < .01), HRpeak (111.08 ± 16.67 vs 111.08 ± 16.67bpm, p < .01), HRpeak/pre (71.19 ± 10.06 vs 96.00 ± 21.13, p = .002), percentage of HRR-1min decay > 12bpm (33.3% vs 100%, p < .01), systolic blood pressure (155.81 ± 31.83 vs 175.83 ± 17.84 mmHg, p = .01). (3) Divided Parkinson's disease patients into high V'O2peak group (V'O2peak ≥ 15 mL/kg/min) and low V'O2peak group (V'O2peak < 15 mL/kg/min). The age of patients, Hoehn-Yahr grade and incidence of symptom fluctuation in high V'O2peak group were lower (p < .05, respectively), percentage of males and percentage of HRR-1 min decay > 12 bpm were higher (p < .05, respectively); p < .05 is considered a statistically significant difference. Detailed data: age of patients(61.05 ± 6.93 vs 68.57 ± 7.99 years, p = .005), Hoehn-Yahr grade(1.75 ± 0.48 vs 2.18 ± 0.64, p = .028), incidence of symptom fluctuation (59.1 vs 92.9%, p = .03), percentage of males (77.7 vs 42.9%, p = .041), percentage of HRR-1 min decay > 12 bpm (50 vs 7.1%, p = .008). CONCLUSIONS: Cardiopulmonary exercise test was safe to perform and the cardiorespiratory fitness is significantly reduced in patients with early and middle stage Parkinson's disease. Patients with Parkinson's disease presented blunted heart rate and systolic blood pressure responses to exercise test. Females, older age, fluctuating symptoms, high H-Y staging and higher activities of daily living may be associated with lower oxygen uptake.

Persistent and Bioaccumulative Halogenated Natural Products in Various Tropical Reef Fish Species from the Seychelles, Western Indian Ocean.

Gas chromatography with electron capture negative ion mass spectrometry (GC/ECNI-MS) was used to quantify and compare halogenated natural products (HNPs) and selected anthropogenic persistent organic pollutants (POPs) in individual samples of 17 fish species from the Seychelles (Western Indian Ocean). The sum-HNP amounts (9.5-1100 ng/g lipid mass (lm)) were between 1 and 2 orders of magnitude higher than those of the sum of seven abundant polychlorinated biphenyl (PCB) congeners (0.2-15 ng/g lm) and dichlorodiphenyltrichloroethane-related compounds (DDTs) (<1.1-43 ng/g lm). Within the group of HNPs, the two tetrabrominated phenoxyanisoles (aka methoxylated diphenyl ethers, MeO-BDEs), 2'-MeO-BDE 68 ≫ 6-MeO-BDE 47, were predominant in most cases. Pearson correlation analysis showed that MeO-BDE levels were positively correlated with less abundant HNPs (2,2'-diMeO-BB 80, 2',6-diMeO-BDE 68, and Br6-DBP) (p < 0.01). Accordingly, HNPs, rather than PCBs and DDTs, were the predominant polyhalogenated contaminants in the current species.

Hexagon MXene based heterojunction interface with high ion adsorption and electron transfer efficiency for soft-package potassium-ions aqueous supercapacitors.

Potassium-ion hybrid capacitors (PIHC) are considered as ideal large-scale rechargeable energy storage devices due to their low-cost, high-power density and environmental protection. However, a low energy density is the main factor restricting the practical application of PIHC. The interface is formed on the surface of electrode material of PIHC through strong correlation to construct heterojunction, which can significantly improve the performance of ion energy storage. However, how to reveal the influence of the interfacial state of the heterojunction on the adsorption and electron transmission of energy storage ions at the atomic level is still one of the key scientific problems in this field. In this work, metal ion intercalation and microwave-assisted in-situ etching are used to construct the Hexagon MXene Ti3C2 heterojunction with TiOHO strong correlation. At the interface of heterojunction, TiOHO highway for electron transmission is developed to improve the rate performance of PIHC. Through experimental and theoretical calculation, the optimum adsorption position and maximum adsorption amount of potassium-ion at the single interface of heterojunction are obtained, and the specific energy density of PIHC is increased. This lays a foundation for the practical application of high-performance soft-package PIHC.

From Struggle to Strength: Coping with Abusive Supervision in Project Teams through Proactive Behavior and Team Building.

While considerable attention has been devoted to positive leadership patterns in the realm of project management, the dark side of leadership has rarely been studied within project teams. To address this gap, we focus on abusive supervision in project teams and develop a team-level moderated mediation model to examine whether, how, and when abusive supervision influences project outcomes by drawing from the Proactive Motivation Theory. Survey data were collected from 132 project teams containing 132 project managers and 392 project members using a multi-source time-lagged survey design. Our findings reveal significant negative relationships between abusive supervision and both project performance and project team creativity. Furthermore, we found that a team's proactive behavior plays a mediating role in these relationships. More importantly, our study identifies that team building mitigates the direct negative impact of abusive supervision on proactive behavior and the indirect effects of abusive supervision on project performance and project team creativity. These findings provide valuable theoretical and managerial implications for abusive supervision and project management scholars and practitioners.

Comparative Analysis Between Directly Measured and Parent-Evaluated Executive Function: Predicting Children's Academic Achievement and Social Development in a One-Year Longitudinal Study.

Purpose: The purpose of this study was to examine differences between directly measured and parent-evaluated executive function in predicting children's academic achievement and social development, and to explore the mediating roles of peer status and social competence in the effects of executive function on social behavior. Patients and Methods: The study followed 106 first-grade children in an elementary school in China for one year. Regression and mediation analyses were conducted using SPSS 26.0 and AMOS 21.0 to test the hypotheses. Results: First, in a comparison of the predictive role of directly measured and parent-evaluated executive function, directly measured executive function played a more important role in predicting academic achievement, while parent-evaluated executive function played a greater role in predicting social development. Second, parent-evaluated executive function influenced social behavior primarily through social competence and peer status, with social competence playing a more significant mediating role than peer status. Conclusion: Compared with previous studies, the results of the present study provide more direct evidence for the relationship and differences between directly measured and parent-evaluated executive function, further suggesting that they have different efficacy and predictive goals, while the present study also describes the pathways through which executive function influences social behavior: the mediating role of peer status and social competence. This suggests that, on the one hand, educators or researchers need to choose appropriate measures of executive function for their own purposes and, on the other hand, in order to promote the development of children's social behavior, they need to focus on the development of children's executive function, social competence and peer relationships.

Discovery and Engineering of a Bacterial (+)-Pulegone Reductase for Efficient (-)-Menthol Biosynthesis.

The biosynthesis of valuable plant-derived monoterpene (-)-menthol from readily available feedstocks (e.g., (-)-limonene) is of great significance because of the high market demand for this product. However, biotransforming (+)-pulegone into (-)-menthone, the (-)-menthol precursor, through (+)-pulegone reductase (PGR) catalysis is inefficient because of the poor protein expression or catalytic efficiency (kcat/Km) of plant origin PGRs. In this study, a novel bacterial PGR from Pseudomonas resinovorans (PrPGR) was identified, and the most successful variant, PrPGRM2-1 (A50V/G53W), was obtained, showing respective 20-fold and 204-fold improvements in specific activity and catalytic efficiency. PrPGRM2-1 was employed to bioreduce (+)-pulegone, resulting in 4.4-fold and 35-fold enhancements in (-)-menthone titers compared with the bioreductions catalyzed by wild-type (WT) PrPGR and MpPGR, respectively. Furthermore, a whole-cell biocatalyst containing PrPGRM2-1, MpMMR, and BstFDH was constructed and achieved the highest (-)-menthol titer reported to date without externally supplemented NADPH/NADP+. Overall, this study details an efficient PGR with high catalytic efficiency that possesses great potential for (-)-menthol biosynthesis.

A multivariate to multivariate approach for voxel-wise genome-wide association analysis.

The joint analysis of imaging-genetics data facilitates the systematic investigation of genetic effects on brain structures and functions with spatial specificity. We focus on voxel-wise genome-wide association analysis, which may involve trillions of single nucleotide polymorphism (SNP)-voxel pairs. We attempt to identify underlying organized association patterns of SNP-voxel pairs and understand the polygenic and pleiotropic networks on brain imaging traits. We propose a bi-clique graph structure (ie, a set of SNPs highly correlated with a cluster of voxels) for the systematic association pattern. Next, we develop computational strategies to detect latent SNP-voxel bi-cliques and an inference model for statistical testing. We further provide theoretical results to guarantee the accuracy of our computational algorithms and statistical inference. We validate our method by extensive simulation studies, and then apply it to the whole genome genetic and voxel-level white matter integrity data collected from 1052 participants of the human connectome project. The results demonstrate multiple genetic loci influencing white matter integrity measures on splenium and genu of the corpus callosum.

In Vitro and In Vivo Analyses Reveal Tumor-Derived Exosome miR-558 Promotes Angiogenesis in Tongue Squamous Cell Carcinoma by Targeting Heparinase.

This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.