Catalyst: Fast and flexible modeling of reaction networks.

We introduce Catalyst.jl, a flexible and feature-filled Julia library for modeling and high-performance simulation of chemical reaction networks (CRNs). Catalyst supports simulating stochastic chemical kinetics (jump process), chemical Langevin equation (stochastic differential equation), and reaction rate equation (ordinary differential equation) representations for CRNs. Through comprehensive benchmarks, we demonstrate that Catalyst simulation runtimes are often one to two orders of magnitude faster than other popular tools. More broadly, Catalyst acts as both a domain-specific language and an intermediate representation for symbolically encoding CRN models as Julia-native objects. This enables a pipeline of symbolically specifying, analyzing, and modifying CRNs; converting Catalyst models to symbolic representations of concrete mathematical models; and generating compiled code for numerical solvers. Leveraging ModelingToolkit.jl and Symbolics.jl, Catalyst models can be analyzed, simplified, and compiled into optimized representations for use in numerical solvers. Finally, we demonstrate Catalyst's broad extensibility and composability by highlighting how it can compose with a variety of Julia libraries, and how existing open-source biological modeling projects have extended its intermediate representation.

Metrics of Sexual Behavior Stigma Among Cisgender Men Who Have Sex With Men in 9 Cities Across the United States.

Men who have sex with men (MSM) in the United States are stigmatized for their same-sex practices, which can lead to risky sexual behavior, potentiating risk for human immunodeficiency virus (HIV) infection. Improved measurement is necessary for accurately reporting and mitigating sexual behavior stigma. We added 13 sexual behavior stigma items to local surveys administered in 2017 at 9 sites in the Centers for Disease Control and Prevention's National HIV Behavioral Surveillance system, which uses venue-based, time-sampling procedures to survey cisgender MSM in US Census Metropolitan Statistical Areas. We performed exploratory factor analytical procedures on site-specific (Baltimore, Maryland; Denver, Colorado; Detroit, Michigan; Houston, Texas; Nassau-Suffolk, New York; Portland, Oregon; Los Angeles, California; San Diego, California; and Virginia Beach-Norfolk, Virginia) and pooled responses to the survey items. A 3-factor solution-"stigma from family" (α = 0.70), "anticipated health-care stigma" (α = 0.75), and "general social stigma" (α = 0.66)-best fitted the pooled data and was the best-fitting solution across sites. Findings demonstrate that MSM across the United States experience sexual behavior stigma similarly. The results reflect the programmatic utility of enhanced stigma measurement, including tracking trends in stigma over time, making regional comparisons of stigma burden, and supporting evaluation of stigma-mitigation interventions among MSM across the United States.

Associations between HIV testing and multilevel stigmas among gay men and other men who have sex with men in nine urban centers across the United States.

BACKGROUND: Complex manifestation of stigma across personal, community, and structural levels and their effect on HIV outcomes are less understood than effects in isolation. Yet, multilevel approaches that jointly assesses HIV criminalization and personal sexual behavior stigma in relation to HIV testing have not been widely employed or have only focused on specific subpopulations. The current study assesses the association of three types of MSM-related sexual behavior-related stigma (family, healthcare, general social stigma) measured at both individual and site levels and the presence/absence of laws criminalizing HIV transmission with HIV testing behaviors to inform HIV surveillance and prevention efforts among HIV-negative MSM in a holistic and integrated way. METHODS: We included nine National HIV Behavioral Surveillance (NHBS) 2017 sites: Baltimore, MD; Denver, CO; Detroit, MI; Houston, TX; Long Island/Nassau-Suffolk, NY; Los Angeles, CA; Portland, OR; San Diego, CA; and Virginia Beach and Norfolk, VA. Multivariable generalized hierarchical linear modeling was used to examine how sexual behavior stigmas (stigma from family, anticipated healthcare stigma, general social stigma) measured at the individual and site levels and state HIV criminalization legislation (no, HIV-specific, or sentence-enhancement laws) were associated with past-year HIV testing behaviors across sites (n = 3,278). RESULTS: The majority of MSM across sites were tested for HIV in the past two years (n = 2,909, 95.4%) with the average number of times tested ranging from 1.79 (SD = 3.11) in Portland, OR to 4.95 (SD = 4.35) in Los Angeles, CA. In unadjusted models, there was a significant positive relationship between stigma from family and being tested for HIV in the past two years. Site-level HIV-specific criminalization laws were associated with an approximate 5% reduction in the prevalence of receiving any HIV test in the past two years after individual level stigma and sociodemographic covariate adjustments (PR = 0.94, 95% CI, 0.90-0.99). CONCLUSIONS: Structural barriers faced by MSM persist and ending the HIV epidemic in the US requires a supportive legal environment to ensure effective engagement in HIV services among MSM. Home-based solutions, such as self-testing, used to deliver HIV testing may be particularly important in punitive settings while legal change is advocated for on the community and state levels.

Stiff neural ordinary differential equations.

Neural Ordinary Differential Equations (ODEs) are a promising approach to learn dynamical models from time-series data in science and engineering applications. This work aims at learning neural ODEs for stiff systems, which are usually raised from chemical kinetic modeling in chemical and biological systems. We first show the challenges of learning neural ODEs in the classical stiff ODE systems of Robertson's problem and propose techniques to mitigate the challenges associated with scale separations in stiff systems. We then present successful demonstrations in stiff systems of Robertson's problem and an air pollution problem. The demonstrations show that the usage of deep networks with rectified activations, proper scaling of the network outputs as well as loss functions, and stabilized gradient calculations are the key techniques enabling the learning of stiff neural ODEs. The success of learning stiff neural ODEs opens up possibilities of using neural ODEs in applications with widely varying time-scales, such as chemical dynamics in energy conversion, environmental engineering, and life sciences.

Radiometric Performance Evaluation of FY-4A/AGRI Based on Aqua/MODIS.

Fengyun-4A (FY-4A) is the first satellite of the Chinese second-generation geostationary orbit meteorological satellites (FY-4). The Advanced Geostationary Radiation Imager (AGRI), onboard FY-4A does not load with high-precision calibration facility in visible and near infrared (VNIR) channel. As a consequence, it is necessary to comprehensively evaluate its radiometric performance and quantitatively describe the attenuation while using its VNIR data. In this paper, the radiometric performance at VNIR channels of FY-4A/AGRI is evaluated based on Aqua/MODIS data using the deep convective cloud (DCC) target. In order to reduce the influence of view angle and spectral response difference, the bi-directional reflectance distribution function (BRDF) correction and spectral matching have been performed. The evaluation result shows the radiometric performance of FY-4A/AGRI: (1) is less stable and with obvious fluctuations; (2) has a lower radiation level because of 24.99% lower compared with Aqua/MODIS; 3) has a high attenuation with 9.11% total attenuation over 2 years and 4.0% average annual attenuation rate. After the evaluation, relative radiometric normalization between AGRI and MODIS in VNIR channel is performed and the procedure is proved effective. This paper proposed a more reliable reference for the quantitative applications of FY-4A data.

LncRNA NEAT1 promotes autophagy via regulating miR-204/ATG3 and enhanced cell resistance to sorafenib in hepatocellular carcinoma.

Long noncoding RNAs (lncRNAs) has been acknowledged in tumorigenesis gradually because of the great importance in different cancers. LncRNA nuclear enriched abundant transcript 1 (NEAT1) is a novel lncRNA and has been reported to promote multiple cancer progression. However, the biological roles of NEAT1 in hepatocellular carcinoma (HCC) is not cleared nowadays. In the present research, the level of NEAT1 was found to be upregulated in HCC by The Cancer Genome Atlas. In addition, NEAT1 expression is negatively correlated with the survival rate in HCC. Further investigation revealed that NEAT1 upregulation inhibited sorafenib efficacy and promoted autophagy. We found that NEAT1 could be a sponge for microRNA-204 (miR-204) and inhibits its level to upregulate ATG3 expression. In addition to the above, we demonstrated that miR-204 mimics also attenuated tumor autophagy. And rescue assays demonstrated that NEAT1 promotes HCC autophagy through modulating miR-204/ATG3 pathway. Collectively, this study first demonstrated that a novel NEAT1/miR-204/ATG3 signaling regulates HCC progression.

Focus on the morphogenesis, fate and the role in tumor progression of multivesicular bodies.

Multivesicular bodies (MVBs) are endosome organelles that are gradually attracting research attention. Initially, MVBs were considered as important components of the endosomal-lysosomal degradation pathway. In recent years, with an increase in extracellular vesicle (EV) research, the biogenesis, fate, and pathological effects of MVBs have been increasingly studied. However, the mechanisms by which MVBs are sorted to the lysosome and plasma membrane remain unclear. In addition, whether the trafficking of MVBs can determine whether exosomes are released from cells, the factors are involved in cargo loading and regulating the fate of MVBs, and the roles that MVBs play in the development of disease are unknown. Consequently, this review focuses on the mechanism of MVB biogenesis, intraluminal vesicle formation, sorting of different cargoes, and regulation of their fate. We also discuss the mechanisms of emerging amphisome-dependent secretion and degradation. In addition, we highlight the contributions of MVBs to the heterogeneity of EVs, and their important roles in cancer. Thus, we attempt to unravel the various functions of MVBs in the cell and their multiple roles in tumor progression. Video Abstract.

LncRNA CCAT1 promotes autophagy via regulating ATG7 by sponging miR-181 in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant clinical challenge, and the mechanisms underlying HCC pathogenesis remain incompletely understood. Colon cancer associated transcript 1 (CCAT1), is one novel long noncoding RNA (lncRNA) which is upregulated in HCC. Autophagy is a vital process in HCC progression, and it is unknown whether CCAT1 regulates autophagy in HCC. MATERIALS AND METHODS: Immunofluorescence staining and transmission electron microscopy were used to analyze autophagy activity. Luciferase assay was performed to confirm miRNA-181a-5p (miR-181a-5p) bind CCAT1 and ATG7. RESULTS: CCAT1 levels were higher in tissue and cell lines of HCC. In function research, we found that CCAT1 facilitates HCC cell autophagy and cell proliferation. Our results show that, mechanistically, CCAT1 promotes autophagy through functioning as a sponge for miR-181a-5p, and then regulating ATG7 expression. CONCLUSION: Our findings indicate CCAT1 may play a role in regulating autophagy by sponging miR-181a-5p in HCC.

Long non-coding RNA HOTAIR promotes exosome secretion by regulating RAB35 and SNAP23 in hepatocellular carcinoma.

BACKGROUND: Emerging evidence indicates that tumor cells release a large amount of exosomes loaded with cargos during tumorigenesis. Exosome secretion is a multi-step process regulated by certain related molecules. Long non-coding RNAs (lncRNAs) play an important role in hepatocellular carcinoma (HCC) progression. However, the role of lncRNA HOTAIR in regulating exosome secretion in HCC cells remains unclear. METHODS: We analyzed the relationship between HOTAIR expression and exosome secretion-related genes using gene set enrichment analysis (GSEA). Nanoparticle tracking analysis was performed to validate the effect of HOTAIR on exosome secretion. The transport of multivesicular bodies (MVBs) after overexpression of HOTAIR was detected by transmission electron microscopy and confocal microscopy analysis of cluster determinant 63 (CD63) with synaptosome associated protein 23 (SNAP23). The mechanism of HOTAIR's regulation of Ras-related protein Rab-35 (RAB35), vesicle associated membrane protein 3 (VAMP3), and SNAP23 was assessed using confocal co-localization analysis, phosphorylation assays, and rescue experiments. RESULTS: We found an enrichment of exosome secretion-related genes in the HOTAIR high expression group. HOTAIR promoted the release of exosomes by inducing MVB transport to the plasma membrane. HOTAIR regulated RAB35 expression and localization, which controlled the docking process. Moreover, HOTAIR facilitated the final step of fusion by influencing VAMP3 and SNAP23 colocalization. In addition, we validated that HOTAIR induced the phosphorylation of SNAP23 via mammalian target of rapamycin (mTOR) signaling. CONCLUSION: Our study demonstrated a novel function of lncRNA HOTAIR in promoting exosome secretion from HCC cells and provided a new understanding of lncRNAs in tumor cell biology.

The role of YAP/TAZ activity in cancer metabolic reprogramming.

In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.

Adaptation of the HIV Care Continuum as a Method for Evaluating Syphilis and Gonorrhea Disease Control Activities in Los Angeles County.

BACKGROUND: Treatment verification and contact elicitation are core approaches used to control the spread of sexually transmitted diseases (STDs). Methodology adapted from the HIV care continuum is presented as an evaluation and communication tool for STD control activities. METHODS: Sexually transmitted disease surveillance and program data for Los Angeles County in 2013 were used to construct a 2-part continuum to examine syphilis (all stages) and gonorrhea outcomes among index patients and elicited contacts. The Index Case Continuum (Part 1) assesses the proportion of patients who were treated, assigned for interview, interviewed, and provided name and locating information for at least 1 contact. The Elicited Contact Continuum (Part 2) assesses the proportion of contacts who were located, interviewed, and treated. RESULTS: Among 3668 patients with syphilis, 97% (n = 3556) were treated, 72% (n = 2633) were interviewed, and 25% (n = 920) provided name and locating information for at least 1 contact. The corresponding numbers for 12,541 gonorrhea cases were 95% (n = 11,936), 45% (n = 5633), and 16% (1944), respectively. Among the 1392 contacts elicited from syphilis cases, 53% (n = 735) were either interviewed or determined to not need an interview and 43% (n = 595) were treated. The corresponding numbers for the 2323 contacts elicited from gonorrhea cases were 53% (n = 1221) and 46% (n = 1075), respectively. CONCLUSIONS: Adaptation of the HIV continuum is a useful tool for evaluating treatment verification and contact elicitation activities. In Los Angeles County, this approach revealed significant drop-offs in the proportion of index cases naming contacts and in the proportion of contacts who are interviewed and treated.

Prevalence and circulation patterns of variant, atypical and resistant HIV in Los Angeles County (2007-2009).

The prevalence of transmitted HIV drug resistance (TDR) in Los Angeles County remains unknown, due in part to the absence of reliable genotypic data. The specific objectives of this study are to estimate the prevalence of TDR, to describe the demographic characteristics associated with TDR and to investigate the distribution of HIV-1 subtypes among persons newly diagnosed with HIV in Los Angeles County. From 2007 through 2009, 1,414 sequences were obtained from 7,100 persons newly diagnosed with HIV through HIV resistance surveillance. Overall, 257 (18%) sequences had some genetic evidence of drug resistance. Of these, 122 (9%) exhibited evidence of resistance to non-nucleoside reverse transcriptase inhibitors, 121 (9%) to nucleoside reverse transcriptase inhibitors and 76 (5%) to protease inhibitors. Subtype B was dominant (97%), followed by subtypes C (1.2%), CRF01_AE (0.8%), CRF02_AG (0.4%), A (0.3%), and F (0.1%). With a TDR prevalence of 18%, Los Angeles County ranks high compared with other jurisdictions across the nation. The prevalence of TDR in recent (19%) and long-standing (17%) HIV cases were similar, thus providing additional support for the notion that TDR-associated mutations may persist well beyond the period of recent infection. HIV-1 CRF01_AE, observed historically in central Africa and Asia, was observed to be circulating among men who have sex with men and heterosexuals in Los Angeles County. These findings underscore the need for continued and expanded HIV resistance surveillance to inform healthcare providers, policy makers and at-risk populations of emerging trends in HIV drug resistance.

Association between plant-based dietary index and gallstone disease: A cross sectional study from NHANES.

BACKGROUND: The relationship between plant-based diets and gallstone disease has been debated. This study aimed to shed light on the association between plant-based dietary index and the risk of developing gallstone disease. METHODS: Eligible participants were selected from National Health and Nutrition Examination Survey (NHANES) 2017-2020. Three plant-based diet indexes (PDI, healthy PDI, unhealthy PDI) were calculated using data from two NHANES 24-h dietary recall interviews. Restricted Cubic Spline and multivariate logistic regression were used to analyze the associations. Subgroup analysis was adopted to make the results more robust. RESULTS: A total of 5673 eligible participants were analyzed. After adjusting for various confounding variables, uPDI was positively associated with gallstone disease (OR = 1.53, 95%CI: 1.02-2.29). No association was found between PDI/hPDI and gallstone disease (p > 0.05). The results of subgroup analysis did not show any positive association between uPDI and gallstones in specific groups. CONCLUSION: Our study shows that the elevated uPDI are linked to a higher risk of gallstone disease.

Association of Serum Complement C1q and C3 Level with Age-Related Macular Degeneration in Women.

PURPOSE: To investigate the association between serum complement components and age-related macular degeneration (AMD). PATIENTS AND METHODS: A total of 118 AMD patients and age- and sex-matched 106 control subjects were included. Demographic data and the level of serum complement component (C)1q, C3 and C4 were evaluated. Based on sex, the subjects were stratified into male and female subgroups. RESULTS: The level of C1q (226.31±45.33mg/dL) was significantly higher and C3 (121.14±15.76mg/dL) was significantly lower than that in control group (200.03±38.54mg/dL) (128.42±19.81mg/dL) in the female AMD patients (p = 0.005, p = 0.045). Logistic regression showed that increased C1q (OR = 1.132, p = 0.016) and decreased C3 (OR = 0.960, p = 0.048) were independent risk factors for female AMD patients. No statistical significance was observed in the male. CONCLUSION: Increased C1q and decreased C3 were associated with increased risk of AMD, suggesting that the complement classical pathway probably be involved in AMD, especially in female.

Intra-tumor heterogeneity and prognostic risk signature for hepatocellular carcinoma based on single-cell analysis.

Intra-tumor heterogeneity poses a serious challenge in the treatment of cancer, including hepatocellular carcinoma (HCC). Recent developments in single-cell RNA sequencing (scRNA-seq) make it possible to examine the heterogeneity of tumor cells. The Gene Expression Omnibus (GEO) database was retrieved to obtain scRNA-seq data of 13 HCC and 8 para cancer samples, and the cells were clustered using FindNeighbors and FindClusters functions. Cell subsets were defined using the "Enricher" function of the clusterProfiler package. Monocle was used to predict cell developmental trajectory. The LIMMA package included in the R program was utilized to detect differentially expressed genes (DEGs) between HCC and paracancerous tissues. Univariate Cox analysis and Least Absolute and Selection Operator (Lasso) Cox regression analysis were conducted to establish a risk assessment model. Thirteen cell subpopulations were identified from the sequencing data of 64,634 single cells. Four cell subgroups (dendritic cells, hepatocytes, liver bud hepatic cells, and liver progenitor cells) in tumor tissues were highly enriched. Between HCC and para cancer tissues, 3024 DEGs were identified, and 641 were specific markers of four cell subgroups. To develop a prognostic risk model, 9 genes among the 641 genes were selected. In the training and validation sets, the model demonstrated a higher 5-year AUC and independently served as a prognostic marker as confirmed by multivariate and univariate Cox analyses. This study revealed the characteristics of different cell subpopulations of immune cells and tumor cells from the HCC microenvironment. We established a novel nine-gene prognostic model to determine the death risk of HCC patients. The discoveries in this research improved the current knowledge of HCC heterogeneity and may inspire future research.

Brain fingerprints along the language hierarchy.

Recent studies have shown that the brain functional connectome constitutes a unique fingerprint that allows the identification of individuals from a group. However, what information encoded in the brain that makes us unique remains elusive. Here, we addressed this issue by examining how individual identifiability changed along the language hierarchy. Subjects underwent fMRI scanning during rest and when listening to short stories played backward, scrambled at the sentence level, and played forward. Identification for individuals was performed between two scan sessions for each task as well as between the rest and task sessions. We found that individual identifiability tends to increase along the language hierarchy: the more complex the task is, the better subjects can be distinguished from each other based on their whole-brain functional connectivity profiles. A similar principle is found at the functional network level: compared to the low-order network (the auditory network), the high-order network is more individualized (the frontoparietal network). Moreover, in both cases, the increase in individual identifiability is accompanied by the increase in inter-subject variability of functional connectivities. These findings advance the understanding of the source of brain individualization and have potential implications for developing robust connectivity-based biomarkers.

Retraction Notice to: YAP1 Inhibition in HUVECs Is Associated with Released Exosomes and Increased Hepatocarcinoma Invasion and Metastasis.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.021.].

Neutrophil-To-Lymphocyte Ratio as a Potential Biomarker of Neovascular Glaucoma.

Purpose: To evaluate blood count-derived inflammation indexes as a detection or predictive marker for neovascular glaucoma (NVG) secondary to retinal vein occlusion (RVO) and diabetic retinopathy (DR).Methods: This was a retrospective, case-control study design. The level of white blood cell (WBC), neutrophil (N), neutrophil/lymphocyte ratio (NLR), and lymphocyte/monocyte ratio (LMR) were evaluated in NVG patients secondary to RVO or DR.Results: A significant difference was found in those biomarkers between control group and NVG secondary to RVO or DR. Logistic regression analysis revealed these indexes were associated with the risk of NVG in DR and RVO patients. Multiple linear regression analysis showed a significant correlation between NLR and visual fields mean deviation in the NVG-RVO group.Conclusions: This study indicated that WBC, N, NLR, and LMR were related to NVG, and NLR may be useful as an potential inflammation biomarker indicating the risk and severity for NVG secondary to RVO.

Association between Red Blood Cell Distribution Width and Diabetic Retinopathy: A 5-Year Retrospective Case-Control Study.

PURPOSE: Red blood cell distribution width (RDW) has been regarded as an emerging biomarker of the general population and cardiovascular disease. In this study, we aimed to evaluate the association between RDW and diabetic retinopathy (DR). METHODS: This case-control study included 167 patients with DR, 131 patients with diabetes mellitus (DM), and 170 age- and sex-matched healthy controls from April 2014 to May 2019. Demographic data, laboratory parameters, and ocular examinations were collected. RESULTS: RDW values of the DR group were significantly higher than those of the healthy control (p < 0.001) and DM group (p=0.002). A similar trend was observed when RDW was compared among the 3 groups with respect to age and gender. Logistic regression analysis has shown the OR of RDW was 3.791 (2.33-6.168; p < 0.001) against the control group and was 1.348 (0.997-1.823; p=0.047) against the DM group. CONCLUSION: RDW values were significantly elevated in DR patients, and an elevated RDW was associated with an increased incidence of DR in patients with DM.

LINC00511 drives invasive behavior in hepatocellular carcinoma by regulating exosome secretion and invadopodia formation.

BACKGROUND: Tumor cells are known to release large numbers of exosomes containing active substances that participate in cancer progression. Abnormally expressed long noncoding RNAs (lncRNAs) have been confirmed to regulate multiple processes associated with tumor progression. However, the mechanism by which lncRNAs affect exosome secretion remains unclear. METHODS: The underlying mechanisms of long noncoding RNA LINC00511 (LINC00511) regulation of multivesicular body (MVB) trafficking, exosome secretion, invadopodia formation, and tumor invasion were determined through gene set enrichment analysis (GSEA), immunoblotting, nanoparticle tracking analysis, confocal colocalization analysis, electron microscopy, and invasion experiments. RESULTS: We revealed that the tumorigenesis process is associated with a significant increase in vesicle secretion in hepatocellular carcinoma (HCC). Additionally, LINC00511 was significantly more highly expressed in HCC tissues and is related to vesicle trafficking and MVB distribution. We also found that in addition to the formation of invadopodia in HCC progression, abnormal LINC00511 induces invadopodia formation in HCC cells by regulating the colocalization of vesicle associated membrane protein 7 (VAMP7) and synaptosome associated protein 23 (SNAP23) to induce the invadopodia formation, which are key secretion sites for MVBs and control exosome secretion. Finally, we revealed that LINC0051-induced invadopodia and exosome secretion were involved in tumor progression. CONCLUSIONS: Our experiments revealed novel findings on the relationship between LINC00511 dysregulation in HCC and invadopodia production and exosome secretion. This is a novel mechanism by which LINC00511 regulates invadopodia biogenesis and exosome secretion to further promote cancer progression.