Development of D-π-A organic dyes for discriminating HSA from BSA and study on dye-HSA interaction.

HSA (human serum albumin), a most abundant protein in blood serum, plays a key role in maintaining human health. Abnormal HSA level is correlated with many diseases, and thus has been used as an essential biomarker for therapeutic monitoring and biomedical diagnosis. Development of small-molecule fluorescent probes allowing the selective and sensitive recognition of HSA in in vitro and in vivo is of fundamental importance in basic biological research as well as medical diagnosis. Herein, we reported a series of new synthesized fluorescent dyes containing D-π-A constitution, which exhibited different optical properties in solution and solid state. Among them, dye M-H-SO3 with a hydrophilic sulfonate group at electron-acceptor part displayed selectivity for discrimination of HSA from BSA and other enzymes. Upon binding of dye M-H-SO3 with HSA, a significant fluorescence enhancement with a turn-on ratio about 96-fold was triggered. The detection limit was estimated to be âˆ¼ 40 nM. Studies on the interaction mechanism revealed that dye M-H-SO3 could bind to site III of HSA with a 1:1 binding stoichiometry. Furthermore, dye M-H-SO3 has been applied to determine HSA in real urine samples with good recoveries, which provided a useful method for HSA analysis in biological fluids.

Validation of the international MOGAD panel proposed criteria: a single-centre US study.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is a demyelinating disorder of the central nervous system. We aimed to evaluate the diagnostic performance of recently proposed MOGAD diagnostic criteria in a real-world patient cohort at a tertiary referral centre. METHODS: We identified all patients who were evaluated at Johns Hopkins and were MOG-IgG seropositive by cell-based assay. We retrospectively applied the proposed MOGAD diagnostic criteria. RESULTS: Among the 122 patients included in this study, 109 fulfilled the diagnostic criteria. Of 64 patients with clear positive MOG-IgG titre, 63 patients also satisfied the supporting clinical or MRI features. Of 58 patients with low positive or unknown MOG-IgG titre, 46 met criteria by fulfilment of the supporting features. The medical records were independently reviewed by two investigators with expertise in demyelinating disease, and patients were assigned empirical clinical diagnoses, with agreement with the application of the MOGAD diagnostic criteria in the majority of cases (90%). CONCLUSIONS: Our findings support the diagnostic utility of the proposed MOGAD diagnostic criteria. Patients with MOGAD met the supporting clinical or MRI features almost universally, which suggests that the criteria can be used to accurately differentiate MOGAD from mimics with low-titre MOG-IgG seropositivity.

Dental Artificial Intelligence Systems: A Review of Various Data Types.

With the rapid development of dental artificial intelligence systems (DAIS), a new field known as "Data Dentistry", proposed by Schwendicke in 2021, has successfully bridged the gap between medicine and engineering. This literature review introduces advanced techniques in data collection, outlines the current state of DAIS in data processing, and anticipates the future of DAIS by emphasizing the importance of more extensive and enhanced datasets. The key findings include: Versatility of imaging data: Various types of imaging data, such as X-ray, cone beam computed tomography (CBCT), facial photos, and face and oral scans, can be transformed into datasets used by artificial intelligence systems. Uniform rules in electronic dental record (EDR) systems: EDR systems require standardized rules for general use in DAIS, ensuring compatibility and seamless integration. Potential of wearable device data: Data from wearable devices, including bioelectric signals (such as electromyography), stress sensors, AR glasses, etc., show great potential for enhancing DAIS capabilities. Current DAIS performance focus: Presently, DAIS demonstrate superior performance in object location and disease diagnosis compared to information integration and clinical decision-making. Need for data quality and quantity improvement: Further improvements are needed in both the quality and quantity of data for DAIS.

Graphitic Armor: A Natural Molecular Sieve for Robust Hydrogen Electroxidation.

Carbon coating layers have been found to improve the catalytic performance of transition metals, which is usually explained as an outcome of electronic synergistic effect. Herein we reveal that the defective graphitic carbon, with a unique interlayer gap of 0.342 nm, can be a highly selective natural molecular sieve. It allows efficient diffusion of hydrogen molecules or radicals both along the in-plane and out-of-plane direction, but sterically hinders the diffusion of molecules with larger kinetic diameter (e.g., CO and O2) along the in-plane direction. As a result, poisonous species lager than 0.342 nm are sieved out, even when their adsorption on the metal is thermodynamically strong; at the same time, the interaction between H2 and the metal is not affected. This natural molecular sieve provides a very chance for constructing robust metal catalysts for hydrogen-relevant processes, which are more tolerant to chemical or electrochemical oxidation or CO-relevant poisoning.

Longitudinal evaluation of serum MOG-IgG titers in MOGAD after initiation of maintenance immunoglobulin: A case series.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct demyelinating disease of the central nervous system. Immunoglobulin (Ig) has been used as a maintenance therapy to prevent relapses in MOGAD, but the impact of Ig on serum MOG-IgG titers is unclear. OBJECTIVE: To characterize the variation in serum MOG-IgG titers after initiation of Ig treatment in people with MOGAD. METHODS: We conducted a retrospective study of 10 patients with a diagnosis of MOGAD and available serum MOG-IgG titers before and after initiation of maintenance Ig treatment. RESULTS: We found that most of the patients remained MOG-IgG seropositive while on Ig treatment with a reduced or unchanged titer, despite a lack of disease activity. CONCLUSIONS: This case series suggests that the mechanism of action of Ig therapy in MOGAD is not exclusively dependent on MOG-IgG titer reduction.

Image Feature Detectors in Agricultural Harvesting: An Evaluation.

Image feature detection serves as the cornerstone for numerous vision applications, and it has found extensive use in agricultural harvesting. Nevertheless, determining the optimal feature extraction technique for a specific situation proves challenging, as the Ground Truth correlation between images is exceedingly elusive in harsh agricultural harvesting environments. In this study, we assemble and make publicly available the inaugural agricultural harvesting dataset, encompassing four crops: rice, corn and soybean, wheat, and rape. We develop an innovative Ground Truth-independent feature detector assessment approach that amalgamates efficiency, repeatability, and feature distribution. We examine eight distinct feature detectors and conduct a thorough evaluation using the amassed dataset. The empirical findings indicate that the FAST detector and ASLFeat yield the most exceptional performance in agricultural harvesting contexts. This evaluation establishes a trustworthy bedrock for the astute identification and application of feature extraction techniques in diverse crop reaping situations.

Toward real-time and accurate dense 3D mapping of crop fields for combine harvesters using a stereo camera.

Fast and accurate 3D scene perception is a crucial prerequisite for the autonomous navigation and harvesting of combine harvesters. However, crop field scenarios pose severe challenges for vision-based perception systems due to repetitive scenes, illumination changes and real-time constraints on embedded computing platforms. In this paper, we propose a feature-based, two-stage approach for real-time dense 3D mapping for combine harvesters. In the first stage, our approach constructs a sparse 3D map using reliable feature matching, which provides prior knowledge about the environment. In the second stage, our method formulates per-pixel disparity calculation as probabilistic inference. The key to our approach is the ability to compute dense 3D maps by combining Bayesian estimation with efficient and discriminative point cues from images, exhibiting tolerance against visual measurement uncertainties due to repetitive textures and uneven lighting in crop fields. We validate the performance of the proposed method using real crop field data, and the results demonstrate that our dense 3D maps provide detailed spatial metric information while maintaining a balance between accuracy and efficiency. This makes our approach highly valuable for online perception in combine harvesters operating with resource-limited systems.

Confidence in dementia care and care approach toward dementia among the nursing staff in long-term care facilities in China: a cross-sectional survey.

Background: Confidence and appropriate care approach toward dementia among nursing staff (nurses and care assistants) are crucial manifestations of competency to deal with the complexity of dementia care in long-term care facilities (LTCFs). The purpose of this study was to investigate the confidence in dementia care and care approach among nursing staff in LTCFs in mainland China. Methods: A cross-sectional study design was utilized in LTCFs in Shandong Province, mainland China. A convenient sample included of 317 nursing staff drawn from 15 LTCFs. Survey questions included (a) demographics, (b) dementia knowledge, (c) dementia care confidence, and (d) approach to care for people with dementia. Data were analyzed with descriptive statistics. Factors associated with confidence and care approach for people with dementia were examined using Pearson's correlation and multivariate regression analyses. Results: Dementia care confidence was generally moderate. Factors affecting confidence to care for people with dementia included educational level, months of caring dementia patients, and dementia knowledge. Most nursing staff did not use a person-centered care approach which was significantly associated with their age, dementia-learning experience, and knowledge and confidence toward caring for people with dementia. Conclusion: A positive correlation was identified between confidence to care for people with dementia and nursing staff care approach. Clinical recommendations are provided to further develop education strategies tailored for nursing staff to meet the growing demand for dementia care services.

Research on land cover type classification method based on improved MaskFormer for remote sensing images.

High-resolution remote sensing images have the characteristics of wide imaging coverage, rich spectral information and unobstructed by terrain and features. All of them provide convenient conditions for people to study land cover types. However, most existing remote sensing image land cover datasets are only labeled with some remote sensing images of low elevation plain areas, which is highly different from the topography and landscape of highland mountainous areas. In this study, we construct a Qilian County grassland ecological element dataset to provide data support for highland ecological protection. To highlight the characteristics of vegetation, our dataset only includes the RGB spectrum fused with the near-infrared spectrum. We then propose a segmentation network, namely, the Shunted-MaskFormer network, by using a mask-based classification method, a multi-scale, high-efficiency feature extraction module and a data-dependent upsampling method. The extraction of grassland land types from 2 m resolution remote sensing images in Qilian County was completed, and the generalization ability of the model on a small Gaofen Image Dataset (GID) verified. Results: (1) The MIoU of the optimised network model in the Qilian grassland dataset reached 80.75%, which is 2.37% higher compared to the suboptimal results; (2) the optimized network model achieves better segmentation results even for small sample classes in data sets with unbalanced sample distribution; (3) the highest MIOU of 72.3% is achieved in the GID dataset of open remote sensing images containing five categories; (4) the size of the optimized model is only one-third of the sub-optimal model.

Interaction of hydrocortisone and illness severity on head growth in cohort of ELBW infants.

BACKGROUND: Extremely low birth weight (ELBW) infants comprise a fragile population at risk for neurodevelopmental disabilities (NDD). Systemic steroids were previously associated with NDD, but more recent studies suggest hydrocortisone (HCT) may improve survival without increasing NDD. However, the effects of HCT on head growth adjusted for illness severity during NICU hospitalization are unknown. Thus, we hypothesize that HCT will protect head growth, accounting for illness severity using a modified neonatal Sequential Organ Failure Assessment (M-nSOFA) score. METHODS: We conducted a retrospective study that included infants born at 23-29 weeks gestational age (GA) and < 1000 g. Our study included 73 infants, 41% of whom received HCT. RESULTS: We found negative correlations between growth parameters and age, similar between HCT and control patients. HCT-exposed infants had lower GA but similar normalized birth weights; HCT-exposed infants also had higher illness severity and longer lengths of hospital stay. We found an interaction between HCT exposure and illness severity on head growth, such that infants exposed to HCT had better head growth compared to those not exposed to HCT when adjusted for illness severity. CONCLUSION: These findings emphasize the importance of considering patient illness severity and suggest that HCT use may offer additional benefits not previously considered. IMPACT: This is the first study to assess the relationship between head growth and illness severity in extremely preterm infants with extremely low birth weights during their initial NICU hospitalization. Infants exposed to hydrocortisone (HCT) were overall more ill than those not exposed, yet HCT exposed infants had better preserved head growth relative to illness severity. Better understanding of the effects of HCT exposure on this vulnerable population will help guide more informed decisions on the relative risks and benefits for HCT use.

Pan-cancer analysis identifies LPCATs family as a prognostic biomarker and validation of LPCAT4/WNT/ß-catenin/c-JUN/ACSL3 in hepatocellular carcinoma.

Lipid remodeling regulators are now being investigated as potential therapeutic targets for cancer therapy as a result of their involvement, which includes promoting cancer cells' adaptation to the restricted environment. Lysophosphatidylcholine acyltransferases (LPCATs, LPCAT1-4) are enzymes that regulate the remodeling of bio-membranes. The functions of these enzymes in cancer are largely unknown. In the current study, we found that genes belonging to the LPCAT family participated in tumor advancement and were strongly linked to dismal prognosis in many different malignancies. We constructed the LPCATs scores model and explored this model in pan-cancer. Malignant pathways in pan-cancer were positively related to LPCATs scores, and all pathways had strong links to the tumor microenvironment (TME). Multiple immune-associated features of the TME in pan-cancer were likewise associated with higher LPCATs scores. In addition, the LPCATs score functioned as a prognostic marker for immune checkpoint inhibitor (ICI) therapies in patients with cancer. LPCAT4 enhanced cell growth and cholesterol biosynthesis by up-regulating ACSL3 in hepatocellular carcinoma (HCC). WNT/ß-catenin/c-JUN signaling pathway mediated LPCAT4's regulation on ACSL3. These findings demonstrated that genes in the LPCAT family might be used as cancer immunotherapy and prognosis-related biomarkers. Specifically, LPCAT4 could be a treatment target of HCC.

EBV-Upregulated B7-H3 Inhibits NK cell-Mediated Antitumor Function and Contributes to Nasopharyngeal Carcinoma Progression.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated epithelial malignancy characterized by the presence of prominent infiltration of lymphocytes, including natural killer (NK) cells. Although NK cells can directly target EBV-infected tumor cells without restriction by the MHC, EBV-positive (EBV+) NPC cells often develop resistance mechanisms that allow them to evade immune surveillance by NK cells. Elucidating the mechanisms involved in EBV-induced NK-cell dysfunction will contribute to the design of novel NK cell-based immunotherapies to treat NPC. Herein, we confirmed that the cytotoxic function of NK cells was impaired in EBV+ NPC tissues and found that EBV infection-induced expression of B7-H3 in NPC negatively correlated with NK-cell function. The inhibitory effect of EBV+ tumor expression of B7-H3 on NK-cell function was clarified in vitro and in vivo. Mechanistically, activation of the PI3K/AKT/mTOR signaling pathway via EBV latent membrane protein 1 (LMP1) was responsible for EBV infection-induced upregulation of B7-H3 expression. In an NPC xenograft mouse model with adoptive transfer of primary NK cells, deletion of B7-H3 on tumor cells in combination with anti-PD-L1 treatment restored NK cell-mediated antitumor activity and significantly improved the antitumor efficacy of NK cells. On the basis of our findings, we conclude that EBV infection can inhibit NK cell-mediated antitumor function by inducing upregulation of B7-H3 expression and provide a rationale for NK cell-based immunotherapies in combination of PD-L1 blockade and overcoming the immunosuppression of B7-H3 to treat EBV-associated NPC.

Comparative analysis of sugar, acid, and volatile compounds in CPPU-treated and honeybee-pollinated melon fruits during different developmental stages.

Plant growth regulator N-(2-chloro-4-pyridyl)-N'-phenylurea (CPPU) is widely used in fruit production. However, the mechanism in which CPPU affects melon fruit quality, especially aroma compound, remains unclear. Here, gas chromatography-mass spectrometry was performed to detect the sugar, citric acid, and aroma content in CPPU-treated and pollinated melon fruit. Results showed that the application of CPPU decreased the sugar and aroma content in melon fruit. The relative content of several important esters, including isobutyl acetate, ethyl acetate, 2-methylbutyl acetate, methyl acetate, benzyl acetate, and phenethyl acetate, in CPPU-treated fruits was significantly lower than that in honeybee-pollinated fruits. The content of many amino acids (isoleucine, leucine, valine, methionine, and l-phenylalanine), which could be metabolized into aroma compounds, in CPPU-treated fruits was significantly higher than that in honeybee-pollinated fruits. In conclusion, CPPU application interferes with amino-acid metabolism and affects the production of aromatic esters in melon fruit.

KRAS mutation predict response and outcome in advanced non-small cell lung carcinoma without driver alterations receiving PD-1 blockade immunotherapy combined with platinum-based chemotherapy: a retrospective cohort study from China.

Background: The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Kirsten rat sarcoma (KRAS) mutation is the most frequent molecular alteration found in advanced non-small cell lung carcinoma (NSCLC). We explored whether KRAS mutation status predicted the effects of first-line immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy in Chinese patients with advanced NSCLC. Methods: Clinical data were extracted from medical records of patients with advanced NSCLC at the First Affiliated Hospital of Guangzhou Medical University in China between January 2019 and March 2020. Overall survival (OS) and progression-free survival (PFS) rates were compared via log-rank tests, and independent prognostic factors were identified via Cox regression. Results: Patients with advanced NSCLC without driver alterations who were treated with ICI and platinum-based chemotherapy (N=80) were identified, including 28.7% with KRAS mutations and 71.3% with non-KRAS mutations. Tumor programmed death-ligand 1 (PD-L1) expression was analyzed using a 1% cutoff, and 32.5% of patients were negative and 67.5% were positive. The median tumor mutational burden (TMB) was 7.29 mutations per megabase (muts/Mb) (range, 0.08-44.8 muts/Mb), with 32.5% of cases <5 muts/Mb and 67.5% ≥5 muts/Mb. The median PFS and OS for the entire cohort were 9.8 (95% CI: 9.1-10.5) and 17.6 (95% CI: 14.4-20.8) months, respectively. The 6-month PFS rate was 67.5% and the 1-year OS rate was 72.5%. Thirty-five patients survived until the last follow-up. The OS and PFS of patients with KRAS mutations were significantly higher than those in the non-KRAS mutant group (P<0.05). The Cox multivariate analyses showed that brain metastasis [hazard ratio (HR) =0.232, 95% CI: 0.102-0.530; P=0.001], TMB (HR =5.675, 95% CI: 1.948-16.535; P=0.001), KRAS mutation (HR =2.552, 95% CI: 1.141-5.708; P=0.023) were independent predictors of OS in patients treated with ICIs and platinum-based chemotherapy. Liver metastasis (HR =0.344, 95% CI: 0.191-0.619; P<0.001) and KRAS/tumor protein p53 (TP53) co-mutation (HR =0.220, 95% CI: 0.067-0.725; P=0.013) were the prognostic factor for PFS of qualified patients. Conclusions: This work provides evidence that KRAS mutation in advanced NSCLC may be served as a potential predictive biomarker for immunotherapeutic efficacy.

Stereovision-Based Ego-Motion Estimation for Combine Harvesters.

Ego-motion estimation is a foundational capability for autonomous combine harvesters, supporting high-level functions such as navigation and harvesting. This paper presents a novel approach for estimating the motion of a combine harvester from a sequence of stereo images. The proposed method starts with tracking a set of 3D landmarks which are triangulated from stereo-matched features. Six Degree of Freedom (DoF) ego motion is obtained by minimizing the reprojection error of those landmarks on the current frame. Then, local bundle adjustment is performed to refine structure (i.e., landmark positions) and motion (i.e., keyframe poses) jointly in a sliding window. Both processes are encapsulated into a two-threaded architecture to achieve real-time performance. Our method utilizes a stereo camera, which enables estimation at true scale and easy startup of the system. Quantitative tests were performed on real agricultural scene data, comprising several different working paths, in terms of estimating accuracy and real-time performance. The experimental results demonstrated that our proposed perception system achieved favorable accuracy, outputting the pose at 10 Hz, which is sufficient for online ego-motion estimation for combine harvesters.

Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion.

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.

Retraction notice to "Chronic fluoxetine treatment in vivo enhances excitatory synaptic transmission in the hippocampus" [Neuropharmacology, 150 (15th May 2019) 38-45].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. After publication, Scott M. Thompson found significant concerns about the data and duly notified The University of Maryland. The University of Maryland conducted an internal investigation which confirmed that the article was compromised. Namely in Figure 2B, the Investigation Committee determined that the western blots used to create the figure were not the ones used for the quantification and concluded that the figure was falsified to fit the hypothesis. In Figure 2C and D, the Investigation Committee determined that the densitometry data (pCaMKII, pS831, CamKII and GluA1) used to create the histogram were falsified to fit the hypothesis.

A Neutralizing Antibody Targeting gH Provides Potent Protection against EBV Challenge In Vivo.

Epstein-Barr virus (EBV) is an oncogenic herpesvirus that is associated with 200,000 new cases of cancer and 140,000 deaths annually. To date, there are no available vaccines or therapeutics for clinical usage. Recently, the viral heterodimer glycoprotein gH/gL has become a promising target for the development of prophylactic vaccines against EBV. Here, we developed the anti-gH antibody 6H2 and its chimeric version C6H2, which had full neutralizing activity in epithelial cells and partial neutralizing activity in B cells. C6H2 exhibited potent protection against lethal EBV challenge in a humanized mouse model. The cryo-electron microscopy (cryo-EM) structure further revealed that 6H2 recognized a previously unidentified epitope on gH/gL D-IV that is critical for viral attachment and subsequent membrane fusion with epithelial cells. Our results suggest that C6H2 is a promising candidate in the prevention of EBV-induced lymphoproliferative diseases (LPDs) and may inform the design of an EBV vaccine. IMPORTANCE Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes lifelong persistence and is related to multiple diseases, including cancers. Neutralizing antibodies (NAbs) have proven to be highly effective in preventing EBV infection and subsequent diseases. Here, we developed an anti-EBV-gH NAb, 6H2, which blocked EBV infection in vitro and in vivo. This 6H2 neutralizing epitope should be helpful to understand EBV infection mechanisms and guide the development of vaccines and therapeutics against EBV infection.

EBV Infection in Epithelial Malignancies Induces Resistance to Antitumor Natural Killer Cells via F3-Mediated Platelet Aggregation.

Nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) are two major EBV-associated epithelial malignancies, both of which are characterized by the infiltration of a large number of lymphocytes, including natural killer (NK) cells. Although NK cells can prevent the development of EBV-associated epithelial malignancies, EBV-infected tumor cells often develop resistance to surveillance by NK cells. Elucidating the interactions between NK cells and EBV-infected tumor cells will facilitate the development of more effective NK-mediated therapies for treating EBV-associated malignancies. Here we investigated the cytotoxic function of NK cells in EBV-associated epithelial malignancies and discovered that EBV infection-induced upregulation of F3 expression correlates with NK-cell dysfunction in NPC and EBVaGC. The subsequent inhibitory effect of F3-mediated platelet aggregation on NK-cell function was verified in vitro and in vivo. Mechanistically, EBV latent membrane protein 2A (LMP2A) mediated upregulation of F3 through the PI3K/AKT signaling pathway. In an NPC xenograft mouse model, inhibition of F3 restored the antitumor function of NK cells and showed therapeutic efficacy when administered with NK-cell transfer. On the basis of these findings, EBV infection induces F3-mediated platelet aggregation that inhibits the antitumor function of NK cells, providing a rationale for developing and combining NK-cell-based therapies with F3 inhibitors to treat EBV-associated epithelial malignancies. SIGNIFICANCE: This study reveals a mechanism by which EBV-associated epithelial malignancies escape NK-cell-mediated immune surveillance, providing a new target for improving NK-cell immunotherapy.

IGF2BP3-induced activation of EIF5B contributes to progression of hepatocellular carcinoma cells.

In this study, we investigated the functional role of eukaryotic initiation factor 5B (EIF5B) in hepatocellular carcinoma (HCC) and the underlying mechanisms. Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues. Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells. Furthermore, EIF5B knockdown suppressed epithelial-mesenchymal transition (EMT) and the cancer stem cell (CSC) phenotype. Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil (5-FU). In the HCC cells, activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing. IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner. Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.