Inhibiting Ion Migration Through Chemical Polymerization and Chemical Chelation Toward Stable Perovskite Solar Cells.

The migration of ions is known to be associated with various detrimental phenomena, including current density-voltage hysteresis, phase segregation, etc., which significantly limit the stability and performance of perovskite solar cells, impeding their progress toward commercial applications. To address these challenges, we propose incorporating a polymerizable organic small molecule monomer, N-carbamoyl-2-propan-2-ylpent-4-enamide (Apronal), into the perovskite film to form a crosslinked polymer (P-Apronal) through thermal crosslinking. The carbonyl and amino groups in Apronal effectively interact with shallow defects, such as uncoordinated Pb2+ and iodide vacancies, leading to the formation of high-quality films with enhanced crystallinity and reduced lattice strain. Furthermore, the introduction of P-Apronal improves energy level alignment, and facilitates charge carrier extraction and transport, resulting in a champion efficiency of 25.09 %. Importantly, P-Apronal can effectively suppress the migration of I- ions and improve the long-term stability of the devices. The present strategy sets forth a path to attain long-term stability and enhanced efficiency in perovskite solar cells.

Thermally Crosslinked F-rich Polymer to Inhibit Lead Leakage for Sustainable Perovskite Solar Cells and Modules.

High-performance perovskite solar cells have demonstrated commercial viability, but still face the risk of contamination from lead leakage and long-term stability problems caused by defects. Here, an organic small molecule (octafluoro-1,6-hexanediol diacrylate) is introduced into the perovskite film to form a polymer through in situ thermal crosslinking, of which the carbonyl group anchors the uncoordinated Pb2+ of perovskite and reduces the leakage of lead, along with the -CF2 - hydrophobic group protecting the Pb2+ from water invasion. Additionally, the polymer passivates varieties of Pb-related and I-related defects through coordination and hydrogen bonding interactions, regulating the crystallization of perovskite film with reduced trap density, releasing lattice strain, and promoting carrier transport and extraction. The optimal efficiencies of polymer-incorporated devices are 24.76 % (0.09 cm2 ) and 20.66 % (14 cm2 ). More importantly, the storage stability, thermal stability, and operational stability have been significantly improved.

Analysis of the expression and prognosis for leukocyte immunoglobulin-like receptor subfamily B in human liver cancer.

BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B (LILRB), including 5 subtypes, is a group of inhibitory receptors in the immune system. The LILRB family is known to be involved in the tumor progression of various cancer types, especially liver cancer. However, the expression patterns and prognostic values of LILRB family members in liver cancer tissues remain unclear. METHODS: We used the Oncomine database, GEPIA database, Kaplan-Meier Plotter, Timer, and TISIDB to assess the expression and prognostic value of the LILRB family in liver cancer patients. We also verified the expression of the LILRB family in tumor tissues and tumor-free liver tissues at the protein level by using immunohistochemistry. The STRING website was used to explore the interaction between the LILRB family and their related genes. The DAVID database was used to perform the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Flow cytometry was used to assess the infiltrated NK cells in liver cancer tissues. RESULTS: Our study revealed that the mRNA expression of LILRB1, LILRB2, LILRB3, and LILRB5 was downregulated, while compared with normal tissues, the mRNA expression of LILRB4 was upregulated in liver cancer tissues. Survival analysis revealed that LILRB2 and LILRB5 mRNA expression levels were significantly positively associated with overall survival (OS) and disease-free survival (DSS) and that the mRNA expression of all LILRB family members was significantly positively correlated with recurrence-free survival (RFS) and progression-free survival (PFS). Next, we further found that the mRNA expression of all LILRB family members was significantly associated with the infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in liver cancer. Finally, GO and KEGG analyses found that the LILRB family and its related genes were involved in antigen processing and presentation and natural killer cell-mediated cytotoxicity pathways. CONCLUSIONS: Our study suggested that LILRB family expression was associated with the prognosis of liver cancer patients and infiltrated immune cells. The LILRB family might be involved in antigen processing and presentation and natural killer cell-mediated cytotoxicity pathways.

Glioma-derived extracellular vesicles promote tumor progression by conveying WT1.

Glioma persists as one of the most aggressive primary tumors of the central nervous system. Glioma cells are known to communicate with tumor-associated macrophages/microglia via various cytokines to establish the tumor microenvironment. However, how extracellular vesicles (EVs), emerging regulators of cell-cell communication networks, function in this process is still elusive. We report here that glioma-derived EVs promote tumor progression by affecting microglial gene expression in an intracranial implantation glioma model mouse. The gene expression of thrombospondin-1 (Thbs1), a negative regulator of angiogenesis, was commonly downregulated in microglia after the addition of EVs isolated from different glioma cell lines, which endogenously expressed Wilms tumor-1 (WT1). Conversely, WT1-deficiency in the glioma-derived EVs significantly attenuated the Thbs1 downregulation and suppressed the tumor progression. WT1 was highly expressed in EVs obtained from the cerebrospinal fluid of human patients with malignant glioma. Our findings establish a novel model of tumor progression via EV-mediated WT1-Thbs1 intercellular regulatory pathway, which may be a future diagnostic or therapeutic target.

Gelsolin inhibits malignant phenotype of glioblastoma and is regulated by miR-654-5p and miR-450b-5p.

We have previously shown that gelsolin (GSN) levels are significantly lower in the blood of patients with glioblastoma (GBM) than in healthy controls. Here, we analyzed the function of GSN in GBM and examined its clinical significance. Furthermore, microRNAs involved in GSN expression were also identified. The expression of GSN was determined using western blot analysis and found to be significantly lower in GBM samples than normal ones. Gelsolin was mainly localized in normal astrocytes, shown using immunohistochemistry and immunofluorescence. Higher expression of GSN was correlated with more prolonged progression-free survival and overall survival. Gelsolin knockdown using siRNA and shRNA markedly accelerated cell proliferation and invasion in GBM in vitro and in vivo. The inactive form of glycogen synthase kinase-3ß was dephosphorylated by GSN knockdown. In GBM tissues, the expression of GSN and microRNA (miR)-654-5p and miR-450b-5p showed an inverse correlation. The miR-654-5p and miR-450b-5p inhibitors enhanced GSN expression, resulting in reduced proliferation and invasion. In conclusion, GSN, which inhibits cell proliferation and invasion, is suppressed by miR-654-5p and miR-450b-5p in GBM, suggesting that these miRNAs can be targets for treating GBM.

RDCPF: A Redundancy-Based Duty-Cycling Pipelined-Forwarding MAC for Linear Sensor Networks.

Existing duty-cycling and pipelined-forwarding (DCPF) protocols applied in battery-powered wireless sensor networks can significantly alleviate the sleep latency issue and save the energy of networks. However, when a DCPF protocol applies to a linear sensor network (LSN), it lacks the ability to handle the bottleneck issue called the energy-hole problem, which is mainly manifested due to the excessive energy consumption of nodes near the sink node. Without overcoming this issue, the lifespan of the network could be greatly reduced. To that end, this paper proposes a method of deploying redundant nodes in LSN, and a corresponding enhanced DCPF protocol called redundancy-based DCPF (RDCPF) to support the new topology of LSN. In RDCPF, the distribution of energy consumption of the whole network becomes much more even. RDCPF also brings improvements to the network in terms of network survival time, packet delivery latency, and energy efficiency, which have been shown through the extensive simulations in comparison with existing DCPF protocols.

Inhibition of autophagy induced by quercetin at a late stage enhances cytotoxic effects on glioma cells.

Glioma is the most common primary brain tumor in the central nervous system (CNS) with high morbidity and mortality in adults. Although standardized comprehensive therapy has been adapted, the prognosis of glioma patients is still frustrating and thus novel therapeutic strategies are urgently in need. Quercetin (Quer), an important flavonoid compound found in many herbs, is shown to be effective in some tumor models including glioma. Recently, it is reported that adequate regulation of autophagy can strengthen cytotoxic effect of anticancer drugs. However, it is not yet fully clear how we should modulate autophagy to achieve a satisfactory therapeutic effect. 3-Methyladenine (3-MA) and Beclin1 short hairpin RNA (shRNA) were used to inhibit the early stage of autophage while chloroquine (CQ) to inhibit the late stage. MTT assay was implemented to determine cell viability. Transmission electron microscopy, western blot, and immunohistochemistry were adopted to evaluate autophagy. Western blot, flow cytometry, and immunohistochemistry were used to detect apoptosis. C6 glioma xenograft models were established to assess the therapeutic effect (the body weight change, the median survival time, and tumor volume) in vivo. Quercetin can inhibit cell viability and induce autophagy of U87 and U251 glioma cells in a dose-dependent manner. Inhibition of early-stage autophagy by 3-MA or shRNA against Beclin1 attenuated the quercetin-induced cytotoxicity. In contrast, suppression of autophagy at a late stage by CQ enhanced the anti-glioma efficiency of quercetin. Therapeutic effect of quercetin for malignant glioma can be strengthened by inhibition of autophagy at a late stage, not initial stage, which may provide a novel opportunity for glioma therapy.

XBP1 silencing decreases glioma cell viability and glycolysis possibly by inhibiting HK2 expression.

Glioma cells rely on glycolysis to obtain energy and sustain their survival under microenvironmental stress in vivo. The mechanisms of regulation of glycolysis in glioma cells are unclear. Signaling pathway mediated by the transcription factor X box-binding protein 1 (XBP1) is one of the most important pathways of unfolded protein response which is comprehensively activated in cancer cells upon the microenvironmental stress. Here we showed that XBP1 was significantly activated in glioma tissues in vivo. XBP1 silencing resulted in decreasing of glioma cell viability and ATP/lactate production under hypoxia, which is possibly mediated by inhibition of Hexokinase II (HK2)'s expression. More importantly, XBP1 silenced glioma cells showed the decrease of tumor formation capacity. Our results revealed that XBP1s activation was involved in glioma glycolysis regulation and might be a potential molecular target for glioma treatment.

Impact of autophagy inhibition at different stages on cytotoxic effect of autophagy inducer in glioblastoma cells.

BACKGROUND/AIMS: Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a poor prognosis. Combination treatment of autophagy inducer and autophagy inhibitor may be a feasible solution to improve the therapeutic effects. However, the correlation between them is unclear. The purpose of this study was to investigate the effect of autophagy inhibition at different stages on cytotoxicity of autophagy inducers in glioblastoma cells. METHODS: Autophagy inhibition at early stage was achieved by 3-methyladenine (3-MA) or Beclin 1 shRNA. Autophagy inhibition at late stage was achieved by chloroquine (CQ) or Rab7 shRNA. Cell viability was assessed by MTT assay. Autophagy was measured using transmission electron microscopy and western blot. Apoptosis was measured using western blot and flow-cytometry. RESULTS: Inhibition of early steps of autophagy by 3-MA or Beclin 1 knockdown decreased the toxic effect of arsenic trioxide (ATO) in GBM cell lines. In contrast, blockade of autophagy flux at late stage by CQ or Rab7 knockdown enhanced the cytotoxicity of ATO, and caused accumulation of degradative autophagic vacuoles and robust apoptosis. Moreover, depletion of Beclin 1 abolished the synergistic effect of ATO and CQ by reducing autophagy and apoptosis. Combination of CQ with other autophagy inducers also induced synergistic apoptotic cell death. CONCLUSION: These results suggest that inhibition of late process of autophagy, not initial step, increases the cytotoxic effect of autophagy inducers via autophagy and apoptosis, which may contribute to GBM chemotherapy.

MiR-212-3p inhibits glioblastoma cell proliferation by targeting SGK3.

Glioblastoma multiforme (GBM) is the most malignant brain tumor in humans. Previous studies have demonstrated that microRNA plays important roles in the development and proliferation of GBM cells. Here we defined the mechanism by which miR-212-3p regulated the proliferation of GBM. In this study, we showed that miR-212-3p expression was significantly down-regulated and negatively correlated with serum and glucocorticoid-inducible kinase 3 (SGK3) in GBM. Either over-expression of miR-212-3p or silence of SGK3 decreased viability of GBM cells. Moreover, miR-212-3p directly bound to 3'UTR of SGK3 and inhibited its mRNA and protein expression. And over-expression of SGK3 rescued the decreased proliferation of GBM cells induced by miR-212-3p. Importantly, miR-212-3p also suppressed tumor growth in vivo. Collectively, our results demonstrated that miR-212-3p inhibited proliferation of GBM cells by directly targeting SGK3, and could potentially serve as a new therapeutic target for GBM.

Hot-Carrier Cooling Regulation for Mixed Sn-Pb Perovskite Solar Cells.

The rapid relaxation of hot carriers leads to energy loss in the form of heat and consequently restricts the theoretical efficiency of single-junction solar cells; However, this issue has not received much attention in tin-lead perovskites solar cells. Herein, tin(II) oxalate (SnC2O4) is introduced into tin-lead perovskite precursor solution to regulate hot-carrier cooling dynamics. The addition of SnC2O4 increases the length of carrier diffusion, extends the lifetime of carriers, and simultaneously slows down the cooling rate of carriers. Furthermore, SnC2O4 can bond with uncoordinated Sn2+ and Pb2+ ions to regulate the crystallization of perovskite and enable large grains. The strongly reducing properties of the C2O4 2- can inhibit the oxidation of Sn2+ to Sn4+ and minimize the formation of Sn vacancies in the resulting perovskite films. Additionally, as a substitute for tin(II) fluoride, the introduction of SnC2O4 avoids the carrier transport issues caused by the aggregation of F- ions at the interface. As a result, the SnC2O4-treated Sn-Pb cells show a champion efficiency of 23.36%, as well as 27.56% for the all-perovskite tandem solar cells. Moreover, the SnC2O4-treated devices show excellent long-term stability. This finding is expected to pave the way toward stable and highly efficient all-perovskite tandem solar cells.

Hidden risks: Simulated leakage of domestic sewage to secondary water supply systems poses serious microbiological risks.

There are continuous reports about the pollution of the secondary water supply systems (SWSSs), among which domestic sewage leakage is the most serious. In this study, a pilot experiment lasting 70 days was conducted to explore the changes in physicochemical water quality and the microbial profiles in SWSSs polluted by different doses of domestic sewage through qPCR and high-throughput sequencing methods. The results showed that when domestic sewage entered the simulated water storage tank, a large amount of organic matter brought by domestic sewage quickly consumed chlorine disinfectants. High pollution levels (pollution index ≥ 1/1000) were accompanied by significant increases in turbidity and ammonia nitrogen concentration (p < 0.05) and by abnormal changes in sensory properties. Although different microbial community structures were found only at high pollution levels, qPCR results showed that the abundance of the bacterial 16S rRNA gene and some pathogenic gene markers in the polluted tank increased with the pollution level, and the specific gene marker of pathogens could be detected even at imperceptible pollution levels. In particular, the high detection frequency and abundance of Escherichia coli and Enterococcus faecails in polluted tank water samples demonstrated that they can be used for early warning. Moreover, it seems that the microorganisms that came with the domestic sewage lost their cultivability soon after entering SWSSs but could recover their activities during stagnation. In addition, the biofilm biomass in the polluted tank with high pollution levels increased faster at the initial stage, while after a longer contact time, it tended to remain at the same level as the control tank. This study emphasized the high microbial risk introduced by sewage water leakage even at imperceptible levels and could provide scientific suggestions for early warning and prevention of pollution to SWSSs.

Signal-off electrochemical sensor for matrix metalloproteinase 9 detection based on sacrificial FeMOF and host-guest strategy.

Matrix metalloproteinase-9 (MMP-9) has been implicated in various tumor cell invasions and metastases. In light of the limitations of traditional methods for MMP-9 detection, we have constructed a novel biosensor depending on cucurbit[8]uril (CB[8]) -mediated host-guest interactions and a sacrificial iron metal-organic framework (FeMOF). Herein, MMP9-specific peptides modified on the gold bare electrode are bonded to the FeMOF@AuNPs@peptide complex through CB[8] addition. The connection between MMP9-specific peptides and signal peptides via CB[8] provides stability as well as enables the immobilization of FeMOF on the electrode surface. When Fe3+ from the FeMOF interacts with electrochemical buffer K4Fe(CN)6, Prussian blue will be generated on the gold electrode surface, and a significantly enlarged current response can be detected. However, in the presence of MMP-9, their peptide substrates are specifically cleaved at the site between serine (S) and Leucine (L), which causes an abrupt decrease in the electrochemical signal. The change of signal can reflect MMP-9 concentration. This sensor can reach an ultrahigh sensitivity with a wide detection range of 0.5 pg⋅mL-1 to 500 ng⋅mL-1 and a low detection limit of 1.30 pg⋅mL-1. Importantly, this sensor is very simple, relying solely on self-sacrificial label of FeMOF, rather than complex functional materials. Additionally, it has been well used in serum samples, showing attractive potential for practical applications.

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC.

For hepatocellular carcinoma (HCC) patients, we attempted to establish a new oxidative stress (OS)-related prognostic model for predicting prognosis, exploring immune microenvironment, and predicting the immunotherapy response. Significantly differently expressed oxidative stress-related genes (DEOSGs) between normal and HCC samples from the Cancer Genome Atlas (TCGA) were screened, and then based on weighted gene coexpression network analysis (WGCNA), HCC-related hub genes were discovered. Based on the least absolute shrinkage and selection operator (LASSO) and cox regression analysis, a prognostic model was developed. We validated the prognostic model's predictive power using an external validation cohort: the International Cancer Genome Consortium (ICGC).Then a nomogram was determined. Furthermore, we also examined the relationship of the risk model and clinical characteristics as well as immune microenvironment. 434 DEOSGs, comprising 62 downregulated and 372 upregulated genes (p < 0.05 and |log2FC| ≥ 1), and 257 HCC-related hub genes were recognized in HCC. Afterward, we built a five-DEOSG (LOX, CYP2C9, EIF2B4, EZH2, and SRXN1) prognostic risk model. Using the nomogram, the risk model was shown to have good prognostic value. Compared to the low risk group, HCC patients with high risk had poorer outcomes, worse pathological grades, and advanced tumor stages (p < 0.05). There were significant increases in LOX, EIF2B4, EZH2, and SRXN1 expression in HCC samples, while CYP2C9 expression was decreased. Finally, Real-time PCR (RT-qPCR) confirmed the mRNA expressions of five genes (CYP2C9, EIF2B4, EZH2, SRXN1, LOX) in HCC cell lines. Our study constructed a prognostic OS-related model with strong predictive power and potential as an immunosuppressive biomarker for HCC leading to improving prediction and providing new insights for HCC immunotherapy.

Inflammatory mechanisms of Ginkgo Biloba extract in improving memory functions through lncRNA-COX2/NF-κB pathway in mice with status epilepticus.

PURPOSE: This study was to explore whether Ginkgo biloba extract (GBE) improve memory impairment by alleviating neuroinflammation signaling in mice with status epilepticus. METHODS: The status epilepticus (SE) mice model was established by pilocarpine and treated with 100 mg / kg of GBE for 14 days. Spontaneous alternation of Y-maze and new object recognition were used to explore memory impairment. To examine glial cell activation, we performed immunohistochemistry and immunofluorescence staining. The activation of NF-κB signaling and the expression level of lncRNA-COX2 were detected by Western blot and qRT-PCR, respectively. Adeno-associated virus lncRNA-COX2 was injected into mice for overexpression of lncRNA-COX2. RESULTS: After GBE treatment, the spontaneous alternation rate and the recognition coefficient in SE mice were both increased. Moreover, activation of glial cells, NF-κB signaling and lncRNA-COX2 were significantly decreased in SE mice. In the GBE-treated SE mice with lncRNA-COX2 overexpression, NF-κB signaling was up-regulated again; the reduced level of inflammation factors was reversed; the GBE-rescued spontaneous alternation rate of Y-maze was eliminated. CONCLUSION: Our results suggested that GBE reduces the hippocampal inflammation by down-regulating lncRNA-COX2 / NF-κB signaling in the SE mice, leading to the decrease of neuronal damage and the improvement of memory functions.

Charge order driven by multiple-Q spin fluctuations in heavily electron-doped iron selenide superconductors.

Intertwined spin and charge orders have been widely studied in high-temperature superconductors, since their fluctuations may facilitate electron pairing; however, they are rarely identified in heavily electron-doped iron selenides. Here, using scanning tunneling microscopy, we show that when the superconductivity of (Li0.84Fe0.16OH)Fe1-xSe is suppressed by introducing Fe-site defects, a short-ranged checkerboard charge order emerges, propagating along the Fe-Fe directions with an approximately 2aFe period. It persists throughout the whole phase space tuned by Fe-site defect density, from a defect-pinned local pattern in optimally doped samples to an extended order in samples with lower Tc or non-superconducting. Intriguingly, our simulations indicate that the charge order is likely driven by multiple-Q spin density waves originating from the spin fluctuations observed by inelastic neutron scattering. Our study proves the presence of a competing order in heavily electron-doped iron selenides, and demonstrates the potential of charge order as a tool to detect spin fluctuations.

AHSA1 Promotes Proliferation and EMT by Regulating ERK/CALD1 Axis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. AHSA1 as a chaperone of HSP90 promotes the maturation, stability, and degradation of related cancer-promoting proteins. However, the regulatory mechanism and biological function of AHSA1 in HCC are largely unknown. Actually, we found that AHSA1 was significantly upregulated in HCC tissues and cell lines and was notably correlated with the poor clinical characteristics and prognosis of HCC patients in this study. Furthermore, both in vitro and in vivo, gain- and loss-of-function studies demonstrated that AHSA1 promoted the proliferation, invasion, metastasis, and epithelial-mesenchymal transition (EMT) of HCC. Moreover, the mechanistic study indicated that AHSA1 recruited ERK1/2 and promoted the phosphorylation and inactivation of CALD1, while ERK1/2 phosphorylation inhibitor SCH772984 reversed the role of AHSA1 in the proliferation and EMT of HCC. Furthermore, we demonstrated that the knockdown of CALD1 reversed the inhibition of proliferation and EMT by knocking AHSA1 in HCC. We also illustrated a new molecular mechanism associated with AHSA1 in HCC that was independent of HSP90 and MEK1/2. In summary, AHSA1 may play an oncogenic role in HCC by regulating ERK/CALD1 axis and may serve as a novel therapeutic target for HCC.

Nomogram for Predicting Postoperative Portal Venous Systemic Thrombosis in Patients with Cirrhosis Undergoing Splenectomy and Esophagogastric Devascularization.

Objectives: The aim of the study is to develop a nomogram for predicting postoperative portal venous systemic thrombosis (PVST) in patients with cirrhosis undergoing splenectomy and esophagogastric devascularization. Methods: In total, 195 eligible patients were included. Demographic characteristics were collected, and the results of perioperative routine laboratory investigations and ultrasound examinations were also recorded. Blood cell morphological traits, including the red cell volume distribution width (RDW), mean platelet volume, and platelet distribution width, were identified. Univariate and multivariate logistic regressions were implemented for risk factor filtration, and an integrated nomogram was generated and then validated using the bootstrap method. Results: A color Doppler abdominal ultrasound examination on a postoperative day (POD) 7 (38.97%) revealed that 76 patients had PVST. The results of the multivariate logistic regression suggested that a higher RDW on POD3 (RDW3) (odds ratio (OR): 1.188, 95% confidence interval (CI): 1.073-1.326), wider portal vein diameter (OR: 1.387, 95% CI: 1.203-1.642), history of variceal hemorrhage (OR: 3.407, 95% CI: 1.670-7.220), and longer spleen length (OR: 1.015, 95% CI: 1.001-1.029) were independent risk parameters for postoperative PVST. Moreover, the nomogram integrating these four parameters exhibited considerable capability in PVST forecasting. The nomogram's receiver operating characteristic curve reached 0.83 and achieved a sensitivity and specificity of 0.711 and 0.848, respectively, at its cutoff. The nomogram's calibration curve demonstrated that it was well calibrated. Conclusion: The nomogram exhibited excellent performance in PVST prediction and might assist surgeons in identifying vulnerable patients and administering timely prophylaxis.

LncRNA SNHG17 Contributes to Proliferation, Migration, and Poor Prognosis of Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNAs) have been substantially reported to have critical roles in regulating tumorigenesis in recent years. However, the expression pattern and biological function of SNHG17 in hepatocellular carcinoma (HCC) remain unclear. Bioinformatics analysis and qRT-PCR were performed to detect the expression pattern of SNHG17 in HCC tissues, adjacent nontumorous tissues, and cell lines. The effect of SNHG17 on proliferation, migration, and apoptosis of HCC was investigated by knockdown and overexpressing SNHG17 in HCC cell lines. RNA sequencing was utilized to explore the underlying mechanism. Utilizing publicly available TCGA-LIHC, GSE102079 HCC datasets, and qRT-PCR, we found SNHG17 was significantly upregulated in HCC tissues and cell lines and was notably associated with larger tumor size, poorly differentiation, presence of vascular invasion, and advanced TNM stage. Furthermore, gain- and loss-of-function studies demonstrated that SNHG17 promoted cell proliferation and migration and inhibited apoptosis of HCC. By employing RNA sequencing, we found knockdown of SNHG17 caused 1037 differentially expressed genes, highly enriched in several pathways, including metabolic, PI3K-Akt, cell adhesion, regulation of cell proliferation, and apoptotic pathway; among them, 92 were overlapped with SNHG17-related genes in the TCGA-LIHC dataset. Furthermore, ERH, TBCA, TDO2, and PDK4 were successfully validated and found significantly dysregulated in HCC tissues. Moreover, HCC patients with higher SNHG17 expression had a relatively poor overall survival and disease-free survival, and ERH and PDK4 also played a marked role in the prognosis of HCC. Broadly, our findings illustrate that SNHG17 acts as a noncoding oncogene in HCC progression, suggesting its potential value as a novel target for HCC therapy.

EFNA4 promotes cell proliferation and tumor metastasis in hepatocellular carcinoma through a PIK3R2/GSK3ß/ß-catenin positive feedback loop.

Rapid tumor progression, metastasis, and diagnosis in advanced stages of disease are the main reasons for the short survival time and high mortality rate of patients with hepatocellular carcinoma (HCC). Ephrin A4 (EFNA4), the ligand of the EPH family, participates in the development of blood vessels and epithelium by regulating cell migration and rejection. In our study, based on bioinformatics analyses, we found that EFNA4 was highly expressed and led to poor prognosis in patients with HCC. We demonstrated that overexpression of EFNA4 significantly promoted HCC cell proliferation and migration in vivo or in vitro. In addition, knockdown of EFNA4 inhibited the proliferation and migration of HCC cells. Furthermore, EFNA4 was found to directly interact with EPHA2 and promote its phosphorylation at Ser897, followed by recruitment of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) and activation of the glycogen synthase kinase-3beta (GSK3ß)/ß-catenin signaling pathway. Moreover, overexpression of ß-catenin further promoted the expression of PIK3R2, which formed a positive feedback loop. The results revealed that abnormal expression of EFNA4 is the main switch of the PIK3R2/GSK3ß/ß-catenin loop that influenced the proliferation and migration of HCC cells and suggest that EFNA4 is a potential prognostic marker and a prospective therapeutic target in patients with HCC.