Exploring the autophagy-related pathogenesis of active ulcerative colitis.

BACKGROUND: The pathogenesis of ulcerative colitis (UC) is complex, and recent therapeutic advances remain unable to fully alleviate the condition. AIM: To inform the development of novel UC treatments, bioinformatics was used to explore the autophagy-related pathogenesis associated with the active phase of UC. METHODS: The GEO database was searched for UC-related datasets that included healthy controls who met the screening criteria. Differential analysis was conducted to obtain differentially expressed genes (DEGs). Autophagy-related targets were collected and intersected with the DEGs to identiy differentially expressed autophagy-related genes (DEARGs) associated with active UC. DEARGs were then subjected to KEGG, GO, and DisGeNET disease enrichment analyses using R software. Differential analysis of immune infiltrating cells was performed using the CiberSort algorithm. The least absolute shrinkage and selection operator algorithm and protein-protein interaction network were used to narrow down the DEARGs, and the top five targets in the Dgree ranking were designated as core targets. RESULTS: A total of 4822 DEGs were obtained, of which 58 were classified as DEARGs. SERPINA1, BAG3, HSPA5, CASP1, and CX3CL1 were identified as core targets. GO enrichment analysis revealed that DEARGs were primarily enriched in processes related to autophagy regulation and macroautophagy. KEGG enrichment analysis showed that DEARGs were predominantly associated with NOD-like receptor signaling and other signaling pathways. Disease enrichment analysis indicated that DEARGs were significantly linked to diseases such as malignant glioma and middle cerebral artery occlusion. Immune infiltration analysis demonstrated a higher presence of immune cells like activated memory CD4 T cells and follicular helper T cells in active UC patients than in healthy controls. CONCLUSION: Autophagy is closely related to the active phase of UC and the potential targets obtained from the analysis in this study may provide new insight into the treatment of active UC patients.

Short-branched alkyl sulfobetaine-passivated CsPbBr3 nanocrystals for efficient green light emitting diodes.

Inorganic cesium lead bromide nanocrystals (CsPbBr3 NCs) hold promising prospects for high performance green light-emitting diodes (LEDs) due to their exceptional color purity and high luminescence efficiency. However, the common ligands employed for passivating these indispensable NCs, such as long-chain organic ligands like oleic acid and oleylamine (OA/OAm), display highly dynamic binding and electronic insulating issues, thereby resulting in a low efficiency of the as-fabricated LEDs. Herein, we report a new zwitterionic short-branched alkyl sulfobetaine ligand, namely trioctyl(propyl-3-sulfonate) ammonium betaine (TOAB), to in situ passivate CsPbBr3 NCs via a feasible one-step solution synthesis, enabling efficiency improvement of CsPbBr3 NC-based LEDs. The zwitterionic TOAB ligand not only strengthened the surface passivation of CsPbBr3 NCs with a high photoluminescence quantum yield (PLQY) of 97%, but also enhanced the carrier transport in the fabricated CsPbBr3 NC thin films due to the short-branched alkyl design. Consequently, CsPbBr3 NCs passivated with TOAB achieved a green LED with an external quantum efficiency (EQE) of 7.3% and a maximum luminance of 5716 cd m-2, surpassing those of LEDs based on insulating long-chain ligand-passivated NCs. Our work provides an effective surface passivation ligand design to enhance the performance of CsPbBr3 NC-based LEDs.

Oxygen-deficient FeNbO4-x In-situ Growth in Honey-derived N-doping Porous Carbon for Overall Water Splitting.

It is still a great challenge to reasonably design green, low cost, high activity and good stability catalysts for overall water splitting (OWS). Here, we introduce a novel catalyst with ferric niobate (FeNbO4) in-situ growing in honey-derived porous carbon of high specific surface area, and its catalytic activity is further enhanced by micro-regulation (oxygen vacancy and N-doping). From the experimental results and density functional theory (DFT) calculations, the oxygen vacancy in catalyst FeNbO4-x@NC regulates the local charge density of active site, thus increasing conductivity and optimizing hydrogen/oxygen species adsorption energy. FeNbO4 in-situ grows within N-doping honey-derived porous carbon, which can enhance active specific surface area exposure, strengthen gaseous substances escape rate, and accelerate electrons/ions transfer and electrolytes diffusion. Moreover, in-situ Raman also confirms O-species generation in oxygen evolution reaction (OER). As a result, the catalyst FeNbO4-x@NC shows good electrochemical performance in OER, HER and OWS.

Bidirectional optical response hydrogel with adjustable human comfort temperature for smart windows.

Smart windows are effective in reducing the energy consumption of air conditioning and lighting systems, while contributing to maintaining the comfort zone of temperature in the indoor environment. Currently used smart windows mainly rely on traditional single-phase thermochromic material in which only one abrupt optical change occurs during temperature changes, and their inherent characteristics may not be suited for a practical balance of energy saving and privacy protection. Here, we developed a novel bidirectional optically responsive smart window (BSW) with unique bidirectional optical response features by introducing sodium dodecyl sulfate (SDS)/potassium tartrate (PTH) micelles into PNIPAM hydrogel to form a composite hydrogel, which was encapsulated in two glass panels. The upper critical solution temperature (UCST) and lowest critical solution temperature (LCST) of the material can be individually adjusted and are capable of matching the human comfort zone of temperature. In addition, the smart window exhibits remarkable transparency (92.5%), visible light transmission ratio (Tlum = 91.31%), and excellent solar modulation (ΔTsol,UCST = 76.34%, ΔTsol,LCST = 76.75%). Moreover, it possesses selectivity in transmitting light in the infrared band of solar radiation and can complete the "transparent-opaque" transition in a very narrow temperature range (<1 °C). When at comfortable temperatures, the highly transparent smart windows facilitate interior light and appreciation of the view. At low temperatures, SDS/PTH micelles aggregate to form large micelles, blocking the transmission of light and protecting customer privacy. At high temperatures, PNIPAM can undergo a "sol-gel" transition, thus blocking incident solar radiation. Taken together, these proposed materials with bidirectional optical response characteristics would be harnessed as a promising platform for building energy conservation, anti-counterfeiting, information encryption, and temperature monitoring.

Transparent, High Stretchable, Environmental Tolerance, and Excellent Sensitivity Hydrogel for Flexible Sensors and Capacitive Pens.

The prospect of ionic conductive hydrogels in multifunctional sensors has generated widespread scientific interest. The new generation of flexible materials should be combined with superior mechanical properties, high conductivity, transparency, sensitivity, good self-restoring fatigue properties, and other multifunctional characteristics, while the current materials are difficult to meet these requirements. Herein, we prepared poly(acrylamide-acrylic acid) (P(AM-AA))/gelatin/glycerol-Al3+ (PG1G2A) ionic conducting hydrogel by one-pot polymerization under UV light. The prepared PG1G2A ionic conductive hydrogel had high tensile strength (539.18 kPa), excellent tensile property (1412.96%), good fast self-recovery and fatigue resistance, high transparency (>80%), excellent moisturizing, and antifreezing/drying properties. In addition, the ionic conductive hydrogel-based strain sensor can respond to mechanical stimulation and generate accurate, stable, and recyclable electrical signals, with excellent sensitivity (GF 5.81). In addition, the PG1G2A hydrogel could be used as flexible wearable devices for monitoring multiple strain and subtle movements of different body parts at different temperatures. Interestingly, the PG1G2A hydrogel capacitive pen embedded in the mold can be used to write and draw on the screen of a phone or tablet. This new multifunctional ionic conducting hydrogel shows broad application prospects in E-skin, motion monitoring, and human-computer interaction in extreme environments.

Hepatocellular carcinoma cells remodel the pro-metastatic tumour microenvironment through recruitment and activation of fibroblasts via paracrine Egfl7 signaling.

BACKGROUND: The tumour microenvironment consists of a complex and dynamic milieu of cancer cells, including tumour-associated stromal cells (leukocytes, fibroblasts, vascular cells, etc.) and their extracellular products. During invasion and metastasis, cancer cells actively remodel the tumour microenvironment and alterations of microenvironment, particularly cancer-associated fibroblasts (CAFs), can promote tumour progression. However, the underlying mechanisms of the CAF formation and their metastasis-promoting functions remain unclear. METHODS: Primary liver fibroblasts and CAFs were isolated and characterized. CAFs in clinical samples were identified by immunohistochemical staining and the clinical significance of CAFs was also analysed in two independent cohorts. A transwell coculture system was used to confirm the role of HCC cells in CAF recruitment and activation. qRT-PCR, western blotting and ELISA were used to screen paracrine cytokines. The role and mechanism of Egfl7 in CAFs were explored via an in vitro coculture system and an in vivo mouse orthotopic transplantation model. RESULTS: We showed that CAFs in hepatocellular carcinoma (HCC) are characterized by the expression of α-SMA and that HCC cells can recruit liver fibroblasts (LFs) and activate them to promote their transformation into CAFs. High α-SMA expression, indicating high CAF infiltration, was correlated with malignant characteristics. It was also an independent risk factor for HCC survival and could predict a poor prognosis in HCC patients. Then, we demonstrated that EGF-like domain multiple 7 (Egfl7) was preferentially secreted by HCC cells, and exhibited high potential to recruit and activate LFs into the CAF phenotype. The ability of Egfl7 to modulate LFs relies upon increased phosphorylation of FAK and AKT via the receptor ανß3 integrin. Strikingly, CAFs activated by paracrine Egfl7 could further remodel the tumour microenvironment by depositing fibrils and collagen and in turn facilitate HCC cell proliferation, invasion and metastasis. CONCLUSION: Our data highlighted a novel role of Egfl7 in remodelling the tumour microenvironment: it recruits LFs and activates them to promote their transformation into CAFs via the ανß3 integrin signaling pathway, which further promotes HCC progression and contributes to poor clinical outcomes in HCC patients. Video Abstract.

Survey and analysis of the current status of research in the field of outdoor navigation for the blind.

PURPOSE: In this article, we comprehensively review the current situation and research on technology related to outdoor travel for blind and visually impaired people (BVIP), given the diverse types and incomplete functionality of navigation aids for the blind. This aims to provide a reference for related research in the fields of outdoor travel for BVIP and blind navigation. MATERIALS AND METHODS: We compiled articles related to blind navigation, of which a total of 227 of them are included in the search criteria. One hundred and seventy-nine articles are selected from the initial set, from a technical point of view, to elaborate on five aspects of blind navigation: system equipment, data sources, guidance algorithms, optimization of related methods, and navigation maps. RESULTS: The wearable form of assistive devices for the blind has the most research, followed by the handheld type of aids. The RGB data class based on vision sensor is the most common source of navigation environment information data. Object detection based on picture data is also particularly rich among navigation algorithms and associated methods, indicating that computer vision technology has become an important study content in the field of blind navigation. However, research on navigation maps is relatively less. CONCLUSIONS: In the study and development of assistive equipment for BVIP, there will be an emphasis on prioritizing attributes, such as lightness, portability, and efficiency. In light of the upcoming driverless era, the research focus will be on the development of visual sensors and computer vision technologies that can aid in navigation for the blind.IMPLICATIONS FOR REHABILITATIONThe visual deficiency can easily help blind and visually impaired people (BVIP) to develop psychological disorders.There are few, if any, devices to meet the outdoor travel needs of BVIP in all aspects.There is no comprehensive summary and overview in the field of outdoor navigation for the blind.The selection of appropriate assistive devices can help BVIP better understand the information of their surroundings and make safer and more effective outdoor trips.

Pseudohalogen Resurfaced CsPbBr3 Nanocrystals for Bright, Efficient, and Stable Green-Light-Emitting Diodes.

Lead halide perovskite nanocrystals (LHP NCs) are regarded as promising emitters for next-generation ultrahigh-definition displays due to their high color purity and wide color gamut. Recently, the external quantum efficiency (EQE) of LHP NC based light-emitting diodes (PNC LEDs) has been rapidly improved to a level required by practical applications. However, the poor operational stability of the device, caused by halide ion migration at the grain boundary of LHP NC thin films, remains a great challenge. Herein, we report a resurfacing strategy via pseudohalogen ions to mitigate detrimental halide ion migration, aiming to stabilize PNC LEDs. We employ a thiocyanate solution processed post-treatment method to efficiently resurface CsPbBr3 NCs and demonstrate that the thiocyanate ions can effectively inhibit bromide ion migration in LHP NC thin films. Owing to thiocyanate resurfacing, we fabricated LEDs with a high EQE of 17.3%, a maximum brightness of 48000 cd m-2, and an excellent operation half-life time.

A Fe2(SO4)3-assisted approach towards green synthesis of cuttlefish ink-derived carbon nanospheres for high-performance supercapacitors.

The conversion of renewable biomass resources into advanced electrode materials through green, simple, and economical methods has become an important research direction in energy storage. In this study, Fe-decorated N/S-codoped porous carbon nanospheres have been successfully fabricated from cuttlefish ink through Fe2(SO4)3-assisted hydrothermal carbonization coupled with heat treatment. The effects of Fe2(SO4)3 dosage on the structure, chemical composition, and capacitive property of carbon nanospheres were investigated. Herein, environmentally friendly Fe2(SO4)3 plays a multifunctional role as the graphitization catalyst, dopant, and morphology-regulating agent. Benefitting from the moderate graphitization degree, great heteroatom content and hierarchical porous structure, the prepared carbon nanospheres exhibit high specific capacitance (311.9 F g-1 at a current density of 0.5 A g-1), good rate capability (19.1% decrease in specific capacitance as current density increases from 0.5 to 10 A g-1), and ideal cycling stability (94.3% capacitance retention after 5000 cycles). In addition, the symmetric supercapacitor assembled with the carbon nanosphere electrodes achieves an energy density of 9.7 Wh kg-1 at a power density of 0.25 kW kg-1 and maintains 91.3% capacitance after 10,000 cycles. The desirable electrochemical performance of cuttlefish ink-derived carbon nanosphere material makes it a potential electrode candidate for supercapacitors.

Porous biscuit-like nanoplate FeNb11O29-x@C for lithium-ion storage and oxygen evolution.

The development of efficient and stable electrode materials for lithium-ion batteries (LIBs) and the oxygen evolution reaction (OER) is critical for clean and sustainable energy storage and conversion. In this work, porous biscuit-like nanoplate FeNb11O29-x@C is reasonably prepared by morphology control and microstructure modification, and presents many advantages in LIBs and the OER. In particular, FeNb11O29-x@C displays a large specific surface area, abundant active sites and a significant edge effect, thus improving the Li+ reactivity and OER kinetics. Meanwhile, the oxygen vacancies and lattice defects in FeNb11O29-x@C enhance the Li+ transport rate and reduce the OER barrier. In addition, the carbon layer structure not only inhibits the irreversible reaction between the electrolyte and metal ions, but promotes the stability, cycling ability and conductivity of LIBs and the OER. Generally, FeNb11O29-x@C demonstrates good electrochemical performance in LIBs (providing 240.8 mA h g-1 reversible capacity at a current density of 0.25C and just 0.98% capacity attenuation after 500 cycles at a current density of 10C). Again, it also shows high catalytic performance in the OER (a low overpotential (290 mV@10 mA cm-2), a small Tafel slope (44.4 mV dec-1) and desirable catalytic stability).

N,S co-doped V3Nb17O50@C fibers used for lithium-ion storage.

Bimetallic oxides deliver high specific capacity in energy storage, but their disadvantages, such as poor electrical conductivity, low ion diffusion rate and interatomic instability, limit their application. In this work, lattice defects (N,S co-doping) and carbon interfaces are introduced into S-V3Nb17O50@NC nanofibers to improve the electron/ion kinetic stability, electrical conductivity and electrochemical activity. Firstly, the lattice defects constructed by N,S co-doping produce more unmatched electrons, widen the lattice channels of S-V3Nb17O50@NC, provide more active sites, improve the material affinity to the electrolyte and enhance its electron/ion transport kinetics. Secondly, the carbon interfacial layer protects the lattice defects, inhibits the adverse reactions between the bimetal oxides and electrolyte, and boosts the stability and uniformity of ion transport. In addition, the volume effect of S-V3Nb17O50@NC is alleviated under the synergistic effect of the carbon layer and carbon fiber network, thus improving the cycling performance of the electrode material. In general, benefitting from N,S co-doping and interface protection, S-V3Nb17O50@NC nanofibers show good electrochemical performance in lithium-ion hybrid capacitors.

Multidefect N-Nb2 O5- x @CNTs Incorporated into Capillary Transport Framework for Li+ /Na+ Storage.

As an ion-embedded material with small strain and low transport energy barrier, the limited ion transport rate and conductivity of niobium pentaoxide (Nb2 O5 ) are the main factors limiting its application in lithium/sodium storage systems. In this work, the microsphere composites (N-Nb2 O5- x @CNTs) are prepared by combining Nb2 O5 , rich in nitrogen doping and vacancy defects, with carbon nanotubes (CNTs) penetrating the bulk phase. With the capillary effect, CNTs can enable the rapid electrolyte infiltration into the microspheres, thus shorting the Li+ /Na+ transport path. In addition, CNTs also hinder the direct contact between the electrolyte and Nb2 O5 , and inhibit the irreversible reaction. Meanwhile, nitrogen doping and oxygen vacancy defects reduce the energy barrier of Li+ /Na+ transport, and improve their transport rate, proved by density functional theory. Highly conductive CNTs and unpaired electrons from defects also ameliorate the insulation property of Nb2 O5 . Therefore, N-Nb2 O5- x @CNTs display good electrochemical performance in both Li/Na half-cell and Li/Na hybrid capacitors. Interestingly, kilogram-scale microsphere composites can be produced in laboratory conditions by using industrial grade raw materials, implying its potential for practical application.

Piezo1 promoted hepatocellular carcinoma progression and EMT through activating TGF-ß signaling by recruiting Rab5c.

BACKGROUND: Piezo1 has been revealed to play a regulatory role in vascular development and progression of variety tumors. However, whether and how the progression of hepatocellular carcinoma (HCC) regulated by Piezo1 remains elusive. This study aimed to elucidate the effect and mechanisms of Piezo1 in HCC. METHODS: The mRNA and protein expression level of Piezo1 in HCC samples and cell lines was determined by qRT-PCR, western blot and immunohistochemistry analyses. Two independent study cohorts containing 280 patients were analyzed to reveal the association between Piezo1 expression and clinicopathological characteristics. Series of in vitro and in vivo experiments were used to validate the function of Piezo1 in HCC. Gene set enrichment analysis (GSEA) was performed to explore the signaling pathway of Piezo1. Immunoprecipitation, immunofluorescence and in vitro and in vivo experiments were used to explore the molecular mechanism of Piezo1 in HCC progression. RESULTS: Our results demonstrated the Piezo1 expression was significantly upregulated in HCC tissues and cell lines, and upregulation of Piezo1 closely correlated with aggressive clinicopathological features and poor prognosis. Knockdown of Piezo1 in HCCLM3 and Hep3B cells significantly restrained proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells in vitro, and tumor growth, metastasis, EMT in vivo. TGF-ß signaling pathway was most significant enriched pathway in GSEA. Finally, tumor promotion effect of Piezo1 was found to exerted through recruiting and combining Rab5c to activating TGF-ß signaling pathway. CONCLUSIONS: Piezo1 significantly related to poor prognosis and promotes progression of hepatocellular carcinoma via activating TGF-ß signaling, which suggesting that Piezo1 may serve as a novel prognostic predictor and the potential therapeutic target for HCC patients.

Ischemia-Reperfusion Injury and Immunosuppressants Promote Polyomavirus Replication Through Common Molecular Mechanisms.

Background: BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) causes renal allograft dysfunction and graft loss. However, the mechanism of BKPyV replication after kidney transplantation is unclear. Clinical studies have demonstrated that immunosuppressants and renal ischemia-reperfusion injury (IRI) are risk factors for BKPyV infection. Studying the pathogenic mechanism of BKPyV is limited by the inability of BKPyV to infect the animal. Mouse polyomavirus (MPyV) is a close homolog of BKPyV. We used a model of MPyV infection to investigate the core genes and underlying mechanism of IRI and immunosuppressants to promote polyomavirus replication. Materials and Methods: One-day-old male C57BL/6 mice were intraperitoneally injected with MPyV. At week 9 post-infection, all mice were randomly divided into IRI, immunosuppressant, and control groups and treated accordingly. IRI was established by clamping the left renal pedicle. Subsequently, kidney specimens were collected for detecting MPyV DNA, histopathological observation, and high-throughput RNA sequencing. Weighted gene correlation network analysis (WGCNA), protein-protein interaction network analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to screen for core genes and common signaling pathways involved in promoting MPyV replication by IRI and immunosuppressants. Results: After primary infection, MPyV established persistent infection in kidneys and subsequently was significantly increased by IRI or immunosuppressant treatment individually. In the IRI group, viral loads peaked on day 3 in the left kidney, which were significantly higher than those in the right kidney and the control group. In the immunosuppressant group, viral loads in the left kidney were significantly increased on day 3, which were significantly higher than those in the control group. Protein-protein interaction network analysis and WGCNA screened complement C3, epidermal growth factor receptor (EGFR), and FN1 as core genes. Pathway enrichment analysis based on the IRI- or immunosuppressant-related genes selected by WGCNA indicated that the NF-κB signaling pathway was the main pathway involved in promoting MPyV replication. The core genes were further confirmed using published datasets GSE47199 and GSE75693 in human polyomavirus-associated nephropathy. Conclusions: Our study demonstrated that IRI and immunosuppressants promote polyomavirus replication through common molecular mechanisms. In future studies, knockdown or specific inhibition of C3, EGFR, FN1, and NF-κB signaling pathway will further validate their critical roles in promoting polyomavirus replication.

Ultrafast and stable ion/electron transport of MnNb2O6 in LIC/SC via interface protection and lattice defects.

Interface protection and kinetics optimization could effectively relieve the shortcomings of bimetallic oxides, such as low conductivity, strong hydrophobicity, insufficient ion diffusion rate and metal interatomic instability. In this work, ultrathin amorphous carbon shells and lattice defects (heteroatoms and vacancies) are introduced into the MnNb2O6 nanofiber surface to improve the electron/ion kinetic stability, conductivity and electrochemical activity. The ultrathin carbon interface protects unstable lattice with defects, thus restraining the adverse reaction between bimetallic oxides and electrolyte. Especially, ultrathin amorphous carbon layer enhances the stability and uniformity of ion transport as the substitute of solid-liquid ion exchange membrane. Lattice defects (N doping and oxygen vacancy) also enhance the ionic kinetics of the material. MnNb2O6 nanofiber, being optimized by interface protection and lattice defects, shows excellent electrochemical performances in Lithium-ion battery and supercapacitor.

GNA14's interaction with RACK1 inhibits hepatocellular carcinoma progression through reducing MAPK/JNK and PI3K/AKT signaling pathway.

Gαq subfamily proteins play critical roles in many biological functions including cardiovascular development, angiogenesis, and tumorigenesis of melanoma. However, the understanding of G Protein Subunit Alpha 14 (GNA14) in diseases, especially in cancers is limited. Here, we revealed that GNA14 was significantly low expression in Human hepatocellular carcinoma (HCC) samples. Low GNA14 expression was correlated with aggressive clinicopathological features. Moreover, the overall survival (OS) and disease-free survival (DFS) of high GNA14 expression HCC patients were much better than low GNA14 expression group. Lentivirus-mediated GNA14 knockdown significantly promoted the growth of liver cancer in vitro and in vivo. However, opposing results were observed when GNA14 is upregulated. Mechanistically, We identified receptor for activated C kinase 1 (RACK1) as a binding partner of GNA14 by co-immunoprecipitation and mass spectrometry (MS). Glutathione-S-transferase (GST) pull-down assay further verified the direct interaction between GNA14 and RACK1. RNA-Seq and loss- and gain-of-function assays also confirmed that GNA14 reduced the activity of both MAPK/JNK and PI3K/AKT signaling pathways through RACK1. GNA14 synergized with U73122 (PLC inhibitor) to enhance this effect. Further studies suggested that GNA14 potentially competed with protein kinase C (PKC) to bind with RACK1, consequently reducing the stability of PKC. Moreover, we also showed that GNA14'supression of p-AKT protein level depended on sufficient RACK1 expression. In conclusion, we indicated a different role of GNA14, which acted as a suppressor inhibiting liver cancer progression through MAPK/JNK and PI3K/AKT signaling pathways. Due to this, GNA14 served as a potentially valuable prognostic biomarker for liver cancer.

Programmed cell death 10 promotes metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma via PP2Ac-mediated YAP activation.

Tumour metastasis is the main cause of postoperative tumour recurrence and mortality in patients with hepatocellular carcinoma (HCC), but the underlying mechanism remains unclear. Accumulating evidence has demonstrated that programmed cell death 10 (PDCD10) plays an important role in many biological processes. However, the role of PDCD10 in HCC progression is still elusive. In this study, we aimed to explore the clinical significance and molecular function of PDCD10 in HCC. PDCD10 is significantly upregulated in HCC, which also correlates with aggressive clinicopathological characteristics and predicts poor prognosis of HCC patients after liver resection. High PDCD10 expression promotes HCC cell proliferation, migration, and invasion in vitro and tumour growth, metastasis in vivo. In addition, PDCD10 could facilitate epithelial-to-mesenchymal transition (EMT) of HCC cells. In terms of the mechanism, PDCD10 directly binds to the catalytic subunit of protein phosphatase 2A (PP2Ac) and increases its enzymatic activity, leading to the interaction of YAP and dephosphorylation of the YAP protein. This interaction contributes to YAP nuclear translocation and transcriptional activation. PP2Ac is necessary for PDCD10-mediated HCC progression. Knocking down PP2Ac abolished the tumour-promoting role of PDCD10 in the migration, invasion and EMT of HCC. Moreover, a PP2Ac inhibitor (LB100) could restrict tumour growth and metastasis of HCC with high PDCD10 expression. Collectively, PDCD10 promotes EMT and the progression of HCC by interacting with PP2Ac to promote YAP activation, which provides new insight into the mechanism of cancer metastasis. PDCD10 may be a potential prognostic biomarker and therapeutic target for HCC.

Serum epidermal growth factor-like domain 7 serves as a novel diagnostic marker for early hepatocellular carcinoma.

BACKGROUND: Epidermal growth factor-like domain 7 (Egfl7), a recently identified secreted protein, was significantly increased in patients with HCC by our previous studies. However, its efficacy in the diagnosis of early HCC remains unknown. In this study, we therefore evaluate the efficacy of serum Egfl7 for early HCC diagnosis and compare it with alpha-fetoprotein (AFP). METHODS: Serum Egfl7 levels in testing cohort (1081 participants) and validation cohort (476 participants) were measured by a sandwich enzyme-linked immunoassay (ELISA). The cut-off value of Egfl7 was determined by Youden's index and the efficacies of Egfl7 and AFP in diagnosing early HCC were estimated by receiver operating characteristic (ROC). RESULTS: Serum Egfl7 was significantly elevated in patients with early HCC than all non-HCC controls in whatever Testing Cohort or Validation Cohort. In the Testing Cohort, ROC curves showed the optimum cut-off value of Egfl7 was 2610 ng/mL and Egfl7 showed a significantly higher sensitivity than AFP in discriminating early HCC from healthy individuals (77.4% vs. 65.3%, P = 0.0013) but the area under ROC (AUROC) and accuracy of Egfl7 and AFP were similar (0.860 vs. 0.868, P = 0.704; 80.2% vs. 83.8%, P = 0.184). In distinguishing patients with early HCC from patients with chronic liver disease (CLD), the AUROC, sensitivity, specificity and accuracy of Egfl7 were 0.800, 75.2, 71.7 and 73.5%, which were all significantly higher than AFP (0.675, 61.8, 62.0 and 61.9% in order). Egfl7 also showed a significant higher sensitivity and accuracy than AFP (76.6% vs. 64.0%, P = 0.0031; 79.9% vs. 66.1%, P < 0.0001) in differentiating early HCC patients from non-HCC individuals. Additionally, 70.8% of early HCC patients with negative AFP could be diagnosed by Egfl7 and the combined use of Egfl7 and AFP increased the sensitivity to 91.0%. These results were confirmed by a validation cohort. CONCLUSION: Egfl7 is a valuable serum marker in the diagnosis of early HCC and could complement the efficacy of AFP, especially in distinguishing early HCC from CLD and identifying patients with AFP-negative early HCC.

Metabolomics profiling for identification of potential biomarkers in chickens infected with avian leukosis virus subgroup J (ALV-J).

There are currently no vaccines or effective drugs to prevent the disorders caused by avian leukosis virus subgroup J (ALV-J). Hence, it is critical to identify potential biomarkers in ALV-J-infected chickens to prevent ALV-J-induced disorders. We hypothesized that ALV-J infection alters metabolic profile in chickens. In the present study, a nontargeted metabolomics approach based on liquid chromatography coupled with mass spectrometry (LC-MS) was used to find differential metabolites in plasma samples from ALV-J-infected chickens and healthy controls. The parametric statistical test (Student's t-test) and fold change analysis were used for univariate analysis. Multivariate statistical analyses included principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The levels of methyl bromide, pyraclonil, hexaflumuron, lythidathion, 3-phosphoglycerol-glutathione, bis-4-nitrophenyl phosphate, 4-ketocyclophosphamide, oxidized photinus luciferin, phenyl sulfate, and aryl sulfate significantly decreased, whereas the levels of 2-methylthiobenzothiazole, irinotecan, methadone, 3-o-ethyl-l-ascorbic acid, and o-acetylneuraminic acid markedly increased in ALV-J-infected chickens as compared to those in healthy controls. These data provide metabolic evidence and potential biomarkers for ALV-J-induced alterations in plasma metabolism.

ATE1 Inhibits Liver Cancer Progression through RGS5-Mediated Suppression of Wnt/ß-Catenin Signaling.

Arginyltransferase (ATE1) plays critical roles in many biological functions including cardiovascular development, angiogenesis, adipogenesis, muscle contraction, and metastasis of cancer. However, the role of ATE1 in hepatocellular carcinoma (HCC) remains unknown. In this study, we find that ATE1 plays an essential role in growth and malignancy of liver cancer. ATE1 expression is significantly reduced in human HCC samples compared with normal liver tissue. In addition, low ATE1 expression is correlated with aggressive clinicopathologic features and is an independent poor prognostic factor for overall survival and disease-free survival of patients with HCC. Lentivirus-mediated ATE1 knockdown significantly promoted liver cancer growth, migration, and disease progression in vitro and in vivo. Opposing results were observed when ATE1 was upregulated. Mechanistically, ATE1 accelerated the degradation of ß-catenin and inhibited Wnt signaling by regulating turnover of Regulator of G Protein Signaling 5 (RGS5). Loss- and gain-of-function assays confirmed that RGS5 was a key effector of ATE1-mediated regulation of Wnt signaling. Further studies indicated that RGS5 might be involved in regulating the activity of GSK3-ß, a crucial component of the cytoplasmic destruction complex. Treatment with a GSK inhibitor (CHIR99021) cooperated with ablation of ATE1 or RGS5 overexpression to promote Wnt/ß-catenin signaling, but overexpression of ATE1 or RGS5 knockdown did not reverse the effect of GSK inhibitor. IMPLICATIONS: ATE1 inhibits liver cancer progression by suppressing Wnt/ß-catenin signaling and can serve as a potentially valuable prognostic biomarker for HCC.