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Pancreatic cancer is one of the common malignant tumors of the digestive system, and its clinical treatment is still very challenging. Most of the pancreatic cancer chemotherapeutic drugs have poor plasma stability, low cell uptake efficiency, and are prone to developing drug resistance and toxic side effects. Besides, pancreatic cancer often has a dense extracellular matrix, which consists of collagens, hyaluronic acid, and other proteoglycans. Among them, hyaluronic acid is a key component of the dense matrix, which results in vascular compression and insufficient perfusion, and hinders the delivery of chemotherapeutic drugs. In this study, we explore using hyaluronidase in tumor-bearing mice to eliminate the hyaluronic acid barrier, to reduce blood vessel compression and reshape the tumor microenvironment. In addition, we evaluate using doxorubicin-loaded nanoprobes to improve the stability and local tumor-killing effect of the drug. The nanoprobes have the characteristics of near-infrared optical imaging, which are used to monitor the tumor size in real-time during the treatment process, and dynamically observe the tumor inhibitory effect. The results show that elimination of the hyaluronic acid barrier combined with the doxorubicin-loaded nanoprobes can greatly increase drug penetration into tumor tissue and improve the effectiveness of chemotherapy drugs. This study provides a novel strategy for the treatment of pancreatic cancer.

Doping of metals is highly effective in improving electrochemical performance of lithium iron phosphate. Here, based on a first-principles calculation result that Ru doping at the Fe sites has positive effects on promoting the ability of electron and Li+ transmission by reducing the lattice parameter and band gap, as well as the increase in Fermi energy, we constructed Ru-doped LiFe1-x Ru x PO4/C through the sol-gel preparation technology as cathode materials for Li-ion batteries. As a result, LFP-1 (x = 0.01) delivers excellent specific capacities of 162.6 and 110.6 mA h g-1 under 0.1 and 10 C, respectively. At the same time, LFP-1 emerges with excellent cycling performance, with a capacity retention of up to 95.6% after 300 cycles at 5 C. Ru doping is beneficial for improving the lithium diffusion coefficient and electrical conductivity, therefore strongly increasing electrochemical performance. This work represents a significant addition to exploring a new class of lithium iron phosphates with excellent performance in new energy storage and transition systems.

Core-shell structured iron/zinc oxide (Fe/ZnO) nanocomposites have been successfully prepared via a low-temperature wet chemical method. The electromagnetic wave absorbing performances of all the Fe/ZnO nanocomposites are significantly improved in comparison with single α-Fe and ZnO. With the ZnO content increasing, the effective absorption band (reflection loss below −10 dB) moves toward the high frequency orientation. When the thickness is 1.59 mm, the Fe/ZnO nanocomposite with a Fe/Zn ratio of 1:0.75 can gain the optimal reflection loss at 15.55 GHz, which reaches up to −48.28 dB, and the effective absorption bandwidth (reflection loss below −10 dB) is 3.50 GHz (12.925–16.425 GHz). In addition, the maximum effective absorption bandwidth (reflection loss below −10 dB) reaches up to 5.10 GHz (10.79–15.89 GHz) at the thickness of 1.9 mm for Fe/Zn ratio of 1:0.75. The excellent electromagnetic wave absorption performance of Fe/ZnO nanocomposite benefits from the effects of dielectric loss, magnetic loss and suitable impedance matching. Therefore, the Fe/ZnO nanocomposites are promising to be applied in the field of Ku band wave absorption.

Vitreous, a transparent tissue in our body, contains anti-angiogenesis factors. Our previous work reported that vitreous activates the signaling pathway of epidermal growth factor receptor (EGFR), which plays a critical role in angiogenesis. The aim of this study was to determine the role of EGFR in vitreous-induced angiogenesis-related cellular responses in vitro. Using a pharmacologic and molecular approach, we found that vitreous increased proliferation and migration via EGFR in human umbilical vein endothelial cells (HUVECs). Furthermore, we demonstrated that vitreous promoted tube formation via EGFR in HUVECs. Subsequently, depletion of EGFR using CRISPR/Cas9 and blockage with EGFR inhibitor AG1478 suppressed vitreous-induced Akt activation and cell proliferation, migration, and tube formation in HUVECs. The significance of the angiogenic effect derived from vitreous demonstrates the importance of vitreous in the ocular physiology and the pathobiology of angiogenesis-related ophthalmic diseases, such as proliferative diabetic retinopathy.

Receptor‐interacting protein 3 (RIP3) plays an important role in the necroptosis signaling pathway. Our previous studies have shown that the RIP3/mixed lineage kinase domain‐like protein (MLKL)‐mediated necroptosis occurs in retinal ganglion cell line 5 (RGC‐5) following oxygen‐glucose deprivation (OGD). However, upstream regulatory pathways of RIP3 are yet to be uncovered. The purpose of the present study was to investigate the role of p90 ribosomal protein S6 kinase 3 (RSK3) in the phosphorylation of RIP3 in RGC‐5 cell necroptosis following OGD. Our results showed that expression of RSK3, RIP3, and MLKL was upregulated in necroptosis of RGC‐5 after OGD. A computer simulation based on our preliminary results indicated that RSK3 might interact with RIP3, which was subsequently confirmed by co‐immunoprecipitation. Further, we found that the application of a specific RSK inhibitor, LJH685, or rsk3 small interfering RNA (siRNA), downregulated the phosphorylation of RIP3. However, the overexpression of rip3 did not affect the expression of RSK3, thereby indicating that RSK3 could be a possible upstream regulator of RIP3 phosphorylation in OGD‐induced necroptosis of RGC‐5 cells. Moreover, our in vivo results showed that pretreatment with LJH685 before acute high intraocular pressure episodes could reduce the necroptosis of retinal neurons and improve recovery of impaired visual function. Taken together, our findings suggested that RSK3 might work as an upstream regulator of RIP3 phosphorylation during RGC‐5 necroptosis.

Agglomeration occurs during municipal sewage sludge (MSS) fluidized bed co-combustion which might affect heavy metal distribution in the bottom ash. A study on the mobility and speciation of heavy metals accompanied with agglomeration behavior and phosphorus addition should be noticed during the MSS co-combustion. The aim of this study was to evaluate the total content and speciation of heavy metals (Pb, Cd and Cr) during the MSS fluidized bed co-combustion by chemical sequential extraction and thermodynamics Equilibrium Calculation. Results indicated that the effect of phosphorus on the agglomeration/defluidization as the function of inhabitation and promotion. Distribution of heavy metals (Pb, Cd and Cr) show similar trends with the presence of a lower ratio of P/Na: the relative concentration of heavy metals in solid phase with the increased of phosphorus. In addition, the relative concentration of heavy metals in solid phase show the raise tendency with the increased of phosphorus under the circumstance of the higher ratio of P/Na due to the formation of the lower-melting-points compounds like NaPO3, the proportion of Pb and Cr residual form increased. While the percentage of Cd residual form reduced with the increasing of the amount of phosphorus. This phenomenon can be contributed by the H3PO4 would priority to react with Al2O3 and reduced the form of a stable compound CdO-Al2O3. Defluidization behavior is found with various P/Na ratios which resulting significantly different influences on particle agglomeration. High-melting-point compound, Na3PO4 (1613 K), is observed to inhibit Na2O-SiO2 formation at lower P/Na ratio. On the contrary, defluidization time decreases with increasing the P/Na ratio due to low-melting-point species Na-phosphates, NaPO3 (900 K) was formed in system.

Methamphetamine (METH) is one of the most widely abused synthetic drugs in the world. The users generally present hyperthermia (HT) and psychiatric symptoms. However, the mechanisms involved in METH/HT-induced neurotoxicity remain elusive. Here, we investigated the role of heat shock protein 90 alpha (HSP90α) in METH/HT (39.5°C)-induced necroptosis in rat striatal neurons and an in vivo rat model. METH treatment increased core body temperature and up-regulated LDH activity and the molecular expression of canonical necroptotic factors in the striatum of rats. METH and HT can induce necroptosis in primary cultures of striatal neurons. The expression of HSP90α increased following METH/HT injuries. The specific inhibitor of HSP90α, geldanamycin (GA), and HSP90α shRNA attenuated the METH/HT-induced upregulation of receptor-interacting protein 3 (RIP3), phosphorylated RIP3, mixed lineage kinase domain-like protein (MLKL), and phosphorylated MLKL. The inhibition of HSP90α protected the primary cultures of striatal neurons from METH/HT-induced necroptosis. In conclusion, HSP90α plays an important role in METH/HT-induced neuronal necroptosis and the HSP90α-RIP3 pathway is a promising therapeutic target for METH/HT-induced neurotoxicity in the striatum.

Purpose: Evidences suggest that during ischemia/reperfusion events, neuronal loss in ganglion cell layers (GCLs) occurs initially in the peripheral retinae followed by the central. However, which key molecule or factor mediates this selective loss needs elucidation. In the present study, we detected the regional expression of active matrix metalloproteinase 3 (Act-MMP3) in the central and peripheral rat retinae following acute retinal ischemia/reperfusion (RI/R) injury and explored the effects and mechanisms of this regional expression on the selective neuronal loss in GCLs.Methods: QPCR and Western Blotting were used to detect the expression of Act-MMP3 in the central part and peripheral part of the adult rat retinae. Immunofluorescence and double immunofluorescence were used to assess the number of NeuN-positive cells in the GCLs and Iba-1+CD 68-positive cells were determined. Additionally, the Linear-regression analysis was performed to test the correlation between the ODV of Act-MMP3 and the neuronal loss in the GCLs/Iba-1+CD 68 positive cells in retinae.Results: An evident up-regulation of active matrix metalloproteinase 3 (Act-MMP3) in peripheral retinae preceded to that in central region following acute RI/R. We found Act-MMP3 up-regulation to be associated with the selective neuronal loss in GCLs (central: r = 0.7566, p < .0001, r2 = 0.5724; peripheral: r = 0.8241, p < .0001, r2 = 0.6792). Suppressing Act-MMP3 ameliorated the selective neuronal loss in GCLs following acute RI/R. Furthermore, the activation of microglia in the peripheral retinae also preceded to that in the central and was found to be correlated with the regional expression of Act-MMP3 (Central: r = 0.8540, p < .0001, r2 = 0.7294; Peripheral: r = 0.7820, p < .0001, r2 = 0.6116). Suppressing Act-MMP3 ameliorated the microglia regional activation following acute RI/R.Conclusion: The regional expression of Act-MMP3 in the rat retinae may contribute to the selective neuronal loss in GCLs and microglia regional activation in acute RI/R.

Precise atomic-level control of composition and geometric structure at the interface between two catalyst components can effectively tune the catalytic properties. Herein, we found a “chimney effect” formed on the interface between the metal oxide and Nickel metal for the hydrogen evolution reaction, using density functional theory calculations and experimental methods. This special chemical environment around the interface leads the neighboring sites to be immune to the H2O* and OH* adsorption and to only selectively adsorb H* properly. Meanwhile, it is also beneficial for the smooth adsorption of the reactant (H*) on the interface and the easy desorption of the product (H2) from the catalyst surface (ΔGH* close to zero). This phenomenon appears similar to a chimney of hydrogen evolution around the metal oxide/metal interface. Such “chimney effect” is a result of the interfacial charge transfer between the metal and metal oxide, and should be the nature of the interface-induced synergistic effect in metal oxide/metal composite catalysts for HER. Experiments further confirm that the catalytic activity of metal oxide/metal composites for HER can be enhanced by increasing the amount of the chimney - the interfacial metal atoms.

Background One of the main problems associated with the development of osteochondral reparative materials is that the accurate imitation of the structure of the natural osteochondral tissue and fabrication of a suitable scaffold material for osteochondral repair are difficult. The long-term outcomes of single- or bilayered scaffolds are often unsatisfactory because of the absence of a progressive osteochondral structure. Therefore, only scaffolds with gradient pore sizes are suitable for osteochondral repair to achieve better proliferation and differentiation of the stem cells into osteochondral tissues to complete the repair of defects. Methods A silk fibroin (SF) solution, chitosan (CS) solution, and nano-hydroxyapatite (nHA) suspension were mixed at the same weight fraction to obtain osteochondral scaffolds with gradient pore diameters by centrifugation, freeze-drying, and chemical cross-linking. Results The scaffolds prepared in this study are confirmed to have a progressive structure starting from the cartilage layer to bone layer, similar to that of the normal osteochondral tissues. The prepared scaffolds are cylindrical in shape and have high internal porosity. The structure consists of regular and highly interconnected pores with a progressively increasing pore distribution as well as a progressively changing pore diameter. The scaffold strongly absorbs water, and has a suitable degradation rate, sufficient space for cell growth and proliferation, and good resistance to compression. Thus, the scaffold can provide sufficient nutrients and space for cell growth, proliferation, and migration. Further, bone marrow mesenchymal stem cells seeded onto the scaffold closely attach to the scaffold and stably grow and proliferate, indicating that the scaffold has good biocompatibility with no cytotoxicity. Conclusion In brief, the physical properties and biocompatibility of our scaffolds fully comply with the requirements of scaffold materials required for osteochondral tissue engineering, and they are expected to become a new type of scaffolds with gradient pore sizes for osteochondral repair.

Hypothesis Nanoparticles functionalized with ligands which can on-demand and remotely be detached have recently attracted interest as stimuli-responsive materials. Research is now focused on multi-responsive systems, with applications in environmental science and biomedicine. The possibility to covalently couple two different ligands on a single nanoparticles, and to release them independently is investigated. This concept of nanoparticles functionalized with dual on-demand cleavable ligands is exploited in ground water decontamination and radionuclides separation. Efficient separation of contaminants in a single step is expected, simplifying partitioning process and decreasing generation of secondary waste by nuclear industry. Experiments Sub−10 nm Janus superparamagnetic nanoparticles are functionalized by click-chemistry (thiol and Diels-Alder) with two different Actinide-specific chelators. The reversible covalent bonds allow to detach chelators independently by either pH- or thermo-stimulation. The nanoparticles decorated with diethylenetriamine-pentaacetic acid (DTPA) and [(2-furan-2-yl-2-hydroxy-ethylcarbamoyl)-methoxy]-acetic acid (FHECMAA) are incubated with UO22+ and La3+ (as substitute for Pu3+) at pH = 3 and 7 before chelator-metal complexes are released. Metal contents are measured to determine separation efficiency. Findings Chelators can be detached from Janus nanoparticles with perfect selectivity. The nanoparticles are highly efficient for extraction of metals in acidic medium and show good ability for separation of U and La at neutral pH.

While cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with oral squamous cell carcinoma (OSCC), the cisplatin-resistance poses a major challenge for its clinical application. Recent studies have shown that quercetin, a natural flavonoid found in various plants and foods possesses an anti-cancer effect. The following study examined the combined effect of quercetin and cisplatin on OSCC apoptosis in vitro and in vivo (using a mice tumor model). We found that quercetin promotes cisplatin-induced apoptosis in human OSCC (cell lines Tca-8113 and SCC-15) by down-regulating NF-κB. Pretreatment of cancer cells with quercetin inhibited the phosphorylation Akt and IKKβ, and led to the suppression of NF-κB and anti-apoptotic protein xIAP. In addition, we observed that the pretreatment of cancer cells with quercetin improves extrinsic and intrinsic apoptosis by activating caspase-8 and caspase-9, respectively. Our in vivo data also indicated that the combination of quercetin and cisplatin may inhibit the xenograft growth in mice. To sum up, our results provide a new evidence for the application of quercetin and cisplatin in OSCC therapy.

The ability of Mycobacterium tuberculosis (Mtb) to adopt a slowly growing or nongrowing state within the host plays a critical role for the bacilli to persist in the face of a prolonged multidrug therapy, establish latency and sustain chronic infection. In our previous study, we revealed that genome maintenance via MazG-mediated elimination of oxidized dCTP contributes to the antibiotic tolerance of nongrowing Mtb. Here, we provide evidence that housecleaning of pyrimidine nucleotide pool via MazG coordinates metabolic adaptation of Mtb to nongrowing state. We found that the ΔmazG mutant fails to maintain a nongrowing and metabolic quiescence state under dormancy models in vitro. To investigate bacterial metabolic changes during infection, we employed RNA-seq to compare the global transcriptional response of wild-type Mtb and the ΔmazG mutant after infection of macrophages. Pathway enrichment analyses of the differentially regulated genes indicate that the deletion of mazG in Mtb not only results in DNA instability, but also perturbs pyrimidine metabolism, iron and carbon source uptake, catabolism of propionate and TCA cycle. Moreover, these transcriptional signatures reflect anticipatory metabolism and regulatory activities observed during cell cycle re-entry in the ΔmazG mutant. Taken together, these results provide evidence that pyrimidine metabolism is a metabolic checkpoint during mycobacterial adaptation to nongrowing state.

Host-derived fatty acids are an important carbon source for pathogenic mycobacteria during infection. How mycobacterial cells regulate the catabolism of fatty acids to serve the pathogenicity, however, remains unknown. Here, we identified a TetR-family transcriptional factor, FdmR, as the key regulator of fatty acid catabolism in the pathogen Mycobacterium marinum by combining use of transcriptomics, chromatin immunoprecipitation followed by sequencing, dynamic (13)C-based flux analysis, metabolomics, and lipidomics. An M. marinum mutant deficient in FdmR was severely attenuated in zebrafish larvae and adult zebrafish. The mutant showed defective growth but high substrate consumption on fatty acids. FdmR was identified as a long-chain acyl-coenzyme A (acyl-CoA)–responsive repressor of genes involved in fatty acid degradation and modification. We demonstrated that FdmR functions as a valve to direct the flux of exogenously derived fatty acids away from β-oxidation toward lipid biosynthesis, thereby avoiding the overactive catabolism and accumulation of biologically toxic intermediates. Moreover, we found that FdmR suppresses degradation of long-chain acyl-CoAs endogenously synthesized through the type I fatty acid synthase. By modulating the supply of long-chain acyl-CoAs for lipogenesis, FdmR controls the abundance and chain length of virulence-associated lipids and mycolates and plays an important role in the impermeability of the cell envelope. These results reveal that despite the fact that host-derived fatty acids are used as an important carbon source, overactive catabolism of fatty acids is detrimental to mycobacterial cell growth and pathogenicity. This study thus presents FdmR as a potentially attractive target for chemotherapy.

Biomolecular systems actively control their local environment on a sub-nm scale via changes in molecular configuration from their flexible structures and derive emergent functions. Although this functional emergence based on local environmental control is attracting a great deal of attention in chemistry, it remains challenging to realize this artificially. Herein, we report the tuning of the thermo-responsive properties of oligo(ethylene glycol) (OEG) derivatives attached on gold nanoparticles via local environmental control not only by the hydrophobic moiety at their terminus but also by their molecular configuration. OEG-attached alkane thiol-modified AuNPs showed thermo-responsive assembly/disassembly in water through the hydration/dehydration of the OEG portions in a manner dependent both on the hydrophobicity at their terminus and the surface curvature of the core nanoparticles. Further, the assembly temperature (T-A) was also tuned by ligand mixing with a non-thermo-responsive ligand with a shorter OEG length. Molecular dynamics simulations show that the distribution of the hydrophobic terminus in the normal direction along the gold surface varied in accordance with the surface curvature, indicating variations in molecular configuration. It is expected that a bent configuration could accelerate the thermo-responsiveness of OEG by allowing them greater accessibility to the hydrophobic terminus. Experimental and simulation results support the notion that local OEG density tuning by surface curvature or ligand mixing with a different OEG length leads to different degrees of accessibility to the hydrophobic terminus via changes in molecular configuration, promoting local environmental control-directed assembly temperature tuning.

Multiple scarce nutrients, such as iron and nickel, are essential for bacterial growth. Gram-negative bacteria secrete chelators to bind these nutrients from the environment competitively. The transport of the resulting complexes into bacterial cells is mediated by TonB-dependent transporters (TBDTs) located at the outer membrane in Gram-negative bacteria. The characteristics of TBDTs, including surface exposure, protective immunogenicity, wide distribution, inducible expression in vivo, and essential roles in pathogenicity, make them excellent candidates for vaccine development. The possible application of a large number of TBDTs in immune control of the corresponding pathogens has been recently investigated. This paper summarizes the latest progresses and current major issues in the application.

BackgroundChronic kidney disease (CKD) and diabetic retinopathy (DR) are two serious complications of diabetes. However, the association between retinal neurodegeneration in DR and renal function decline is still unclear. Our objective was to evaluate the association by measure estimated glomerular filtration rate (eGFR), macular ganglion cell–inner plexiform layer (GC–IPL) and ganglion cell complex (GCC) thickness in patients with type 2 diabetes mellitus (T2DM).MethodsWe analyzed the baseline data of the Guangzhou Diabetic Eye Study. T2DM patients from communities in Guangzhou were enrolled and all participants went through ophthalmic and general examinations. The thickness of the macular GC–IPL and GCC in their right eyes were measured by swept-source optical coherence tomography. CKD was defined as eGFR < 60 mL/min/1.73 m2.Results1,309 patients were included (mean age 64.4 ± 7.6 years, 59.1% female), and fifty-eight (4.4%) of them had CKD. Average macular GC-IPL thickness was significantly thinner in CKD patients (96.5 ± 9.1 μm) than non-CKD patients (101.3 ± 9.2 μm) (p < 0.01). Average macular GCC thickness was also significantly thinner in CKD patients (123.5 ± 13.2 μm) than non-CKD patients (129.9 ± 12.8 μm) (p < 0.01). The significant thinning of macular GC-IPL and GCC thickness presented in every gird in macula (all, p < 0.05) except for central grid (p ≥ 0.05). In the patients without DR, the eGFR was linearly correlated with the average macular GC–IPL thickness (β = 0.07 [95% CI 0.02–0.12], p < 0.01) and GCC thickness (β = 0.09 [95% CI 0.03–0.16], p < 0.01) after adjustment for age, sex, axial length, intraocular pressure and combination of hypertension. However, no linear correlation was found between eGFR and macular GC-IPL or GCC thickness in DR patients.ConclusionsRenal function decreases is associated with the thinning of the macular GC–IPL and GCC in T2DM patients, suggesting the potential value of ganglion cell lose to detect early function decline in the kidney in diabetic patients, especially in patients without DR.

Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associated with neuronal injury in the development of RION. Both the pharmacological inhibition of Cdk5 by roscovitine and the inhibition of Drp1 by mdivi-1 inhibited mitochondrial fission and the production of ROS associated with radiation-induced neuronal loss. Taken together, these findings may have clinical significance in preventing the development of RION.

Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies.

Extracellular vesicles (EVs) contain specific proteins, lipids, and nucleic acids that can be passed to other cells as signal molecules to alter their function. However, there are many problems and challenges in the conversion and clinical application of EVs. Storage and protection of EVs is one of the issues that need further research. To adapt to potential clinical applications, this type of problem must be solved. This review summarizes the storage practices of EVs in recent years, and explains the impact of temperature on the quality and stability of EVs during storage based on current research, and explains the potential mechanisms involved in this effect as much as possible.

It is of great significance to develop low cost, high-efficiency and environment-friendly electrocatalysts for hydrogen evolution reaction (HER) from water splitting. Herein, nickel telluride nanosheets grown on Ni Foam (NF) with three different crystal phases (NiTe, Ni2.6Te2 and Ni2.86Te2) are fabricated by one-step hydrothermal tellurization followed annealing process. The non-stoichiometric Ni2.86Te2/NF exhibits superior electrocatalytic HER performance compared to the NiTe/NF and Ni2.6Te2/NF, which is comparable to the state-of-the-art 20 wt% Pt/C catalyst at high current density. The Ni2.86Te2/NF only requires an overpotential of 348 mV to drive the current density of 200 mA cm−2 in a 1.0 M KOH electrolyte. Similarly, The Ni2.86Te2/NF delivered current densities of 200 mA cm−2 at the overpotential of 279 mV in 0.5 M H2SO4. Such excellent performance could be ascribed to the fast electron transfer and positive shift of d d-band center from its rich defective effect of crystal phase transition, as well as to the exposure of active sites provided by the two-dimensional nanosheets with large specific surface area. This work provides valuable insights for the rational modulation of the crystal phase on the nickel telluride for catalyzing HER.

The mesoporous Co/KIT-6 catalysts with 10 wt% Co loading were prepared at different reduction temperatures. The physicochemical properties of the Co/KIT-6 catalysts were characterized by TEM, BET, XRD, XPS, and CO2-TPD, and the effect of reduction temperature on CO2 hydrogenation catalytic performance of Co/KIT-6 catalysts was studied. The results show that reduction temperature has a significant impact on the specific surface area, crystallinity and content of Co0 species, and CO2 adsorption performance of the prepared Co/KIT-6 catalysts. The low reduction temperature is not conduct to the reduction of CoOx, while the high reduction temperature lead to the increase of Co0 species crystallinity and the formation of Co2SiO4 and/or CosbndOsbndSi species which are unfavorable to the form Co0 species. The RT400 catalyst exhibits the highest Co0 species content and the best CO2 adsorption performance. Both the CO2 hydrogenation catalytic activity and CH4 selectivity of the Co/KIT-6 catalysts follow the order: RT400 > RT350 > RT450 > RT500 > RT550, with a small amount of by-product CO. At the reaction temperature of 340 °C, the CO2 reaction rate (CO2 conversion) of the RT400 catalyst can reach 2.98 × 10−5 mol/gcat/s (40%), the CH4 and CO selectivity are 86.7% and 13.3%, respectively.

Electrochemical-phosphorization as a cost-effective and ecofriendly approach is proposed to fabricate an amorphous Ni–P shell partially covering the surface of ordered porous Ni (p-Ni) for the first time. The obtained Ni–P/p-Ni shows superior catalytic activity for the hydrogen evolution reaction (HER), compared with the Ni2P/p-Ni prepared by a traditional solid-phosphorization process at high temperature. Such enhanced catalytic activity for the Ni–P/p-Ni is contributed to by the high intrinsic activity from a synergistic effect of amorphous Ni–P and the neighbouring nickel containing hydroxides/oxides.

A thin-layer of Ni(OH)2 was in situ formed on the surface of Ni2P nanopillars (Ni(OH)2@Ni2P/E-NF) via a facile hydrothermal treatment in H2O. Ni(OH)2@Ni2P/E-NF exhibits superior activity for the hydrogen evolution reaction with an overpotential of only 43 mV to achieve 10 mA cm−2 and a good durability during the long-term operation in an alkaline medium. The excellent performance of Ni(OH)2@Ni2P/E-NF is likely ascribed to the strong interfacial coupling of Ni(OH)2 and Ni2P, which promotes the dissociation of water and concomitantly converts hydrogen intermediates (Had) to H2. Keywords: Nickel hydroxide, Nickel phosphide, Etching, Hydrogen evolution reaction

The mesoporous Co/SiO2 catalysts with 10 wt.% Co loading were prepared by grind-impregnation method for CO2 hydrogenation, and the mesoporous SiO2 materials with different structures were used as the supports. The physicochemical properties of the Co/SiO2 catalysts were characterized by TEM, BET, H2-TPR, XRD, and CO2-TPD. The results indicate that the pore size, specific surface area, and the Co° species crystallinity of the Co/SiO2 catalyst increase with increasing crystallization temperature of preparing SiO2 support. The Co/SiO2 catalyst has the best CO2 adsorption property when SiO2 support is prepared at the crystallization temperature of 100 °C. The CO2 reaction rate (CO2 conversion) of the Co/SiO2 catalysts is as follows: CK100 > CK080 > CK120 > CK060 > CK140 > CK040, and the CH4 selectivity follows the order: CK100 > CK080 > CK120 > CK140 > CK060 > CK040, accompanied by a certain amount of by-product CO molecules. At 360 °C, the CO2 reaction rate (CO2 conversion) of the CK100 catalyst is up to 3.29 × 10−5 mol/gcat/s (44.3%), the CH4 and CO selectivity are 86.5% and 13.5%, respectively.

The ordered mesoporous Co/KIT-6 catalysts with different Co loading (15–30 wt%) were prepared by impregnation method for CO2 hydrogenation. The physicochemical properties of the catalysts were characterized by H2-TPR, XRD, BET, H2-TPD, and CO2-TPD. The results show that the crystal size of Co species increases with the increasing Co content and the dispersion of Co species reveals an opposite trend. The adsorption capacities of H2 and/or CO2 molecules achieve a maximum value at the Co loading of 25 wt%. The CO2 reaction rate and CH4 selectivity are in the following order: Co15

Purpose The purpose of this paper is to investigate the tribological performance and mechanisms of BN/calcium borate nanocomposites (BCBNs) as additives in lubricating oil. Design/methodology/approach BCBNs were prepared by heterogeneous deposition method. And the morphology and structure of samples were analysed by transmission electron microscopy, Fourier transform infrared spectra and X-ray powder diffraction pattern. The maximum non-seizure load (PB) of samples was tested using four-ball friction tester. The average friction coefficients and wear tracks were obtained. In addition, tribological mechanism was also investigated using optical microscope, energy dispersive spectroscopy and X-ray photoelectron spectroscope. Findings It was found that the nanocomposites present core-shell nanostructure with the thickness of shell around 12 nm and the diameter of particles 100-200 nm, and tribological tests indicate that the PB value of BCBNs was increased by 113 per cent, whereas the average friction coefficient was decreased by 23.6 per cent and the bloom’s wear area was also decreased by 25.2 per cent. Originality/value This paper involves investigation on tribological properties and mechanism of the BCBNs with core-shell structure.

Ni-HT, Ni-ST, Ni-PC, and Ni-CA catalysts were synthesized using hard-template, soft-template, co-precipitation, and complex methods, respectively, characterized by XRD, BET, H 2 -TPR, and H 2 -TPD technology. The catalytic hydrodeoxygenation performance of the prepared Ni catalysts was evaluated by using ethyl acetate as the model compound. The prepared Ni catalyst activities are in the following order: Ni-HT > Ni-ST > Ni-PC > Ni-CA. Ni-HT and Ni-ST catalysts have developed pore structure; they show large specific surface area of 90.2 and 45.4 m 2 /g, respectively. The active phase of the catalyst is well dispersed, the active sites are widely distributed, thereby promoting the effective activation for reactant molecules. Ethyl acetate can be completely converted over Ni-HT and Ni-ST catalysts at 300 °C and 320 °C, respectively, and the ethane selectivity reaches 97.8% and 97.2%. Ni-PC and Ni-CA catalysts are mainly composed of dense particles, and have low specific surface areas of 11.2 and 2.4 m 2 /g, respectively. The crystallinity of the active phase is poor, the activation ability for the hydrogen molecule is obviously weaker than that of Ni-HT and Ni-ST catalysts. Ethyl acetate can be completely converted with the activity of Ni-PC and Ni-CA catalysts at 360 °C and 380 °C, and the ethane selectivity reached 96.7% and 93.5%, respectively.

Colloidal particles based on self-assembled Cu2+ coordination polymers were fabricated following a one-step process. These particles were shown to be stimuli-responsive. In particular they can be readily disassembled in acidic conditions. This effect originates from a pH-induced fragmentation of the polymer chains into dinuclear Cu2+ complexes.

Calcium phosphate cement (CPC) with good injectability and osteoconductivity plays important roles in bone grafting application. Much attention has been paid to achieve multifunctionality through incorporating trace elements into CPC. Silicon and zinc can be used as additives to endow CPC with biological functions of osteogenesis, angiogenesis and anti-osteoclastogenesis. In this study, zinc and silicate ions were co-incorporated into CPC through mixing with submicron zinc silicate (Zn2SiO4, ZS) to obtain zinc silicate-modified CPCs (ZS/CPCs) with different contents. The results revealed that the addition of ZS increased the compressive strength, prolonged the setting time, and densified the structure of CPC. Low addition content of ZS facilitated the formation of surface apatite layer in the early mineralization stage. Incorporating ZS significantly induced osteogenesis of mouse bone marrow stromal cells (mBMSCs) and angiogenesis of human umbilical vein endothelial cells (HUVECs), and moreover, restricted osteoclastogenesis of Raw 264.7 in vitro. Silicate and zinc ions could be steadily released from ZS/CPCs into the culture medium. With the synergistic effect of silicate and zinc ions, ZS/CPCs provided an appropriate microenvironment for the immune cells to facilitate the osteogenesis of mBMSCs and angiogenesis of HUVECs further. Taken together, it can be concluded that incorporating ZS is an effective way to endow CPC with multifunctionality and better bone regeneration for bone defect repair.

In the absence of external assistance, autogenous healing of bone fracture is difficult due to impaired regeneration ability under osteoporosis pathological conditions. In this study, a reduced graphene oxide/zinc silicate/calcium silicate (RGO/ZS/CS) conductive biocomposite with an optimal surface electroconductivity of 5625 S/m was prepared by a two-step spin-coating method. The presence of lamellar apatite nanocrystals on the surfaces of the biocomposite suggests that it has good in vitro biomineralization ability. The silicon and zinc released from the biocomposite induced a significant increase in the osteogenesis of mouse bone mesenchymal stem cells (mBMSCs). Furthermore, alkaline phosphatase activities were further promoted when 3 μA direct current was applied to stimulate the mBMSCs that were cultured on the RGO/ZS/CS surface. However, electrical stimulation failed to further upregulate the osteogenesis-related gene expression. Moreover, RGO/ZS/CS extracts were found to suppress the receptor activator of nuclear factor-κB ligand-induced osteoclastic differentiation of mouse leukemic monocyte macrophages (RAW264.7 cells). Although the zinc ions in the RGO/ZS/CS extracts showed an inhibitory role in human umbilical vein endothelial cell (HUVEC) proliferation, dilutions of the RGO/ZS/CS extracts (1/16, 1/32, and 1/64) promoted HUVEC proliferation, and their angiogenesis-related gene expression was also upregulated. On the basis of the results of the in vitro angiogenesis model, more interconnected tubes formed when the above dilutions of RGO/ZS/CS extracts were added to ECMatrix. The new RGO/ZS/CS electroconductive biocomposite has potential to be used for stimulating osteoporotic bone regeneration.

Extracellular vesicles (EVs) are the structures that all cells release into the environment. They are separated by a lipid bilayer and contain the cellular components that release them. To date, most studies have been performed on EVs derived from cell supernatants or different body fluids, while the number of studies on EV isolation directly from tissues is still limited. Studies of EV isolation directly from tissues may provide us with better information. This review summarizes the role of EV in the extracellular matrix, the protocol for isolation of EV in the tissue interstitium, and the application of the protocol in different tissues.

The sluggish kinetics of the oxygen evolution reaction (OER) is the bottleneck of water electrolysis for hydrogen generation. Developing cost-effective OER materials with a high value of practical application is a prerequisite to achieve extreme performance in both activity and stability. Herein, we report a “dual ligand synergistic modulation” strategy to accurately tune the structure of transition-metal materials at atomic level, which finally achieves satisfactory results for the unity between robust stability and high activity. Remarkably, the elaborately designed S and OH dual-ligand NiCo2(SOH)x catalyst exhibits an excellent OER activity with a very small overpotential of 0.29 V at a current density of 10 mA cm–2 and a strong durability even after 30 h accelerated aging at a large current density of 100 mA cm–2, both of which are superior to most of the state-of-the-art OER catalysts so far. The density functional theory (DFT) calculations disclose that the synergy of OH and S ligands on the surface...

To improve the visible light absorption and photocatalytic activity of titanium dioxide nanotube arrays (TONTAs), ZnFe2O4 (ZFO) nanocrystals were perfused into pristine TONTA pipelines using a novel bias voltage-assisted perfusion method. ZFO nanocrystals were well anchored on the inner walls of the pristine TONTAs when the ZFO suspensions (0.025 mg mL−1) were kept under a 60 V bias voltage for 1 h. After annealing at 750 °C for 2 h, the heterostructured ZFO/Fe2TiO5 (FTO)/TiO2 composite nanotube arrays were successfully obtained. Furthermore, Fe3+ was reduced to Fe2+ when solid solution reactions occurred at the interface of ZFO and the pristine TONTAs. Introducing ZFO significantly enhanced the visible light absorption of the ZFO/FTO/TONTAs relative to that of the annealed TONTAs. The coexistence of type I and staggered type II band alignment in the ZFO/FTO/TONTAs facilitated the separation of photogenerated electrons and holes, thereby improving the efficiency of the ZFO/FTO/TONTAs for photocatalytic degradation of methylene blue when irradiated with simulated sunlight.

In this study, CeCu composite catalysts with different Ce/Cu mole ratios were prepared by a hard-template, and their performances in the reverse water–gas shift (RWGS) reaction were investigated. The catalysts were characterized using H2-TPR, XRD, in-situ XPS, AAS, CO2-TPD, and H2-TPD. The characterizations showed that the oxygen vacancies and active Cu0 species as active sites were formed in the CeCu catalysts by the H2 reduction at 400 °C. The synergistic effect of the surface oxygen vacancies and active Cu0 species enhanced catalytic activity of the studied CeCu composite catalysts. The electronic effect between Cu and Ce species boosted the adsorption and activation performances of the reactant CO2 and H2 molecules on the corresponding CeCu catalysts. The Ce1.1Cu1 catalyst demonstrated high stability and the highest CO2 conversion rate in the RWGS reaction, reaching 1.38 mmol gcat−1 min−1 at 400 °C. Its excellent catalytic performance in the RWGS reaction was related to the complete synergistic interaction between the active species via Ce3+-□-Cu0 (□: oxygen vacancy). A CeCu composite material is a superior catalyst for the RWGS reaction because of its high CO2 conversion, 100% CO selectivity, and high stability.

This study aimed to examine the biocompatibility of calcium titanate (CaTiO3) coating prepared by a simplified technique in an attempt to assess the potential of CaTiO3 coating as an alternative to current implant coating materials. CaTiO3-coated titanium screws were implanted with hydroxyapatite (HA)-coated or uncoated titanium screws into medial and lateral femoral condyles of 48 New Zealand white rabbits. Imaging, histomorphometric and biomechanical analyses were employed to evaluate the osseointegration and biocompatibility 12 weeks after the implantation. Histology and scanning electron microscopy revealed that bone tissues surrounding the screws coated with CaTiO3 were fully regenerated and they were also well integrated with the screws. An interfacial fibrous membrane layer, which was found in the HA coating group, was not noticeable between the bone tissues and CaTiO3-coated screws. X-ray imaging analysis showed in the CaTiO3 coating group, there was a dense and tight binding between implants and the bone tissues; no radiation translucent zone was found surrounding the implants as well as no detachment of the coating and femoral condyle fracture. In contrast, uncoated screws exhibited a fibrous membrane layer, as evidenced by the detection of a radiation translucent zone between the implants and the bone tissues. Additionally, biomechanical testing revealed that the binding strength of CaTiO3 coating with bone tissues was significantly higher than that of uncoated titanium screws, and was comparable to that of HA coating. The study demonstrated that CaTiO3 coating in situ to titanium screws possesses great biocompatibility and osseointegration comparable to HA coating.

The CeO 2 , which were prepared by hard-template method, soft-template method, and precipitation method, were used as support to prepare Ni/CeO 2 catalysts (named as NCT, NCS, and NCP catalysts, respectively). The prepared catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET). Hydrogen temperature-programmed reduction (H 2 -TPR) was also used to study the reducibility of the support nickel precursors. Moreover, CO 2 catalytic hydrogenation methanation was used to investigate the catalytic properties of the prepared NCT, NCS, and NCP catalysts. H 2 -TPR and XRD results showed that the NiO can be reduced by H 2 to produce metal Ni species, and the surface oxygen species existing on the surface of the support CeO 2 can also be reduced by H 2 to form surface oxygen vacancies. Low-angle XRD, TEM, and BET results indicated that the NCT and NCS catalysts had developed mesoporous structure and high specific surface area of 104.7 m 2 g −1 and 53.6 m 2 g −1 , respectively. The NCT catalyst had the highest CO 2 methanation activity among the studied NCT, NCS, and NCP catalysts. The CO 2 conversion and CH 4 selectivity of the NCT catalyst can reach 91.1% and 100% at 360 °C and atmospheric pressure. The NCP catalyst, which had low specific surface area and low porosity, performed less CO 2 conversion and higher CH 4 selectivity than the NCT and NCS catalysts till 400 °C.

Au is a chemically inert metal, while Os is quite active to react with oxygen. Although Au and Os are in the two extremes in chemical properties, unexpectedly, both of them can enhance the oxygen reduction reaction (ORR) activity of Pt-based alloys. In this work, a systematical density functional theory calculation was used to elucidate the mechanisms of enhanced activity in PtM/Pd with doped atoms changing from chemically inert Au to active Os. The calculations show that different sites on the PtAu/Pd and the PtOs/Pd surface adopt different ORR mechanisms due to the heterogeneous electronic structures, such as uneven surface charge and unequal d-band center. More importantly, all of the ORR steps on the sites far away from the doped atoms in the PtAu/Pd and PtOs/Pd display similar activation energy corresponding to better catalytic activity than the other sites. The catalytic activity is mainly affected by the ligand effect, and a proper distance between the doped atoms and the Pt atoms should induce the...

Necroptosis is a type of regulated cell death that has been implicated in various diseases. Receptor-interacting protein 3 (RIP3), a member of the RIP family, is an important mediator of the necroptotic pathway. Cleavage of RIP3 at Asp328 by caspase-8 abolishes the kinase activity of RIP3, which is critical for necroptosis. Moreover, RIP3 is significantly upregulated during the early stages of acute high intra-ocular pressure and oxygen glucose deprivation. In this study, the effects of RIP3 during elevated hydrostatic pressure (EHP) were investigated and the possible mechanism through which caspase-8 regulated RIP3 cleavage was explored. Flow cytometry analysis revealed that the number of EHP-induced necrotic retinal ganglion cell 5 (RGC-5) cells was reduced after RIP3-knockdown. Furthermore, malondialdehyde (MDA) levels and glycogen phosphorylase (PYGL) activity in normal RGC-5 cells were much higher than those in RIP3-knockdown cells after EHP. EHP-induced RGC-5 necrosis was significantly reduced after treatment with butylated hydroxyanisole (BHA), a reactive oxygen species (ROS) scavenger. MDA levels and PYGL activity were lower in normal RGC-5 cells than those in cells with caspase-8 inhibition after EHP. Western blot analysis demonstrated that the RIP3 cleavage product was upregulated in cells with caspase-8 inhibition. Additionally, flow cytometry analysis revealed that the number of EHP-induced necrotic RGC-5 cells was increased after caspase-8 inhibition. Our results suggested that RGC-5 necroptosis following EHP was mediated by RIP3 through induction of PYGL activity and subsequent ROS accumulation. Thus, caspase-8 may participate in the regulation of RGC-5 necroptosis via RIP3 cleavage.

An efficient and environmentally friendly method for the synthesis of cellulose carbamate from a mixture of cellulose pulp or the activated cellulose pulp and urea was presented in this paper. Cellulose carbamate with a nitrogen content of 1.21 % and 3.29 % were successfully synthesized via esterification reaction in the high-boiling aprotic and polar N-methyl-2-pyrrolidone solvents (hereinafter NMP). The structures of cellulose carbamate were characterized by Fourier transform infrared spectroscopy (FTIR), Kjeldahl analysis, thermo-gravimetric analysis, scanning electron microscopy (SEM), X-ray diffractometry (XRD), and 13C-solid-state NMR. The results showed that some functional groups of the alkali cellulose were substituted by amino in the high-boiling aprotic and polar solvents, then the cellulose carbamate was prepared with the reduced crystallinity and thermal decomposition temperature. In addition, the product was prepared with uniform substitution and distribution of carbamate group in the cellulose chain, which guaranteed its good solubility in aqueous alkali as well as its spinnability to produce fiber.

International audience; Hypothesis: superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as building block of colloidal nanocomposites for biomedical applications. Strategies employed to embed them in a biodegradable and biocompatible polymer matrix often fail to achieve a high density of loading which would greatly benefit to applications such as imaging and hyperthermia. In this study, poly(acrylic acid) coated SPION (γ-Fe2O3-PAA) are self-assembled with hydrolysable poly(serine ester) by electrostatic complexation, leading to perfectly defined spherical particles with ultra-high density of magnetic material and an ability to auto-degrade into individual SPION and biocompatible byproducts.Experiments: self-assembly and auto-degradation of γ-Fe2O3-PAA/poly(serine ester) and γ-Fe2O3-PAA/poly(serine ester)-b-PEG colloidal particles are studied by light scattering and microscopy. Colloidal stability in bio-fluids, hyperthermia under alternating magnetic field, cellular uptake, cytotoxicity and degradation of γ-Fe2O3-PAA/poly(serine ester)-b-PEG in living cells are investigated.Findings: a remarkably slow electrostatic complexation leads to dense superparamagnetic γ-Fe2O3-PAA/poly(serine ester)-b-PEG polyion complexes (PICs) with controlled sizes (150 – 500 nm) and times of degradation in aqueous solvents (700 – 5000 h). The material shows good sustainability during hyperthermia, is well taken up by MC3T3 cells and non-cytotoxic. TEM images reveal a mechanism of degradation by “peeling” and fragmentation. In cells, PICs are reduced into individual SPIONs within 72 h.

Retinal ganglion cells (RGCs) play a key role in the pathogenesis and development of glaucoma. The present study aims to investigate the underlying mechanism of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in glaucoma development through regulating the apoptosis of RGCs. Rat models of chronic glaucoma were successfully established by translimbal laser photocoagulation. Retinal tissues were collected to determine the density of RGCs through Toluidine blue staining. The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) was transfected into RGCs after in vitro pressurization culture to examine the function of GAS5 in RGC apoptosis. The involvement of EZH2 and ATP-binding cassette transporter A1 (ABCA1) was further identified. Cell apoptosis after laser treatment and transfection was assessed by flow cytometry. We found abundant GAS5 expression and a reduction in RGC density in the retinal tissues of glaucoma rats. Silencing of GAS5 led to increased EZH2 expression and decreased ABCA1 expression in RGCs. In addition, upregulation of EZH2 promoted trimethylation of lysine 27 on histone H3, thereby suppressing ABCA1 expression and eventually leading to the inhibition of RGC apoptosis. These findings provide further understanding of the function of GAS5 in RGC apoptosis. We conclude that downregulation of GAS5 could help relieve glaucoma symptoms. GAS5 is therefore a promising target for developing novel therapeutic approaches for treating patients with glaucoma.

BACKGROUND AND AIMS Heat shock factor (HSF4) plays a vital role in carcinogenesis and tumour progression. However, its clinical significance implications in hepatocellular carcinoma (HCC) remained elusive. METHODS RT-PCR and western blot were used to detect the HSF4 expression levels in HCC cells and tissues. Immunohistochemistry staining was performed on a tissue microarray containing 104 HCC patients received radical resection. In vitro effects of HSF4 on proliferation, migration and invasion were determined by colony formation and transwell assays in HCCLM3, Huh7, MHCC97L and SMMC7721 cells. Epithelial-mesenchymal transition (EMT) was identified by RT-PCR, WB and immunofluorescence in HCCLM3 and MHCC97L cells. AKT pathway activation was detected by WB and dual luciferase report system in HCCLM3 and MHCC97L cells. RESULTS HSF4 expression was higher in primary HCC tissues derived from recurrent patients, and positively correlated with invasiveness potentials of cell lines. Clinically, patients with high HSF4 expression had significant poorer prognosis. In vitro experiments showed HSF4 silencing inhibited HCC cell proliferation, migration and invasion, whereas HSF4 overexpression had inverse effects. Moreover, silence of HSF4 induced an epithelial-like phenotype, whereas the overexpression of HSF4 resulted in a mesenchymal-like phenotype in HCC by activating AKT pathway. Further experiments showed that HSF4 could activate AKT pathway in a hypoxia-inducible factor-1α (HIF-1α) dependent, but transforming growth factor-β (TGF-β) independent manner. CONCLUSIONS HSF4 is upregulated in HCC, resulting in greater proliferation, migration and invasion capacities. Moreover, high HSF4 expression is a promising predictive indicator of poor outcome after radical resection. HSF4 may promote aggressive tumour behaviour by enhancing EMT through activating AKT pathway in a HIF1α-dependent manner.