Assessment of toxic effects of thallium on the earthworm Eisenia fetida using the biomarker response index.

Thallium (Tl), though not essential for biological systems, is widely used in industrial activities, resulting in soil pollution and adverse effects on soil biota. Systematic toxicological studies on Tl, especially concerning soil organisms, are relatively rare. This research evaluates the toxic effects of Tl on earthworms by measuring oxidative stress biomarkers, such as superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG), and by assessing the expression of functional genes, such as heat shock protein 70 (Hsp70), metallothionein (MT), and annetocin (ANN). Additionally, this study employs the Biomarker Response Index (BRI) and two-way ANOVA to comprehensively assess the cumulative toxicity of Tl in earthworms. The findings indicate that Tl exposure significantly exacerbates oxidative stress and cellular damage in earthworms, particularly under conditions of high concentration and prolonged exposure. BRI results demonstrate a continuous decline in the physiological state of earthworms with increasing Tl concentration and exposure duration. Two-way ANOVA reveals significant dose-responsive increases in SOD and CAT activities, as well as in ANN gene expression. Apart from GST activity, other biomarkers significantly increased over time, and the changes in biomarkers such as SOD, CAT, MDA, and 8-OHdG were significantly influenced by dose and time. LSD post hoc tests show significant effects of dose, time, and their interactions on all biomarkers except for GST. These findings are valuable for gaining a deeper understanding of the ecological risks of Tl in soil environments and its potential threats to soil biota, aiding in the management of ecological risks associated with Tl-contaminated soils.

Biometabolically Derived Selenium Nanoparticles Armed with Protein Protective Suit toward High-Performance Li-Se Batteries.

Selenium (Se) serves as a burgeoning high-energy-density cathode material in lithium-ion batteries. However, the development of Se cathode is strictly limited by low Se utilization and inferior cycling stability arising from intrinsic volume expansion and notorious shuttle effect. Herein, a microbial metabolism strategy is developed to prepare "functional vesicle-like" Se globules via Bacillus subtilis subsp. from selenite in sewage, in which Se nanoparticles are armed with a natural biological protein membrane with rich nitrogen and phosphorus, achieving the eco-efficient conversion of trash into treasure (selenite, SeO3 2- → Selenium, Se). The appealing-design "functional vesicle-like" Se globules are beneficial to accommodate volume changes of Se in electrochemical reactions, confining polyselenides via chemisorption, and enhancing mechanical strength of electrode by associated bacteria debris, realizing comprehensive utilization of microorganism. By conceptualizing "functional vesicle-like" Se globules, rather than artificial Se-host composites, as cathode for lithium-selenium batteries, it exhibits outstanding cycling stability and improved rate performance. This strategy opens the door to design smart electrode materials with unattainable structure that cannot be achieved by traditional approaches, achieving eco-efficient conversion of pollutants into energy-storage nanomaterials, which will be a promising research field for interdisciplinary of energy, biology, and environment.

Rhamnolipids stabilized essential oils microemulsion for antimicrobial and fruit preservation.

Essential oils, well-known for their antifungal properties, are widely utilized to combat fruit decay. However, their application faces big challenges due to their high volatility and hydrophobic traits, which leads to strong odor, short effective time and poor dispersivity. This study aimed to address these challenges by formulating microemulsions consisting of essential oils and rhamnolipids. The optimized microemulsion, featuring a small particle size of 6.8 nm, exhibited higher stability and lower volatility than conventional emulsion. Notably, the prepared microemulsions demonstrated remarkable antimicrobial efficacy against E. coli, S. aureus, C. albicans, S. cerevisiae, and A. niger. The application of these microemulsions proved to be highly effective in preventing blueberry decay while preserving fruit's quality, particularly by minimizing the loss of essential nutrients such as anthocyanins. Consequently, essential oil microemulsions emerge as a highly effective postharvest preservative for fruits, offering a promising solution to extend their shelf life and enhance overall quality.

MOF-on-MOF heterojunction-derived Co3O4-CuCo2O4 microflowers for low-temperature catalytic oxidation.

Through the exchange-extended growth method (EEGM), MOF-on-MOF heteroarchitectures with distinct crystallography were produced and pyrolyzed into hybrid metal oxides. The strong exchange ability of organometallic compounds realized the component reconstruction of the MOF matrix and enhanced the interfacial forces between MOFs, showing an excellent performance in low-temperature catalytic oxidation.

Novel Thin Film Nanocomposite Forward Osmosis Membranes Prepared by Organic Phase Controlled Interfacial Polymerization with Functional Multi-Walled Carbon Nanotubes.

Novel high-quality thin film nanocomposite (TFN) membranes for enhanced forward osmosis (FO) were first synthesized through organic phase controlled interfacial polymerization by utilizing functional multi-walled carbon nanotubes (MWCNTs). As 3-aminopropyltriethoxysilane (APTES) grafted MWCNTs via an amidation reaction significantly promoted the dispersion in organic solution, MWCNTs-APTES with better compatibility effectively restricted the penetration of trimesoyl chloride (TMC), thus adjusting the morphology and characters of TFN membranes. Various techniques such as Fourier transform infrared spectra (FTIR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), sessile droplet analysis and FO experiments and reverse osmosis (RO) operation were taken to characterize and evaluate the performance of nanocomposites and membranes. The prepared TFN FO membranes exhibited good hydrophilicity and separation efficiency, in which water flux was about twice those of thin film composite (TFC) membranes without MWCNTs-APTES in both AL-DS and AL-FS modes. Compared with the original TFC membrane, the membrane structural parameter of the novel TFN FO membrane sharply was cut down to 60.7%. Based on the large number of low mass-transfer resistance channels provided by functional nanocomposites, the progresses may provide a facile approach to fabricate novel TFN FO membranes with advanced selectivity and permeability.

Preparation of Amino-Functional UiO-66/PIMs Mixed Matrix Membranes with [bmim][Tf2N] as Regulator for Enhanced Gas Separation.

Development of mixed matrix membranes (MMMs) with excellent permeance and selectivity applied for gas separation has been the focus of world attention. However, preparation of high-quality MMMs still remains a big challenge due to the lack of enough interfacial interaction. Herein, ionic liquid (IL)-modified UiO-66-NH2 filler was first incorporated into microporous organic polymer material (PIM-1) to prepare dense and defect-free mixed matrix membranes via a coating modification and priming technique. IL [bmim][Tf2N] not only improves the hydrophobicity of UiO-66-NH2 and facilitates better dispersion of UiO-66-NH2 nanoparticles into PIM-1 matrix, but also promotes the affinity between MOFs and polymer, sharply reducing interface non-selective defects of MMMs. By using this strategy, we can not only facilely synthesize high-quality MMMs ignoring non-selective interfacial voids, but also structurally regulate MOF nanoparticles in the polymer substrate and greatly improve interface compatibility and stability of MMMs. The method also gives suitable level of generality for fabrication of versatile defect-free MMMs based on different combination of MOFs and PIMs. The prepared UiO-66-NH2@IL/PIM-1 membrane exhibited outstanding gas separation behavior with large CO2 permeation of 8283.4 Barrer and high CO2/N2 selectivity of 22.5.

Synergistic effects of glyphosate and multiwall carbon nanotubes on Arabidopsis thaliana physiology and metabolism.

Agricultural chemicals have the potential to become pollutants that adversely affect plant growth. Interactions between these compounds are likely, but potential synergies are under-researched. Multiwall carbon nanotubes are increasingly finding novel uses in agriculture, as delivery mechanisms and as slow-release fertilizers. There is potential for nanotubes to interact with other agricultural chemicals in unpredictable ways. To investigate this possibility, we examined interactions with glyphosate, a widely used herbicide that is also attracting increasing concern over its potential for non-target effects. Here we examined potential synergistic effects on hydroponically grown Arabidopsis thaliana. Single treatments did not affect plant growth significantly, or did only mildly. However, combined treatment significantly affected both plant root and shoot growth. High-level content of malondialdehyde and up-regulated of metabolic antioxidant molecules in plant indicated that combined group caused the strong oxidative damage, while the decreased of antioxidant enzyme activities indicated an imbalance between reactive oxygen species (ROS)and the antioxidant defense system due to the continuously generated ROS. Besides, several intermediate metabolites of unsaturated fatty acids synthesis pathways were up-regulated in combined treatment, which clarified that combined group changed membrane components. The increase of intermediate metabolites in combined group also reflected more energy consumption in the repairment of the disrupt of combined treatment. The synergistic effect observed was attributed to the accumulation of glyphosate resulting from permeability and transportability of the carbon nanotubes. Overall, the risk of nanotube-herbicide interaction suggests a caution use of nanotubes in agricultural applications.

In-situ self-assembly of robust Fe (III)-carboxyl functionalized polyacrylonitrile polymeric bead catalyst for efficient photo-Fenton oxidation of p-nitrophenol.

From the view of channel confinement and functional site capture, we develop an in-situ self-assembly strategy to fabricate the carboxyl functionalized Fe-HPAN bead catalyst with highly stable and uniformly dispersed metallic sites for efficient photo-Fenton oxidation of p-nitrophenol (p-NP). BET and FTIR analysis reveal that numerous carboxyl groups and mesopores exist in Fe-HPAN beads, which acts to capture and immobilize iron ions. Catalytic results show that the degradation rate and TOC removal for p-NP were up to 99.78 and 91.68% under the optimal condition. Even at near neutral pH, the degradation rate almost keep the same and the TOC removal can still reach 73.05%. Due to the autocatalytic cycle of FeIII/FeII, the apparent rate constant of Fe-HPAN (0.2247 min-1) was 5.4 times as high as unmodified Fe-PAN (0.0415 min-1) in the presence of H2O2 and visible light irradiation, which was 2-3 orders of magnitude larger than that of other reaction systems. More importantly, Fe-HPAN bead catalyst exhibited little loss of activity even after 20 cycles of re-utilization. The possible degradation pathway of p-NP was also proposed based on GC/MS analysis. The present work may provide a new perspective for the use of synthetic polymer to prepare low-cost, efficient and robust photo-Fenton oxidation catalysts.

Biological Metabolism Synthesis of Metal Oxides Nanorods from Bacteria as a Biofactory toward High-Performance Lithium-Ion Battery Anodes.

Increasing awareness toward environmental remediation and renewable energy has led to a vigorous demand for exploring a win-win strategy to realize the eco-efficient conversion of pollutants ("trash") into energy-storage nanomaterials ("treasure"). Inspired by the biological metabolism of bacteria, Acidithiobacillus ferrooxidans (A. ferrooxidans) is successfully exploited as a promising eco-friendly sustainable biofactory for the controllable fabrication of α-Fe2 O3 nanorods via the oxidation of soluble ferrous irons to insoluble ferric substances (Jarosite, KFe3 (SO4 )2 (OH)6 ) and a facile subsequent heat treatment. It is demonstrated that the stable solid electrolyte interphase layers and marvelous cracks in situ formed in biometabolic α-Fe2 O3 nanorods play important roles that not only significantly enhance the structure stability but also facilitate electron and ion transfer. Consequently, these biometabolic α-Fe2 O3 nanorods deliver a superior stable capacity of 673.9 mAh g-1 at 100 mA g-1 over 200 cycles and a remarkable multi-rate capability that observably prevails over the commercial counterpart. It is highly expected that such biological synthesis strategies can shed new light on an emerging field of research interconnecting biotechnology, energy technology, environmental technology, and nanotechnology.

A Suitable Option for Gustilo and Anderson Grade III Injury.

BACKGROUND The management of Gustilo and Anderson grade III injury remains difficult, particularly due to the incidence of wound infections, delayed fracture union, and traumatic extremity amputation. However, little data is available on delayed skin graft or flap reconstructions of Gustilo grade III injury, especially using new technologies of wound coverage, such as vacuum sealing drainage (VSD) combined with limited internal and/or external fixation. MATERIAL AND METHODS Between June 2008 and May 2013, we performed the VSD technique combined with limited internal and/or external fixation on 38 patients (22 males and 16 females, with a mean age of 36.5 years) with Gustilo and Anderson grade III injury. VSD was regularly changed and delayed skin grafts or flaps were used to cover the defect. Two patients were lost to follow-up, and the remaining 36 were available for evaluation. The complications, wound healing, infections, and bony union were assessed for a mean duration of 2.5 years (range, 1-4 years). RESULTS Complications were seen in 5 of the 36 cases: 2 cases had infection alone, 1 case had delayed union or nonunion, 1 case had infection and delayed union, and 1 case had wound necrosis, infection, and nonunion. VSD was regularly changed 2-6 times. Morphological appearance and functional recovery were satisfactory in all cases. CONCLUSIONS Using VSD before skin grafts or flaps coverage, combined with limited internal and/or external fixation, is a suitable option for Gustilo and Anderson grade III injury.

Clinical characteristics and therapeutic analysis of 51 patients with Marjolin's ulcers.

Marjolin's ulcers, which are epidermoid carcinomas arising on non-healing scar tissue, may be of various pathological types, including squamous cell carcinoma. The pathogenesis of squamous cell carcinoma arising in an ulcer differs from that of the primary cutaneous squamous cell carcinoma. This squamous cell carcinoma is aggressive in nature, and has a high rate of metastasis. Between January 2001 and September 2013, 51 patients with Marjolin's ulcers were admitted to the Departments of Plastic Surgery of the Affiliated Foshan Hospital and the Second Affiliated Hospital of Sun Yat-sen University. The ulcers included 43 cases of squamous cell carcinoma, six of melanoma, one of basal cell carcinoma and one of epithelioid sarcoma. The clinical data of these patients were retrospectively analyzed. Patients were followed until mortality. Among the patients with squamous cell carcinoma, 30.23% exhibited sentinel lymph node metastasis and 11.63% had distant metastasis. Among the patients with melanoma, 66.67% had sentinel lymph node metastasis and 33.33% had distant metastasis. Sentinel lymph node metastasis was successfully detected in 11 patients with Marjolin's ulcer using 18F-fluorodeoxyglucose positron emission tomography-computed tomography and B-mode ultrasound guided biopsy. Squamous cell carcinoma was often treated by extended resection and skin grafting or skin flap repair. Patients with deep, aggressive squamous cell carcinoma of an extremity and sentinel lymph node metastasis underwent amputation and lymph node dissection. This treatment was also used for melanoma type Marjolin's ulcers.

A submerged membrane bioreactor with pendulum type oscillation (PTO) for oily wastewater treatment: membrane permeability and fouling control.

In this study, a novel submerged membrane bioreactor (SMBR) with pendulum type oscillation (PTO) hollow fiber membrane modules was developed to treat oily wastewater and control the problem of membrane fouling. To assess the potential of PTO membrane modules, the effect of oscillation orientation and frequency on membrane permeability was investigated in detail. The forces exerted on sludge flocs in the oscillating SMBR were analyzed to evaluate the impact of membrane oscillating on the cake layer resistance reduction. Results showed that the optimized PTO SMBR system exhibited 11 times higher membrane permeability and better fouling controllability than the conventional MBR system. By hydrodynamic analysis, it was found that the cooperative effect of bubble-induced turbulence and membrane oscillation in PTO SMBR system generated strong shear stress at liquid-membrane interface in vertical and horizontal direction and effectively hindered the particles from depositing on membrane surface.

6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in part via a mechanism dependent upon orphan nuclear receptor NR4A3.

The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on metabolism remain unknown; however, 6-MP was recently found to activate the orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of insulin sensitivity in adipocytes. To further explore the role of NR4A3 activation in insulin action, we explored whether 6-MP activation of NR4A3 could modulate glucose transport system activity in L6 skeletal muscle cells. We found that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and enhanced glucose transport activity via increasing GLUT4 translocation in both basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore, 6-MP increased levels of phospho-AS160, although this effect was not modulated by NR4A3 overexpression or knockdown. These primary findings provide a novel proof of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose uptake in insulin target cells, although this occurs via both NR4A3-dependent and -independent actions; the latter is related to an increase in phospho-AS160. These results establish a novel target for development of new treatments for insulin resistance.

Influence of azo dye-TiO2 interactions on the filtration performance in a hybrid photocatalysis/ultrafiltration process.

Filtration performances of hollow fiber ultrafiltration membrane were investigated in a photocatalysis/ultrafiltration process used for dyeing wastewater treatment. Special attentions were focused on the dye-TiO(2) interactions and their effect on membrane flux and dye rejection. Solution pH was proved to be the predominant force that controlled the interactions by changing the surface charge characteristics of TiO(2) and altering the size and fractal dimension of TiO(2) aggregates which determined the property and structure of deposit layer. Dye-TiO(2) interaction had pronounced effect on membrane flux in adsorptive regions, but this effect became insignificant in non-adsorptive regions. The rejection of dye in the presence of TiO(2) was found to decrease markedly due to the deposition of TiO(2) particles on membrane interface. Bridging effect of TiO(2) between membrane interface and dyes produced by electronic interaction, coordination, and hydrogen bonding was responsible for the decrease in dye rejection. In view of the results presented in this paper, the interactions between pollutant and photocatalysts and their effect on the performance of membrane in hybrid photocatalysis/membrane process should be taken into consideration in the future practice.

Enhanced submerged membrane bioreactor combined with biosurfactant rhamnolipids: performance for frying oil degradation and membrane fouling reduction.

In this study, a novel submerged membrane bioreactor (SMBR) combined with rhamnolipids was developed to treat frying oil wastewater and control the problem of membrane fouling. To validate the feasibility of this new design, a hybrid SMBR with additional rhamnolipids (RSMBR) and a controlled SMBR (CSMBR) were run in parallel. Results demonstrated that RSMBR not only held high removal efficiency of oil up to 90% at short hydraulic time, but also exhibited 10 times higher membrane permeability in comparison to CSMBR. The presence of rhamnolipids greatly enhanced the contact and reaction between the microorganism and oil molecules. The great improvement in membrane filterability was associated with an increase in hydrophobicity of flocs as well as the increase of particle size from 53.06 to 145.54 µm. The oil strongly adhered to the surface of flocs by rhamnolipids, and consequently prevented larger oil droplets directly depositing on the membrane surface.

Gli1 promotes cell survival and is predictive of a poor outcome in ERalpha-negative breast cancer.

Gli1 is a transcription factor and oncogene with documented roles in the progression of several cancer types, including cancers of the skin and pancreas. The contribution of Gli1 to the progression of breast cancer is less established. In order to investigate the functional impact of Gli1 in breast cancer, expression of Gli1 and its contribution to cell growth was assessed in breast cancer cell lines. These in vitro results were compared to expression of Gli1, determined by immunohistochemistry, in 171 breast cancers. In these cancers, the association of Gli1 with expression of estrogen receptor alpha (ERalpha) and progesterone receptor (PR), ErbB2, p53, the rate of proliferation, and clinicopathologic parameters and outcome was assessed. Expression of Gli1 and ERalpha mRNA was strongly correlated in ERalpha-positive cell lines (r = 0.999). Treatment with estrogen increased expression of Gli1 in 2 of 3 ERalpha-positive cell lines; this increase was prevented by treatment with the ERalpha-specific antagonist MPP. Silencing of Gli1 by shRNA markedly reduced the survival of two ERalpha-negative cell lines, but caused only a modest reduction in ERalpha-positive cell lines. In breast cancer tissues, cancers with nuclear localization of Gli1 had a higher ERalpha (P=0.027) and lower p53 expression (P=0.017) than those without nuclear localization of Gli1. However, nuclear localization of Gli1 was predictive of a poorer cancer-specific survival in ERalpha-negative, including triple negative, cancers (P = 0.005), but not ERalpha-positive cancers. In conclusion, we demonstrate a positive association between expression of Gli1 and ERalpha; however, our data indicate a greater functional effect of Gli1 in ERalpha-negative cancers.

Promoter cloning and characterization of the anti-vascular proliferation gene, R-ras: role of Ets- and Sp-binding motifs.

The R-ras gene encodes a small GTPase of the ras family that is closely related to H-ras and K-ras. Unlike the prototypic ras genes, the disruption of the R-ras gene in mice results in enhanced angiogenesis in tumor implants and sustained neointimal hyperplasia in response to arterial injury, indicating the in vivo role of R-ras as a negative regulator of vascular proliferation. R-ras is abundantly expressed in normal mature blood vessels but significantly down-regulated in pathologically regenerating vasculature. In this study, we investigated the roles of cis-acting elements in the transcription of the human R-ras gene, as well as the transcription factors that interact with these sequences in cultured endothelial cells and arterial smooth muscle cells. The findings from vascular cells were then compared with findings from epithelial tumor cells that aberrantly express R-ras. Deletion analyses on 5 kb of 5'-flanking DNA of the human R-ras gene revealed the functional importance of the region between -727/-476, which contains two Ets and one Sp1 consensus binding motifs. Mutation analyses of various consensus binding motifs within this region suggest both cell type-dependent and -independent regulatory mechanisms for the R-ras gene transcription. Electrophoretic mobility shift and antibody disruption assays demonstrated that an Ets transcription factor family protein, GA-binding protein (GABP), binds to the R-ras-derived sequence. Chromatin immunoprecipitation analyses determined the association of endogenous GABP as well as Sp3 proteins with the -727/-476 region of the R-ras promoter in intact cells grown in culture. Forced expression of GABP significantly enhanced R-ras mRNA expression level in endothelial cells. These results map the functional elements in the R-ras promoter sequence and suggest that the GABP may be critical for transcription of R-ras and for maintenance of normal blood vessel functions through the regulation of this gene.

[Repairing large perforation of nasal septum with titanium membrane and local pedicled mucoperiosteum flap].

OBJECTIVE: To study a new treatment to repair large perforation of nasal septum with medical titanium membrane and local padicled mucoperiosteum flap. METHOD: The bottom mucoperiosteum of nasal cavity around the perforation of nasal septum were separated from the bone surface except with the margin part of perforation. Then the distal part of mucoperiosteum flap was incised and turn over to cover the perforation, free edge of the flap was sutured to secure immobilization. Finally, the Titanium membrane was cut to the right size to tuck into subperiosteal pocket around the perforation, and was sutured to the mucoperiosteal for added immobilization. RESULT: The perforations of nasal septum in 11 patients were closed satisfactorily. Perforation of nasal septum did not recur and the follow-up time ranged from half a year to 1 year. CONCLUSION: Titanium membrane is easy of application, and has good tissue tolerance. In our study, it is a good material to repair large perforation of nasal septum.

Nuclear localization signal of ING4 plays a key role in its binding to p53.

ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53 and negatively regulate the cell growth with significant G2/M arrest of cell cycle in HepG2 cells through upregulation of p53-inducible gene p21. However, which region of ING4 could have contributed to the binding to p53 remains largely unclear. Herein, the GST-pulldown experiments revealed that the middle region of ING4, a potential bipartite nuclear localization signal (NLS), could be involved in the binding to p53. Furthermore, the interaction of ING4 to p53 was abrogated in vitro and in vivo when certain mutations or the entire deletion of the NLS domain occurred. More interestingly, the mutations of the NLS domain could alter the ING4 nuclear localization, disrupt the interaction of ING4 with p53, and even, deregulate the p53-inducible gene p21 in MCF-7 cells. All data indicated that the NLS domain of ING4 is essential for the binding of ING4 to p53 and the function of ING4 associated with p53.

ING4 induces G2/M cell cycle arrest and enhances the chemosensitivity to DNA-damage agents in HepG2 cells.

The known members of inhibitor of growth (ING) gene family are considered as candidate tumor suppressor genes. ING4, a novel member of ING family, is recently reported to interact with tumor suppressor p53, p300 (a major component of histone acetyl transferase complexes), and p65(RelA) subunit of NF-kappaB. In this study, we investigated the cellular behaviors of HepG2 cells with exogenous ING4. Interestingly, the overexpression of ING4 negatively regulated the cell growth with significant G2/M arrest of cell cycle, and moreover, enhanced the cell apoptosis triggered by serum starvation in HepG2 cells. Furthermore, the exogenous ING4 could upregulate endogenous p21 and Bax in HepG2 cells, not in p53-deficient Saos-2 cells, suggesting that G2/M arrest induced by ING4 could be mediated by the increased p21 expression in a p53-dependent manner, although there is no significant increase of p53 expression in HepG2 cells. Moreover, HepG2 cells with exogenous ING4 could significantly increase cell death, as exposed to some DNA-damage agents, such as etoposide and doxorubicin, implying that ING4 could enhance chemosensitivity to certain DNA-damage agents in HepG2 cells.