Synthesis of Bitten Gold Nanoparticles with Single-Particle Chiroptical Responses.

The introduction of structural complexity to nanoparticles brings them interesting properties. Regularity breaking has been challenging in the chemical synthesis of nanoparticles. Most reported chemical methods for synthesizing irregular nanoparticles are complicated and laborious, largely hindering the exploration of structural irregularity in nanoscience. In this study, the authors have combined seed-mediated growth and Pt(IV)-induced etching to synthesize two types of unprecedented Au nanoparticles, bitten nanospheres and nanodecahedrons, with size control. Each nanoparticle has an irregular cavity on it. They exhibit distinct single-particle chiroptical responses. Perfect Au nanospheres and nanorods without any cavity do not show optical chirality, which demonstrates that the geometrical structure of the bitten opening plays a decisive role in the generation of chiroptical responses.

Nanohelix-Induced Optical Activity of Liquid Metal Nanoparticles.

Liquid metals (such as gallium or Ga) exist in liquid states under ambient conditions and are hardly sculpted in chiral structures. Herein, through electron-beam evaporation of Ga, hemispherical achiral Ga nanoparticles (NPs) are randomly immobilized along helical surfaces of SiO2 nanohelices (NHs), functioning as a chiral template. Helical assembly of Ga NPs shows chiroplasmonic optical activity owing to collective plasmon-plasmon interactions, which can be tuned as a function of a helical SiO2 pitch (P) and the amount of Ga evaporated. At a P of ≈150 nm, the chiroplasmonic optical activity, evaluated with anisotropic g-factor, can be as large as ≈0.1. Because the SiO2 NHs and Ga NPs have high environmental stability of nanostructures, the chiroplasmonic optical activity shows excellent anti-aging stability, despite slight blue shift and chiroplasmonic degradation for the first 2 weeks. Spontaneous oxidation of the Ga NPs enables the formation of dense Ga2 O3 layers covering Ga cores to prevent further oxidation and thus to stabilize the chiroplasmonic optical activity. This work devises an alternative approach to impose optical activity onto Ga NPs, providing an additional degree of freedom (i.e., chirality) for Ga-based flexible electronic devices to develop advanced applications of 3D display, circular polarizers, bio-imaging, and bio-detection.

Chiral Nanoparticles with Enhanced Thermal Stability of Chiral Structures through Alloying.

Metallic chiral nanoparticles (CNPs) promisingly function as asymmetric catalysts but lack an important study in thermal stability of optical activity that stems from metastable chiral lattices. In this work, annealing is applied to silver (Ag) CNPs, fabricated by glancing angle deposition (GLAD), and causes elimination of optical activity at 200 °C, mainly ascribed to chiral-to-achiral lattice transformation. The Ag CNPs are remarkedly enhanced in thermal stability through an alloying with aluminum (Al) via layer-by-layer GLAD to generate binary Ag0.5 Al0.5 CNPs composed of solid-state liquids, whose optical activity vanishes at 700 °C. Ease in the diffusion of Al atoms in the host Ag CNPs and thermal insulation from the Al2 O3 layers partially covering the binary CNPs effectively prohibit structural relaxation of the metastable chiral lattices, accounting for the significant enhancement in thermal stability of chiral lattices. This is a pioneering work to investigate the fundamental principles determining the thermal stability of metallic CNPs in terms of chiral structures and optical activity. It paves the way toward applying metallic CNPs to asymmetric catalysis at high temperature to accelerate an asymmetric synthesis of enantiomers with designable chirality, which is one of the most important topics in modern chemistry.

Chiral Ligand-Free, Optically Active Nanoparticles Inherently Composed of Chiral Lattices at the Atomic Scale.

Bulk metals lack chirality. Recently, metals have been sculptured with metastable chirality varying from the micro- to nano-scale. The manipulation of molecular chirality could be novelly performed using metals composed of chiral lattices at atomic scales (i.e., chiral nanoparticles or CNPs) if one could fundamentally understand the interactions between molecules and the chiral metal lattices. The incorporation of chiral ligands has been generally adapted to form metal CNPs. However, post-fabrication removal of chiral ligands usually causes relaxation of the metastable chiral lattices to thermodynamically stable achiral structures, and thus the coexisting chiral ligands will unavoidably disturb or screen the interactions of interest. Herein, a concept of metal CNPs that are free of chiral ligands and consist of atomically chiral lattices is introduced. Without chiral ligands, shear forces applied by substrate rotation along with the translation of incident atoms lead to imposing the metastable chiral lattices onto metals. Metal CNPs show not only the chiroptical effect but the enantiospecific interactions of chiral lattices and molecules. These two unique chiral effects have resulted in the applications of enantiodifferentiation and asymmetric synthesis. Prospectively, the extension in composition space and constituent engineering will apply alloy CNPs to enantiodiscrimination, enantioseperation, bio-imaging, bio-sensing, and asymmetric catalysis.

Binary Chiral Nanoparticles Exhibit Amplified Optical Activity and Enhanced Refractive Index Sensitivity.

Metallic chiral nanoparticles (CNPs) with a nominal helical pitch (P) of sub-10 nm contain inherent chirality and are promisingly applied to diverse prominent enantiomer-related applications. However, the sub-wavelength P physically results in weak optical activity (OA) to prohibit the development of these applications. Herein, a facile method to amplify the CNPs' OA by alloying the host CNPs with metals through a three-step layer-by-layer glancing angle deposition (GLAD) method is devised. Promoted by the GLAD-induced heating effect, the solute metallic atoms diffuse into the host CNPs to create binary alloy CNPs. Chiral alloying not only induces the plasmonic OA of the diffused solute and the created alloys but also amplifies that of the host CNPs, generally occurring for alloying Ag CNPs with diverse metals (including Cu, Au, Al, and Fe) and alloying Cu CNPs with Ag. Furthermore, the chiral alloying leads to an enhancement of refractive index sensitivity of the CNPs. The alloy CNPs with amplified plasmonic OA pave the way for potentially developing important chirality-related applications in the fields of heterogeneous asymmetric catalysis, enantiodifferentiation, enantioseparation, biosensing, and bioimaging.

Baicalin Regulates Proliferation, Apoptosis, Migration, and Invasion in Mesothelioma.

BACKGROUND Baicalin, one of the main bioactive components extracted from the traditional Chinese medicine baical Skullcap root, has an anti-tumor activity which had been studied in several cancers. However, its role in human mesothelioma remains unknown. In this study, we investigated the anti-tumor mechanisms of baicalin in the mesothelioma cell line MESO924. MATERIAL AND METHODS Effects of baicalin on mesothelioma were assessed by measuring cell viability, apoptosis, migration, invasion, inactivation of signaling intermediates, and cell-cycle alterations. RESULTS Baicalin inhibited the proliferation, migration, and invasion of human mesothelioma cells and increased their apoptosis, all in a dose-dependent manner. Specifically, baicalin decreased the expression of p-EGFR, p-AKT, p-MAPK, p-S6, Bcl-2, and VEGF and increased the expression of Bax in mesothelioma cells. The suppressed mesothelioma cellular proliferation is due to the arrest of the S cell cycle by baicalin. Inhibition of the PI3K/AKT/mTOR signaling pathway by a PI3K/AKT/mTOR inhibitor augmented the anti-proliferation effects induced by baicalin. In addition, baicalin increased the sensitivity of MESO924 to the chemotherapeutic drugs doxorubicin, cisplatin, and pemetrexed. CONCLUSIONS These results highlight the roles of baicalin in inhibiting cell growth, migration, and invasion of mesothelioma cells while increasing apoptosis and sensitizing cells to chemotherapeutic agents through the PI3K/AKT/mTOR signaling pathway, which indicates that baicalin could be a useful drug for mesothelioma therapy.

Co-preparation of pectin and cellulose from apple pomace by a sequential process.

Apple pomace contains a plentiful pectin and cellulose resource which coexist with lignin and hemicellulose by a complex chemical and physical association in the plant cell walls. To increase the value and promote the utilization of apple pomace, it was used to produce pectin and cellulose by chemical treatments. In the case of 110 min, 10% (w/w) acetic acid and 100 °C, extraction yield of pectin reached 19.6%. Response surface methodology was applied to determine the main factors affecting the lignin removal rate (LR). LR was optimal at 70 °C, pH 4.0 and 6.0% NaClO2 concentration for 2 h in a 20% (w/v) ratio. These conditions removed 89.8% lignin from depectinated apple pomace followed by sodium hydroxide treatment for the cellulose. Cellulose was achieved more than 80.7%. Consequently, a large-scale experimental analysis showed that 196.0 g of pectin and 243.9 g of cellulose (90.4% purity) was collectively prepared from 1000 g of apple pomace.

Hydroxysafflor-Yellow A Induces Human Gastric Carcinoma BGC-823 Cell Apoptosis by Activating Peroxisome Proliferator-Activated Receptor Gamma (PPARγ).

BACKGROUND Anti-tumor properties of hydroxysafflor-yellow A (HSYA) have been recently revealed, as a series of apoptotic factors were confirmed to be regulated by HSYA and associated with peroxisome proliferator-activated receptor Gamma (PPARγ). In this study, we investigated the cell apoptosis mechanism of HSYA via activated PPARγ signal in human gastric carcinoma cells. MATERIAL AND METHODS BGC-823 cells were cultured and divided into 5 independent groups: Tumor, HSYA, HSYA+PPARγ inhibitor (GW9662), and PPARg agonist (RGZ), RGZ+GW9662. Cell proliferative activity was measured by MTT. Apoptosis and cell cycle were detected by flow cytometry. The nuclear translocation of PPARγ was detected by immunofluorescence staining chemistry, and mRNA levels of PPARγ and caspase-3 were measured by real-time qPCR. RESULTS Compared to the RGZ group, the HSYA group (100 µM) showed a similar inhibitory effect on the proliferation process of BGC-823 cells, inducing their apoptosis. As a result, the transition of BGC-823 cells from G0/G1 phase to S phase was blocked. HSYA was also found to promote the nuclear translocation of PPARγ, leading to increased expression of PPARγ and caspase-3. The regulatory effect of HSYA on BGC-823 cells could be further inhibited by PPARγ inhibitor in group GW9662. CONCLUSIONS We report the inhibitory effect of HSYA on the proliferation of BGC-823 cells, which results in activating PPARg-dependent cell cycle blocking and cell apoptosis, suggesting that PPARg is a specific type of HSYA that can induce apoptosis of BGC-823 cells.

The Role of E-Cadherin/ß-Catenin in Hydroxysafflor Yellow A Inhibiting Adhesion, Invasion, Migration and Lung Metastasis of Hepatoma Cells.

Liver cancer is the second leading cause of cancer death. Due to treatments failures from drug resistance and cancer metastasis, discovering more effective treatments is imperative. As an angiogenesis inhibitor extracted from the Chinese herb-Safflower, hydroxysafflor yellow A (HSYA) inhibits the tumor growth in H22-bearing mice. Poorly differentiated hepatoma cells showed the ability to invade and metastasize, which are dependent on the angiogenesis. Accordingly, we hypothesized that HSYA could inhibit the metastasis of liver cancer cells. We investigated the metastasizing potential of human hepatic carcinoma SMMC-7721 cells treated with HSYA. A pulmonary metastatic model of mouse hepatoma H22 cells was established to evaluate the effect and possible mechanism of HSYA on lung metastasis from liver cancer. The results showed that HSYA inhibited the proliferation, invasion and migration of SMMC-7721 cells and reduced its adhesion to the extracellular matrix (ECM). In H22 mice treated with HSYA, the formation of E-cadherin/ß-catenin complex resulted in the activation of peroxisome proliferator-activated receptor γ and inhibition of matrix metalloproteinase-2. As a result, the degradation of ECM was reduced and epithelial-mesenchymal transition was prevented. The present findings indicate that HSYA can prevent pulmonary metastasis in liver cancer, which provides strong evidence for the application of HSYA in treatments.

Cholesterol Partition and Condensing Effect in Phase-Separated Ternary Mixture Lipid Multilayers.

The cholesterol partitioning and condensing effect in the liquid-ordered (Lo) and liquid-disordered (Ld) phases were systematically investigated for ternary mixture lipid multilayers consisting of 1:1 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-sn-glycero-3-phosphocholine with varying concentrations of cholesterol. X-ray lamellar diffraction was used to deduce the electron density profiles of each phase. The cholesterol concentration in each phase was quantified by fitting of the electron density profiles with a newly invented basic lipid profile scaling method that minimizes the number of fitting parameters. The obtained cholesterol concentration in each phase versus total cholesterol concentration in the sample increases linearly for both phases. The condensing effect of cholesterol in ternary lipid mixtures was evaluated in terms of phosphate-to-phosphate distances, which together with the estimated cholesterol concentration in each phase was converted into an average area per molecule. In addition, the cholesterol position was determined to a precision of (±0.7Å) and an increase of disorder in the lipid packing in the Lo phase was observed for total cholesterol concentration of 20∼30%.

Anomalous partitioning of water in coexisting liquid phases of lipid multilayers near 100% relative humidity.

Ternary lipid mixtures incorporating cholesterol are well-known to phase separate into liquid-ordered (L(o)) and liquid-disordered (L(d)) phases. In multilayers of these systems, the laterally phase separated domains register in columnar structures with different bilayer periodicities, resulting in hydrophobic mismatch energies at the domain boundaries. In this paper, we demonstrate via synchrotron-based X-ray diffraction measurements that the system relieves the hydrophobic mismatch at the domain boundaries by absorbing larger amounts of inter-bilayer water into the L(d) phase with lower d-spacing as the relative humidity approaches 100%. The lamellar repeat distance of the L(d) phase swells by an extra 4 Å, well beyond the equilibrium spacing predicted by the inter-bilayer forces. This anomalous swelling is caused by the hydrophobic mismatch energy at the domain boundaries, which produces a surprisingly long-range effect. We also demonstrate that the d-spacings of the lipid multilayers at 100% relative humidity do not change when bulk water begins to condense on the sample.

Accurate calibration and control of relative humidity close to 100% by X-raying a DOPC multilayer.

In this study, we have designed a compact sample chamber that can achieve accurate and continuous control of the relative humidity (RH) in the vicinity of 100%. A 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) multilayer can be used as a humidity sensor by measuring its inter-layer repeat distance (d-spacing) via X-ray diffraction. We convert from DOPC d-spacing to RH according to a theory given in the literature and previously measured data of DOPC multilamellar vesicles in polyvinylpyrrolidone (PVP) solutions. This curve can be used for calibration of RH close to 100%, a regime where conventional sensors do not have sufficient accuracy. We demonstrate that this control method can provide RH accuracies of 0.1 to 0.01%, which is a factor of 10-100 improvement compared to existing methods of humidity control. Our method provides fine tuning capability of RH continuously for a single sample, whereas the PVP solution method requires new samples to be made for each PVP concentration. The use of this cell also potentially removes the need for an X-ray or neutron beam to pass through bulk water if one wishes to work close to biologically relevant conditions of nearly 100% RH.

The detoxification ability of sex-role reversed seahorses determines the sexual dimorphism in immune responses to benzo[a]pyrene exposure.

Sexual dimorphism in immune responses is an essential factor in environmental adaptation. However, the mechanisms involved remain obscure owing to the scarcity of data from sex-role-reversed species in stressed conditions. Benzo[a]pyrene (BaP) is one of the most pervasive and carcinogenic organic pollutants in coastal environments. In this study, we evaluated the potential effects on renal immunotoxicity of the sex-role-reversed lined seahorse (Hippocampus erectus) toward environmental concentrations BaP exposure. Our results discovered the presence of different energy-immunity trade-off strategies adopted by female and male seahorses during BaP exposure. BaP induced more severe renal damage in female seahorses in a concentration-dependent manner. BaP biotransformation and detoxification in seahorses resemble those in mammals. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide (BPDE) and 9-hydroxybenzo[a]pyrene (9-OH-BaP) formed DNA adducts and disrupted Ca2+ homeostasis may together attribute the renal immunotoxicity. Sexual dimorphisms in detoxification of both BPDE and 9-OH-BaP, and in regulation of Ca2+, autophagy and inflammation, mainly determined the extent of renal damage. Moreover, the mechanism of sex hormones regulated sexual dimorphism in immune responses needs to be further elucidated. Collectively, these findings contribute to the understanding of sexual dimorphism in the immunotoxicity induced by BaP exposure in seahorses, which may attribute to the dramatic decline in the biodiversity of the genus.

Long-range interlayer alignment of intralayer domains in stacked lipid bilayers.

Liquid-crystalline phases of stacked lipid bilayers represent a pervasive motif in biomolecular assemblies. Here we report that, in addition to the usual smectic order, multicomponent multilayer membranes can exhibit columnar order arising from the coupling of two-dimensional intralayer phase separation and interlayer smectic ordering. This coupling propagates across hundreds of membrane lamellae, producing long-range alignment of phase-separated domains. Quantitative analysis of real-time dynamical experiments reveals that there is an interplay between intralayer domain growth and interlayer coupling, suggesting the existence of cooperative multilayer epitaxy. We postulate that such long-range epitaxy is solvent-assisted, and that it originates from the surface tension associated with differences in the network of hydrogen-bonded water molecules at the hydrated interfaces between the domains and the surrounding phase. Our findings might inspire the development of self-assembly-based strategies for the long-range alignment of functional lipid domains.

Halide-assisted differential growth of chiral nanoparticles with threefold rotational symmetry.

Enriching the library of chiral plasmonic nanoparticles that can be chemically mass-produced will greatly facilitate the applications of chiral plasmonics in areas ranging from constructing optical metamaterials to sensing chiral molecules and activating immune cells. Here we report on a halide-assisted differential growth strategy that can direct the anisotropic growth of chiral Au nanoparticles with tunable sizes and diverse morphologies. Anisotropic Au nanodisks are employed as seeds to yield triskelion-shaped chiral nanoparticles with threefold rotational symmetry and high dissymmetry factors. The averaged scattering g-factors of the L- and D-nanotriskelions are as large as 0.57 and - 0.49 at 650 nm, respectively. The Au nanotriskelions have been applied in chiral optical switching devices and chiral nanoemitters. We also demonstrate that the manipulation of the directional growth rate enables the generation of a variety of chiral morphologies in the presence of homochiral ligands.

Phenethylferulate as a natural inhibitor of inflammation in LPS-stimulated RAW 264.7 macrophages: focus on NF-κB, Akt and MAPK signaling pathways.

BACKGROUND: Notopterygii Rhizoma et Radix (NRR) is commonly used for the treatment of inflammation-linked diseases. Phenethylferulate (PF) is high content in NRR crude, but its anti-inflammatory effect remains unclear. Therefore, we aimed to investigate the anti-inflammatory properties of PF and its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. METHODS: The effect of PF on cell viability was measured by MTT assay. The anti-inflammatory properties of PF were studied by detecting the levels of inflammatory mediators and cytokines using enzyme-linked immunosorbent assay (ELISA). Furthermore, the anti-inflammatory mechanisms of PF were determined by Western blot analysis. RESULTS: PF was not cytotoxic to RAW 264.7 macrophages at the concentrations of below 48 µM. ELISA showed that PF conspicuously inhibited overproduction of prostaglandin E2 (PGE2), tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Western blot analysis showed that PF remarkably suppressed overproduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), the phosphorylation of inhibitor of NF-κB kinase α (IκB-α), protein kinase B (Akt), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38, as well as the degradation and subsequent nuclear translocation of p65. CONCLUSIONS: PF is a potent inhibitor of inflammation acting on nuclear factor kappa-B (NF-κB), Akt and mitogen-activated protein kinase (MAPK) signaling pathways in LPS-stimulated RAW 264.7 macrophages. This work provides evidence for the suitability of PF as a therapeutic candidate for the management of inflammatory-mediated immune disorders.

Mesoporous alloy chiral nanoparticles with high production yield and strong optical activities.

Applying galvanic replacement reactions (GRRs) to the host chiral nanoparticles (CNPs) is an exclusive method to generate alloy CNPs with mesoporous structures through chirality transfer. However, the GRR-mediated chirality transfer is too inefficient to impose strong optical activities on the alloy mesoporous CNPs (or m-CNPs). Here we dope the host with gold (Au) to significantly enhance the chirality transfer, and additionally employ the Au adhesion layer to increase the production yield (PY) of binary m-CNPs.

From wound response to repair - lessons from C. elegans.

As a result of evolution, the ability to repair wounds allows organisms to combat environment insults. Although the general process of wound healing at the tissue level has been described for decades, the detailed molecular mechanisms regarding the early wound response and rapid wound repair at the cellular level remain little understood. Caenorhabditis elegans is a model organism widely used in the field of development, neuroscience, programmed cell death etc. The nematode skin is composed of a large epidermis associated with a transparent extracellular cuticle, which likely has a robust capacity for epidermal repair. Yet, until the last decades, relatively few studies had directly analyzed the wound response and repair process. Here we review recent findings in how C. elegans epidermis responds to wounding and initiates early actin-polymerization-based wound closure as well as later membrane repair. We also discussed some remained outstanding questions for future study.

Hydroxysafflor yellow A induces autophagy in human liver cancer cells by regulating Beclin 1 and ERK expression.

Hydroxysafflor yellow A (HSYA) is a water-soluble component of the safflower (Carthamus tinctorius), and research has revealed that HSYA exhibits antitumor effects. In the present study, the effects of HSYA on the autophagy of a Hep-G2 liver cancer cell line, as well as the underlying mechanisms, were investigated. Hep-G2 cells were treated with HSYA and the viability of cells was measured using an MTT assay. Western blotting and immunofluorescence assays were performed to determine the expression of light chain 3 II (LC3-II) and p62, as well as the autophagy regulators Beclin 1 and ERK1/2. Transmission electron microscopy was performed to observe the formation of autophagosomes. The combined effects of HSYA and the autophagy inhibitor chloroquine (CQ) were also determined. The results revealed that the viability of Hep-G2 cells decreased with increasing concentrations of HSYA. Furthermore, LC3-II expression increased significantly and the level of p62 decreased significantly in the HYSA group compared with the control group. Additionally, an increase in Beclin 1 expression and a decrease in phosphorylated-ERK1/2 expression was observed in Hep-G2 cells treated with HYSA. Following treatment with CQ and HSYA, a significant increase in the viability of Hep-G2 cells was observed compared with the HSYA group. Collectively, the results indicated that HSYA induced autophagy by promoting the expression of Beclin 1 and inhibiting the phosphorylation of ERK in liver cancer cells. Therefore, HSYA may serve as a potential therapeutic agent for liver cancer.

Hydroxyl safflower yellow A regulates the tumor immune microenvironment to produce an anticancer effect in a mouse model of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious threat to human health. Chemotherapy drugs such as cisplatin are widely used in cancer treatment, but can cause severe side effects. Hydroxyl safflower yellow A (HSYA) is a water-soluble chalcone glycoside substance extracted from safflowers (Carthamus tinctorius L.) that has been reported to inhibit tumor growth with few side effects. The tumor immune microenvironment is crucial for the proliferation and invasiveness of tumor cells, and it is mediated by forkhead box P3-positive (FOXP3+) regulatory T cells (Tregs) and retinoic acid receptor-related orphan receptor-γ (RORγ)-expressing Th17 cells. FOXP3+ Tregs inhibit immunoreaction and FOXP3 is a key indicator of Tregs. RORγ isoform 2, also known as RORγt, is an important transcription factor in Th17 cells that may promote cancer progression. In the present study, the antitumor effect of HSYA on HCC was investigated, as well as its impact on the tumor immune microenvironment. Following the establishment of a mouse model for HCC, hematoxylin and eosin staining were performed to observe histological changes in liver tumors, and the spleen and thymus were weighed to calculate the spleen and thymus indexes. The proportion of FOXP3+ Tregs in the spleen was determined by flow cytometry, and expression levels of Foxp3 and Rorγt were examined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The results of the present study showed that cisplatin inhibited tumor growth, caused weight loss and reduced the immunoreactivity of the mice. HSYA inhibited tumor growth without causing significant weight loss. The proportion of FOXP3-expressing Tregs in the spleen and the expression of Foxp3 and Rorγt mRNA decreased following treatment with certain doses of HSYA. In conclusion, HSYA inhibited tumor growth without detrimental effects on the weight of the mice, indicating that HSYA may be suitable as a novel therapy for HCC patients.