CYP2E1 deficit mediates cholic acid-induced malignant growth in hepatocellular carcinoma cells.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

Selective Lattice Doping Enables a Low-Cost, High-Capacity and Long-Lasting Potassium Layered Oxide Cathode for Potassium and Sodium Storage.

Layered transition metal oxides are highly promising host materials for K ions, owing to their high theoretical capacities and appropriate operational potentials. To address the intrinsic issues of KxMnO2 cathodes and optimize their electrochemical properties, a novel P3-type oxide doped with carefully chosen cost-effective, electrochemically active and multi-functional elements is proposed, namely K0.57Cu0.1Fe0.1Mn0.8O2. Compared to the pristine K0.56MnO2, its reversible specific is increased from 104 to 135 mAh g-1. In addition, the Cu and Fe co-doping triples the capacity under high current densities, and contributes to long-term stability over 500 cycles with a capacity retention of 68 %. Such endeavor holds the potential to make potassium-ion batteries particularly competitive for application in sustainable, low-cost, and large-scale energy storage devices. In addition, the cathode is also extended for sodium storage. Facilitated by the interlayer K ions that protect the layered structure from collapsing and expand the diffusion pathway for sodium ions, the cathode shows a high reversible capacity of 144 mAh g-1, fast kinetics and a long lifespan over 1000 cycles. The findings offer a novel pathway for the development of high-performance and cost-effective sodium-ion batteries.

Concentration-Driven Interfacial Amorphization toward Highly Stable and High-Rate Zn Metal Batteries.

The interfacial structure holds great promise in suppressing dendrite growth and parasitic reactions of zinc metal in aqueous media. Current advancements prioritize novel component fabrication, yet the local crystal structure significantly impacts the interfacial properties. In addition, there is still a critical need for scalable synthesis methods for expediting the commercialization of aqueous zinc metal batteries (AZMBs). Herein, we propose a scalable concentration-controlled method for realizing crystalline to amorphous transformation of the Zn metal interface with exceptional scalability (>1 m2) and processing consistency (>30 trials). Theoretical and experimental analyses highlight the advantages of amorphous ZnO, which exhibits moderate adsorption energy, strong desolvation ability, and hydrophilicity. Employing the amorphous ZnO-coated zinc metal anode (AZO-Zn) significantly enhances the cycling performance, impressively maintaining 1000 cycles at 100 mA cm-2. The prototype AZO-Zn||MnO2@CNT pouch cell demonstrates a capacity of 15.7 mAh and maintains 91% of its highest capacity over 100 cycles, presenting promising avenues for the future commercialization of AZMBs.

Comparison of burr hole drainage and craniotomy for acute liquid epidural hematoma in pediatric patients.

PURPOSE: To compare the impact of burr hole drainage and craniotomy for acute liquid epidural hematoma (LEDH) in pediatric patients. METHODS: This retrospective study enrolled pediatric patients with LEDH who underwent surgery in the Affiliated Hospital of Nanyang Medical College, China, between October 2011 and December 2019. According to the surgical procedure, patients were divided into the craniotomy group and the burr hole drainage group. RESULTS: A total of 21 pediatric patients were enrolled (14 males, aged 7.19 ± 2.77 years), including 13 cases in the burr hole drainage group and 8 patients in the craniotomy group. The operation time and hospitalization period in the burr hole drainage group were 33.38 ± 6.99 min and 9.85 ± 1.07 days, respectively, which were significantly shorter than that in the craniotomy group (74.25 ± 9.68 min and 13.38 ± 1.71 days, respectively; all p < 0.05). The Glasgow Coma Scale (GCS) score after burr hole drainage was significantly improved than before (median: 15 vs 13, p < 0.05). No serious complications were observed in either group; one patient in the craniotomy group developed an infection at the incision point. All patients were conscious (GCS score was 15) at discharge. CONCLUSION: Compared with craniotomy, burr hole drainage was associated with better clinical outcomes and early recovery in patients with LEDH.

Small Things Make a Big Difference: Conductive Cross-Linking Sodium Alginate@MXene Binder Enables High-Volumetric-Capacity and High-Mass-Loading Li-S Battery.

Binders are crucial for maintaining the integrity of an electrode, and there is a growing need for integrating multiple desirable properties into the binder for high-energy batteries, yet significant challenges remain. Here, we successfully synthesized a new binder by cross-linking sodium alginate (SA) with MXene materials (Ti3C2Tx). Besides the improved adhesion and mechanical properties, the integrated SA@Ti3C2Tx binder demonstrates much improved electronic conductivity, which enables ruling out the fluffy conductive additive from the electrode component with enhanced volumetric capacity. When SA@Ti3C2Tx is used to fabricate sulfur (S) cathodes, the conductive-additive-free electrode demonstrates extremely high capacity (1422 mAh cm-3/24.5 mAh cm-2) under an S loading of 17.2 mg cm-2 for Li-S batteries. Impressively, the SA@Ti3C2Tx binder shows remarkable feasibility in other battery systems such as Na-S and LiFePO4 batteries. The proposed strategy of constructing a cross-linking conductive binder opens new possibilities for designing high-mass-loading electrodes with high volumetric capacity.

Electrochemically induced crystalline-to-amorphization transformation in sodium samarium silicate solid electrolyte for long-lasting sodium metal batteries.

Exploiting solid electrolyte (SE) materials with high ionic conductivity, good interfacial compatibility, and conformal contact with electrodes is essential for solid-state sodium metal batteries (SSBs). Here we report a crystalline Na5SmSi4O12 SE which features high room-temperature ionic conductivity of 2.9 × 10-3 S cm-1 and a low activation energy of 0.15 eV. All-solid-state symmetric cell with Na5SmSi4O12 delivers excellent cycling life over 800 h at 0.15 mA h cm-2 and a high critical current density of 1.4 mA cm-2. Such excellent electrochemical performance is attributed to an electrochemically induced in-situ crystalline-to-amorphous (CTA) transformation propagating from the interface to the bulk during repeated deposition and stripping of sodium, which leads to faster ionic transport and superior interfacial properties. Impressively, the Na|Na5SmSi4O12|Na3V2(PO4)3 sodium metal batteries achieve a remarkable cycling performance over 4000 cycles (6 months) with no capacity loss. These results not only identify Na5SmSi4O12 as a promising SE but also emphasize the potential of the CTA transition as a promising mechanism towards long-lasting SSBs.

Binary Metallic CuCo5 S8 Anode for High Volumetric Sodium-Ion Storage.

With the rapid improvement of compact smart devices, fabricating anode materials with high volumetric capacity has gained substantial interest for future sodium-ion batteries (SIBs) applications. Herein, a novel bimetal sulfide CuCo5 S8 material is proposed with enhanced volumetric capacity due to the intrinsic metallic electronic conductivity of the material and multi-electron transfer during electrochemical procedures. Due to the intrinsic metallic behavior, the conducting additive (CA) could be removed from the electrode fabrication without scarifying the high rate capability. The CA-free CuCo5 S8 electrode can achieve a high volumetric capacity of 1436.4 mA h cm-3 at a current density of 0.2 A g-1 and 100 % capacity retention over 2000 cycles in SIBs, outperforming most metal chalcogenides, owing to the enhanced electrode density. Reversible conversion reactions are revealed by combined measurements for sodium systems. The proposed new strategy offers a viable approach for developing innovative anode materials with high-volumetric capacity.

Autophagy blockage and lysosomal dysfunction are involved in diallyl sulfide-induced inhibition of malignant growth in hepatocellular carcinoma cells.

Diallyl sulfide (DAS), as a major component of garlic extracts, has been shown to inhibit growth of hepatocellular carcinoma cells (HCC), but the underlying mechanism is still elusive. In this study, we aimed to explore the involvement of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We studied growth of DAS-treated HepG2 and Huh7 cells using the MTS and clonogenic assays. Autophagic flux was examined by immunofluorescence and confocal microscopy. The expression levels of autophagy-related proteins AMPK, mTOR, p62, LC3-II, LAMP1, and cathepsin D in the HepG2 and Huh7 cells treated with DAS as well as the tumors formed by HepG2 cells in the nude mice in the presence or absence of DAS were examined using western blotting and immunohistochemistry analysis. We found that DAS treatment induced activation of AMPK/mTOR, and accumulation of LC3-II and p62 both in vivo and in vitro. DAS inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. Furthermore, DAS induced an increase in lysosomal pH and inhibition of Cathepsin D maturation. Co-treatment with an autophagy inhibitor (Chloroquine, CQ) further enhanced the growth inhibitory activity of DAS in HCC cells. Thus, our findings indicate that autophagy is involved in DAS-mediated growth inhibition of HCC cells both in vitro and in vivo.

High-Entropy Solid-State Na-Ion Conductor for Stable Sodium-Metal Batteries.

Solid-state sodium-metal batteries (SSBs) hold great promise for their merits in low-cost, high energy density, and safety. However, developing solid electrolyte (SE) materials for SSBs with high performance is still a great challenge. In this study, high-entropy Na4.9 Sm0.3 Y0.2 Gd0.2 La0.1 Al0.1 Zr0.1 Si4 O12 was synthesized at comparatively low sintering temperature of 950 °C with high room-temperature ionic conductivity of 6.7×10-4  S cm-1 and a low activation energy of 0.22 eV. More importantly, the Na symmetric cells using high-entropy SE show a high critical current density of 0.6 mA cm-2 , outstanding rate performance with fairly flat potential profiles at 0.5 mA cm-2 and steady cycling over 700 h under 0.1 mA cm-2 . Solid-state Na3 V2 (PO4 )3 ||high-entropy SE||Na batteries are further assembled manifesting a desirable cycling stability with almost no capacity decay after 600 cycles and high Columbic efficiency over 99.9 %. The findings present opportunities for the design of high-entropy Na-ion conductors toward the development of SSBs.

Downregulation of estrogen receptor-α36 expression attenuates metastasis of hepatocellular carcinoma cells.

This study aimed to examine the role of estrogen receptor (ER)-α36 in the metastasis of hepatocellular carcinoma (HCC) and in the epithelial-mesenchymal transition (EMT). HCC HepG2 and Huh7 cells with the knocked-down level of ER-α36 expression were established. Cell growth and migration of the HepG2 and Huh7 cell variants were studied using MTS, transwell, and wound-healing assays, and the metastatic abilities of HepG2 cell variants were examined using a tail-vein injection model in nude mice. Levels of EMT markers, Src phosphorylation in HepG2 and Huh7 cell variants, and tumors formed by HepG2 cell variants in the nude mice were examined using Western blot and immunohistochemistry. We found that the growth and metastatic abilities of HepG2 and Huh7 cells with the knocked-down level of ER-α36 expression (HepG2/Si36 and Huh7/Si36) were significantly reduced, with increased levels of cytokeratin and E-Cadherin expression, and decreased levels of Vimentin, Snail, Slug and the Src phosphorylation, compared to the HCC cells transfected with an empty vector (HepG2/Vector and Huh7/Vector). We also found ER-α36 knockdown suppressed the lung metastasis of HepG2 cells with the involvement of EMT and the Src pathway in vivo. The Src inhibitor PP2 suppressed the growth and migration of HepG2/Vector and Huh7/Vector cells with decreased Vimentin, Snail, and Slug and increased cytokeratin and E-Cadherin expressions, but failed to induce the migration and the EMT markers in HepG2/Si36 and Huh7/Si36 cells. ER-α36 is involved in the metastasis of HCC cells through the regulation of EMT and the Src signaling pathway.

Estrogen receptor-α36 is involved in diallyl sulfide-induced inhibition of malignant growth of HepG2 and Huh7 hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is a highly malignant disease that currently lacks effective treatment. Epidemiological studies have suggested the preventive role of raw garlic intake in different tumors, such as HCC. Although diallyl sulfide (DAS), the main component of garlic extracts, has been reported to inhibit the growth of HCC cells, the underlying mechanism remains elusive. This study aimed to investigate the inhibitory effect of DAS on the growth of HepG2 and Huh7 hepatocellular carcinoma cells and its underlying mechanism. HepG2 and Huh7 cells were treated with DAS and nude mice were intrahepatically injected with human HCC HepG2 cells and maintained with or without DAS administration for 28 days. MTS and clonogenic assays revealed that DAS inhibited the growth and clonogenicity of HepG2 and Huh7 hepatocellular carcinoma cells. Furthermore, DAS inhibited the growth of xenograft tumors accompanied by a decreased rate of pathological karyomitosis as observed by H&E staining. The expression levels of estrogen receptor-α36 (ER-α36) and epidermal growth factor receptor (EGFR) in HepG2 and Huh7 cells and in xenograft tumors derived from HepG2 cells after DAS treatment were detected by immunohistochemistry and western blotting. We found that DAS disrupted the positive regulatory loop between ER-α36 and EGFR, and decreased the phosphorylation of AKT at Ser 473 both in vivo and in vitro. DAS also induced cell apoptosis, as evidenced by Hoechst and TUNEL staining. Western blotting revealed activation of caspase3, increased BAX and decreased Bcl-2 expression. However, the ER-α36 expression knockdown attenuated DAS-induced ERK and AKT phosphorylation in HCC cells. DAS was also able to inhibit ER-α36-mediated activation of the MAPK/ERK signaling induced by estrogen. Thus, our results indicate that ER-α36 signaling is involved in DAS-induced inhibition of HCC cell growth both in vitro and in vivo.

Polymorph Engineering for Boosted Volumetric Na-Ion and Li-Ion Storage.

To meet the ever-growing demand for advanced rechargeable batteries with light weight and compact size, much effort has been devoted to improving the volumetric capacity of electrodes. Herein, an effective strategy of polymorph engineering is proposed to boost the volumetric capacity of FeSe. Owing to the inherent metallic electronic conductivity of tetragonal-FeSe, a conductive additive-free electrode (hereafter denoted as CA-free) can be assembled with an enhanced sodium storage volumetric capacity of 1011 mAh cm-3 , significantly higher than semiconducting hexagonal-FeSe. Impressively, the CA-free electrode can achieve an extremely high active material utilization of 96.7 wt% and high initial Coulombic efficiency of 96%, superior to most of the anodes for Na-ion storage. Moreover, the design methodology is branched out using tetragonal FeSe as the cathode for Li-ion batteries. The CA-free tetragonal-FeSe electrode can achieve a high volumetric energy density of 1373 Wh L-1 and power density of 7200 W L-1 , outperforming most metal chalcogenides. Reversible conversion reactions are revealed by in situ XRD for both sodium and lithium systems. The proposed design strategy provides new insight and inspiration to aid in the ongoing quest for better electrode materials.

Layered P3-Type K0.4Fe0.1Mn0.8Ti0.1O2 as a Low-Cost and Zero-Strain Electrode Material for both Potassium and Sodium Storage.

Layered transition metal oxides are ideal Na+/K+ host materials due to their high theoretical capacities and appropriate working potentials, and the pursuit of cost-effective and environmentally friendly alternatives with high energy density and structural stability has remained a hot topic. Herein, we design and synthesize a low-cost and zero-strain cathode material, P3-type K0.4Fe0.1Mn0.8Ti0.1O2, which demonstrates superior properties for both potassium and sodium storage. The cathode delivers a reversible potassium storage capacity of 117 mA h g-1 at 20 mA g-1 and a fast rate capability of 71 mA h g-1 at 1000 mA g-1. In situ X-ray diffraction reveals a solid-solution transition with a negligible volume change of 0.5% upon K+ insertion/deinsertion that ensures long cycling stability over 300 cycles. When the material is employed for sodium storage, a spontaneous ion-exchange process with Na+-containing electrolytes occurs. Thanks to the positive effects of the remaining K+ ions that protect the layered structure from collapse as well as expand the interlayer structure, and the resulting K0.12Na0.28Fe0.1Mn0.8Ti0.1O2 demonstrates a high sodium storage capacity of 160 mA h g-1 and superior cycling stability with capacity retention of 81% after 300 cycles as well as fast kinetics.

Self-Assembled FeSe2 Microspheres with High-Rate Capability and Long-Term Stability as Anode Material for Sodium- and Potassium-Ion Batteries.

Sodium- and potassium-ion batteries have attracted intensive attention recently as low-cost alternatives to lithium-ion batteries with naturally abundant resources. However, the large ionic radii of Na+ and K+ render their slow mobility, leading to sluggish diffusion in host materials. Herein, hierarchical FeSe2 microspheres assembled by closely packed nano/microrods are rationally designed and synthesized through a facile solvothermal method. Without carbonaceous material incorporation, the electrode delivers a reversible Na+ storage capacity of 559 mA h g-1 at a current rate of 0.1 A g-1 and a remarkable rate performance with a capacity of 525 mA h g-1 at 20 A g-1 . As for K+ storage, the FeSe2 anode delivers a high reversible capacity of 393 mA h g-1 at 0.4 A g-1 . Even at a high current rate of 5 A g-1 , a discharge capacity of 322 mA h g-1 can be achieved, which is among the best high-rate anodes for K+ storage. The excellent electrochemical performance can be attributed to the favorable morphological structure and the use of an ether-based electrolyte during cycling. Moreover, quantitative study suggests a strong pseudocapacitive contribution, which boosts fast kinetics and interfacial storage.

Co9S8@carbon nanofiber as the high-performance anode for potassium-ion storage.

Thanks to their intrinsic merits of low cost and natural abundance, potassium-ion batteries have drawn intense interest and are regarded as a possible replacement for lithium-ion batteries. The larger radius of potassium, however, provides slow mobility, which normally leads to sluggish diffusion of host materials and eventual expansion of volume, typically resulting in electrode failure. To address these issues, we design and synthesize an effective micro-structure with Co9S8 nanoparticles segregated in carbon fiber utilizing a concise electrospinning process. The anode delivers a high K+ storage capacity of 721 mA h g-1 at 0.1 A g-1 and a remarkable rate performance of 360 mA h g-1 at a high current density of 3 A g-1. A small charge-transfer resistance and a high pseudocapacitive contribution that benefit fast potassium ion migration are indicated by quantitative analysis. The outstanding electrochemical performance can be attributed to the distinct architecture design facilitating high active electrode-electrolyte area and fast kinetics as well as controlled volume expansion.

Layered Oxide Cathode for Potassium-Ion Battery: Recent Progress and Prospective.

Rechargeable potassium-ion batteries (KIBs) have demonstrated great potential as alternative technologies to the currently used lithium-ion batteries on account of the competitive price and low redox potential of potassium which is advantageous to applications in the smart grid. As the critical component determining the energy density, appropriate cathode materials are of vital need for the realization of KIBs. Layered oxide cathodes are promising candidates for KIBs due to high reversible capacity, appropriate operating potential, and most importantly, facile and easily scalable synthesis. In light of this trend, the recent advancements and progress in layered oxides research for KIBs cathodes, covering material design, structural evolution, and electrochemical performance are comprehensively reviewed. The structure-performance correlation and some effective optimization strategies are also discussed. Furthermore, challenges and prospects of these layered cathodes are included, with the purpose of providing fresh impetus for future development of these materials for advanced energy storage systems.

In Situ Electrochemical Coating Mechanism of NASICON-Structured AgTi2(PO4)3 for Sodium-Ion Batteries.

The development of high-performance electrode materials is of great significance for the next-generation room-temperature sodium-ion batteries. In this work, a new Na super-ionic conductor (NASICON) negative electrode, AgTi2(PO4)3, is prepared by a facile solid-state reaction and employed as a sodium storage material for the first time. In situ X-ray diffraction during battery operation reveals an electrochemically Ag nanoparticle coating mechanism upon sodiation, facilitating the electron transfer in the complex. In addition, two steps of highly reversible biphasic transformation are observed. As a result, a reversible capacity of 214.9 mA h g-1 can be achieved, corresponding to the insertion/extraction of nearly four sodium ions. The AgTi2(PO4)3 electrode also demonstrates better kinetic properties than the bare NaTi2(PO4)3 material. Such an "in situ" decorating method can open up a new direction for the design of NASICON-structured materials.

Reversible intercalation of methyl viologen as a dicationic charge carrier in aqueous batteries.

The interactions between charge carriers and electrode structures represent one of the most important considerations in the search for new energy storage devices. Currently, ionic bonding dominates the battery chemistry. Here we report the reversible insertion of a large molecular dication, methyl viologen, into the crystal structure of an aromatic solid electrode, 3,4,9,10-perylenetetracarboxylic dianhydride. This is the largest insertion charge carrier when non-solvated ever reported for batteries; surprisingly, the kinetic properties of the (de)insertion of methyl viologen are excellent with 60% of capacity retained when the current rate is increased from 100 mA g-1 to 2000 mA g-1. Characterization reveals that the insertion of methyl viologen causes phase transformation of the organic host, and embodies guest-host chemical bonding. First-principles density functional theory calculations suggest strong guest-host interaction beyond the pure ionic bonding, where a large extent of covalency may exist. This study extends the boundary of battery chemistry to large molecular ions as charge carriers and also highlights the electrochemical assembly of a supramolecular system.

An Aqueous Dual-Ion Battery Cathode of Mn3 O4 via Reversible Insertion of Nitrate.

We report reversible electrochemical insertion of NO3 - into manganese(II, III) oxide (Mn3 O4 ) as a cathode for aqueous dual-ion batteries. Characterization by TGA, FTIR, EDX, XANES, EXAFS, and EQCM collectively provides unequivocal evidence that reversible oxidative NO3 - insertion takes place inside Mn3 O4 . Ex situ HRTEM and corresponding EDX mapping results suggest that NO3 - insertion de-crystallizes the structure of Mn3 O4 . Kinetic studies reveal fast migration of NO3 - in the Mn3 O4 structure. This finding may open a new direction for novel low-cost aqueous dual-ion batteries.

Graphene oxide wrapped Cu3V2O7(OH)2 · 2H2O nanocomposite with enhanced electrochemical performance for lithium-ion storage.

Transition metal oxides (TMOs) are widely accepted as one of the alternatives for the graphite anode in lithium-ion batteries (LIBs) owing to the high specific capacity and facile synthesis of nanoscale materials facilitating fast ionic transfer. However, the lower electronic conductivity always impedes the application of TMOs. Herein, we report a graphene oxide wrapped layer-structured Cu3V2O7(OH)2 · 2H2O nanocomposite (CVO/GO) synthesized via an in situ co-precipitation method. It is corroborated that the introduction of GO not only provides more active sites for lithium-ion storage, but also improves the charge transfer rate of the electrode, issuing an enhanced electrochemical performance. As expected, the CVO/GO nanocomposite exhibits an ultrahigh specific capacity of 870 mA h g-1 at 0.1 A g-1 compared with CVO nanoparticles. Even at a high current density of 5 A g-1, a specific capacity of 158 mA h g-1 could be achieved for the CVO/GO nanocomposite.