Glutathione (GSH) has long been recognised for its antioxidant and detoxifying effects on the liver. The hepatoprotective effect of GSH involves the activation of antioxidative systems such as NRF2; however, details of the mechanisms remain limited. A comparative analysis of the biological events regulated by GSH under physiological and oxidative stress conditions has also not been reported. In this study, DNA microarray analysis was performed with four experiment arms including Control, GSH, hydrogen peroxide (HP), and GSH + HP treatment groups. The GSH-treated group exhibited a significant upregulation of genes clustered in cell proliferation, growth, and differentiation, particularly those related to MAPK, when compared with the Control group. Additionally, liver functions such as alcohol and cholesterol metabolic processes were significantly upregulated. On the other hand, in the HP-induced oxidative stress condition, GSH (GSH + HP group) demonstrated a significant activation of cell proliferation, cell cycle, and various signalling pathways (including TGFß, MAPK, PI3K/AKT, and HIF-1) in comparison to the HP group. Furthermore, several disease-related pathways, such as chemical carcinogenesis-reactive oxygen species and fibrosis, were significantly downregulated in the GSH + HP group compared to the HP group. Collectively, our study provides a comprehensive analysis of the effects of GSH under both physiological and oxidative stress conditions. Our study provides essential insights to direct the utilisation of GSH as a supplement in the management of conditions associated with oxidative stress.
Antioxidants , Phosphatidylinositol 3-Kinases , Humans , Antioxidants/pharmacology , Hep G2 Cells , Phosphatidylinositol 3-Kinases/metabolism , Glutathione/metabolism , Oxidative Stress , Reactive Oxygen Species/metabolism , Gene Expression Profiling , Hydrogen Peroxide/pharmacology , NF-E2-Related Factor 2/metabolism
Precisely controlled heteroatom-doped metal-free carbon catalysts are highly desirable for use in various renewable energy conversion and storage devices. Herein, we report a nitrogen-doped metal-free carbon catalyst for the oxygen reduction reaction (ORR) using a facile and cost-effective synthetic method. The obtained catalysts (NC-1100) were synthesized in two steps via an amino-acid complex coating and high-temperature carbonization. The various physical characteristics revealed that NC-1100 has a unique morphology, a controlled nitrogen bonding configuration, and a uniform pore distribution. The resulting catalyst shows excellent catalytic performance toward direct 4-electron oxygen reduction reaction (ORR) in an alkaline electrolyte, with a high onset potential of 0.95 V versus RHE and limiting current density (4.5 mA cm-2). Furthermore, the developed catalysts showed superior long-term operating stability and methanol durability compared to those of commercial Pt/C. This study provides a promising guideline for the development of next-generation electrocatalysts for fuel cells and wider applications.
N-doped carbon materials have attracted considerable attention as highly functional materials because nitrogen doping distorts the carbon lattice, changes the charge density, and introduces additional defects. Among various positions of N atoms in N-doped carbon compounds, pyridinic-N, pyrrolic-N, and valley-N, which are doped at edge sites, exhibit specific electrocatalytic activities during the oxygen reduction reaction (ORR). However, it is difficult to selectively introduce these N atoms into a carbon matrix because the synthesis procedure typically includes high-temperature heat treatment. In this study, we applied a zeolite templating method to synthesize edge site-rich N-doped carbon materials. The sample fabricated using a zeolite template possessed high concentrations of pyridinic-N and valley-N atoms, demonstrating a significantly higher ORR catalytic activity than the sample synthesized without a zeolite template. Additional experiments conducted using various zeolites confirmed the positive effect of N-doped carbons on the ORR catalytic performance. This work demonstrated that the zeolite templating method not only increased the specific surface area and the number of active sites but also selectively created edge sites and improved the quality of the active sites.
The manufacture of efficient and low-cost hydrogen evolution reaction (HER) catalysts is regarded as a critical solution to achieve carbon neutrality. Herein, we developed an economical method to synthesize a CoP-anchored N-doped carbon catalyst via one-step pyrolysis using inexpensive starting materials (cobalt ion salt, phytic acid, and glycine). The size of the CoP nanoparticles was controlled by adjusting the Co/P ratio of the catalysts. Nanoscale CoP particles with adequate exposure to active sites were uniformly anchored on the surface of the conductive nitrogen-doped carbon substrate, ensuring the rapid transfer of electrons and species. When Co/P=0.89, the as-made catalyst exhibited outstanding HER activity, with an extraordinarily low overpotential of 202â mV at 10â mA cm-2 and long-term stability.
Nanostructured materials with high aspect ratios have been widely studied for their unique properties. In particular, nanosheets have safety, dispersibility, and nanosized effects, and nanosheets with exceptionally small thicknesses exhibit unique properties. For non-exfoliable materials, the bottom-up nanosheet growth using various interfaces as templates have been investigated. This review article presents the synthesis of nanosheets at the interfaces and layered structure; it explains the features of each interface type, its advantages, and its uniqueness. The interfaces work as templates for nanosheet synthesis. We can easily use the liquid-liquid and gas-liquid interfaces as the templates; however, the thickness of nanosheets usually becomes thick because it allows materials to grow in thickness. The solid-gas and solid-liquid interfaces can prevent nanosheets from growing in thickness. However, the removal of template solids is required after the synthesis. The layered structures of various materials provide two-dimensional reaction fields between the layers. These methods have high versatility, and the nanosheets synthesized by these methods are thin. Finally, this review examines the key challenges and opportunities associated with scalable nanosheet synthesis methods for industrial production.
Chemical sensors have targeted various substances. Most sensors electrically amplify signals. Here, we propose a visual detection system that uses a hyperswollen lamellar phase and detects targets in a solution without electric amplification. Amphiphiles with an oligo(ethylene glycol) chain can catch alkali and alkaline earth metal ions and amplify to macroscopic birefringence.
To improve the pore uniformity and volume of ordered mesoporous carbons produced by soft templating under solvent-free conditions, magnesium nitrate inorganic salt was incorporated into the precursors during the synthesis. The addition of magnesium nitrate in this procedure lowered the melting point of resorcinol, increased the diffusivity of the resorcinol-Pluronic F127 complex, and promoted self-assembly. The entry of Mg species into the core of the micelle of Pluronic F127 resulted in a modification of the pore structure resembling a channel-like hexagonal structure. In addition, the MgO in the pores effectively prevented the shrinkage of the mesopores under high-temperature conditions. Correspondingly, the uniformity and the mesopore volume of the mesoporous carbon obtained were also enhanced. Moreover, when used as electrodes, this ordered mesoporous carbon was able to significantly increase the capacity of electric double-layer capacitors. Thus, the current study proposes a novel method for regulating the structure and distribution of ordered mesoporous carbons.
Zeolites catalyze some reactions in their molecular-sized pores, but large molecules can react only on their external surface. Zeolite-nanosheets (NSs) have been developed as catalysts for large molecules. The previously reported methods to synthesize zeolite-NSs are specialized for each zeolite type. Here we propose a new method to synthesize various zeolite-NSs from the same amorphous aluminosilicate NSs (AAS-NSs) as a universal precursor. We successfully synthesized the unprecedented AAS-NSs in the hydrophilic space of the stable hyperswollen lyotropic lamellar (HL) phase. The four zeolite types could be obtained from the single-species AAS-NSs. These results imply that this method enables us to synthesize almost all types of zeolite-NSs. Moreover, the synthesized CHA-NSs have great potential for various applications because of their thickness and large external surface area.
A decrease in the intracellular level of nicotinamide adenine dinucleotide (NAD+), an essential coenzyme for metabolic activity, causes various age-related diseases and metabolic abnormalities. Both in-vivo and in-vitro studies have shown that increasing certain NAD+ levels in cell or tissue by supplementing nicotinamide mononucleotide (NMN), a precursor of NAD+, alleviates age-related diseases and metabolic disorders. In recent years, several clinical trials have been performed to elucidate NMN efficacy in humans. However, previous clinical studies with NMN have not reported on the safety of repeated daily oral administration of ≥ 1000 mg/shot in healthy adult men and women, and human clinical trials on NMN safety are limited. Therefore, we conducted a randomized, double-blind, placebo-controlled, parallel-group study to evaluate the safety of 1250 mg of ß-NMN administered orally once daily for up to 4 weeks in 31 healthy adult men and women aged 20-65 years. Oral administration of ß-NMN did not result in changes exceeding physiological variations in multiple clinical trials, including anthropometry, hematological, biochemical, urine, and body composition analyses. Moreover, no severe adverse events were observed during the study period. Our results indicate that ß-NMN is safe and well-tolerated in healthy adult men and women an oral dose of 1250 mg once daily for up to 4 weeks.Trial registration Clinicaltrials.gov Identifier: UMIN000043084. Registered 21/01/2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000049188 .
NAD , Nicotinamide Mononucleotide , Administration, Oral , Adult , Aged , Female , Humans , Male , Middle Aged , NAD/metabolism , Young Adult
Nicotinamide mononucleotide (NNM) is an orally bioavailable NAD+ precursor that has demonstrated beneficial effects against aging and aging-associated diseases in animal models. NMN is ultimately converted to NAD+, a redox cofactor that mediates many metabolic enzymes. NAD+ also serves as the substrate for poly(ADP-ribose) polymerase (PARP) and sirtuins, and regulates various biological processes, such as metabolism, DNA repair, gene expression, and stress responses. Previous mouse models showed that NMN administration can increase NAD+ in various organs and ameliorate aging-related diseases, such as obesity, diabetes, heart failure, stroke, kidney failure, and Alzheimer's disease through NAD+-mediated pathways. However, evidence of its effect on humans is still scarce. In this study, we conducted a placebo-controlled, randomized, double blind, parallel-group trial to investigate the safety of orally administered NMN and its efficacy to increase NAD+ levels in thirty healthy subjects. Healthy volunteers received 250 mg/day of NMN (n = 15) or placebo (n = 15) for 12 weeks, and physiological and laboratory tests were performed during this period. In addition, NAD+ and its related metabolites in whole blood were examined. Oral supplementation of NMN for 12 weeks caused no abnormalities in physiological and laboratory tests, and no obvious adverse effects were observed. NAD+ levels in whole blood were significantly increased after NMN administration. We also observed the significant rise in nicotinic acid mononucleotide (NAMN) levels, but not in NMN. We also found that the increased amount of NAD+ was strongly correlated with pulse rate before the administration of NMN. These results suggest that oral administration of NMN is a safe and practical strategy to boost NAD+ levels in humans. Clinical Trial Registration: JRCT [https://jrct.niph.go.jp/], identifier: [jRCTs041200034].
Nowadays, the increase in plastic waste is causing serious environmental problems. Catalytic cracking has been considered a promising candidate to solve these problems. Catalytic cracking has emerged as an attractive process that can produce valuable products from plastic wastes. Solid acid catalysts such as zeolites decompose the plastic waste at a lower temperature. The lower decomposition temperature may be desirable for practical use. Herein, we synthesized both Zr- and Al-incorporated Beta zeolite using amorphous ZrO2-SiO2. The optimized Zr content in the dry gel allowed the enhancement of Lewis acidity without a significant loss of Brønsted acidity. The enhancement of Lewis acidity was mainly due to Zr species incorporated into the zeolite framework. Thanks to the enhanced Lewis acidity without any significant loss of Brønsted acidity, higher polymer decomposition efficiency was achieved than a conventional Beta zeolite.
Invited for this month's cover are the collaborating groups of Dr. Yoshiaki Uchida from Osaka University, Japan, Prof. Rui Tamura and Prof. Masahito Sugiyama from Kyoto University, Japan and Dr. Dmitriiâ G. Mazhukin from Novosibirsk State University, Russia. The cover picture depicts a contrast between localized spins and conductive ions in the newly-synthesized ionic liquid crystalline (ILC) nitroxide radicals. The ILC droplet of the new compounds is magnetically manipulable. More information can be found in the Full Paper by Yoshiaki Uchida, Rui Tamura, and co-workers.
With a view to fabricating a new remote input-output system by applying functional ionic liquid crystalline (ILC) materials, we have developed novel ILC compounds containing a nitroxide radical unit in the organic cations, which show an enantiotropic smectic A (SmA) phase. We have implemented the magnetic manipulation of a droplet of one of the ILC compounds on the basis of the intermolecular magnetic interactions between radical moieties. This ILC monoradical compound shows a 55 % larger increase in paramagnetic susceptibility at the solid-to-LC melting point in the first heating process than the non-ionic LC monoradical compounds. It is most likely owing to the nanosegregation of strongly bonded ionic and non-ionic moieties. The increased molar magnetic susceptibility is preserved not only in the SmA phase but also in the isotropic liquid and solid phases during the first cooling process.
The preparation method of nanosheets using hyperswollen lyotropic lamellar phases, the 'two-dimensional reactor in amphiphilic phases (TRAP) method', has successfully provided nanosheets of various non-layered materials. Previously reported examples started from a single hydrophobic or hydrophilic precursor and multiple hydrophobic precursors. Here, we propose a synthesis method of nanosheets of ZIF-8, zinc 2-methylimidazolate, with a sodalite-like framework. They grow up to a few nanometers of thickness and several hundred nanometers of width with neither aggregation nor impurities from multiple hydrophilic precursors in the stoichiometric ratio inside the hydrophilic TRAPs consisting of the amphiphile Brij L4. The thin nanosheets of ZIF-8 doped with Co2+ (Co-ZIF-8) synthesized by the same method maintained a high specific surface area after calcination. Therefore, the oxygen reduction reaction (ORR) activity of the calcined Co-ZIF-8 NSs for fuel cells becomes higher than that of the calcined conventional Co-ZIF-8 crystals.
Adenocarcinoma, Clear Cell , Adenocarcinoma , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma, Clear Cell/diagnosis , Adenocarcinoma, Clear Cell/pathology , Cytodiagnosis , Diagnosis, Differential , Female , Humans , Middle Aged , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/pathology , Ovary/pathology
The nanosheets of highly symmetric materials with a face-centered cubic lattice such as gold have been synthesized by adsorbing the precursors on a flat surface, whose chemical specificity induces the anisotropy of growth rates. We have succeeded in the fabrication of gold nanosheets in a hydrophilic space inside highly separated bilayers, which work as two-dimensional hydrophilic reactors, in a hyperswollen lamellar liquid crystalline phase of an amphiphile solution. One of the physical properties, amphiphilicity, confines the ingredients therein. The nanosheets can only grow in the in-plane direction due to the inhibition of the out-of-plane growth rather than the anisotropy of growth rates probably. Thus, the synthesis can be accelerated; the particles can be completed within 15 min. As not relying on chemical specificity, silver nanosheets could also be synthesized in the same way. The suspension of gold and silver nanosheets without any amphiphiles could be obtained, and the solvent is replaceable. We found that the width of the obtained gold nanosheets is proportional to the Reynolds number of the solution because the area of the bilayer in the hyperswollen lamellar phase depends on shear stress. This implies that the areas of gold nanosheets depend on the areas of the bilayers, and it can be controlled by changing the Reynolds number. This method could be widely used to continuously obtain large-area nanosheets of various materials in a roll-to-roll manufacturing process.
A liquescent dihydrophenazine radical cation, 1.+ â NTf2 - , showed drastic changes in near-infrared (near-IR) transparency and opaqueness through hysteretic phase transitions with no measurable degradation of the compound even under aerated conditions. During the heating and slow cooling process (0.5â K min-1 ), its electronic and magnetic properties were altered clearly and repeatedly changed between solid and liquid states. The liquid state was transparent to near-IR light (940â nm), but the solid state was opaque, despite both samples exhibiting a similar green color under room light. Additionally, the liquid state was changed to a glass state under a fast cooling process (2-10â K min-1 ). UV/Vis/near-IR and electron spin-resonance spectroscopy revealed that these drastic changes were attributable to the dynamic dissociation and association of a π-dimer structure for 1.+ accompanying with the solid-liquid phase transitions even under the neat conditions.
Human amnion epithelial cells (hAECs), derived from discarded term placenta, is anticipated as a new stem cell resource because of their advantages over embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), such as no risk of tumorigenicity and minimal ethical issue. hAECs have been reported to differentiate into hepatic-like cells (HLCs) with variable functionalities suitable for cell-based therapy of end-stage liver diseases, drug screening, and drug toxicity tests. On the other hand, a new research stream has been evolving to use natural compounds as stimulants of stem cell differentiation because of their high availability and minimum side effects. Isorhamnetin is a naturally occurring flavonoid commonly found in fruits and vegetables and has been reported to improve hepatic fibrosis and steatosis. In this present study, we have screened the differentiation potential of isorhamnetin in hAECs. The cells were grown on 3D cell culture and were treated with 20 µM of synthesized isorhamnetin for 10 days without adding any additional growth factors. DNA microarray global gene expression analysis was conducted for differentially expressed genes between isorhamnetin-treated and untreated control cells, gene expression validation was carried out using RT-qPCR method, and finally, several hepatic functions were assessed. Microarray analysis showed that isorhamnetin could activate essential biological processes, molecular functions, and signaling pathways for hepatic differentiation. Hepatic progenitor markers, EPCAM and DLK1, were upregulated in the isorhamnetin-treated hAECs. AFP was downregulated, while ALB was upregulated on Day 10. Furthermore, isorhamnetin-treated cells could show increased CYP enzyme mRNA levels, ICG uptake and release, glycogen storage activity, and urea secretion. Additionally, isorhamnetin-treated cells did not show any trace of transdifferentiation evident by significant downregulation of several colon- and cholangiocyte-specific markers. However, longer treatment with isorhamnetin did not promote hepatic maturation. Altogether, our findings indicate that isorhamnetin has a promising effect on directing the hepatic-lineage specific differentiation in hAECs.
Against a sensible expectation that molecular mobility in fluids generally disrupts magnetic orderings that depend on intermolecular interactions, some molecular compounds with isolated electrons, which are called radicals, exhibit the increase of magnetic susceptibility in melting. Here we first propose a simple model to explain the thermomagnetic anomaly unique to fluids; the effect of the magnetic interactions in each of the contacts could be accumulated on each of the molecular spins as if the molecular motion amplified the first coordination number of each molecule hundredfold. The huge coordination number theoretically guarantees the retention of memory of interactions at equilibrium; molecules might be able to conserve the memory of molecular conformations, configurations, electric charges, energies as well as magnetic memory with each other.
