FPFT-2216, a Novel Anti-lymphoma Compound, Induces Simultaneous Degradation of IKZF1/3 and CK1α to Activate p53 and Inhibit NFκB Signaling.

Reducing casein kinase 1α (CK1α) expression inhibits the growth of multiple cancer cell lines, making it a potential therapeutic target for cancer. Herein, we evaluated the antitumor activity of FPFT-2216-a novel low molecular weight compound-in lymphoid tumors and elucidated its molecular mechanism of action. In addition, we determined whether targeting CK1α with FPFT-2216 is useful for treating hematopoietic malignancies. FPFT-2216 strongly degraded CK1α and IKAROS family zinc finger 1/3 (IKZF1/3) via proteasomal degradation. FPFT-2216 exhibited stronger inhibitory effects on human lymphoma cell proliferation than known thalidomide derivatives and induced upregulation of p53 and its transcriptional targets, namely, p21 and MDM2. Combining FPFT-2216 with an MDM2 inhibitor exhibited synergistic antiproliferative activity and induced rapid tumor regression in immunodeficient mice subcutaneously transplanted with a human lymphoma cell line. Nearly all tumors in mice disappeared after 10 days; this was continuously observed in 5 of 7 mice up to 24 days after the final FPFT-2216 administration. FPFT-2216 also enhanced the antitumor activity of rituximab and showed antitumor activity in a patient-derived diffuse large B-cell lymphoma xenograft model. Furthermore, FPFT-2216 decreased the activity of the CARD11/BCL10/MALT1 (CBM) complex and inhibited IκBα and NFκB phosphorylation. These effects were mediated through CK1α degradation and were stronger than those of known IKZF1/3 degraders. In conclusion, FPFT-2216 inhibits tumor growth by activating the p53 signaling pathway and inhibiting the CBM complex/NFκB pathway via CK1α degradation. Therefore, FPFT-2216 may represent an effective therapeutic agent for hematopoietic malignancies, such as lymphoma. SIGNIFICANCE: We found potential vulnerability to CK1α degradation in certain lymphoma cells refractory to IKZF1/3 degraders. Targeting CK1α with FPFT-2216 could inhibit the growth of these cells by activating p53 signaling. Our study demonstrates the potential therapeutic application of CK1α degraders, such as FPFT-2216, for treating lymphoma.

Insight into the effects of different oxygen heteroatoms on nicotine adsorption from cigarette mainstream smoke.

Cigarette smoke contains many chemicals, including nicotine, which is harmful and can cause health problems such as carcinogenesis disease, cardiovascular, respiratory, renal, and reproductive systems. Removal of nicotine from mainstream smoke can be done through adsorption with filters or solid adsorbents. In this study, we explored the use of activated carbons for the removal of nicotine from cigarette mainstream smoke. Activated carbons were prepared from dried hemp (Cannabis sativa) stem at an activation temperature of 350-550 °C using phosphoric acid as an activating agent. The results showed that the activated carbons with variable surface functional groups and porosity exhibited high efficiency for nicotine adsorption, removing 68-88% of nicotine from cigarette mainstream smoke. Through X-ray photoelectron spectroscopy and temperature-programmed desorption analyses, we identified that oxygen-containing functional groups, particularly carboxylic groups, exhibited a superior ability to adsorb nicotine. The computational analysis with DFT simulations further supported the importance of oxygen-containing surface functional groups in facilitating nicotine adsorption, with the carboxylic group providing the lowest adsorption energy among other functional groups.

Chemistry of zipping reactions in mesoporous carbon consisting of minimally stacked graphene layers.

The structural evolution of highly mesoporous templated carbons is examined from temperatures of 1173 to 2873 K to elucidate the optimal conditions for facilitating graphene-zipping reactions whilst minimizing graphene stacking processes. Mesoporous carbons comprising a few-layer graphene wall display excellent thermal stability up to 2073 K coupled with a nanoporous structure and three-dimensional framework. Nevertheless, advanced temperature-programmed desorption (TPD), X-ray diffraction, and Raman spectroscopy show graphene-zipping reactions occur at temperatures between 1173 and 1873 K. TPD analysis estimates zipping reactions lead to a 1100 fold increase in the average graphene-domain, affording the structure a superior chemical stability, electrochemical stability, and electrical conductivity, while increasing the bulk modulus of the framework. At above 2073 K, the carbon framework shows a loss of porosity due to the development of graphene-stacking structures. Thus, a temperature range between 1873 and 2073 K is preferable to balance the developed graphene domain size and high porosity. Utilizing a neutron pair distribution function and soft X-ray emission spectra, we prove that these highly mesoporous carbons already consist of a well-developed sp2-carbon network, and the property evolution is governed by the changes in the edge sites and stacked structures.

Water-Dispersible Carbon Nano-Test Tubes as a Container for Concentrated DNA Molecules.

Invited for the cover of this issue are Takashi Kyotani, Tetsuji Itoh and co-workers at Tohoku University, Gunma University and AIST. The image depicts the synthesis of water-dispersible carbon nano-test tubes by using a template technique and the selective adsorption of DNA into the inner space of these test tubes. Read the full text of the article at 10.1002/chem.202301422.

Water-Dispersible Carbon Nano-Test Tubes as a Container for Concentrated DNA Molecules.

Water-dispersible carbon nano-test tubes (CNTTs) with an inner and outer diameter of about 25 and 35 nm, respectively, were prepared by the template technique and then their inner carbon surface was selectively oxidized to introduce carboxy groups. The adsorption behavior of DNA molecules on the oxidized CNTTs (Ox-CNTTs) was examined in the presence of Ca2+ cations. Many DNA molecules are attracted to the inner space of Ox-CNTTs based on the Ca2+ -mediated electrostatic interaction between DNA phosphate groups and carboxylate anions on the inner carbon surface. Moreover, the total net charge of the DNA adsorbed was found to be equal to the total charge of the carboxylate anions. This selective adsorption into the interior of Ox-CNTTs can be explained from the fact that the electrostatic interaction onto the inner concave surface is much stronger than that on the outer convex surface. On the other hand, the desorption of DNA easily occurs whenever Ca2+ cations are removed by washing with deionized water. Thus, each of Ox-CNTTs works well as a nano-container for a large amount of DNA molecules, thereby resulting in the occurrence of DNA enrichment in the nanospace.

Synthesis of Polynorbornadiene within the Pores of Activated Carbons: Effects on EDLC and Hydrogen Adsorption Performances.

Norbornadiene (NBD) is adsorbed on activated carbon (AC), and the adsorbed NBD is polymerized within the pores of AC. Two kinds of ACs─AC-2 with only micropores of ∼2 nm and AC-4 with not only micropores but also mesopores below 4 nm─are examined to study the effects of the hybridized polynorbornadiene (PNBD) on the electric double-layer capacitor and hydrogen adsorption performance. Various measurements are performed to determine the form of the hybridized PNBD inside the pores of AC. Scanning and transmittance electron microscopy observations of the AC/PNBD hybrids confirm that PNBD is hybridized inside the pores of AC, and there is little PNBD on the surface of AC particles. The nitrogen adsorption/desorption measurement for the hybrids of AC-4 reveals that PNBD is not hybridized preferentially inside micropores rather than mesopores irrespective of the amount of PNBD. In addition, both micropore and mesopore volumes decrease at a constant rate with increasing amounts of PNBD. These results suggest that PNBD is hybridized not as a layer but as an agglomerate for both ACs, and the agglomerate delocalizes over the whole AC pores, which is supported by the results of electrochemical measurements and hydrogen adsorption behavior of the hybrids.

Towards universal neural network potential for material discovery applicable to arbitrary combination of 45 elements.

Computational material discovery is under intense study owing to its ability to explore the vast space of chemical systems. Neural network potentials (NNPs) have been shown to be particularly effective in conducting atomistic simulations for such purposes. However, existing NNPs are generally designed for narrow target materials, making them unsuitable for broader applications in material discovery. Here we report a development of universal NNP called PreFerred Potential (PFP), which is able to handle any combination of 45 elements. Particular emphasis is placed on the datasets, which include a diverse set of virtual structures used to attain the universality. We demonstrated the applicability of PFP in selected domains: lithium diffusion in LiFeSO4F, molecular adsorption in metal-organic frameworks, an order-disorder transition of Cu-Au alloys, and material discovery for a Fischer-Tropsch catalyst. They showcase the power of PFP, and this technology provides a highly useful tool for material discovery.

Sulfur-Doped Carbons from Durian Peels, Their Surface Characteristics, and Electrochemical Behaviors.

Durian peels are an agricultural waste in Asian countries, including Thailand, Indonesia, and Malaysia, which can be used as a precursor for the production of activated carbon. The objective of this work is to produce activated carbon from durian peels by chemical activation using sodium sulfite (Na2SO3) as an activating and sulfur-doping agent. The process parameter investigated in this study was the activation temperature (500-900 °C) at a fixed impregnation ratio (durian to activating agent of 1:1, by weight). Specific surface areas and pore structures were determined by nitrogen adsorption and desorption measurements, and elemental compositions were characterized by CHNSO analysis. The chemical structure and surface functionality were examined by X-ray photoelectron spectroscopy. The electrochemical behavior of the obtained activated carbon was characterized in 6 M KOH using a three-electrode configuration. It was found that the sulfur content decreases with activation temperature. In contrast, the specific surface area of the activated carbon increases with activation temperature. However, the sample activated at 900 °C with the highest specific surface area (1499 m2 g-1) has a lower specific capacitance (166 F g-1) than the one activated at 700 °C (183 F g-1). This could be due to the presence of a pseudocapacitance caused by the organic sulfur functional groups such as thiophene, sulfone, and sulfoxide, which can trigger a surface redox reaction, leading to a higher capacitance.

Direct conversion of lignin to high-quality graphene-based materials via catalytic carbonization.

Methods for effectively utilizing lignin are necessary for the realization of a sustainable society. Herein, we report a method for directly converting lignin to graphene-based materials. Fe-supported lignin is prepared by dissolving lignin in an aqueous FeCl2 solution, followed by freeze drying. Graphene is then produced by catalytically carbonizing this Fe-supported lignin at 1200 °C. The characteristics of both the Fe catalyst and lignin are crucial for the production of high-quality graphene. Specifically, the lignin should disperse well in water, freeze dry, and carbonize via solid-state carbonization. The obtained graphene-based material is highly resistant to electrochemical oxidation, as observed in other graphene-based materials. The direct conversion of lignin to graphene described herein is an unprecedented method for synthesizing large amounts of graphene-based material at low cost, as well as being an excellent use for lignin.

Synthesis of P- and N-doped carbon catalysts for the oxygen reduction reaction via controlled phosphoric acid treatment of folic acid.

Herein, we synthesized P- and N-doped carbon materials (PN-doped carbon materials) through controlled phosphoric acid treatment (CPAT) of folic acid (FA) and probed their ability to catalyze the oxygen reduction reaction (ORR) at the cathode of a fuel cell. Precursors obtained by heating FA in the presence of phosphoric acid at temperatures of 400-1000 °C were further annealed at 1000 °C to afford PN-doped carbon materials. The extent of precursor P doping was maximized at 700 °C, and the use of higher temperatures resulted in activation and increased porosity rather than in increased P content. The P/C atomic ratios of PN-doped carbon materials correlated well with those of the precursors, which indicated that CPAT is well suited for the preparation of PN-doped carbon materials. The carbon material prepared using a CPAT temperature of 700 °C exhibited the highest ORR activity and was shown to contain -C-PO2 and -C-PO3 moieties as the major P species and pyridinic N as the major N species. Moreover, no N-P bonds were detected. It was concluded that the presence of -C-PO2 and -C-PO3 units decreases the work function and thus raises the Fermi level above the standard O2/H2O reduction potential, which resulted in enhanced ORR activity. Finally, CPAT was concluded to be applicable to the synthesis of PN-doped carbon materials from N-containing organic compounds other than FA.

Warped graphitic layers generated by oxidation of fullerene extraction residue and its oxygen reduction catalytic activity.

Carbon-based oxygen reduction reaction (ORR) catalysts are regarded as a promising candidate to replace the currently used Pt catalyst in polymer electrolyte fuel cells (PEFCs); however, the active sites remain under discussion. We predicted that warped graphitic layers (WGLs) are responsible for the ORR catalytic activity in some carbon catalysts (i.e., carbon alloy catalysts (CACs)). To prove our assumption, we needed to use WGLs consisting of carbon materials, but without any extrinsic catalytic elements, such as nitrogen, iron, or cobalt, which effectively enhance ORR activity. The present study employed a fullerene extraction residue as a starting material to construct WGLs. The oxidation of the material at 600 °C exposed the WGLs by removing the surrounding amorphous moieties. Transmission electron microscopy (TEM) observations revealed the formation of WGLs by oxidation treatment at 600 °C in an O2/N2 stream. Extending the oxidation time increased the purity of the WGL phase, but also simultaneously increased the concentration of oxygen-containing surface functional groups as monitored by temperature programmed desorption (TPD). The specific ORR activity increased with oxidation up to 1 h and then decreased with the intensive oxidation treatment. Correlations between the specific ORR activity and other parameters confirmed that the development of the WGL and the increase in the O/C ratio are the competing factors determining specific ORR activity. These results explain the maximum specific ORR activity after 1 h of oxidation time. WGLs were found to lower the heat of adsorption for O2 and to increase the occurrence of heterogeneous electron transfer.

Single-Step Synthesis of W2C Nanoparticle-Dispersed Carbon Electrocatalysts for Hydrogen Evolution Reactions Utilizing Phosphate Groups on Carbon Edge Sites.

A novel, one-step protocol for the selective synthesis of W2C nanoparticles from phosphotungstic acid (H3PW12O40), a low-cost and commercially available tungsten compound, was developed. The nanoparticles had diameters of 1-50 nm and were dispersed on a carbon substrate. The W2C nanoparticles were prepared by a simple operation sequence, involving impregnation of carbon black with H3PW12O40 followed by calcination at 1000 °C. X-ray diffraction study revealed the selective formation of the W2C phase in the samples prepared, whereas the tungsten carbide (WC) phase was present in the control prepared from H2WO4. Stable W2C nanoparticles were obtained using this method owing to the presence of phosphate at the interfaces between the W2C nanoparticles and the carbon substrates, which inhibited the diffusion of carbon atoms from the carbon substrates to the W2C nanoparticles, leading to the formation of WC. The W2C nanoparticles prepared showed an excellent catalytic activity for the hydrogen evolution reaction (HER), with low Tafel slopes of ∼50 mV/decade. The HER catalytic activity was notably high, being comparable to that of MoS2, which is a promising alternative to Pt. The present method can potentially be applied to produce highly effective, low-cost, Pt-free electrocatalysts for the HER.

Heat treatment effect on the electronic and magnetic structures of nanographene sheets investigated through electron spectroscopy and conductance measurements.

The heat treatment effect on the electronic and magnetic structures of a disordered network of nanographene sheets has been investigated by in situ measurements of X-ray photoemission spectroscopy, near-edge X-ray absorption fine structure (NEXAFS), and electrical conductance, together with temperature-programmed desorption measurements. Oxygen-containing functional groups bonded to nanographene edges in the pristine sample are almost completely decomposed under heat treatment up to 1300-1500 K, resulting in the formation of edges primarily terminated by hydrogen. The removal of the oxygen-containing groups enhances the conductance owing to the decrease in the electron transport barriers between nanographene sheets. Heat treatment above 1500 K removes also the hydrogen atoms from the edges, promoting the successive fusion of nanographene sheets at the expense of edges. The decrease in the π* peak width in NEXAFS indicates the progress of the fusion reaction, that is, the extension of the π-conjugation, which agrees with the increase in the orbital susceptibility previously reported. The fusion leads to the formation of local π/sp(2) bridges between nanographene sheets and brings about an insulator-to-metal transition at 1500-1600 K, at which the bridge network becomes infinite. As for the magnetism, the intensity of the edge state peak in NEXAFS, which corresponds to the number of the spin-polarized edge states, decreases above 1500 K, though the effective edge-state spin density per edge state starts decreasing at approximately 200 K lower than the temperature of the edge state peak change. This disagreement indicates the development of antiferromagnetic short range ordering as a precursor of a spin glass state near the insulator-metal transition, at which the random network of inter-nanographene-sheet exchange interactions strengthened with the formation of the π/sp(2) bridges becomes infinite.

Towards ultrahigh volumetric capacitance: graphene derived highly dense but porous carbons for supercapacitors.

A small volumetric capacitance resulting from a low packing density is one of the major limitations for novel nanocarbons finding real applications in commercial electrochemical energy storage devices. Here we report a carbon with a density of 1.58 g cm(-3), 70% of the density of graphite, constructed of compactly interlinked graphene nanosheets, which is produced by an evaporation-induced drying of a graphene hydrogel. Such a carbon balances two seemingly incompatible characteristics: a porous microstructure and a high density, and therefore has a volumetric capacitance for electrochemical capacitors (ECs) up to 376 F cm(-3), which is the highest value so far reported for carbon materials in an aqueous electrolyte. More promising, the carbon is conductive and moldable, and thus could be used directly as a well-shaped electrode sheet for the assembly of a supercapacitor device free of any additives, resulting in device-level high energy density ECs.

Microscopic polyangiitis in a girl with severe anemia and no respiratory symptoms.

ANCA-positive microscopic polyangiitis is a rare in children. We reported an 11-year-old girl without respiratory symptoms with sever anemia which shows signs of hemolytic anemia in test data. Chest X-ray and computed tomography scans suggested alveolar hemorrhage. The patent developed night hypoxia and moderate proteinuria. Serum MPO-antibody was highly positive and renal biopsy demonstrated segmental necrosis or crescent formation. A diagnosis of microscopic polyangiitis was made. She responded to pulsed methylprednisolon and pulsed Endoxan therapy. Microscopic polyangitiis should be considered early in the differential diagnosis of patients presenting with anemia of an unknown origin.