Developing highly active and stable cathode catalysts is of pivotal importance for proton exchange membrane fuel cells (PEMFCs). While carbon‐supported nanostructured Pt‐based catalysts have so far ...been the most active cathode catalysts, their durability and single‐cell performance are yet to be improved. Herein, self‐supported mesostructured Pt‐based bimetallic (Meso‐PtM; M = Ni, Fe, Co, Cu) nanospheres containing an intermetallic phase are reported, which can combine the beneficial effects of transition metals (M), an intermetallic phase, a 3D interconnected framework, and a mesoporous structure. Meso‐PtM nanospheres show enhanced oxygen reduction reaction (ORR) activity, compared to Pt black and Pt/C catalysts. Notably, Meso‐PtNi containing an intermetallic phase exhibits ultrahigh stability, showing enhanced ORR activity even after 50 000 potential cycles, whereas Pt black and Pt/C undergo dramatic degradation. Importantly, Meso‐PtNi with an intermetallic phase also demonstrated superior activity and durability when used in a PEMFC single‐cell, with record‐high initial mass and specific activities.
Self‐supported mesostructured PtM (Meso‐PtM) nanospheres containing an intermetallic phase have been prepared, which show enhanced oxygen reduction reaction (ORR) activity compared to Pt/C and Pt black catalysts. Meso‐PtNi containing an intermetallic phase exhibits ultrahigh stability, showing enhanced ORR activity even after 50 000 potential cycles. In a proton exchange membrane fuel cell single‐cell test, Meso‐PtNi with intermetallic phase demonstrates record‐high initial performances and very high durability.
OBJECT Moyamoya disease (MMD) is an idiopathic cerebrovascular occlusive disorder prevalent in East Asia. In the pathogenesis of MMD, the important role of genetic factors is being elucidated, and ...RNF213 has recently been identified as a susceptibility gene for MMD. The aim of this retrospective study was to investigate the RNF213 genotype in patients with MMD and to determine their genotype-phenotype associations. METHODS The study involved 165 Korean MMD patients from 155 unrelated families who were diagnosed with MMD at a single center from 1995 to 2013. Their demographic, radiological, and clinical findings were evaluated. Direct sequencing of the major RNF213 single nucleotide polymorphisms was performed. The association of the common RNF213 variant with MMD risk was evaluated using historical controls for comparison. Correlations between RNF213 genotype and phenotype were statistically analyzed. RESULTS The c.14429G>A (p.R4810K) variant was identified in 125 (75.8%) of 165 MMD patients. Most patients (112) were heterozygous, and 13 patients had 2 copies of the c.14429G>A variant. A novel heterozygous variant, c.12086A>G (p.Q4029R), was found in 1 additional patient. The minor allele frequency of the c.14429G>A variant was significantly higher in the MMD group (138 41.8% of 330 patients) than in the control group (8 1.36% of 588 subjects; p < 0.001). The c.14429G>A (p.R4810K) variant significantly increased the risk of MMD in Korean patients, with an OR of 52.11 (p < 0.001) compared with controls. Moreover, c.14429G>A (p.R4810K) genotypes occurred more frequently in patients with a family history of MMD. The homozygous variant was highly associated with early-onset MMD (age at onset < 5 years), cerebral infarction at diagnosis, and cognitive impairment in long-term outcome. CONCLUSIONS The findings indicate that the c.14429G>A (p.R4810K) allele of RNF213 is strongly associated with Korean patients with MMD. The homozygous c.14429G>A (p.R4810K) variant is particularly related to early-onset MMD, severe symptomatic manifestations at diagnosis, and poor prognosis. This genotypic variant may be a useful biomarker for early-onset MMD or unstable MMD with cerebral infarction, which requires early diagnosis and revascularization treatment.
Homogeneous olefin polymerization catalysts are activated in situ with a co-catalyst (PhN(Me)2-H+B(C6F5)4− or Ph3C+B(C6F5)4−) in bulk polymerization media. These co-catalysts are insoluble in ...hydrocarbon solvents, requiring excess co-catalyst (>3 eq.). Feeding the activated species as a solution in an aliphatic hydrocarbon solvent may be advantageous over the in situ activation method. In this study, highly pure and soluble ammonium tetrakis(pentafluorophenyl)borates (Me(C18H37)2N-H+B(C6F5)4− and (C18H37)2NH2+B(C6F5)4−) containing neither water nor Cl− salt impurities were prepared easily via the acid–base reaction of PhN(Me)2-H+B(C6F5)4− and the corresponding amine. Using the prepared ammonium salts, the activation reactions of commercial-process-relevant metallocene (rac-ethylenebis(tetrahydroindenyl)Zr(Me)2 (1-ZrMe2), Ph2C(Cp)(3,6-tBu2Flu)Hf(Me)2 (3-HfMe2), Ph2C(Cp)(2,7-tBu2Flu)Hf(Me)2 (4-HfMe2)) and half-metallocene complexes ((η5-Me4C5)Si(Me)2(κ-NtBu)Ti(Me)2 (5-TiMe2), (η5-Me4C5)(C9H9(κ-N))Ti(Me)2 (6-TiMe2), and (η5-Me3C7H1S)(C10H11(κ-N))Ti(Me)2 (7-TiMe2)) were monitored in C6D12 with 1H NMR spectroscopy. Stable L-M(Me)(NMe(C18H37)2)+B(C6F5)4− species were cleanly generated from 1-ZrMe2, 3-HfMe2, and 4-HfMe2, while the species types generated from 5-TiMe2, 6-TiMe2, and 7-TiMe2 were unstable for subsequent transformation to other species (presumably, L-Ti(CH2N(C18H37)2)+B(C6F5)4−-type species). L-TiCl(N(H)(C18H37)2)+B(C6F5)4−-type species were also prepared from 5-TiCl(Me) and 6-TiCl(Me), which were newly prepared in this study. The prepared L-M(Me)(NMe(C18H37)2)+B(C6F5)4−-, L-Ti(CH2N(C18H37)2)+B(C6F5)4−-, and L-TiCl(N(H)(C18H37)2)+B(C6F5)4−-type species, which are soluble and stable in aliphatic hydrocarbon solvents, were highly active in ethylene/1-octene copolymerization performed in aliphatic hydrocarbon solvents.
A subset of cancer cells maintains their telomeres without telomerase through the recombination‐based alternative lengthening of telomeres (ALT) pathway. Currently, it is not yet clear in what ...context ALT is induced and how the pathway choice is made. Here, we show that abrogation of Brca2 reinforces break‐induced replication (BIR) and engages with ALT pathway. Brca2 depletion in telomerase‐null mouse cells alleviated the growth defect, accompanied by telomere elongation, suggesting the induction of ALT. We also found that Brca2‐depleted telomerase‐null cells exhibited dynamic clustering of telomeres from G2 phase in Promyelocytic Nuclear (PML) bodies. For Brca2‐deficient ALT induction, Rad51 was dispensable but Mre11 and Rad52 were required. Congruently, conservative telomeric DNA synthesis was apparent in mitosis, indicating that the absence of Brca2 directed towards Rad52‐mediated BIR. Collectively, we propose that Brca2 abrogation can instigate ALT tumourigenesis through the induction of BIR. This study implies that inhibitors of BIR may be useful for BRCA2‐associated ALT‐type cancers. Assessing ALT features may be considered for the tailored therapy of BRCA2‐associated cancers.
Cancer cells activate telomerase to avoid shortening of their telomeres, enabling indefinite DNA replication. However, about 10% of cancer cells do not express telomerase and maintain their telomeres through the recombination‐based alternative lengthening of telomeres (ALT) pathway. Currently, the mechanisms underlying ALT induction are not clear. Here, Hyunsook Lee and colleagues show that Brca2 depletion in telomerase‐null cells induces ALT by reinforcing break‐induced replication (BIR). Rad51 is dispensable for ALT induction in these cells while Rad52 and Mre11 are required, indicating that Brca2 abrogation directs towards Rad52‐mediated BIR. These results suggest that BIR inhibitors could be beneficial for BRCA2‐associated ALT cancers.
•Mesoporous carbon-supported FeK catalyst convert CO2 into liquid fuel.•Fe carbide phases are easily formed on mesoporous carbon support.•Mesoporous carbon support is beneficial to the dissipation of ...heavy products in the pore.
Identifying highly efficient catalysts for direct CO2 hydrogenation to liquid hydrocarbons is crucial for CO2 utilization via chemical conversion using renewable resources, the so-called Power-to-Liquids. In this study, well-defined mesoporous carbon (MPC) of 6.9 nm pore size was synthesized as a support material for Fe oxycarbide nanoparticles, which serve as active sites for the CO2 hydrogenation reaction, combining reverse water-gas shift and Fischer-Tropsch reactions. The unique physicochemical properties of MPC favored the formation of an active carbidic Fe phase and the rapid diffusion of produced hydrocarbons which resulted in an enhanced CO2 conversion and long-chain hydrocarbon selectivity. As a result, the MPC supported Fe catalyst showed C5+ hydrocarbon selectivity of 44.5% with a CO2 conversion rate of 50.6% (300 °C, 2.5 MPa, H2/CO2 = 3).
Background
Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder caused by loss‐of‐function mutations of the NTRK1 gene, affecting the autonomic ...and sensory nervous system. Clinical manifestation is varied and includes recurrent fever, pain insensitivity, anhidrosis, self‐mutilating behavior, and intellectual disability.
Methods
Clinical and genetic features were assessed in two males and one female with genetically confirmed CIPA using exome or genome sequencing.
Results
CIPA symptoms including recurrent fever, pain insensitivity, and anhidrosis manifested at the age of 1 year (age range: 0.3–8 years). Two patients exhibited self‐mutilation tendencies, intellectual disability, and developmental delay. Four NTRK1 (NM_002529.3) mutations, c.851‐33T>A (p.?), c.2020G>T (p.Asp674Tyr), c.2303C>T (p.Pro768Leu), and c.574‐156_850+1113del (exons 5‐7 del) were identified. Two patients exhibited early onset and severe phenotype, being homozygous for c.851‐33T>A (p.?) mutations and compound heterozygous for c.851‐33T>A (p.?) and c.2020G>T (p.Asp674Tyr) mutation of NTRK1. The third patient with compound heterozygous mutations of c.2303C>T (p.Pro768Leu) and c.574‐156_850+1113del (exons 5‐7 del) displayed a late onset and milder clinical manifestation.
Conclusion
All three patients exhibited variable phenotypes and disease severity. This research enriches our understanding of clinical and genetic aspects of CIPA, highlighting variable phenotypes and disease severity.
Patients with congenital insensitivity to pain with anhidrosis typically present with cellulitis in their fingers and toes, often leading to amputation due to self‐mutilating behavior. Osteodystrophy can result from a history of recurrent infections and surgeries.
Platinum monolayer electrocatalyst are known to exhibit excellent oxygen reduction reaction (ORR) activity depending on the type of substrate used. Here we demonstrate a relationship between the ORR ...electrocatalytic activity and the surface electronic structure of Pt monolayer shell induced by various IrM bimetallic cores (M=Fe, Co, Ni or Cu). The relationship is rationalized by comparing density functional theory calculations and experimental results. For an efficient Pt monolayer electrocatalyst, the core should induce sufficient contraction to the Pt shell leading to a downshift of the d-band center with respect to the Fermi level. Depending on the structure of the IrM, relative to that of pure Ir, this interaction not only alters the electronic and geometric structure but also induces segregation effects. Combined these effects significantly enhance the ORR activities of the Pt monolayer shell on bimetallic Ir cores electrocatalysts.
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•Core-shell structured IrM nanoparticles are better substrates than alloyed counterparts for Pt monolayer electrocatalyst.•Geometric, electronic, and segregation effects together are crucial to understand the increase in ORR activity.•DFT calculations demonstrate a volcano type behavior with PtMLIrNi/C at the top of the curve.
Background
Salicylic acid has been used as an anti‐acne agent with its comedolytic property and antimicrobial activity. However, there is a limit to use for leave‐on cosmetics because of the ...transient skin irritation and low efficacy at neutral pH condition. We prepared a salicylic acid‐based ionic pair with L‐carnitine (we named, IP‐BHA) overcoming the limitation of salicylic acid. We examined the effect of IP‐BHA as well as the combination effect with magnolol, a bioactive organic lignan, in order to clarify their efficacy as anti‐acne agents.
Methods
After verifying the structure of IP‐BHA, we confirmed anti‐acne activities including the regulation of exfoliation, lipogenesis, bacterial growth, and inflammation with IP‐BHA and/or magnolol.
Results
The antibacterial activity of IP‐BHA and magnolol was evaluated by determining the minimum antibacterial inhibitory concentration. Magnolol showed strong activity against Cutibacterium acnes, which was better than a medical antibiotic acne drug, clindamycin. The combined application with IP‐BHA was more effective in antibacterial activity by 2.5 times. It was confirmed that testosterone‐induced lipogenesis was significantly inhibited by treatment with IP‐BHA and magnolol, while single treatment had no significant inhibitory effect. Interestingly, MMP‐1 and VEGF were induced by C. acnes lysate in human keratinocytes. We found that these inflammatory molecules were completely inhibited by combined application of IP‐BHA and magnolol. Through ex vivo test, the dose‐dependent exfoliation effect of IP‐BHA was confirmed at pH 5.5, and the synergic exfoliation effect was shown in the combined application of IP‐BHA and magnolol. When topically applied, the emulsion containing IP‐BHA and magnolol relieved the sodium dodecyl sulfate‐induced erythema and improved inflamed acne with papule and pustule.
Conclusion
Our data demonstrate that the ionic paired salicylic acid with L‐carnitine can overcome the limitations of salicylic acid at low concentration and natural skin pH. Based on the dual administration effects, we suggest that IP‐BHA and magnolol may be the potential agent for acne by improving inflammatory skin condition.
Natural killer (NK) cells play important roles in immune surveillance. However, the tumor microenvironment suppresses NK cell function and allows cancer cells to evade immune detection. In this ...study, we investigated whether the thyroid cancer cell microenvironment has this effect on NK cells. We found that prostaglandin (PG) E2 produced by thyroid cancer cells suppressed the cytolytic activity of NK cells by inhibiting the expression of the natural cytotoxicity receptors NKp44 and NKp30 and the death receptor tumor necrosis factor-related apoptosis-inducing ligand. PGE2 and cyclooxygenase-2 were highly expressed in thyroid cancer cells; moreover, anaplastic thyroid cancer cells released higher amounts of PGE2 than the papillary subtype, which was associated with suppression of NK cell-inducing nuclear factor-κB and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways
PGE2 receptor (EP) 2 and EP4 expressed on the NK cell surface. In addition, PGE2 inhibited the functional maturation of NK cells and reduced their cytotoxicity against target cells. These results indicate that PGE2 promotes thyroid cancer progression by inhibiting NK cell maturation and cytotoxicity. Thus, therapeutic strategies that target PGE2 in thyroid cancer could potentiate the immune response and improve patient prognosis.
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