Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them from α,β-unsaturated aldehydes, through the selective hydrogenation of the carbon-oxygen group (in preference to the carbon-carbon group). However, developing effective catalysts for this transformation is challenging, because hydrogenation of the carbon-carbon group is thermodynamically favoured. This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not. This has inspired the use of metal-organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material. Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of α,β-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe, Cr or both (known as MIL-101; refs 19, 20, 21) results in stable catalysts that convert a range of α,β-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon-oxygen rather than the carbon-carbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.

Investigation of the magnetic and transport properties of single-walled small-diameter carbon nanotubes embedded in a zeolite matrix revealed that at temperatures below 20 kelvin, 4 angstrom tubes exhibit superconducting behavior manifest as an anisotropic Meissner effect, with a superconducting gap and fluctuation supercurrent. The measured superconducting characteristics display smooth temperature variations owing to one-dimensional fluctuations, with a mean-field superconducting transition temperature of 15 kelvin. Statistical mechanic calculations based on the Ginzburg-Landau free-energy functional yield predictions that are in excellent agreement with the experiments.

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New insulin-secreting cell lines (INS-1 and INS-2) were established from cells isolated from an x-ray-induced rat transplantable insulinoma. The continuous growth of these cells was found to be dependent on the reducing agent 2-mercaptoethanol. Removal of this thiol compound caused a 15-fold drop in total cellular glutathione levels. These cells proliferated slowly (population doubling time about 100 h) and, in general, showed morphological characteristics typical of native beta-cells. Most cells stained positive for insulin and did not react with antibodies against the other islet hormones. The content of immunoreactive insulin was about 8 micrograms/10(6) cells, corresponding to 20% of the native beta-cell content. These cells synthesized both proinsulin I and II and displayed conversion rates of the two precursor hormones similar to those observed in rat islets. However, glucose failed to stimulate the rate of proinsulin biosynthesis. In static incubations, glucose stimulated insulin secretion from floating cell clusters or from attached cells. Under perifusion conditions, 10 mM but not 1 mM glucose enhanced secretion 2.2-fold. In the presence of forskolin and 3-isobutyl-1-methylxanthine, increase of glucose concentration from 2.8-20 mM caused a 4-fold enhancement of the rate of secretion. Glucose also depolarized INS-1 cells and raised the concentration of cytosolic Ca2+. This suggests that glucose is still capable of eliciting part of the ionic events at the plasma membrane, which leads to insulin secretion. The structural and functional characteristics of INS-1 cells remained unchanged over a period of 2 yr (about 80 passages). Although INS-2 cells have not been fully characterized, their insulin content was similar to that of INS-1 cells and they also remain partially sensitive to glucose as a secretagogue. INS-1 cells retain beta-cell surface antigens, as revealed by reactivity with the antigangloside monoclonal antibodies R2D6 and A2B5. These findings indicate that INS-1 cells have remained stable and retain a high degree of differentiation which should make them a suitable model for studying various aspects of beta-cell function.

Uniform core-shell Pd@IRMOF-3 nanostructures, where single Pd nanoparticle core is surrounded by amino-functionalized IRMOF-3 shell, are prepared by a facile mixed solvothermal method. When used as multifunctional catalysts, the Pd@IRMOF-3 nanocomposites exhibit high activity, enhanced selectivity, and excellent stability in the cascade reaction. Both experimental evidence and theoretical calculations reveal that the high catalytic performance of Pd@IRMOF-3 nanocomposites originates from their unique core-shell structures.

Electrocatalytic reduction reaction of CO 2 (CO 2 RR) is an effective way to mitigate energy and environmental issues. However, very limited catalysts are capable of converting CO 2 resources into high-value products such as hydrocarbons or alcohols. Herein, we first propose a facile strategy for the large-scale synthesis of isolated Cu decorated through-hole carbon nanofibers (CuSAs/TCNFs). This CuSAs/TCNFs membrane has excellent mechanical properties and can be directly used as cathode for CO 2 RR, which could generate nearly pure methanol with 44% Faradaic efficiency in liquid phase. The self-supporting and through-hole structure of CuSAs/TCNFs greatly reduces the embedded metal atoms and produces abundant efficient Cu single atoms, which could actually participate in CO 2 RR, eventually causing −93 mA cm −2 partial current density for C1 products and more than 50 h stability in aqueous solution. According to DFT calculations, Cu single atoms possess a relatively higher binding energy for *CO intermediate. Therefore, *CO could be further reduced to products like methanol, instead of being easily released from the catalyst surface as CO product. This report may benefit the design of efficient and high-yield single-atom catalysts for other electrocatalytic reactions.

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets.

General anesthetics, including etomidate, act by binding to and enhancing the function of GABA type A receptors (GABA A Rs), which mediate inhibitory neurotransmission in the brain. Here, we used a radiolabeled, photoreactive etomidate analog ([ 3 H]azietomidate), which retains anesthetic potency in vivo and enhances GABA A R function in vitro, to identify directly, for the first time, amino acids that contribute to a GABA A R anesthetic binding site. For GABA A Rs purified by affinity chromatography from detergent extracts of bovine cortex, [ 3 H]azietomidate photoincorporation was increased by GABA and inhibited by etomidate in a concentration-dependent manner (IC 50 ϭ 30 M). Protein microsequencing of fragments isolated from proteolytic digests established photolabeling of two residues: one within the ␣M1 transmembrane helix at ␣1Met-236 (and/or the homologous methionines in ␣2,3,5), not previously implicated in etomidate function, and one within the ␤M3 transmembrane helix at ␤3Met-286 (and/or the homologous methionines in ␤1,2), an etomidate sensitivity determinant. The pharmacological specificity of labeling indicates that these methionines contribute to a single binding pocket for etomidate located in the transmembrane domain at the interface between ␤ and ␣ subunits, in what is predicted by structural models based on homology with the nicotinic acetylcholine receptor to be a water-filled pocket ϳ50 Å below the GABA binding site. The localization of the etomidate binding site to an intersubunit, not an intrasubunit, binding pocket is a novel conclusion that suggests more generally that the localization of drug binding sites to subunit interfaces may be a feature not only for GABA and benzodiazepines but also for etomidate and other intravenous and volatile anesthetics.