Overview of the first Wendelstein 7-X long pulse campaign with fully water-cooled plasma facing components

After a long device enhancement phase, scientific operation resumed in 2022. The main new device components are the water cooling of all plasma facing components and the new water-cooled high heat flux divertor units. Water cooling allowed for the first long-pulse operation campaign. A maximum discharge length of 8 min was achieved with a total heating energy of 1.3 GJ. Safe divertor operation was demonstrated in attached and detached mode. Stable detachment is readily achieved in some magnetic configurations but requires impurity seeding in configurations with small magnetic pitch angle within the edge islands. Progress was made in the characterization of transport mechanisms across edge magnetic islands: Measurement of the potential distribution and flow pattern reveals that the islands are associated with a strong poloidal drift, which leads to rapid convection of energy and particles from the last closed flux surface into the scrape-off layer. Using the upgraded plasma heating systems, advanced heating scenarios were developed, which provide improved energy confinement comparable to the scenario, in which the record triple product for stellarators was achieved in the previous operation campaign. However, a magnetic configuration-dependent critical heating power limit of the electron cyclotron resonance heating was observed. Exceeding the respective power limit leads to a degradation of the confinement

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Dual Role of Rh(III) Catalyst Enables Regioselective Halogenation of (Electron-Rich) Heterocycles

The Rh­(III)-catalyzed selective bromination and iodination of electron-rich heterocycles is reported. Kinetic investigations show that Rh plays a dual role in the bromination, catalyzing the directed halogenation and preventing the inherent halogenation of these substrates. As a result, this method gives highly selective access to valuable halogenated heterocycles with regiochemistry complementary to those obtained using uncatalyzed approaches, which rely on the inherent reactivity of these classes of substrates. Furans, thiophenes, benzothiophenes, pyrazoles, quinolones, and chromones can be applied

Rh(III)-Catalyzed Halogenation of Vinylic C–H Bonds: Rapid and General Access to <i>Z</i>‑Halo Acrylamides

Herein, the regio- and stereoselective iodination, along with some examples for the bromination, of readily available acrylamides to access a variety of differently substituted <i>Z</i>-haloacrylic acid derivatives is reported. The reaction proceeds under mild conditions via a Rh(III)-catalyzed C–H-activation/halogenation mechanism and represents a rare example of a direct halogenation of electron-poor acrylic acid derivatives

Electrospray Ionization Mass Spectrometry Reveals an Unexpected Coupling Product in the Copper-Promoted Synthesis of Pyrazoles

The reaction mechanism of the intermolecular oxidative formation of pyrazole <b>2</b> via a C–C/N–N bond-formation cascade of the enaminone <b>1</b> is investigated by means of ESI-MS. No direct reaction intermediates are observed; however, the formation of an unexpected imidazolid-3-one derivative <b>X</b> is observed that involves an oxidative dimerization of <b>1</b> in the presence of dioxygen. The derivative <b>X</b> is isolated and characterized by means of multidimensional ¹H and ¹³C NMR spectroscopy

Docking-Based Virtual Screening of Covalently Binding Ligands: An Orthogonal Lead Discovery Approach

In pharmaceutical industry, lead discovery strategies and screening collections have been predominantly tailored to discover compounds that modulate target proteins through noncovalent interactions. Conversely, covalent linkage formation is an important mechanism for a quantity of successful drugs in the market, which are discovered in most cases by hindsight instead of systematical design. In this article, the implementation of a docking-based virtual screening workflow for the retrieval of covalent binders is presented considering human cathepsin K as a test case. By use of the docking conditions that led to the best enrichment of known actives, 44 candidate compounds with unknown activity on cathepsin K were finally selected for experimental evaluation. The most potent inhibitor, 4-(<i>N</i>-phenylanilino)-6-pyrrolidin-1-yl-1,3,5-triazine-2-carbonitrile (CP243522), showed a <i>K</i>_i of 21 nM and was confirmed to have a covalent reversible mechanism of inhibition. The presented approach will have great potential in cases where covalent inhibition is the desired drug discovery strategy

Triptycene-Based Porous Metal-Assisted Salphen Organic Frameworks: Influence of the Metal Ions on Formation and Gas Sorption

Porous organic polymers (POPs) are chemically and thermally robust materials and have been often investigated for their gas sorption properties. From the related field of metal–organic frameworks (MOFs) it is known that open ligation sites at metal centers can enhance the performance of gas sorption significantly, especially the selectivity toward one gas of a binary mixture, such as CO₂/N₂ or CO₂/CH₄. POPs that contain metal centers are rarer. One possibility to introduce metals into POPs is by the synthesis of metal-assisted salphen organic frameworks (MaSOFs), where the framework development is associated with the formation of the metal–salphen pockets. Based on a hexakissalicylaldehyde, a variety of three-dimensional isostructural porous MaSOFs with different metal ions (Zn²⁺, Ni²⁺, Cu²⁺, Pd²⁺, and Pt²⁺) are introduced. All compounds show a very similar pore structure and comparable specific surface areas, which make these MaSOFs ideal candidates to study the influence of the nature of the incorporated metal center on gas sorption selectivity. Due to the environmental importance, the adsorption of CO₂ in comparison to N₂ and CH₄ was extensively studied. Depending on the metal ions, the heat of adsorption was different as well as the Henry and IAST selectivities. Cu–MaSOF₁₀₀ for instance shows a high <i>Q</i>_st of 31.2 kJ mol^–1 for CO₂ and an uptake of 14.9 wt % at 1 bar and 273 K. The IAST selectivity of CO₂/N₂ for an 80/20 mixture is with <i>S</i>_IAST = 52 very high for a metal containing POP and even comparable to some of the best performing MOFs. The MaSOFs are stable even in boiling water. This, as well as the simple synthesis, makes them potential good candidates for CO₂ removal of binary mixtures

Triptycene-Based Porous Metal-Assisted Salphen Organic Frameworks: Influence of the Metal Ions on Formation and Gas Sorption

Porous organic polymers (POPs) are chemically and thermally robust materials and have been often investigated for their gas sorption properties. From the related field of metal–organic frameworks (MOFs) it is known that open ligation sites at metal centers can enhance the performance of gas sorption significantly, especially the selectivity toward one gas of a binary mixture, such as CO₂/N₂ or CO₂/CH₄. POPs that contain metal centers are rarer. One possibility to introduce metals into POPs is by the synthesis of metal-assisted salphen organic frameworks (MaSOFs), where the framework development is associated with the formation of the metal–salphen pockets. Based on a hexakissalicylaldehyde, a variety of three-dimensional isostructural porous MaSOFs with different metal ions (Zn²⁺, Ni²⁺, Cu²⁺, Pd²⁺, and Pt²⁺) are introduced. All compounds show a very similar pore structure and comparable specific surface areas, which make these MaSOFs ideal candidates to study the influence of the nature of the incorporated metal center on gas sorption selectivity. Due to the environmental importance, the adsorption of CO₂ in comparison to N₂ and CH₄ was extensively studied. Depending on the metal ions, the heat of adsorption was different as well as the Henry and IAST selectivities. Cu–MaSOF₁₀₀ for instance shows a high <i>Q</i>_st of 31.2 kJ mol^–1 for CO₂ and an uptake of 14.9 wt % at 1 bar and 273 K. The IAST selectivity of CO₂/N₂ for an 80/20 mixture is with <i>S</i>_IAST = 52 very high for a metal containing POP and even comparable to some of the best performing MOFs. The MaSOFs are stable even in boiling water. This, as well as the simple synthesis, makes them potential good candidates for CO₂ removal of binary mixtures