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At week 68, in patients who experienced poor weight loss following bariatric surgery, semaglutide was associated with 18.0% weight loss compared to 0.4% weight gain in patients receiving placebo.

An analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.

The authors simulate phytoplankton macromolecular composition—proteins, carbohydrates and lipids—under present and future scenarios. They show increased protein allocation in subtropical phytoplankton but declines in high-latitude populations under warming, with implications for marine food webs.

This work introduces a paradigm where neural networks predict parameters of a quantum semi-empirical Hamiltonian rather than energies directly, achieving DFT accuracy for relative energies, forces, vibrations, and geometries at semi-empirical cost.

Satellite data shows that the Tonga volcanic eruption partly cleaned up its own methane pollution. Volcanic particles created chlorine atoms that broke down methane. Similar chemistry may one day help reduce anthropogenic methane emissions.

Promiscuous interactions underpin natural protein evolution, but ways to harness such promiscuity to design new functions remain underexplored. Now it is shown that mapping this promiscuity with geometric precision in a de novo protein can guide its redesign into a fluorophore binder and an efficient enzyme approaching the diffusion limit.

Contaminants such as CO₂ and H₂S present in natural gas and biogas streams must be removed before use; existing strategies to do so can be rather complex. Here, the authors use a fluorinated porous metal–organic framework to remove CO₂ and H₂S from CH₄-rich feeds in a single step, potentially simplifying the process.

Denitrification is an essential process for the removal of excess nitrogen in aquatic ecosystems, and models informed by lake samples suggest that seasonal stratification changes could weaken the microbial communities responsible for this process.

Brominated trityl radicals form stable enantiomers and present promising candidates for molecular qubits but their inherently weak photoluminescence limits optical spin readout. Here, the authors synthesize three carbazole-functionalized tris(2,4,6-tribromophenyl)methyl radicals with photoluminescence quantum yields of up to 72%.

Cyclic peroxides are highly reactive oxygen-containing species that play important roles in chemical synthesis. Now, the reaction between diazoboranes and triplet oxygen affords a family of cyclic dioxaboriranes, including both neutral and anionic variants. Neutral species behave as electrophilic oxygen-atom donors, whereas anionic analogues are nucleophilic and react with carbon dioxide.

Naphthalene rings are common in drug candidates but suffer from metabolic liabilities and limited three-dimensionality. Aryl-fused bicyclo[3.1.1]heptanes (BCHeps) have been presented as derivatizable bioisosteres of β-naphthalene. Now it has been shown that aryl-fused BCHeps can be synthesized and validated as viable naphthyl replacements with promising structural and drug-like properties.

PoTS is an automated pipeline that maps reaction transition states inside zeolite pores. By identifying hundreds of confined transition states across many frameworks, it explains differences in catalytic selectivity and informs zeolite design.

Structural studies demonstrate that myosin generates forces that cause structural changes in actin, modulating cooperative binding by α-catenin and thus signal transduction and intercellular communication via adhesion complexes.

Classical understanding of aromaticity has been challenged by its emergence in rings featuring only metal atoms. Now, diuranium and dithorium inverse sandwich complexes featuring a central cyclo-Bi₃³⁻ unit have been synthesized. These tribismuth rings exhibit exalted diamagnetism and are σ-aromatic, in contrast to the π-aromaticity in analogous tricarbon rings, providing benchmark data for comparisons between organic and inorganic aromaticity.

Visible-light-mediated intramolecular [2+2] cycloaddition of aza-1,6-dienes gives bridged, not fused, heterocycles, in violation of the ‘rule-of-five’, which dictates that five-membered rings are preferentially formed. This method allows a variety of bridged bicyclic scaffolds to be accessed, enabling drug-relevant properties to be readily tuned.

A permanently porous organic framework assembled and stabilized solely by non-covalent chalcogen bonding is reported. Empirical and computational studies reveal the characteristic influence of the operative Te···N chalcogen bonds on assembly, electronic structure, framework regeneration and lattice dynamics.

Here the authors report that the π-basic cavity of pillar[n]arenes can effectively stabilize bromiranium intermediates generated during olefin halogenation, confining them in a controlled microenvironment. This strategy overrides the intrinsic Markovnikov preference, enabling highly selective anti-Markovnikov halogenation.

Bacteria adjust their metabolism to the cellular energy state. Here, authors identify a layer of regulation of AMP-forming acetyl-CoA synthetase AcsA activity by AcuB acting as energy sensor inhibiting the AcsA deacetylase AcuC in presence of AMP.

ALMA observations of the interstellar comet 3I/ATLAS provide a limit on the deuterium-to-hydrogen ratio in water. This ratio is a sensitive probe of temperature, suggesting that comet 3I formed in an ultracold environment with minimal thermal processing in its home system.

Methane in modern subglacial meltwater coming from the western Greenland Ice Sheet largely dates back to the period following the Holocene Thermal Maximum, when a smaller ice sheet allowed organic matter accumulation and biological methane production after ice readvance.

A phosphine–photoredox catalyst system promotes intermolecular Markovnikov hydroamination of unactivated terminal alkenes with numerous classes of N–H azoles..

Plants use CARD1/HPCA1 to detect signals such as quinones and ROS, but how they distinguish them was unclear. Here, the authors show CARD1 uses a copper-based mechanism for H₂O₂ sensing, revealing a metal-dependent mode of ROS perception in plants.

Here, an in vitro model shows cancer-linked relocation of GALNTs to the ER drives complete mucin 1 Tn antigen occupancy. ST6GALNAC1 then selectively sialylates the T13 site, driving tumourigenesis.

The systemic discovery of metal–small-molecule complexes from biological samples is a difficult challenge. Now, a method based on liquid chromatography and native electrospray ionization mass spectrometry has been developed. The approach uses post-column pH adjustment and metal infusion combined with ion identity molecular networking, and a rule-based informatics workflow, to interrogate small-molecule–metal binding.

Nearly 40 years ago, solid oxide electrochemical cells began to evolve from supplying energy into versatile chemical reactors. Since then, breakthroughs in cell design and demonstrations of efficient value-added chemical reactions led to the exploration of how, for example, interface engineering enables more efficient and sustainable valorization reactions at reduced temperatures.

Iontronic drug delivery is limited to small, charged molecules. Here the authors couple iontronic transport with bio-orthogonal click-to-release chemistry to unlock electrically controlled activation of drugs and proteins beyond size and charge limits.

Homogeneous catalytic hydroboration represents a valuable strategy for the synthesis of alcohols but reports which employ iron-based catalysts are somewhat limited. Here, the authors report an iron metalloborane complex as an efficient pre-catalyst for hydroboration of ketones, cyclic esters and CO₂ with mild conditions.

As presented at the European Congress on Obesity, this randomized, placebo-controlled trial demonstrates that oral orforglipron, a nonpeptide GLP-1 receptor agonist, preserves weight loss and cardiometabolic benefits achieved with injectable GLP-1 receptor agonist therapies, making it a viable oral maintenance strategy.

Methyl groups play a vital role in pharmaceuticals, where their installation onto aryl and heteroaryl moieties of drug candidates can often enhance drug-target interactions. Here, the authors report the methylation of phenols (as tosylates) and aryl halides via a hydrazone-mediated Ni catalyzed cross-coupling reaction, employing formaldehyde hydrazone as the methyl reagent.

Purely organic room temperature phosphorescent materials are of interest for a range of applications, but phosphorescence colour switching is hard to achieve. Here, the authors report the use of a single-component organic crystal with reversible phosphorescence colour switching.

Long-range interactions mediated by protein electric dipole moments have a role in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.

Phosphorus locked in carbonate rocks from seven global sites shows simultaneous marine phosphorus spikes during major mass extinctions. Modelling ties high marine phosphorus to eutrophication, CO2 drawdown, and global cooling.

Leigh syndrome is a severe, currently untreatable mitochondrial neurological disorder. Menacho, Okawa et al. developed a deep-learning drug screening pipeline in brain organoids, identifying azole compounds as promising therapeutic candidates.

In a randomized trial, pasteurized Akkermansia muciniphila improved weight loss maintenance and metabolic health after a low-energy diet, especially in individuals with initially lower Akkermansia levels. The work suggests leveraging gut A. muciniphila as a potential target for weight management.

Dynamic S–S bonds have been leveraged in a variety of applications. Now trisulfides have been found to undergo rapid and spontaneous S–S metathesis in polar aprotic solvents. A mechanistic investigation of this unusual reaction enabled applications in natural product modification, dynamic combinatorial library synthesis and chemically recyclable polymers.

Conventional and time-resolved cryo-electron microscopy reveal how NTSR1 dynamically engages and releases different G proteins, capturing over 20 intermediates and uncovering key mechanistic steps in GDP- and GTP-driven activation, subtype selectivity and distinct dissociation pathways.

Natural hydrogen is generated through chemical and radioactive processes in the Earth’s crust, and could be an important future clean chemical feedstock and energy resource. This Review examines the processes of geological hydrogen generation, migration, accumulation and preservation that enable the development of exploitable reserves.

Processivity is a fundamental principle in biopolymer assembly and breakdown. This study uncovers a tunnel-based processive mechanism for the depolymerization of β(1,3)-glucans, expanding this paradigm to the major classes of β-glucans in nature.

Independently folding domains can be seen as the functional and evolutionary structural units of proteins. Here, the authors assess effects of >7000 mutations in a model PDZ domain, to quantify how two small extensions to a protein domain reshape its energetic and allosteric landscape.

Researchers report real-time molecular detection of oxidized mercury species in the polar atmosphere, revealing discrepancies with current models and advancing understanding of neurotoxic mercury cycling in sensitive ecosystems.

Diastereoselective hydrogenation of multi-substituted (hetero)arenes provides an efficient and industrially valuable route for transforming these compounds into diversified 3D building blocks, with broad applications such as drug discovery. Here, the authors demonstrate that a rationally designed Pt catalyst enables general diastereoselective hydrogenation of a wide variety of multi-substituted and functionalized arenes and heteroarenes under mild conditions.

Neuropathic pain is commonly treated with opioids due to limited alternatives. Here, authors determine cryo-EM structures of the neuronal glycine transporter GlyT2 and develop a reversible inhibitor that provides analgesia in vivo without side effects.

The enzymatic depolymerization of synthetic polyamides remains a major challenge. Here Bell et al. review the current biocatalytic nylon recycling landscape, highlighting the biochemical, structural and material science bottlenecks that limit polyamide deconstruction.