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The results of a clinical trial of mazdutide, a dual glucagon and GLP-1 receptor agonist, in the context of type 2 diabetes show that it could hold promise as an add-on therapy to conventional oral anti-diabetic drugs.

In a small trial of patients with severe systemic lupus erythematosus and nephritis, treatment with allogeneic T cells with a CD19 chimeric antigen receptor inserted into the T cell receptor locus and deletion of the PD-1 (PDCD1) gene were safe and associated with reduced disease activity.

Radiotherapy is the mainstay treatment for nasopharyngeal carcinoma (NPC). Here the authors show that the deubiquitinase, USP44, increases radiosensitivity of NPC cells by promoting the degradation of Ku80, and thus enhancing the levels of DNA damage.

CaV1.2 is crucial in cardiac, vascular and neuronal function, serving as a target for many drugs. Here, authors identify the binding site of herb-derived drug tetrandrine, and explore inhibitory mechanism of L/T-type selective DHP drug benidipine.

Na_V1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of Na_V1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.

This study details a process of duplicated (homoeologous) chromosome ‘scrambling’ in newly formed rice polyploids, indicating the possibility of natural ‘allo-to-autopolyploid’ evolution, with implications for polyploid crop breeding.

In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

Cryo-electron microscopy structures of mGlu2 and mGlu4 bound to heterotrimeric G_i protein shed light on the molecular basis of asymmetric signal transduction by metabotropic glutamate receptors.

Using JWST, more than 40 individual stars have been detected in a distant galaxy, dating back to when the Universe was only half of its current age. The stars appear to be red (super)giants that are magnified by factors of hundreds.

Multi-animal behaviour quantification is pivotal for deciphering animal social behaviours and has broad applications in neuroscience and ecology. Han and colleagues develop a few-shot learning framework for multi-animal 3D pose estimation, identity recognition and social behaviour classification.

The hydrogen evolution reaction is a promising route to produce clean hydrogen fuel; however, its efficient electrolytic generation relies on expensive platinum. Here, the authors show how modulating electron density in a metal sulfide, NiCo₂S₄, boosts hydrogen desorption to achieve high catalytic activity.

Structures of the glucagon receptor bound to β-arrestin 1 are reported, providing further information about the arrestin-mediated modulation of G protein-coupled receptors.

The current use of elastography ultrasound faces challenges, including vulnerability to subjective manipulation, echo signal attenuation, unknown risks of elastic pressure and high imaging hardware cost. Here, the author shows a virtual elastography to empower low-end ultrasound devices with state-of-art elastography function.

An optical-imaging instrument that integrates a visible multispectral imaging system with the detection of near-infrared fluorescence in the first and second windows aids the fluorescence-guided surgical resection of liver tumours in patients.

The cis-peptide bond is rare in natural proteins and its impact on protein folding is elusive. Here the authors break the conventional understanding that cis-amide-favoring residues destabilize proteins, elucidate the principles of peptoid cis-trans isomerization in collagen folding, and showcase the use of cis-amide-favoring residues in building programmable and functional peptidomimetics.

Na_V1.6 channel plays a critical role in neuronal excitability. Here, authors present human Na_V1.6 structures in apo and 4,9-anhydro-tetrodotoxin bound forms, which reveal molecular mechanisms of Na_V1.6 Na⁺ conductance and inhibition by the blocker.

Mechanical integrity issues are one of the main causes of limited long-term cycle stability for Ni-rich cathode materials. Here the authors analyse the roles of cobalt and manganese and utilise a concentration gradient design to mitigate these issues.

Evolution of accretion disk and corona during outbursts in black hole binary systems is still unclear. Here, the authors show spectral analysis of MAXI J1820+070 and propose a scenario of a dynamical corona to explain the evolution of the reflection fraction observed by Insight-HXMT.

Here, using a mouse model of chronic stress, the authors investigate how diet impacts stress and gut microbial structure and epithelial integrity and show that dietary raffinose metabolism to fructose couples stress-induced gut microbial remodeling to intestinal stem cell renewal and epithelial homeostasis.

Technologies allowing for sustainable hydrogen production will contribute to the decarbonization of the future energy supply. Here the authors report that carbon induced orbital modulation can facilitate the otherwise inert MoS₂ electrocatalyst superior alkaline hydrogen evolution reactivity.

Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity.

De novoDNA methylation is carried out by DNA methyltransferase DNMT3A/B, although DNMT3B isoforms without active catalytic domains are widely expressed. Here, the authors show that DNMT3B isoforms stimulate gene body methylation and re-methylation independently of the isoforms' catalytic activity.

A naturally occurring stand-alone and intermolecular Diels–Alderase, MaDA, has been identified from Morus alba cell cultures. MaDA is a FAD-dependent enzyme, which catalyses the intermolecular [4+2] cycloaddition via a concerted but asynchronous pericyclic pathway between morachalcone A and a diene generated from moracin C. Characterization revealed that MaDA possesses good substrate promiscuity towards both dienes and dienophiles.

Huang, Qin, Shang et al. profile double-strand breaks (DSBs) generated by C-to-G base editors (CGBEs) and find that HMCES protects abasic sites and reduces CGBE-triggered DSBs.

Using the lifespan brain chart and two large-scale cross-cultural consortia (ABIDE and CABIC), we disentangle the heterogeneity of brain morphology in ASD into two structural impairment pathways that could disrupt sensory to association functions.