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Here the authors report a phase 3 clinical trial showing that Ecnoglutide, designed as a cAMP-biased GLP-1R agonist, improved glycaemic control versus placebo in adults with type 2 diabetes inadequately controlled with diet and exercise alone or with a single oral hypoglycaemic agent.

The gut microbiome can regulate diverse host metabolic processes, including thermogenesis in adipose tissues. Here, the authors report a reduced abundance of Prevotella copri in patients with obesity and its role in alleviating adiposity.

Chirality amplification and transfer strategies are powerful routes to endow covalent organic polymers with supramolecular helicity, expanding their structural and functional versatility. Here, the authors studied helical polyimines with uniform helicity but that displayed reversed chiroptical signatures upon subtle adjustments to a single polymerization parameter.

Covalent organic frameworks (COF) hold great promise in filtration and separation but combining facile processing, high crystallinity and high separation performance remains challenging. Here, the authors demonstrate that heterocrystalline COF membranes in which high-crystalline regions are tightly linked by low-crystalline regions can improve molecular sieving properties at high solvent flux.

Covalent organic framework (COF) membranes are important in low energy and cost-effective molecular separations but most COF membranes are assembled via a one-step procedure by concurrent polymerization and crystallization which compromises the ordered structure. Here, the authors propose a two-step phase switching strategy for assembling compact and highly crystalline COF membranes decoupling the polymerization and the crystallization process.

The ability of anti-cancer therapies such as radiotherapy, chemotherapy and immunotherapy to induce ferroptosis has been linked to their efficacy. Here, the authors demonstrate that SOX13 promotes ferroptosis-resistance via transactivation of SCAF1, identifying SOX13 as a targeted therapeutic vulnerability in gastric cancer.

Site-specific and efficient RNA editing is achieved with a CasRx editor.

Mechanical energy is ubiquitous but inaccessible for microbial bioproduction. Here, the authors show that the piezocatalyst ZnO, upon mechanical stimulation, transfers charges to autotrophic Cupriavidus necator and enhances bioplastic synthesis.

The development of giant oligomeric donors to replace batch-varied polymer remains challenging. Here, the authors regulate the assembly behaviour of giant dimeric donors, realizing all-giant-oligomeric-based organic solar cells with promising device efficiency and stability.

Chemotherapy-dominated multi-modal therapeutic strategy has the potential for eradicating colorectal tumors. Here this group reports a therapeutic strategy using arsenic-derived nanosheets depleting H2S enriching in CRC microenvironment while eliciting the photothermal activity/cytotoxicity of ultrasmall CuS nanoparticles against CRC cells.

A copper(II)-functionalized Mycobacterium smegmatis porin A nanopore enables direct identification of all 20 proteinogenic amino acids, one unnatural amino acid and two post-translational modifications, and shows potential for peptide discrimination and sequencing.

A Phase 2, randomized, placebo-controlled study evaluated novel GLP-1 analog ecnoglutide in adults with type 2 diabetes. Here we show that ecnoglutide significantly reduced HbA1c from baseline up to -2.39% compared to -0.55% for placebo (P<0.0001), with a safety profile similar to approved GLP-1 analogs.

The decidualization of endometrial stroma is critical for pregnancy maintenance. Here the authors reveal that Menin ensures the expression of PTX3 through H3K4me3 modification, to balance the BMP and FGF signal in the decidua for normal pregnancy.

Biochemical and structural studies of the Fc immunoglobulin E receptor show that it exists as a homodimer on mast cell membranes, but dissociates upon IgE binding, exposing immunoreceptor tyrosine-based activation motifs that enable downstream effector activation.

Silicon (Si) has emerged as a promising next-generation anode material. Here the authors recycle photovoltaic waste for micro-sized Si that can pair with high-voltage cathode for high-performance Li-ion pouch cells.

Fouling is a continuous challenge for the effective application of membranes in oily wastewater treatment. Here, the authors present a hydrophobic chain engineering strategy to regulate the surface of graphene oxide-based membranes at a molecular scale for increased antifouling even at high permeance.

Whole-genome sequencing of lung cancer in never smokers identifies different copy number subtypes and shows a lack of tobacco smoking signatures, even in cases exposed to secondhand smoke.

The E1A binding protein p300 and its close paralogue CREB-binding protein are transcriptional coactivators with intrinsic histone acetyltransferase activity. Here, the authors show that the TAZ2 domain of p300 has a HAT autoinhibitory function that is relieved upon binding of transcription factors.

Tuning electrocatalytic reduction of carbon monoxide to achieve valuable ethanol product with high performance is interesting yet challenging. Here, the authors design a hydrophobic Cu/Cu₂O sheet catalyst showing a FE of 68.8% and partial current density of 111 mA cm⁻² for CO reduction to ethanol.

Delivering genes to and across the brain vasculature efficiently and specifically across species remains challenging. Here, the authors show that endothelial-specific AAVs with serotype flexibility enable redosing and transform the brain vasculature into an in vivo biofactory in genetically diverse rodents. In primates, these vectors cross the blood-brain-barrier and show broad tropism.

Wu et al. optimized the m⁶A mapping method for ultralow-input materials and characterized the transcriptome-wide landscape of m⁶A methylation in mouse oocytes and early embryos.

There is interest in STING for immunotherapy, but it suffers from adverse proinflammatory effects. Here, the authors report on a non-membrane-associated polymeric universal STING mimic which triggers pathways involved in tumour control over proinflammatory pathways, demonstrating application in vivo.

Identification of low abundance proteins interacting with viral proteins can be challenging. Here, Du et al. develop an mRNA display approach with a library of even distribution, identify host proteins interacting with NS1 protein of influenza A virus, and show that one interactor provides a means to regulate cellular fatty acids synthesis.

Energy-efficient and secure wireless body sensor networks can be created by using conductive fabrics that support surface-plasmon-like modes at radio communication frequencies.

Remote tumours cause liver dysfunction by releasing extracellular vesicles and particles containing palmitic acid, which induces TNF signalling in Kupffer cells, resulting in inflammation, fatty deposits and metabolic dysregulation, thus both reducing the efficacy and increasing the toxicity of chemotherapies.

Somatosensory corticospinal neurons facilitate touch sensitivity and touch-evoked neuropathic pain in mice.

Stromal Menin upregulates the expression of SFRP2 and DKK1 through H3K4me3 to limit the excessive activation of the WNT signalling pathway and support normal endometrial receptivity during window of implantation.