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Developing countries are experiencing huge rises in the incidence of type 2 diabetes mellitus (T2DM). In this Perspectives, Justin Echouffo-Tcheugui and Samuel Dagogo-Jack describe factors that underlie the rising prevalence of (T2DM), strategies to tackle the problem and discuss the difficulties that need to be overcome in order to implement solutions.

Intron retention is a conserved mechanism that controls gene expression but its regulation is poorly understood. Here, the authors provide evidence that DNA methylation regulates intron retention and find reduced MeCP2 occupancy and splicing factor recruitment near affected splice junctions.

NADPH acts as a reducing currency in mammalian cells and is thought to be required to maintain redox homeostasis. Here the authors discover an alternative NADPH-independent pathway, based on the conversion of methionine into cysteine, which is capable of sustaining redox homeostasis in the mouse liver.

While photoredox catalysis offers a new dimension to chemical synthesis, there are few heterogeneous organocatalysts for metal-free transformations. Here, authors prepare and perform in-depth studies on polymeric photocatalyst scaffolds for organic chemistry transformations.

Design of anomeric leaving groups with pendant H-bond acceptors results in a stereospecific chemical O-glycosylation with broad scope and applicability to automated synthesis.

Previous studies have shown that cellular electrostatic interactions are influential. Here the authors use cryo-EM and steady-state kinetic studies to investigate electrostatic interactions between cytochrome (cyt.) c and the complex (C) III₂-IV supercomplex from S.cerevisiae at low salinity.

An acoustic sensor that is based on a network of magnetic nanoparticles suspended in a carrier fluid can be used—together with a machine learning algorithm—to create a wearable voice recognition system with an accuracy of 99% in a noisy environment.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Shen et al. identify a noncanonical role for the inflammasome protein NLR family CARD domain-containing protein 4 (NLRC4) to attenuate tumor development. NLRC4 forms a scaffold to assemble the ataxia telangiectasia and Rad3-related DNA repair complex and the repair kinase checkpoint kinase-1 to promote repair of DNA breaks.

When light hits organic semiconductors, bound charge pairs, called excitons, are usually produced. Here, the authors show that in the best performing organic solar material to date, free charges, rather than excitons, are directly created by light.

Clinical diagnosis of Treponema pallidum subspecies pallidum (TPA), the causative agent of syphilis, depends upon serological testing, which has reduced sensitivity for some stages of the disease. Accompanying methods to complement serological testing also have distinct limitations. In this work, authors develop an assay that combines PCR with CRISPR-LwCas13a, and demonstrate sensitivity and specificity on clinically confirmed syphilis samples.

The association of telomere length with age and mortality across racially diverse pulmonary fibrosis populations is unknown. Here, the authors show that leukocyte telomere length associates with chronologic age and is predictive of mortality in pulmonary fibrosis across racial groups.

The authors highlight inconsistencies and divergencies in the literature reporting data on indirect calorimetry for studies on whole-body energy homeostasis, and propose harmonization of standards to facilitate data comparison and interpretation across different datasets.

Seven well defined shortfalls in global biodiversity data must be overcome to meet critical global biodiversity targets. Pollock et al. discuss the current and future roles of AI in bridging these knowledge gaps.

Joining the circulatory system of an old with a young animal has been shown to rejuvenate old tissues. Here the authors describe a comparatively simple blood infusion system that allows for the controlled exchange of blood between two animals, and study the effects of a single exchange on various tissues.

Metal recycling plays a crucial role in mitigating the shortage of critical metals. Here the authors develop an electrothermal chlorination process incorporating direct electric heating into chlorination metallurgy for rapid and selective recovery of metals that are critical in electronics.

Burr et al. analyze multiple primary EGFR-mutant lung tumors from ten patients and define developmental mosaicism as a mechanism underlying multiple tumor presentation in this setting.

Cytotoxic CD8⁺ T cells specific for α-myosin are identified as pivotal players in myocarditis associated with immune checkpoint inhibitor anticancer therapies.

Caveolae can bend and flatten, but how this is regulated is not well understood. Authors use correlative super-resolution light and electron microscopy to map the key proteins that mediate curvature of the caveolar coat.

Antimicrobial resistance constitutes a global health burden and research efforts are aimed at combatting the emergence of resistant microorganisms. In this Viewpoint article, several experts in the field discuss the role that rapid diagnostic tests have in managing the challenge of antimicrobial resistance, the drawbacks of current diagnostic methods, novel diagnostic strategies, and how such rapid diagnostic tools can inform drug development and the surveillance of resistance evolution.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Here, using a multisystem approach, the authors characterize the impact of Moderate Acute Malnutrition (MAM) on the gut-brain axis and its effects on cognitive and microbiome development in one-year-old children from Dhaka, Bangladesh, finding relationships between faecal microbiota (specifically the species Rothia mucilaginosa, Streptococcus salivarius, and Bacteroides fragilis), plasma odd chain fatty acid concentrations, brain activity, and behavioral measurements.

The stereochemical control and bifunctional manipulation of chiral sulfur functional groups is a long-standing challenge. Now, an enantiopure bench-stable S(VI) fluoride exchange reagent enables the asymmetric synthesis of sulfoximines, sulfonimidamides and sulfonimidoyl fluorides. The bifunctional nature of this reagent provides a practical method for the introduction of S(VI) functionality.

Video microscopy is key in studying cell migration, but accomplishing this in a high-throughput manner is still challenging. Here, the authors present an array microscope that can track the movements of thousands of individual cells simultaneously, and that can be used for drug screening studies.

Multimodal spatiotemporal transcriptomic resolution of palatal osteogenesis identifies previously unreported enriched genes in developing palate, paving the way toward viable diagnostic and therapeutic targets for cleft palate disorders.

Cell spatial organization in tissue provides essential insights into diseases. Here, the authors show Ceograph, a graph convolutional network, for the analysis of pathology images to predict patient outcomes, highlighting cellular markers to guide personalized treatments and enhance biological understanding.

The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8⁺ T cells with positive response to anti-PD-1 therapy.

Microorganisms are abundant in many environments and understanding their dispersal between ecosystems is important for ecology and conservation. These authors demonstrate that cyanobacterial populations are specific to hot or cold deserts and that gene flow between different populations does not occur.

Partially unfolded alpha-lactalbumin forms an oleic acid complex with antitumorigenic properties. Here, the authors define a structurally flexible, peptide-based oleate complex and report a phase I/II clinical trial where this complex is used to treat patients with bladder cancer.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

The application and therapeutic success of CAR-T cell approaches are limited by the development of T cell exhaustion. Here, Stewart et al discover a role for IL-4 in driving CD8⁺ CAR-T cell exhaustion and demonstrate the improvement of CAR-T cell effectivity with interruption of IL-4 signalling.

Differentiation and activation of T cells are normally modulated by non-covalent interactions between T cell receptor (TCR) and antigenic peptides. Here the authors use step-wise mutations, biochemical characterization and structural insights to describe the contributions of natural covalent bonds between TCR and antigenic peptides during these processes.

Analysis of tumor biopsies from the pivotal phase 1/2 ZUMA-1 trial identifies pre-treatment T cell–related characteristics that are associated with clinical response and neurologic toxicity after anti-CD19 CAR T cell therapy in patients with large B cell lymphoma.

The integration and organization of growth factor signaling, adhesion, and endocytosis is poorly understood. Here the authors use light and electron microscopy to shed light on the role of flat clathrin lattices and cell adhesion in growth factor signaling.

Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.

SARS-CoV-2 and its variants can be visually detected via easy-to-use Cas13-based nucleic acid tests leveraging lyophilised reagents and fast sample inactivation at ambient temperature.

A dataset of 3D images from more than 200,000 human induced pluripotent stem cells is used to develop a framework to analyse cell shape and the location and organization of major intracellular structures.

Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

The cryo-EM structure and functional analyses of oxytocin bound to its receptor reveal a Mg²⁺ coordination complex in the binding pocket and find that the identity of a single residue determines whether a vasopressin/oxytocin family receptor requires Mg²⁺ as a cofactor.

Focus-locking improves localization precision in single-molecule microscopy, but fiducials are often deposited at random and provide limited 3D compensation. Here, the authors fabricate 3D optical fiducials with nanometer accuracy by two-photon direct laser writing, and demonstrate isotropic 3D focus locking.

A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Wiita and colleagues use cross-linking mass spectrometry and glycoprotein surface capture to identify an activated conformation of integrin β₂ present on AML cells and develop CAR T cells that target this conformation antigen in preclinical models.

Mitochondrial fusion is crucial for cellular homeostasis but its regulation is still not fully understood. Here the authors report that a cross-talk between ubiquitin protease Ubp2 and ligases Mdm30 and Rsp5 modulates mitofusin Fzo1 levels and fatty acids saturation and thus mitochondrial fusion.

Genetic background affects how macrophages integrate multiple stimuli, e.g., to IL-4 in tissue environments. BALB/c macrophages show different transcriptional and epigenomic remodeling compared to C57BL/6, leading to distinct synergistic LPS responses.

Molecular phylogenetics, ancestral sequence reconstruction and biophysical protein characterization are used to investigate the interaction between the orange carotenoid protein and its unrelated regulator, the fluorescence recovery protein (FRP). This interaction evolved when a precursor of FRP was horizontally acquired by cyanobacteria.

Analysis of genomic data from 25 distantly related plant species shows signatures of selection on the same gene families and functions that repeatedly contributed to local adaptation to climate.