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Treating rheumatoid arthritis remains challenging as the pathological development involves multiple cells. Here, the authors develop an engineered microalgae to combat rheumatoid arthritis by suppressing osteoclasts for bone remodeling, and inhibiting macrophages for restoring immune homeostasis.

Targeting ribosome biogenesis with the ribosome inhibitor, homoharringtonine (HHT), is effective in leukaemia but not in solid tumours. Here, the authors demonstrate that in solid tumours, activation of JNK signaling following HHT-induced ribosomal stress promotes Snail1 accumulation in the nucleolus which facilitates ribosome biogenesis and resistance to HHT.

Mitochondria-lysosome interactions are critical for maintaining cellular homeostasis. Here, the authors design a triggerable DNA-based tool to regulate mitochondria-lysosome contacts and manipulate mitochondrial fission and autophagy in cells.

Obesity-related osteoarthritis (OA) involves complex molecular mechanisms governing joint structural changes, which remain poorly understood. Here, the authors show that targeting the p53-FOXO3 loop and ferroptosis in osteoclasts effectively mitigates cartilage degeneration and subchondral bone remodeling in obesity-driven OA.

This manuscript demonstrates a single-step electrified approach using rapid joule heating over an H-ZSM-5 catalyst for effective deconstruction of polyolefin plastic waste into light olefins (C2–C4) in milliseconds.

Characterization of four SALICYLIC ACID-DEFICIENT GENEs in rice identifies an ancestral pathway for biosynthesis of salicylic acid from phenylalanine and provides genetic targets for engineering disease resistance in crop plants.

The efficiency of cellulosic biofuel production from woody biomass is limited by the presence of lignin that impedes efficient processing. Here the authors show that transgenic modification of aspen to depress lignin polymerization can increase ethanol yield without affecting tree growth.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Hypophosphatasia (HPP) is a bone disease caused by mutations in tissue non-specific alkaline phosphatase (TNAP). Here, authors solved the crystal and cryoEM structures of TNAP, shedding light on the molecular mechanisms underlying HPP.

The thymus harbors a complex constitutively active inflammatory network with innate-like T cells representing one of its central nodes. Here, the authors show that these cells can induce tolerance to inflammation-associated self-antigens, a class of molecules that otherwise largely mirrors the spatial and temporal distribution of pathogen-derived antigens.

Pharmacological inhibition of the prolyl isomerase PIN1, highly expressed in cancer cells and cancer associated fibroblasts (CAF), has been proposed for cancer therapy. Here the authors report the design of a DNA-barcoded micellular system functionalized with antibodies targeting CAFs and a T cell recruiting aptamer to deliver the PIN1 inhibitor AG17724, showing antitumor response in preclinical models of pancreatic cancer.

The amorphization of brucite can increase its conductivity at 1 − 2 GPa and 300 − 400 °C, thereby causing high-conductivity anomalies in shallow cold subduction zones, as revealed through integrated multi-anvil press experiments and in situ impedance spectroscopy analysis.

The mechanisms of the natural control of hepatitis B virus infection remain obscured. Here, the authors reveal that matrix stiffness influences HBV replication via YAP-mediated mechanosignaling, uncovering a novel non-cytolytic mechanism for clearing viral infections in the liver.

A unique case from the Colombian cohort of autosomal dominant Alzheimer’s disease is reported in which disease progression is substantially delayed despite unusually high amyloid plaque pathology, possibly related to a rare mutation in APOE3.

Aberrant EGFR activation is commonly found in non-small cell lung cancer (NSCLC). Here the authors show that E3 ubiquitin ligase FBXL2 targets EGFR and EGFR tyrosine kinase inhibitor (TKI)-resistant mutants for proteasome-mediated degradation to inhibit EGFR-driven NSCLC growth and TKI resistance.

Soybean accessions display a variable number of nodules when colonized by rhizobia. The authors identify one locus controlling this trait, a typical TIR–NBS–LRR disease resistance gene called NNL1, and the corresponding bacterial effector called NopP.

Thermoelectric modules can generate electricity directly from heat and have applications to waste heat-energy conversion. Here Zhouet al. have fabricated a thermoelectric module based on an air-stable n-type single-walled carbon nanotube sheet which can reach a high power factor of 1500 μWm⁻¹K⁻².

Upcycling end-of-life tire waste is complex due to the recalcitrant nature of the toxic legacy additive, 6PPD. Here the authors present a new decontamination strategy that can isolate 6PPD, convert it to safe and valuable products, and valorize end-of-life tire waste.

Here the authors develop a chip-scale thin-film lithium niobate microcavity electric field sensor enabling real-time amplitude and phase measurements of various electric field waveforms.

The evolutionally conserved Hippo pathway regulates essential developmental, homeostatic and regenerative processes, and is involved in the host defense against pathogens. Here authors show that in Drosophila Melanogaster and mammalian cells, innate immune stimuli activate Hippo via a pathway emanating from the Tak1 kinase and cascading down to Hippo via STRIPAK-Tao-Hpo signaling.

Metal–metal oxide inverse catalysts are an intriguing class of materials, although the understanding of their structure–activity properties remains elusive. Here, Vlachos and colleagues unravel the complex dynamic interplay between Brønsted acid and redox sites at the surface of a PtWO_x/C inverse catalyst, offering a strategy to tune its acid-catalysed dehydration reactivity.

The venom of the Chinese red-headed centipede causes excruciating pain. Here, Yanget al. identify a novel toxin protein from the centipede venom and find that it can activate the nociceptive TRPV1 ion channel by binding to the channel’s outer pore to potentiate the heat activation machinery.

Incorporating silicon into organic molecules and materials leads to interesting changes in electronic structure and properties; silabenzenes are attractive species for this purpose, but their high reactivity in solution poses challenges. Now, 1D and 2D covalent organic frameworks featuring disilabenzene rings (C₄Si₂) as linkers have been prepared by reacting silicon atoms and polyaromatic hydrocarbon precursors on a Au(111) surface.

In Alzheimer’s disease (AD) tau and neurodegeneration have complex regional relationships. Here, the authors show neuronal hypometabolism discordant with tau burden defines functional resilience or susceptibility to Alzheimer’s pathology via limbic/cortical axes. Susceptible groups have faster cognitive decline and evidence of non-Alzheimer’s pathologies.

The interplay between amyloid and tau pathology in Alzheimer’s disease is still not well understood. Here, the authors show that amyloid-related increased in soluble p-tau is related to subsequent accumulation of tau aggregates and cognitive decline in early stage of the disease.

Alzheimer’s disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The KL-VS haplotype of the Klotho gene has been associated with reduced risk of Alzheimer’s disease and dementia. Here the authors show an association between the KL-VS haplotype and amyloid-dependent tau accumulation using PET data.

The gut-derived orexigenic hormone, ghrelin, enhances neuronal firing in the substantia nigra pars compacta. This study shows that ghrelin enhances firing of nigral dopaminergic neurons by a novel mechanism in which activation of the PLC/PKC pathway inhibits Kv7 channels.

Tau accumulation is associated with disease progression in Alzheimer’s disease. Here the authors use resting state fMRI and tau-PET to demonstrate that baseline connectivity in Alzheimer's disease is associated with tau spreading.

Though flexible pressure sensors are attractive for next-generation applications, limitations in its performance hinder widespread adoption. Here, the authors report an iontronic flexible pressure sensor with graded intrafillable architecture that shows high sensitivity over a broad pressure range.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Brain-iron elevation is implicated in Alzheimer’s disease (AD), but the impact of the metal on disease outcomes has not been analysed in a longitudinal study. Here, the authors examine the association between the levels of ferritin, an iron storage protein, in the cerebrospinal fluid (CSF) of AD patients and show that CSF ferritin levels predict AD outcomes.

Vimentin is an intermediate filament protein responsible for maintaining cell shape. Here, the authors characterise the role of the Salmonella effector SopB on the vimentin network and its contribution to infection.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

Several studies show that APOE-ε4 coding variants are associated with Alzheimer’s disease (AD) risk. Here, Zhou et al. perform fine-mapping of the APOE region and find AD risk haplotypes with non-coding variants in the PVRL2 and APOC1 regions that are associated with relevant endophenotypes.

The tau protein is theorized to spread transneuronally in Alzheimers disease, though this theory remains unproven in humans. Our simulations of epidemic-like protein spreading across human brain networks support this theory, and suggest the spreading dynamics are modified by β-amyloid

The BIN1 SNP rs744373 is associated with higher CSF tau and phosphorylated tau levels. Here the authors show, using PET imaging, that this SNP is associated with tau accumulation in the brain as well as impaired memory in older individuals without dementia.

How genetic variation contributes to brain morphology is still poorly understood. Here Chenet al. combine brain imaging with single-nucleotide polymorphism data to discover that a substantial degree of cortical variation is derived from underlying genetic differences.

Progressive diseases tend to be heterogeneous in their underlying aetiology mechanism, disease manifestation, and disease time course. Here, Young and colleagues devise a computational method to account for both phenotypic heterogeneity and temporal heterogeneity, and demonstrate it using two neurodegenerative disease cohorts.