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Retraction Note: Enhanced human activity recognition in medical emergencies using a hybrid deep CNN and bi-directional LSTM model with wearable sensors

Oyster farming acts as a marine carbon dioxide removal (mCDR) hotspot for climate change mitigation

Bivalve farming, a vital component of global aquaculture, has been proposed as a potential marine carbon dioxide removal (mCDR) strategy, yet its role remains contentious. Using field mesocosms, we demonstrate that oyster filter-feeding enhances mCDR by accelerating the formation of particulate and dissolved organic carbon in the water column and promoting organic carbon deposition in sediments. This process shifts the water column toward a more autotrophic and alkaline state, effectively sequestering CO 2 from the atmosphere. Over the full culture period, the net carbon sequestered by oyster-driven organic carbon production is 2.39 times greater than the CO 2 sequestered in oyster shells. These findings position oyster farming as a scalable, nature-based solution for climate change mitigation, offering dual benefits of carbon sequestration and enhanced food security. Our results underscore the potential of oyster farming to address global challenges such as rising food demand and ocean acidification, making it a critical component of sustainable marine resource management.

Subaerial oxidative uranium mobilization at the culmination of the Great Oxidation Event

Redox-sensitive elements figure prominently in studies of the evolution of Earth’s surface redox state, including the first major rise in atmospheric O 2 , the Paleoproterozoic Great Oxidation Event. Most Precambrian rocks endured multistage tectonothermal histories, however, adding ambiguity to interpretation of their chemistry. Here, we apply U-Th-Pb isotope geochronology to the highly oxidized ~2.06 Ga Kuetsjärvi Volcanic Formation, Pechenga Greenstone Belt, Russia, to constrain the age and extent of U oxidation. By contrasting the relative mobility of U and Th using Pb isotopes, we find that complete to near-complete oxidation and removal of U occurred shortly after eruption. We argue that this likely indicates relatively high atmospheric O 2 , where oxidative weathering and alteration produced a global pulse of U to the oceans. Such a pulse could explain widespread shifts in the U-Th-Pb isotope character of mantle reservoirs at ~2 Ga, including a decrease in the 232 Th/ 238 U ratio of the mid-ocean ridge basalt source and inception of the high- 238 U/ 204 Pb (HIMU) source to ocean island basalts, underscoring the connections between the redox character of the Paleoproterozoic surface and deep Earth. Using 207 Pb- 206 Pb, 238 U- 206 Pb, 235 U- 207 Pb, and 232 Th- 208 Pb geochronology, ~2.06 Ga oxidative loss of U may be distinguished from reintroduction of U at ~1.8 Ga during regional metamorphism, as well as Pb loss during a Phanerozoic tectonothermal event. Our results therefore establish the complex history of redox-sensitive element behavior in the rocks, highlighting the fact that elemental abundances, by themselves, are unlikely to capture straightforward proxy information in rocks that have seen multistage geologic histories.

Pulsed biogenic methane emissions coupled with episodic warming during the Toarcian Oceanic Anoxic Event

Reconstructing carbon release fluxes during ancient climatic warming events is important for improving predictions of carbon cycle and climate dynamics under future anthropogenic warming scenarios. We investigate the extent of biogenic methane release and its contribution to climate variability across the Toarcian Oceanic Anoxic Event (T-OAE) approximately 183 million years ago. To do this, we developed a global biogeochemical model and applied a Bayesian inversion using Markov Chain Monte Carlo (MCMC) simulations. Based on a high-resolution record of carbon isotope excursions from the Yorkshire section, our results indicate that a release of at least 4,700 Gt carbon from biogenic CH 4 (with a carbon isotopic composition, δ 13 C of −50 to −70‰) is necessary to accurately reproduce the pronounced pulsed shift in the δ 13 C, as well as the inferred changes in atmospheric p CO 2 and global temperature. This massive methane release may have led to a substantial increase in atmospheric p CH 4 and contributed to additional global surface warming, perhaps by more than 2 °C. We further elucidate that the liberation of methane may have been facilitated by an upsurge in methanogenesis alongside a concomitant decline in methane oxidation within organic-rich, sulfate-depleted marine environments. An active CH 4 cycle represents a positive feedback mechanism that exacerbates environmental deterioration during climatic warming events, ultimately contributing to mass extinction of marine life.

Therapeutic restoration of mitochondria–endoplasmic reticulum cross talk for osteoarthritis

Osteoarthritis is a prevalent joint disease in the aging population. The hallmark of osteoarthritis is the degeneration of the joint cartilage, characterized by changes in chondrocytes including mitochondrial dysfunction. However, the precise mechanisms of how this affects chondrocyte homeostasis and whether such processes can be explored as therapeutic targets for osteoarthritis remain unclear. Here, we show that impaired mitochondrial function and disrupted cartilage matrix metabolism due to loss of mitofusin-2 (MFN2) expression in chondrocytes leads to the development of osteoarthritis. Sirtuin-3 (SIRT3), a key regulator of mitochondrial function, plays a critical role in modulating MFN2 to restore mitochondrial dynamics, reduce fragmentation, and preserve mitochondrial function in chondrocytes. Specifically, SIRT3 directly deacetylates and indirectly deubiquitinates MFN2, preventing its degradation. MFN2-mediated mitochondrial–endoplasmic reticulum (ER) junctions support cellular homeostasis, alleviate ER stress, and maintain mitochondrial calcium ion balance, which collectively mitigate chondrocyte senescence. Extracellular vesicles engineered with MFN2 mRNA effectively prevented cartilage degeneration and restored mobility in osteoarthritic mice. These findings suggest that targeting MFN2 is a promising strategy to prevent cartilage degeneration and alleviate progression of osteoarthritis.

<i>Pdgf</i> mediates a transient regeneration-activated cell state in planarian tissue regeneration

The role of induced gene expression is crucial for tissue regeneration. The transient regenerative cellular state that discriminates between missing-tissue and non-missing-tissue injuries remains to be fully elucidated. In this study, we identified a homolog of Platelet-Derived Growth Factor (PDGF), named pdgf-like ( pdgfl ), in the planarian Schmidtea mediterranea . This gene exhibits inducible expression following missing-tissue injury in a back-and-forth manner between myosin + muscular cells and piwi-1 + stem cells. The dynamic expression of pdgfl is induced through the elevation of reactive oxygen species (ROS) levels and phosphorylated extracellular signal-regulated kinase (pERK) signaling over short distances. Suppression of pdgfl expression impairs the regrowth of essential structures, including the intestine and central nervous system. Evidence on the decrease of notum and sfrp-1 at the anterior pole, together with the accumulation of myoD + PIWI-1 + progenitors, suggests a role of pdgfl in pole muscular cell differentiation. These findings highlight the significant impact of pdgfl in orchestrating the behavior of specific cell types by the regional specificity of this gene expression.

Using bioinformatics for identifying and plugging metabolic pathway holes

Mechanisms underlying allosteric modulation of antiseizure medication binding to synaptic vesicle protein 2A (SV2A)

Brivaracetam (BRV) and levetiracetam (LEV) are antiseizure medications (ASMs); UCB-J is a PET tracer targeting synaptic vesicle protein 2A (SV2A); UCB7361 is closely related to padsevonil, an experimental anticonvulsant; while UCB1244283 acts as an allosteric modulator for BRV and LEV binding but not for these other ligands. The SV2A-BRV-UCB1244283 structure reveals how UCB1244283 allosterically enhances BRV binding by occupying an allosteric site near the primary binding site, preventing BRV dissociation. This allosteric site, formed by hydrophobic and uncharged residues, is an uncharacterized small-molecule binding site in SV2A. Structural analysis and mutagenesis demonstrate that an allosteric network between the primary and allosteric sites governs high-affinity ASM binding. Our studies suggest that UCB1244283 selectively binds SV2A over SV2B and SV2C, with specific mutations disrupting binding. Structures of SV2A-UCB-J and SV2A-UCB7361 show that UCB1244283 binding is only possible when the primary site ligand does not overlap with the allosteric site, and that repositioning of Ser601, Thr605, and Leu655 is critical for allosteric ligand binding. Structural comparison of multiple SV2A complexes reveals that primary site occupancy shapes the conformation of the lumenal half of the transmembrane domain, influencing how UCB1244283 binds via a connected network that differentially stabilizes TM1 in either an open or closed conformation and repositions key allosteric and primary site residues. These insights provide a foundation for developing therapeutics targeting the allosteric site and modulating SV2A function.

Rethinking early-life pathogen exposure: Lessons from a natural experiment controlling hookworms

Tumor-expressed GPNMB orchestrates Siglec-9 ⁺ TAM polarization and EMT to promote metastasis in triple-negative breast cancer

Metastasis remains the leading cause of cancer-related mortality, driven by complex interactions within the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) play a pivotal role in metastatic progression, yet their molecular diversity and upstream regulators remain poorly defined. Glycoprotein nonmetastatic melanoma protein B (GPNMB), overexpressed in subsets of tumors including triple-negative breast cancer (TNBC), is implicated in epithelial–mesenchymal transition (EMT) and cancer stemness. Recent single-cell RNA sequencing (scRNA-seq) identified GPNMB as a marker of immunosuppressive TAMs associated with poor prognosis, but its mechanistic role in TNBC has remained unclear. Coculturing monocytic cells with three-dimensional TNBC spheres induced GPNMB + TAMs expressing sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9). Tumor-expressed GPNMB promotes monocyte-to-TAM polarization by inducing secondary GPNMB expression in monocytes, establishing a feed-forward amplification loop. GPNMB knockdown in TNBC cells inhibited immunosuppressive TAM subsets, including Siglec-9 + and EMT-associated populations, as determined by deconvolution of bulk RNA-seq data using a custom TAM signature matrix derived from publicly available TNBC scRNA-seq datasets. TNBC-derived GPNMB carried α2,3-sialylation, whereas macrophage-derived GPNMB carried α2,6-sialylation, enabling differential Siglec-9 recognition. Elevated GPNMB and Siglec-9 correlated with poor prognosis in TNBCcohorts. Importantly, dual inhibition of Siglec-E (murine Siglec-9 ortholog) and PD-1 reduced tumor stemness, suppressed IL-6-dependent EMT, and limited lung metastasis in vivo. The GPNMB–Siglec-9 axis thus represents a critical glyco-immunological checkpoint driving TAM-mediated metastasis, providing a promising therapeutic target in TNBC.

Lysosomal reduced thiols are essential for mouse embryonic development

While it has been appreciated for decades that lysosomes can import cysteine, its significance for whole-organism physiology has remained uncertain. Recent work identified MFSD12 as a transmembrane protein required for cysteine import into lysosomes (and melanosomes), enabling genetic interrogation of this pathway. Here, we show that Mfsd12 knockout mice die between embryonic days 10.5 and 12.5, indicating that MFSD12 is essential for organogenesis. Mfsd12 loss results in the expression of genes involved in cellular stress and thiol metabolism and likely disproportionately affects the erythroid, myeloid, and neuronal lineages. Within lysosomes, imported cysteine is largely oxidized to cystine, which is exported to the cytosol by the cystinosin (CTNS) transporter. However, unlike Mfsd12 , loss of Ctns is compatible with viability, suggesting that the essential role of MFSD12 lies not in supplying cystine to the cytosol, but in providing reduced cysteine within the lysosomal lumen. Supporting this model, maternal treatment with cysteamine—a lysosome-penetrant thiol—rescued the development of Mfsd12 knockout embryos, yielding viable adult offspring. These findings establish lysosomal thiol import as a critical metabolic pathway and provide genetic tools to further clarify its physiological and biochemical roles.

Direct measurement of plume velocity to characterize point source emissions

An explosion of recent research uses remote imaging spectroscopy from aircraft and spacecraft to detect and quantify methane point source emissions. These instruments first map the methane enhancement field and then combine this information with the effective wind speed to estimate the source emission rate. This wind speed is typically the largest uncertainty in derived emission rates. It is often, by necessity, inferred from coarse-resolution meteorological reanalysis products which do not match the spatial or temporal extent of wind experienced by the gas plume. Here, we circumvent this problem by simultaneously measuring plume velocity using the same spectrometer that maps the methane plume. Our approach acquires multiple consecutive views of the same point source, with visual tracking of the plume’s features to estimate its ground velocity. This resolves the representational mismatch between reanalysis and effective wind speeds. It provides data with exact spatiotemporal coincidence to the plume being measured. The approach facilitates dramatic improvement in the precision of remote methane point source quantification.

Digital SERS bioanalysis of single-enzyme biomarkers

Digital bioanalysis enables highly sensitive detection of biomolecules at the single-molecule level, making it a widely used technique in biomedical research. However, conventional approaches typically rely on fluorescence detection of single-enzyme reactions, which limits molecular selectivity and the ability to analyze multiple targets simultaneously. To address these limitations, we developed a digital bioanalysis platform based on surface-enhanced Raman scattering spectroscopy and microchamber arrays decorated with silver nanoparticles. This platform achieves a million-fold amplification of Raman signals from products generated by single-enzyme reactions, enabling precise digital counting of enzyme biomarkers with high molecular selectivity and multiplexing capability. We applied this platform to detect and distinguish two closely related enzyme biomarkers, acetylcholinesterase (AChE) and butyrylcholinesterase. By leveraging the sharp and distinct Raman spectral signatures of the reaction products, the platform achieved multiplexed biomarker quantification with femtomolar-level sensitivity. As a proof-of-concept, the platform successfully quantified AChE in human cerebrospinal fluid within 8.5 min, highlighting its potential utility in clinical diagnostics, particularly for differentiating types of dementia based on subtle differences in enzyme levels. Hence, this study presents a valuable alternative to fluorescence-based digital bioanalysis by offering enhanced molecular selectivity and multiplexing capability. Its application extends the scope of digital bioanalysis and broadens its capacity to quantify multiple biomarkers in complex biological samples with high precision and efficiency.

AhR signaling in skin-resident CD207 ⁺ cells is involved in UV-B-induced amelioration of neuroinflammation

Environmental stimuli, including the exposure to ultraviolet (UV)-B light, are known to play a role in the modulation of immune-mediated mechanisms in multiple sclerosis (MS). In experimental autoimmune encephalomyelitis (EAE), we have shown that UV-B irradiation ameliorates disease outcome by regulatory T cells (Treg) expansion. Moreover, the UV-B-mediated induction of Treg numbers was also observed in MS. The aryl hydrocarbon receptor (AhR) can be activated by environmental factors including UV-B-induced photoproducts of tryptophan. Thus, we investigated the role of AhR during the transmission of UV-B irradiation. Therefore, wild-type (WT) and AhR-deficient mice (AhR –/– ) were irradiated with UV-B light and immunized with myelin oligodendrocyte glycoprotein (MOG)-peptide. In WT mice it was shown that UV-B irradiation reduces EAE symptoms by Treg expansion. This effect was abrogated in animals with AhR deficiency. To better understand the underlying mechanisms of AhR regulation, we used mice with a deletion of AhR specifically in different subsets of antigen-presenting cells (APC) that have been shown to mediate the expansion of Treg. Interestingly, we could show that the AhR activation in murine cutaneous APC was sufficient to switch APC from a stimulatory into a regulatory phenotype, and moreover, responsible for APC cell maturation and migration into regional lymph nodes. Thus, our data indicate that AhR activation in APC might be required for UV-B-mediated immunosuppression during MOG-induced EAE. Hence, activation of AHR in tissue-resident APC, potentially by low-dose UV-B irradiation, might be beneficial as an adjuvant treatment in inflammatory or degenerative diseases of the central nervous system.

Surrogate optimization of variational quantum circuits

Variational quantum eigensolvers are touted as a near-term algorithm capable of impacting many applications. However, the potential has not yet been realized, with few claims of quantum advantage and high resource estimates, especially due to the need for optimization in the presence of noise. Finding algorithms and methods to improve convergence is important to accelerate the capabilities of near-term hardware for variational quantum eigensolver or more broad applications of hybrid methods in which optimization is required. To this goal, we look to use modern approaches developed in circuit simulations and stochastic classical optimization, which can be combined to form a surrogate optimization approach to quantum circuits. Using an approximate (classical central processing unit/graphical processing unit) state vector simulator as a surrogate model, we efficiently calculate an approximate Hessian, which is passed as input for a quantum processing unit or exact circuit simulator. This method will lend itself well to parallelization across quantum processing units. We demonstrate the capabilities of such an approach with and without sampling noise and a proof-of-principle demonstration on a quantum processing unit utilizing 40 qubits.

The molecular structure of the master growth regulator in plants emerges into the spotlight

Evolving choice hysteresis in reinforcement learning: Comparing the adaptive value of positivity bias and gradual perseveration

The tendency to repeat past choices more often than expected from the history of outcomes has been repeatedly empirically observed in reinforcement learning experiments. It can be explained by at least two computational processes: asymmetric update and (gradual) choice perseveration. A recent meta-analysis showed that both mechanisms are detectable in human reinforcement learning. However, while their descriptive value seems to be well established, they have not been compared regarding their possible adaptive value. In this study, we address this gap by simulating reinforcement learning agents in a variety of environments with a variant of an evolutionary algorithm. Our results show that positivity bias (in the form of asymmetric update) is evolutionary stable in many situations, while the emergence of gradual perseveration is less systematic and robust. Overall, our results illustrate that biases can be adaptive and selected by evolution, in an environment-specific manner.

Daily liver rhythms: Coupling morphological and molecular oscillations

In mammals, a hierarchically organized circadian timing system orchestrates daily rhythms of nearly all physiology. A master pacemaker in the brain’s suprachiasmatic nucleus (SCN) synchronizes subsidiary clocks in most peripheral organs. By driving anabolic and catabolic cycles of proteins, lipids, and carbohydrates and by detoxifying endo- and xenobiotic components, the liver plays an important role in adapting the metabolic needs to rest-activity rhythms. In keeping with these functions, the liver expresses many clock-controlled genes that are required for these processes. Remarkably, however, this organ also fluctuates in size and morphological parameters. In mice, the mass of the liver increases and decreases by 30 to 40% during the 24-h day. The oscillation in liver mass is accompanied by daily rhythms of similar amplitudes in hepatocyte cell size and global RNA and protein accumulation. The number of ribosomes, which parallels the ups and downs of liver size, appears to be the rate-limiting factor in driving the diurnal rhythms of overall protein synthesis. Obviously, the rapid increase in hepatocyte size within the liver engenders mechanical stress, which must be dealt with by increasing the physical robustness of cells. Indeed, the actin cytoskeleton of hepatocytes undergoes dramatic polymerization cycles. Thus, massive intracellular and subcortical F-actin bundles are assembled during the night, at which the liver reaches its maximal size. In turn, the oscillation in actin polymerization elicits rhythms in myocardin-related transcription factors-serum response factor signaling, which participate in the circadian transcription of the core clock gene Per2 and thereby contribute to the synchronization of hepatocyte clocks.

STmiR: A Novel XGBoost-based framework for spatially resolved miRNA activity prediction in cancer transcriptomics

MicroRNAs (miRNAs) are critical regulators of gene expression in cancer biology, yet their spatial dynamics within tumor microenvironments (TMEs) remain underexplored due to technical limitations in current spatial transcriptomics (ST) technologies. To address this gap, we present STmiR, a novel XGBoost-based framework for spatially resolved miRNA activity prediction. STmiR integrates bulk RNA-seq data (TCGA and CCLE) with spatial transcriptomics profiles to model nonlinear miRNA-mRNA interactions, achieving high predictive accuracy (Spearman’s ρ &gt; 0.8) across four major cancer types (breast, lung, ovarian, prostate), with performance further confirmed through direct comparison with experimentally measured miRNA expression in an independent spatial transcriptomics dataset. Applied to 10X Visium ST datasets from nine cancers, STmiR identifies six pan-cancer conserved miRNAs (e.g., hsa-miR-21, hsa-let-7a) consistently ranked in the top 40 across malignancies, and uncovers cell-type-specific regulatory networks in fibroblasts, B cells, and malignant cells. A breast cancer case study demonstrates STmiR’s utility in uncovering biologically relevant miRNA-target relationships and their association with key cancer pathways. By enabling spatial mapping of miRNA activity, STmiR provides a transformative tool to dissect miRNA-mediated regulatory mechanisms in cancer progression and TME remodeling, with implications for biomarker discovery and precision oncology.

Protocol for a core outcome set for pharmacological treatments in hospitalised patients with acute viral respiratory infections (COSAVRI)

Background Acute viral respiratory infections (AVRIs) rank among the most common causes of hospitalisation worldwide, imposing significant healthcare burdens and driving the development of pharmacological treatments. However, inconsistent outcome reporting across clinical trials limits evidence synthesis and its translation into clinical practice. A core outcome set (COS) for pharmacological treatments in hospitalised adults with AVRIs is essential to standardise trial outcomes and improve research comparability. Objective To develop an internationally agreed COS for pharmacological treatments in hospitalised adults ≥18 years with acute viral respiratory infections (COSAVRI) through stakeholder agreement. Methods This protocol follows a four-stage development process in accordance with Core Outcome Set Handbook guidelines. Stage 1 comprises a rapid scoping review of randomised controlled trials (2015–2025) to systematically catalogue patient-relevant outcomes reported in pharmacological AVRI treatment studies. Semi-automated screening and data extraction will employ machine learning and large language models, with human verification. Stage 2 involves an online Real-Time Delphi survey with international stakeholders, including healthcare professionals, researchers, patients/caregivers, and policymakers, to prioritise identified outcomes using a 9-point scale. Stage 3 consists of structured online consensus meetings utilising anonymous electronic voting to finalise the COS. Stage 4 focuses on dissemination and implementation through academic publications, conferences, and stakeholder engagement. Expected outcomes COSAVRI will provide a standardised minimum set of outcomes for measuring and reporting in future pharmacological trials involving hospitalised adults with AVRIs. This initiative will enhance evidence synthesis, reduce research waste, support regulatory decision-making, and improve pandemic preparedness by facilitating the rapid deployment of harmonised outcomes in trial protocols.