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Secretory proteins are an essential component of interorgan communication networks that regulate animal physiology. Current approaches for identifying secretory proteins from specific cell and tissue types are largely limited to in vitro or ex vivo models which often fail to recapitulate in vivo biology. As such, there is mounting interest in developing in vivo analytical tools that can provide accurate information on the origin, identity, and spatiotemporal dynamics of secretory proteins. Here, we describe i SLET (in situ Secretory protein Labeling via ER-anchored TurboID) which selectively labels proteins that transit through the classical secretory pathway via catalytic actions of Sec61b-TurboID, a proximity labeling enzyme anchored in the ER lumen. To validate i SLET in a whole-body system, we express i SLET in the mouse liver and demonstrate efficient labeling of liver secretory proteins which could be tracked and identified within circulating blood plasma. Furthermore, proteomic analysis of the labeled liver secretome enriched from liver i SLET mouse plasma is highly consistent with previous reports of liver secretory protein profiles. Taken together, i SLET is a versatile and powerful tool for studying spatiotemporal dynamics of secretory proteins, a valuable class of biomarkers and therapeutic targets. The in vivo identification of proteins secreted from a specific cell type or tissue remains challenging. Here, the authors develop a proximity labeling-based method to selectively label secreted proteins and combine it with proteomics to identify liver secretory proteins in mouse plasma.

Sex is a critical determinant of health and disease, yet it remains underrepresented in biomedical research. The identification of blood-based biomarkers facilitates early diagnosis and intervention for various diseases; however, sex-differential differences in the plasma proteome have not been sufficiently explored in mouse models. Understanding the molecular features associated with sex is essential for enhancing the translational potential of clinical research. We utilized Olink technology to analyze sex- and strain-differential plasma protein expression in two widely used mouse strains, C57BL/6 and BALB/c. A total of 36 mice (n = 9 per strain and sex) were analyzed using the ‘Olink Target 48 Mouse Cytokine’ and ‘Olink Target 96 Mouse Exploratory’ panels. Differences in normalized protein expression (NPX) were compared between groups, and proteins with a P-value < 0.05 were considered significantly different. Our analysis identified 55 strain-differential proteins and 33 sex-differential proteins among the 87 proteins analyzed in mouse plasma. Importantly, LPL (Lipoprotein lipase) and GHRL (Appetite-regulating hormone) were also more highly expressed in females in human datasets, suggesting a conserved sex-biased expression pattern across species. This study characterized sex- and strain-differential differences in the plasma proteomes of C57BL/6 and BALB/c mice. Among the identified proteins, LPL and GHRL were significantly elevated in females, consistent with human gene and plasma protein expression trends. These findings highlight the presence of sex-based molecular differences in energy and lipid metabolism and provide a valuable foundation for future mechanistic studies.

Sex is a critical biological variable that influences disease incidence, progression, and therapeutic responses; therefore, it must be incorporated into biomedical research. Despite this, most mouse studies historically have not compared animals by sex. Recently, growing evidence has indicated that sex-specific analyses are important in obesity and metabolic disorders. The ob/ob mouse is a widely used model for metabolic disease research; however, sex differences in plasma biomarkers have not been fully characterized in this model. In this study, male and female ob/ob mice at 8 weeks of age exhibited comparable body weight, blood glucose levels, and adipose tissue mass. Plasma proteomics analysis using the Olink platform revealed that 27% (23/84) of quantified proteins exhibited sex differences, with 91% (21/23) of these proteins elevated in females. Notably, Enolase 2 (ENO2), also known as neuron-specific enolase (NSE), was consistently elevated in female ob/ob mice and showed a similar sex-associated pattern in female patients with non-alcoholic steatohepatitis (NASH). While the human NASH data provide correlative support rather than direct clinical validation, these observations underscore the importance of considering sex as a biological variable in metabolic disease research. Incorporating sex-specific biomarker profiles may help refine mechanistic interpretation and inform future studies toward personalized therapeutic approaches.

Topological defects in matter behave collectively to form highly non-trivial structures called topological textures that are characterised by conserved quantities such as the winding number. Here we show that an epitaxial ferroelectric square nanoplate of bismuth ferrite subjected to a large strain gradient (as much as 10 5  m −1 ) associated with misfit strain relaxation enables five discrete levels for the ferroelectric topological invariant of the entire system because of its peculiar radial quadrant domain texture and its inherent domain wall chirality. The total winding number of the topological texture can be configured from − 1 to 3 by selective non-local electric switching of the quadrant domains. By using angle-resolved piezoresponse force microscopy in conjunction with local winding number analysis, we directly identify the existence of vortices and anti-vortices, observe pair creation and annihilation and manipulate the net number of vortices. Our findings offer a useful concept for multi-level topological defect memory. Exploring topological textures in ferroelectrics facilitates the understanding and application of topological features in matter. Here the authors demonstrate the strain field induced evolution of topological vortices in nanoplatelets of rhombohedral phase BiFeO3 using the angle-resolved piezoresponse force microscopy.

Sex is a key piece of patient information but is often not actively considered in drug use. This is partly due to the lack of molecular evidence at the gene expression level beyond sex chromosomes and sex hormones. We aim to investigate how sex differences in tissue-specific gene expression relate to FDA - approved drugs using the latest database of The Genotype-Tissue Expression (GTEx) V10. Our analysis reveals that 91.4% of FDA-approved drug target genes exhibit sex-differential expression in at least one tissue. The tissues with the most pronounced sex differences include subcutaneous adipose tissue, skeletal muscle, and the pituitary gland, while sex differences are less pronounced in the liver, other brain regions, and the spleen. Sex-differential disease-related genes include those associated with obesity (PPARG, INSR), cancer (FGFR1, CD22), and immunity (IL6R, IL3RA). Based on our findings, we advocate for a policy shift that integrates sex-based molecular data into preclinical studies, drug development, and clinical practices. This paradigm aligns biomedical research with precision medicine, mitigates drug-related risks, and promotes equitable healthcare outcomes.

Proximity labeling (PL) techniques have advanced neuroscience by revealing the molecular interactions that govern neural circuits. From foundational tools such as BioID and APEX to recent innovations such as TurboID and light-activated systems, PL enables precise mapping of protein–protein interactions within living cells. Recent applications have identified dynamic protein networks in synaptic remodeling, calcium-dependent signaling and disease states, such as neurodegenerative and psychiatric disorders. These studies not only deepen our comprehension of the molecular architecture of the brain but also uncover novel therapeutic targets. By integrating PL with cutting-edge multi-omics strategies and advanced imaging technologies, researchers can decode the intricate interplay between structural and functional neural networks. As PL technologies continue to evolve, they bridge molecular and cellular neuroscience, offering a useful framework for unraveling the complexity of brain networks. Here, in this Review, we underscore the potential of PL in neuroscience, furthering our understanding of the molecular basis of neural connectivity in both health and disease. Proximity labeling reveals neural circuit interactions Understanding how the brain works is a big challenge in neuroscience. This article discusses how researchers are using new methods to better understand these connections and brain functions. The study focuses on a technique called proximity labeling (PL), which helps to identify proteins that interact closely within cells. PL uses special enzymes to tag nearby proteins, making it easier to study their interactions. This method is important because it can capture interactions that other techniques might miss, especially in complex areas like the brain. Researchers have used PL to study different parts of the brain and how they work together. For example, they have identified proteins involved in synapse formation and proteins altered in neurological disorders such as autism. The findings show that PL is a powerful tool for studying the brain’s molecular landscape. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

On 15 November 2017, liquefaction phenomena were observed around the epicenter after a 5.4 magnitude earthquake occurred in Pohang in southeast Korea. In this study, we attempted to detect areas of sudden water content increase by using SAR (synthetic aperture radar) and optical satellite images. We analyzed coherence changes using Sentinel-1 SAR coseismic image pairs and analyzed NDWI (normalized difference water index) changes using Landsat 8 and Sentinel-2 optical satellite images from before and after the earthquake. Coherence analysis showed no liquefaction-induced surface changes. The NDWI time series analysis models using Landsat 8 and Sentinel-2 optical images confirmed liquefaction phenomena close to the epicenter but could not detect liquefaction phenomena far from the epicenter. We proposed and evaluated the TDLI (temporal difference liquefaction index), which uses only one SWIR (short-wave infrared) band at 2200 nm, which is sensitive to soil moisture content. The Sentinel-2 TDLI was most consistent with field observations where sand blow from liquefaction was confirmed. We found that Sentinel-2, with its relatively shorter revisit period compared to that of Landsat 8 (5 days vs. 16 days), was more effective for detecting traces of short-lived liquefaction phenomena on the surface. The Sentinel-2 TDLI could help facilitate rapid investigations and responses to liquefaction damage.

A hyperspectral scanning system was developed for three-dimensional (3D) surface mapping in underground spaces, such as mine shafts and tunnels. A hyperspectral line-scanning camera was mounted on the rotating driver unit coaxial with the tunnel to image both the mine wall and the ceiling. Uniform light was illuminated on the target surface to be imaged using a halogen lamp rotating together with the hyperspectral imaging sensor. Inertial Measuring Unit (IMU) was also attached to the sensor unit together with the hyperspectral camera so that sensor’s geometric information could be acquired simultaneously during imaging. All sensor and controller units were mounted on a cart-type platform for easy movement in the tunnel, and a battery mounted on the platform supplied power for system operation and the halogen light source. The developed scanning system was tested in an actual mine, and 3D hyperspectral images of the internal surface of the mine shaft were successfully obtained.

The emergence of a triple phase point in a two-dimensional parameter space (such as pressure and temperature) can offer unforeseen opportunities for the coupling of two seemingly independent order parameters. On the basis of this, we demonstrate the electric control of magnetic order by manipulating chemical pressure: lanthanum substitution in the antiferromagnetic ferroelectric BiFeO 3 . Our demonstration relies on the finding that a multiferroic triple phase point of a single spin-disordered phase and two spin-ordered phases emerges near room temperature in Bi 0.9 La 0.1 FeO 3 ferroelectric thin films. By using spatially resolved X-ray absorption spectroscopy, we provide direct evidence that the electric poling of a particular region of the compound near the triple phase point results in an antiferromagnetic phase while adjacent unpoled regions remain magnetically disordered, opening a promising avenue for magnetoelectric applications at room temperature. The triple point is a well-known feature on pressure–temperature phase diagrams. A multiferroic triple point is now reported for La-doped BiFeO 3 ; La concentration and temperature are the phase variables and the phases display different spin (dis)order.

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis. Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial role for it in maintaining brown adipocyte mitochondrial OXPHOS and thermogenesis upon cold stimulus.