Browse Articles

Identifying molecular signatures underpinning treatment responses to novel therapeutics influencing COVID-19 outcomes

Abstract COVID-19 continues to present ongoing global health challenges driven by diverse immune responses and heterogeneous clinical outcomes. The ACCORD trial evaluated 3 investigational treatments—bemcentinib, tozorakimab, and zilucoplan—in patients hospitalized with COVID-19, each of which has demonstrated clinical efficacy. To better understand their molecular mechanisms, we conducted a mechanistic follow-up study, integrating transcriptomic and clinical data from 65 patients and applying cellular deconvolution, differential expression, coexpression, and pathway enrichment analyses to uncover treatment-specific immune responses. Each therapy induced transcriptional shifts and modulated distinct immune pathways implicated in severe disease. Bemcentinib primarily modulated myeloid cell populations and inflammatory signalling; zilucoplan enhanced B-cell signalling and lymphocyte-associated pathways; and tozorakimab exerted broad immune and cellular responses across immune cell types. Co-expression analysis revealed gene networks associated with clinical improvement, each driven by distinct treatment-specific hub genes, indicating diverse regulatory mechanisms across treatments. Improved outcomes correlated with gene expression shifts in 4 key immunological pathways: B-cell signalling, antiviral defense, innate inflammation, and platelet/coagulation activity. In contrast, nonresponders had persistent dysregulation of 1 or more of these gene signatures. Our findings define molecular signatures of treatment response and failure in COVID-19, providing mechanistic insight into how distinct therapies modulate the immune system. These insights support the need for adaptive precision medicine approaches tailored to individual, evolving immune trajectories. Moreover, the immunological mechanisms targeted by these repurposed immunomodulatory therapies may inform treatment strategies across a broader spectrum of immune-mediated diseases beyond COVID-19.

Durable Seawater Electrolysis Enabled by Spherical Electrostatic Repulsion and Catalyst‐Support Interaction

ABSTRACT The electrolysis of seawater driven by renewable energy for hydrogen production represents a promising strategy toward net‐zero emissions. The high concentration of chloride ions (Cl − ) in seawater not only competes with the oxygen evolution reaction (OER) at the anode but also causes corrosion of the catalyst material. The construction of electrostatic shielding via anions on the catalyst surface can repel Cl − . However, studies on regulating anion distribution through designed geometries to maximize such repulsion remain limited. Herein, a sphere‐like catalyst, constructed with a heterojunction of carbonate‐intercalated nickel‐iron layered double hydroxides in situ grown on malachite microspheres (MM), exhibits enhanced catalytic durability and activity. The spherical electrostatic field induced by carbonate anions protects the catalyst, and the catalyst‐support interaction (CSI) tunes the electronic structure of active sites to boost OER. Finally, the assembled electrolyzer demonstrates outstanding durability over 1000 h and a voltage of 1.83 V at a current density of 1 A per cm 2 . This spherical geometrical design of electrostatic protection offers insights into catalyst optimization for seawater electrolysis.

Experimental and computational investigation of collagen modification in skin chromatic alterations

MiR-221-5p aggravates sepsis-induced myocardial injury by targeting neuropilin-1

Abstract Sepsis-induced cardiac dysfunction is a primary contributor to mortality, and microRNAs (miRNAs) are recognized as crucial mediators in sepsis pathogenesis. This study aims to identify the key regulatory miRNAs involved in cardiac dysfunction stemming from sepsis. We developed a rat model of sepsis using cecal ligation and puncture (CLP). Myocardial tissue from these rats underwent miRNA sequencing and transcriptome sequencing. Echocardiography was utilized to assess heart function, while cardiac damage was evaluated through HE staining, analysis of inflammatory factors, and detection of tissue injury biomarkers. To model inflammation-induced cardiomyocyte injury, rat cardiomyocyte H9C2 cells were treated with lipopolysaccharide (LPS). Cellular viability was determined using CCK8, and apoptosis was assessed via TUNEL staining and flow cytometry. Oxidative stress levels were analyzed by flow cytometry, and related marker levels were quantified by ELISA. Our results demonstrated that the CLP group displayed substantial cardiac dysfunction, myocardial injury, and elevated inflammatory factor levels. MiR-221-5p was found to be upregulated in both the in vivo and in vitro models. Overexpression of miR-221-5p reduced cardiomyocyte survival while increased apoptotic activity and oxidative stress in LPS-stimulated H9C2 cell. Mechanistically, Neuropilin-1 (NRP1) was identified as a target of miR-221-5p. The cardioprotective effect of miR-221-5p inhibition was reversed by NRP1 knockdown. Furthermore, in vivo administration of a miR-221-5p antagomir mitigated cardiac dysfunction and myocardial damage associated with septic conditions. In conclusion, our findings indicate that miR-221-5p exacerbates septic cardiomyopathy by negatively regulating NRP1, suggesting that the miR-221-5p/NRP1 pathway could represent a novel therapeutic strategy for sepsis-related heart complications.

A Self‐Strengthening Hydrogel Coating for Long‐Term Underwater Adhesion in Seawater Over 900 Days

ABSTRACT Reliable underwater adhesion is a prerequisite for the practical application of hydrogels as underwater coatings. Despite extensive efforts to enhance adhesion strength, strong initial adhesion does not ensure long‐term adhesion stability. Achieving durable underwater adhesion of hydrogels remains fundamentally challenging due to interfacial hydration and continuous water‐induced network degradation, particularly in complex aqueous environments such as seawater. To overcome these limitations, a hydrogel coating that achieves persistent underwater adhesion in natural seawater for over 900 days is developed. Strong initial adhesion is established across diverse substrates through synergistic interfacial interactions, while network integrity is maintained during prolonged immersion through multiple cooperative intermolecular interactions and continuous quinone‐mediated oxidative crosslinking. Consequently, the hydrogel exhibits persistently low water uptake (≈162 wt% after 900 days), suppresses swelling‐induced deterioration of interfacial adhesion, and maintains a shear adhesion strength of ≈110 kPa after 900 days of seawater immersion. The hydrogel coating also exhibits antibacterial and anti‐algal activity for marine antifouling, underwater superoleophobicity, and applicability as a gel electrolyte for flexible supercapacitors. This work establishes a design principle for achieving long‐term underwater functional hydrogels beyond previously reported time scales and provides a general strategy for developing continuously curing materials in underwater and marine environments.

Reversing vegetable biodiversity loss to diversify diets

Vegetables are a critical component of diets, with inadequate intake of this essential food group leading to poor dietary quality and malnutrition. Food system assessments identify insufficient production, comparatively high prices, and sociocultural barriers as key constraints to vegetable consumption. We argue that vegetable biodiversity, spanning vegetable species and their varieties, as well as their wild relative species, is a central yet underutilized lever for enhancing vegetable consumption. Vegetables span a wider phylogenetic range than any other plant-derived food group, offering options for different climatic, cultural, and market niches worldwide. However, vegetable biodiversity is declining due to market homogenization, land-use change, and other threats. Its current conservation is insufficient, restricting in turn access to this diversity for research, breeding, and innovation, and making it more difficult to bridge the gap between current and recommended vegetable intake. Reversing this trend globally requires aligning conservation with dietary goals through four complementary action areas: i) Securing vegetable biodiversity by collecting, regenerating, and conserving local crop varieties and wild relatives of key vegetable species in biodiversity hotspots; ii) Harnessing vegetable biodiversity to deliver new varieties through collaborative research, breeding, and variety testing; iii) Promoting vegetable biodiversity to diversify diets, particularly among children and other vulnerable groups, by including nutrient-dense, climate-resilient vegetables into home and school meals; and iv) Integrating vegetable biodiversity into policy frameworks for long-term impact. Implementing this integrated approach in hotspots where vegetable biodiversity and malnutrition overlap can transform an overlooked opportunity into a cornerstone strategy for healthier diets.

Hemispheric contributions to praxis: imitation of gestures and pantomime of tool use following left and right hemisphere damage

Correction to: p38 signaling enhances short-lived effector cell differentiation and weakens central memory CD8+ T-cell formation

Correction to “Elastomeric Micro‐Balloons for Remote Control of Cerebral Blood Flow and Real‐Time In vivo Imaging of Rodent Brain Response to Hypoperfusion”

Assessment of fire susceptibility in Wildland—Urban interfaces according to explainable artificial intelligence: a case study of Antalya province, Mediterranean region, Türkiye

Deficiency in circulating T cells in four core genotypes mice with <i>Sry</i> translocation

Abstract Sex differences exist in the immune responses to infections and in the prevalence and severity of autoimmune and allergic diseases. These sex differences may be caused by sex hormones and/or variable inactivation of X chromosome genes. The 4 core genotypes mice allow for distinction between the effects of sex hormones and chromosomes on physiology and disease pathology. In the FCG mouse model, the Sry gene is deleted from the Y chromosome and inserted into chromosome 3 as multiple copies of a transgene, allowing for phenotypic male and female mice with XX and XY chromosomes. We sought to investigate the role of sex hormones and chromosomes in respiratory syncytial virus infection and allergen-induced airway inflammation. However, in performing these studies, we found that the immune response in FCG males (XXM and XYM) was significantly blunted. XXF and XYF had 4-fold more CD3+CD4+ T cells and over 7-fold more CD3+CD8+ T cells compared to XXM and XYM in the lungs following stimulus. CD4+ and CD8+ T cells were also significantly decreased in XXM and XYM mice in the lungs, spleen, and peripheral blood at baseline with no effect on B cells, NK cells, or myeloid cells. Thymic T cell numbers were similar among groups, and bone marrow progenitors were unchanged between groups. Overall, the translocation of Sry to chromosome 3 resulted in dramatically decreased immune responses to RSV infection and allergen-challenge, indicating that FCG male mice do not mount appropriate immune responses to a respiratory virus infection.

Scalable Synthesis of 3D Hierarchical MoS ₂ as a Durable, High‐Charge‐Retention Friction Layer for the Facile Fabrication of High‐Power Triboelectric Nanogenerators

ABSTRACT Given the increasing demand for sustainable energy and self‐powered devices, energy‐harvesting technologies, such as triboelectric nanogenerators (TENGs), are drawing attention. To address the short charge retention in conventional polymer materials, 2D materials with high surface areas and intrinsic charge‐trapping capabilities, such as MoS 2 , are being utilized as friction layers in TENGs. However, their power generation is too low for practical applications owing to their atomically thin nature, limiting their use as fillers in polymer‐based systems. We report a 2D‐material‐based high‐power TENG using 3D hierarchical MoS 2 (3DH‐MoS 2 ) as a primary friction material. The 3DH‐MoS 2 is synthesized via low‐temperature metal–organic chemical vapor deposition, enabling the direct growth of a uniform, large‐area, 3D‐nanostructured friction layer on a polymer substrate without additional processes. This 3D nanostructure increases the amount of charge‐trapping sites and significantly enhances the durability of the device. The 4 × 4 cm 2 3DH‐MoS 2 ‐based TENG produces a maximum output voltage of 320.1 V and a power density of 0.841 mW cm −2 , proving it can effectively power light‐emitting diodes and a calculator, maintaining its performance over 10 000 cycles. In addition, the device can generate electricity from gas and water flow and human motion, highlighting the potential and versatility of 2D‐material‐based energy‐harvesting systems.

Geochemical assessment of metal and REE concentrations in a region with exploration of petroleum resources, Democratic Republic of the Congo

Identification of a regulatory allosteric site in Arid5a unveils a therapeutic axis for systemic inflammation

Abstract Adenine-thymine (AT)-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) that post-transcriptionally stabilizes mRNAs encoding proinflammatory mediators, including Interleukin-6 (IL-6), thereby amplifying inflammation. However, structural basis and regulatory mechanisms of Arid5a function remain poorly defined. In this study, we identified and characterized a conserved allosteric site within the ARID domain that regulates Arid5a-mediated mRNA stabilization. Using integrative in silico modeling and in vitro assays, 2 picolinamide-based inhibitors, NFP1 and NFP2, were designed to specifically engage the allosteric site constituent residues. Mutational and functional analyses revealed Tyr88 and Val91 as key regulatory elements within the allosteric site, essential for transmitting conformational regulation upon ligand engagement. Pharmacological inhibition of the allosteric site disrupted Arid5a interaction with target RNA stem-loop structure, reduced stability of Il6 mRNA, and attenuated inflammatory responses in Lipopolysaccharide (LPS)-stimulated macrophages. Furthermore, Arid5a inhibitors reduced the stability of other target mRNAs, including Signal transducer and activator of transcription 3 (Stat3) and OX40, in polarized T helper 17 (Th17) cells. In a murine model of LPS-induced septic shock, treatment with NFP1 or NFP2 significantly improved survival, reduced clinical severity, and mitigated tissue damage in vital organs. These findings identify a new mechanism regulating Arid5a activity and present Arid5a allosteric inhibition as a promising therapeutic strategy for managing systemic inflammation including sepsis.

Nanoscale Adhesive Architecture Coordinates With Matrix Stiffness to Regulate Stem Cell Aging via Focal Adhesion‐Mediated Chromatin Remodeling and FOXO1 Activation

ABSTRACT Stem cell aging critically limits the efficacy of regenerative biomaterials, yet how mechanical cues within the microenvironment modulate this process remains insufficiently understood. Here, we reveal that the nanoscale spacing of adhesive ligands imposes stiffness‐dependent effects on mesenchymal stem cell (MSC) senescence. Wider spacing (distance 150 nm) accelerates aging on stiff hydrogels (50 kPa) but mitigates it on soft hydrogels (5 kPa), relative to dense spacing (distance 30 nm). Using a molecular clutch‐based theoretical model, we demonstrate that ligand spacing and matrix stiffness cooperatively regulate cell behaviors through focal adhesion assembly. Enhanced focal adhesion formation amplifies stress fiber‐generated traction forces and nuclear envelope tension, leading to increased chromatin accessibility and transcriptional activation of FOXO1, a central regulator of cellular senescence. These mechanistic insights are further validated in vivo. Collectively, these findings delineate a mechanotransduction mechanism through which nanoscale adhesive architecture and matrix stiffness cooperatively govern stem cell aging.

Swappable and non-swappable homorepeats in orthologous proteins reflect distinct patterns of evolutionary flexibility

Abstract Proteins frequently contain runs of a single repeated amino acid, known as homorepeats or polyX regions. While their presence across orthologous proteins is an indicator of their functional importance, less is understood about whether different types of homorepeats can occupy the same position in related proteins: a concept we term “swappability”. Here we study homorepeat overlaps in orthologs from 695 species, tracking swappable and non-swappable cases to analyze their evolution and functional implications. We obtained 17,415,904 orthologous protein pairs from OrthoMCL, analyzed their homorepeats and aligned each orthologous pair to detect overlaps between these regions. Among more than 8.7 million orthologous pairs, we detected 99,386 non-swappable (same amino acid type) and 5,018 swappable (different amino acid type) overlapping homorepeats. Swappable cases tended to be longer and enriched in acidic residues, whereas non-swappable showed lineage-specific variation. Based on their prevalence in our data, we focused on D/E and A/S overlapping homorepeat pairs. PolyD and polyE were frequently found as swappable, maintaining their functional roles primarily linked to ribosomal biogenesis. PolyA and polyS, by contrast, show divergent enrichment patterns in their non-swappable forms, pointing to distinct functional specializations. This work illustrates the balance between positional conservation and sequence flexibility in homorepeat evolution.

The CXCL10/CXCR3 axis drives actin remodeling to recruit CD4+ T cells to gut epithelium during transmissible gastroenteritis virus infection

Abstract The immune system initially protects hosts against viral pathogens, with chemokines guiding immune cell movement. However, their expression patterns and immune cell recruitment mechanisms during transmissible gastroenteritis virus (TGEV) infection are still not fully understood. Here, we identified a distinct chemokine expression profile in intestinal epithelial cells following TGEV infection. Among these, CXCL10 selectively induced the chemotaxis of CD4+ CXCR3+ T cells, while only modestly recruiting CD8+ CXCR3+ (Tc1) T cells and showing minimal involvement in B cell recruitment, thereby shaping the intestinal immune microenvironment to promote TGEV infection. CXCL10 can also upregulate the expression of its receptor CXCR3, thereby further potentiating the migration of CD4+ T cells to the infected region. During this process, CXCL10 activated the CXCR3-Rho GTPase-cofilin signaling axis, driving actin cytoskeletal remodeling. Through this process, CD4+ T cells are channeled from the lamina propria to the infected intestinal lining, facilitating their functional responses. Collectively, these findings reveal a novel mechanism underlying Th1 cell trafficking during TGEV infection and suggest objectives for therapeutic vaccine creation and disease management.

Reducing Solvent Selectivity via Solid Additive‐Assisted Strategy Enables Organic Solar Cells With Approaching 21% Efficiency

ABSTRACT Currently, high‐performance organic solar cells (OSCs) are predominantly fabricated using chloroform (CF) to achieve an optimal active‐layer morphology. However, its rapid film formation results in a narrow processing window and severely limits industrial scalability. Therefore, reducing solvent selectivity during active‐layer processing is essential to facilitate scalable OSC manufacturing. Herein, this critical issue is finely addressed by a solid‐additive‐assisted strategy, in which 2,6‐dimethylnaphthalene (2,6‐DMN) is incorporated to modulate the film formation dynamic and molecular aggregation in different processing solvents. It is revealed that 2,6‐DMN enables stage‐specific control over the film formation process. Its mechanism involves suppressing acceptor aggregation during spin‐coating and then promoting ordered acceptor self‐assembly during annealing. This two‐stage modulation simplifies donor–acceptor interactions, mitigates excessive aggregation caused by slow solvent drying, and thereby prevents large‐scale phase separation. As a result, 2,6‐DMN induces a highly uniform and favorable active‐layer morphology across various processing solvents, thereby alleviating performance variations in devices caused by solvent effect. Consequently, the 2,6‐DMN‐based PM6:D18:L8‐BO‐X ternary device processed from o ‐xylene achieves a remarkable efficiency of 20.86%, setting a record for non‐halogenated solvent‐processed OSCs. This work provides a practical and efficient solid‐additive‐assisted strategy to mitigate the solvent selectivity in OSCs, demonstrating significant potential for achieving high‐performance OSCs with enhanced processing compatibility.

Genomic and structural analysis of dacB variants associated with cephalosporin resistance in Pseudomonas aeruginosa

Sorting nexin 5 deficiency impairs MHC class II antigen presentation and inflammatory responses during tuberculosis

Abstract Tuberculosis (TB) remains one of the leading causes of death from a single infectious agent worldwide, yet the host pathways that regulate antigen presentation and lung inflammation during Mycobacterium tuberculosis (Mtb) infection are incompletely defined. Sorting nexin 5 (SNX5) is a protein implicated in endosomal trafficking, antigen processing, and antiviral host defense, but its contribution to antibacterial immunity is unknown. Here, we show that SNX5-deficient mice exhibit increased mortality following low-dose aerosol Mtb infection despite unchanged pulmonary bacterial burden compared with wild-type mice. Snx5−/− mice developed exacerbated lung inflammation without major alterations in immune cell recruitment. In macrophages, Snx5 did not affect phagocytosis, vacuolar maturation, intracellular bacterial control, or global transcriptional responses to Mtb but was required for efficient major histocompatibility complex (MHC) class II antigen presentation. Snx5 deficiency was associated with reduced endolysosomal proteolysis and impaired MHC class II antigen presentation in vitro, resulting in reduced activation of antigen-specific CD4+ T cells without altering surface MHC class II abundance or costimulatory molecule expression. Together, these findings identify SNX5 as a regulator of MHC class II antigen presentation that influences inflammatory outcomes during pulmonary Mtb infection.