Search Medical Journals & Research Articles

TVB C++: A Fast and Flexible Back‐End for The Virtual Brain

TVB C++ is a streamlined and fast C++ Back‐End for The Virtual Brain (TVB), designed to make it as flexible as TVB, and FAST. Another pillar is to be fully compatible with TVB so easy bindings can be created from Python. Users can easily configure TVB C++ to execute the same code but with enhanced performance and parallelism. Abstract This study introduces TVB C++, a streamlined and fast C++ Back‐End for The Virtual Brain (TVB), a renowned platform and a benchmark tool for full‐brain simulation. TVB C++ is engineered with speed as a primary focus while retaining the flexibility and ease of use characteristic of the original TVB platform. Positioned as a complementary tool, TVB serves as a prototyping platform, whereas TVB C++ becomes indispensable when performance is paramount, particularly for large‐scale simulations and leveraging advanced computation facilities like supercomputers. Developed as a TVB‐compatible Back‐End, TVB C++ seamlessly integrates with the original TVB implementation, facilitating effortless usage. Users can easily configure TVB C++ to execute the same code as in TVB but with enhanced performance and parallelism capabilities. As a consequence, TVB C++ will enable the widespread use of individualized models that will open the possibility of designed tailored solutions at the individual patient level. TVB C++ is a streamlined and fast C++ Back-End for The Virtual Brain (TVB), designed to make it as flexible as TVB, and FAST. Another pillar is to be fully compatible with TVB so easy bindings can be created from Python. Users can easily configure TVB C++ to execute the same code but with enhanced performance and parallelism. Abstract This study introduces TVB C++, a streamlined and fast C++ Back-End for The Virtual Brain (TVB), a renowned platform and a benchmark tool for full-brain simulation. TVB C++ is engineered with speed as a primary focus while retaining the flexibility and ease of use characteristic of the original TVB platform. Positioned as a complementary tool, TVB serves as a prototyping platform, whereas TVB C++ becomes indispensable when performance is paramount, particularly for large-scale simulations and leveraging advanced computation facilities like supercomputers. Developed as a TVB-compatible Back-End, TVB C++ seamlessly integrates with the original TVB implementation, facilitating effortless usage. Users can easily configure TVB C++ to execute the same code as in TVB but with enhanced performance and parallelism capabilities. As a consequence, TVB C++ will enable the widespread use of individualized models that will open the possibility of designed tailored solutions at the individual patient level. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Leveraging 3D Molecular Spatial Visual Information and Multi‐Perspective Representations for Drug Discovery

A deep learning framework called MolVisGNN is proposed to fuse 3D molecular visual information of drugs with multi‐source features, which proves the importance of 3D molecular visual information of drugs and the advancedness of this model in the field of drug discovery, and provides a reference for how to more comprehensively express small molecule drugs in deep learning in the future. Abstract Drug discovery remains a costly and time‐intensive process, where accurate identification of drug associations is critical for therapeutic development. Existing computational approaches predominantly rely on sequence‐derived or 2D molecular representations, often overlooking the intrinsic 3D complexity of small molecules. Here, a deep learning framework is presented that directly learns from 3D molecular spatial visual information, capturing geometric, topological, and stereochemical features from spatial renderings. By integrating this spatial information with traditional molecular descriptors, unified multi‐perspective representations are constructed that better reflect molecular structure and function. Across benchmark tasks involving drug–microRNA, drug–drug, and drug–protein interaction prediction, this model consistently outperforms conventional fingerprint‐based baselines. Interpretability analyses show that the model attends to biologically relevant substructures, highlighting the value of 3D molecular spatial visual information in molecular recognition. These findings demonstrate the potential of spatially informed learning to enhance predictive performance and provide mechanistic insights in computational drug discovery. A deep learning framework called MolVisGNN is proposed to fuse 3D molecular visual information of drugs with multi-source features, which proves the importance of 3D molecular visual information of drugs and the advancedness of this model in the field of drug discovery, and provides a reference for how to more comprehensively express small molecule drugs in deep learning in the future. Abstract Drug discovery remains a costly and time-intensive process, where accurate identification of drug associations is critical for therapeutic development. Existing computational approaches predominantly rely on sequence-derived or 2D molecular representations, often overlooking the intrinsic 3D complexity of small molecules. Here, a deep learning framework is presented that directly learns from 3D molecular spatial visual information, capturing geometric, topological, and stereochemical features from spatial renderings. By integrating this spatial information with traditional molecular descriptors, unified multi-perspective representations are constructed that better reflect molecular structure and function. Across benchmark tasks involving drug–microRNA, drug–drug, and drug–protein interaction prediction, this model consistently outperforms conventional fingerprint-based baselines. Interpretability analyses show that the model attends to biologically relevant substructures, highlighting the value of 3D molecular spatial visual information in molecular recognition. These findings demonstrate the potential of spatially informed learning to enhance predictive performance and provide mechanistic insights in computational drug discovery. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Topology Optimization of High‐Performance Optomechanical Resonator

Compact mechanical resonators designed to operate at higher‐order modes are presented, achieving high frequencies and enhanced quality factor‐frequency (Qf) products. Using topology optimization, edge losses are reduced and damping is improved. These resonators offer strong performance in a small footprint, making them ideal for quantum transduction, optomechanics, and advanced sensing applications. Abstract High quality mechanical resonators are critical for driving advances in quantum information technologies, precision sensing, and optomechanics. However, achieving compact resonator designs that maintain high performance is a key challenge. In this study, a new class of compact resonators optimized to operate at higher‐order eigenmodes is presented, achieving both high frequencies and enhanced quality factor‐frequency (Qf) products. By employing topology optimization to maximize the damping dilution factor, these resonators achieve minimized edge bending losses and enhanced intrinsic damping. Their high‐(Qf) performance and compact form factor position these resonators as promising candidates for applications in quantum information transduction, advanced optomechanical systems, and next‐generation sensing technologies. Compact mechanical resonators designed to operate at higher-order modes are presented, achieving high frequencies and enhanced quality factor-frequency ( Qf ) products. Using topology optimization, edge losses are reduced and damping is improved. These resonators offer strong performance in a small footprint, making them ideal for quantum transduction, optomechanics, and advanced sensing applications. Abstract High quality mechanical resonators are critical for driving advances in quantum information technologies, precision sensing, and optomechanics. However, achieving compact resonator designs that maintain high performance is a key challenge. In this study, a new class of compact resonators optimized to operate at higher-order eigenmodes is presented, achieving both high frequencies and enhanced quality factor-frequency ( Qf ) products. By employing topology optimization to maximize the damping dilution factor, these resonators achieve minimized edge bending losses and enhanced intrinsic damping. Their high-( Qf ) performance and compact form factor position these resonators as promising candidates for applications in quantum information transduction, advanced optomechanical systems, and next-generation sensing technologies. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Toward Practical Li‐Ion Cells With Li/Mn‐Rich Layered Oxide Cathodes: A Techno‐Economic Perspective on Material and Cell Design

Li/Mn‐rich layered oxide cathodes should be designed systematically according to their phase diagram. Starting from a common composition (point 1), the Li‐richness can be reduced (point 2), the Co content can be lowered (point 3), and finally, the Ni to Co ratio can be adjusted. For a more comprehensive evaluation, comparing LMR at an equal delithiation degree is recommended. Abstract Li/Mn‐rich layered oxide (LMR) cathode active materials offer a pathway towards high specific energy and low‐cost Li ion batteries (LIBs) due to their high practical specific discharge capacity (>250 mAh g−1) at moderate discharge voltages (≈3.5 V). However, oxygen redox requires electrochemical activation at high cathode potentials (> 4.5 V vs Li|Li+), resulting in bulk degradation and surface reactivity. This perspective first summarizes the literature‐known efforts to elucidate the oxygen redox mechanism and then proposes strategies for systematic R&D of LMR, supported with techno‐economic analysis. Initially, bulk degradation should be addressed via compositional tuning and crystal modification. Subsequently, the microstructure, interphase, and electrolyte should be engineered, and finally, the charging protocol should be optimized. The various LMR chemistries with different Li to TM, Ni to Mn, and Co to Ni ratios are techno‐economically analyzed, and perspectives on the ideal LMR composition are presented. Ultimately, the specific energy, energy density, and costs of LMR || graphite cells are compared to state‐of‐the‐art cell chemistries. Li/Mn-rich layered oxide cathodes should be designed systematically according to their phase diagram. Starting from a common composition (point 1), the Li-richness can be reduced (point 2), the Co content can be lowered (point 3), and finally, the Ni to Co ratio can be adjusted. For a more comprehensive evaluation, comparing LMR at an equal delithiation degree is recommended. Abstract Li/Mn-rich layered oxide (LMR) cathode active materials offer a pathway towards high specific energy and low-cost Li ion batteries (LIBs) due to their high practical specific discharge capacity (>250 mAh g −1 ) at moderate discharge voltages (≈3.5 V). However, oxygen redox requires electrochemical activation at high cathode potentials (> 4.5 V vs Li|Li + ), resulting in bulk degradation and surface reactivity. This perspective first summarizes the literature-known efforts to elucidate the oxygen redox mechanism and then proposes strategies for systematic R&D of LMR, supported with techno-economic analysis. Initially, bulk degradation should be addressed via compositional tuning and crystal modification. Subsequently, the microstructure, interphase, and electrolyte should be engineered, and finally, the charging protocol should be optimized. The various LMR chemistries with different Li to TM, Ni to Mn, and Co to Ni ratios are techno-economically analyzed, and perspectives on the ideal LMR composition are presented. Ultimately, the specific energy, energy density, and costs of LMR || graphite cells are compared to state-of-the-art cell chemistries. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Aptamer Engineering: Strategies for Discovering Functional Nucleic Acids for Next‐Generation Diagnostics and Biosensing

The advent of aptamers has highlighted their potential as alternatives to antibodies, overcoming limitations of structural instability and production cost. However, conventional approaches such as SELEX remain slow and labor‐intensive. This review examines recent advances in aptamer engineering, emphasizing in vitro and AI‐driven in silico strategies, and explores emerging applications that may broaden their translational impact. Abstract Aptamers are highly selective nucleic acid ligands that overcome many challenges of antibodies, including structural instability and high production costs. The implementation of aptamers into routine research and commercial applications has advanced steadily, though it has been tempered by the limitations of existing discovery methods, which remain relatively slow and low‐throughput. SELEX, the gold‐standard method for aptamer discovery, has played a pivotal role in the field. As the demand for faster and more tailored solutions grows, there is increasing recognition of the value of newer approaches that can expedite the discovery and optimization of aptamers for specific applications. This review discusses recent advances in the methods used for aptamer engineering, including both wet lab methods performed in vitro, and dry lab methods performed in silico. Applications of engineered aptamers described in recent literature and discuss new developments that could further lead to innovative new applications of aptamers for use both within and outside of the laboratory are discussed. Within the laboratory, these applications include (but are not limited to) target‐binding assays and integration into analytical nanomaterials, and outside of the laboratory, diagnostics and biosensing, which will be discussed at length. The advent of aptamers has highlighted their potential as alternatives to antibodies, overcoming limitations of structural instability and production cost. However, conventional approaches such as SELEX remain slow and labor-intensive. This review examines recent advances in aptamer engineering, emphasizing in vitro and AI-driven in silico strategies, and explores emerging applications that may broaden their translational impact. Abstract Aptamers are highly selective nucleic acid ligands that overcome many challenges of antibodies, including structural instability and high production costs. The implementation of aptamers into routine research and commercial applications has advanced steadily, though it has been tempered by the limitations of existing discovery methods, which remain relatively slow and low-throughput. SELEX, the gold-standard method for aptamer discovery, has played a pivotal role in the field. As the demand for faster and more tailored solutions grows, there is increasing recognition of the value of newer approaches that can expedite the discovery and optimization of aptamers for specific applications. This review discusses recent advances in the methods used for aptamer engineering, including both wet lab methods performed in vitro, and dry lab methods performed in silico. Applications of engineered aptamers described in recent literature and discuss new developments that could further lead to innovative new applications of aptamers for use both within and outside of the laboratory are discussed. Within the laboratory, these applications include (but are not limited to) target-binding assays and integration into analytical nanomaterials, and outside of the laboratory, diagnostics and biosensing, which will be discussed at length. Advanced Science, Volume 13, Issue 2, 9 January 2026.

DNA Origami and Its Applications in Synthetic Biology

This review provides a comprehensive summary of recent advancements in DNA origami for synthetic biology, emphasizing two key areas: the precise construction and dynamic regulation of extracellular‐to‐intracellular, and the synergistic integration with cell‐free systems. By combining in vitro assembly with cellular regulation, DNA origami synergizes with cell‐free platforms, opening new pathways for innovative approaches in artificial life design. The review also addresses the challenges and future prospects of this field. Abstract In recent years, DNA origami technology has advanced rapidly as a groundbreaking method for nanomanufacturing. This technology takes advantage of the unique base‐pairing characteristics of DNA, and has significant advantages in constructing spatially ordered and programmable nanostructures. This capability aligns with synthetic biology's core principle of mimicking, extending, and reconstructing natural biological processes by modularly assembling artificial systems. This article provides a comprehensive overview of DNA origami's innovative applications across various domains, including cell membrane surfaces, intercellular communication, intelligent biosensing, and precise gene editing, progressing from the extracellular to the intracellular environment. Finally, this review highlights the synergistic interaction between this technology and cell‐free synthetic biology, achieved through the integration of in vitro assembly and cellular regulation, thereby opening new pathways for the rational design of artificial life systems. This review provides a comprehensive summary of recent advancements in DNA origami for synthetic biology, emphasizing two key areas: the precise construction and dynamic regulation of extracellular-to-intracellular, and the synergistic integration with cell-free systems. By combining in vitro assembly with cellular regulation, DNA origami synergizes with cell-free platforms, opening new pathways for innovative approaches in artificial life design. The review also addresses the challenges and future prospects of this field. Abstract In recent years, DNA origami technology has advanced rapidly as a groundbreaking method for nanomanufacturing. This technology takes advantage of the unique base-pairing characteristics of DNA, and has significant advantages in constructing spatially ordered and programmable nanostructures. This capability aligns with synthetic biology's core principle of mimicking, extending, and reconstructing natural biological processes by modularly assembling artificial systems. This article provides a comprehensive overview of DNA origami's innovative applications across various domains, including cell membrane surfaces, intercellular communication, intelligent biosensing, and precise gene editing, progressing from the extracellular to the intracellular environment. Finally, this review highlights the synergistic interaction between this technology and cell-free synthetic biology, achieved through the integration of in vitro assembly and cellular regulation, thereby opening new pathways for the rational design of artificial life systems. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Toward Practical Li‐Ion Cells With Li/Mn‐Rich Layered Oxide Cathodes: A Techno‐Economic Perspective on Material and Cell Design (Adv. Sci. 2/2026)

Li/Mn‐Rich Layered Oxide Cathodes Relative to conventional cathodes, the replacement of critical transition metals like Co and Ni with the more “benign”, available, cheaper, and lighter Mn and Li – so‐called Li/Mn‐rich cathodes (LMR), can theoretically further boost the performance, but require system‐characteristic design and refinement. More details can be found in the Review by Johannes Kasnatscheew and co‐workers (DOI: 10.1002/advs.202512467). Li/Mn-Rich Layered Oxide Cathodes Relative to conventional cathodes, the replacement of critical transition metals like Co and Ni with the more “benign”, available, cheaper, and lighter Mn and Li – so-called Li/Mn-rich cathodes (LMR), can theoretically further boost the performance, but require system-characteristic design and refinement. More details can be found in the Review by Johannes Kasnatscheew and co-workers (DOI: 10.1002/advs.202512467 ). Advanced Science, Volume 13, Issue 2, 9 January 2026.

Low‐Temperature, Sustainable Manufacturing of Printed OTFT Backplanes for Electrophoretic and OLED Displays (Adv. Sci. 2/2026)

Sustainable Printed Backplanes for Next‐Generation Displays The cover image illustrates an environmentally harmonious approach to display manufacturing, symbolized by natural motifs of greenery and water. Using reverse offset printing for high‐resolution electrode formation and inkjet printing for organic semiconductors, the authors realize fully printed organic transistor backplanes on flexible films at temperatures below 160 °C and under ambient conditions. By laminating an electrophoretic front panel, the team demonstrates the successful driving of e‐paper displays, highlighting a sustainable and versatile route toward future low‐power, flexible electronics. More details can be found in the Research Article by Yasunori Takeda and co‐workers (DOI: 10.1002/advs.202514091). Sustainable Printed Backplanes for Next-Generation Displays The cover image illustrates an environmentally harmonious approach to display manufacturing, symbolized by natural motifs of greenery and water. Using reverse offset printing for high-resolution electrode formation and inkjet printing for organic semiconductors, the authors realize fully printed organic transistor backplanes on flexible films at temperatures below 160 °C and under ambient conditions. By laminating an electrophoretic front panel, the team demonstrates the successful driving of e-paper displays, highlighting a sustainable and versatile route toward future low-power, flexible electronics. More details can be found in the Research Article by Yasunori Takeda and co-workers (DOI: 10.1002/advs.202514091 ). Advanced Science, Volume 13, Issue 2, 9 January 2026.

Peptide Electrostatic Modulation Directs Human Neural Cell Fate (Adv. Sci. 2/2026)

Human Neural Progenitor Cells Self‐assembling peptides can form dynamic scaffolds that mimic the cellular microenvironment. By tuning their electrostatic charges, these supramolecular fibers create distinct biological outcomes: negatively charged environments support neuronal commitment, while positively charged ones induce cell stress and apoptosis. This study reveals how electrostatic modulation in peptide assemblies can direct human neural cell fate, offering new strategies for regenerative medicine and biomaterial design. More details can be found in the Research Article by Aitziber L. Cortajarena, Zaida Álvarez, Ivan R. Sasselli, and co‐workers (DOI: 10.1002/advs.202507946). Human Neural Progenitor Cells Self-assembling peptides can form dynamic scaffolds that mimic the cellular microenvironment. By tuning their electrostatic charges, these supramolecular fibers create distinct biological outcomes: negatively charged environments support neuronal commitment, while positively charged ones induce cell stress and apoptosis. This study reveals how electrostatic modulation in peptide assemblies can direct human neural cell fate, offering new strategies for regenerative medicine and biomaterial design. More details can be found in the Research Article by Aitziber L. Cortajarena, Zaida Álvarez, Ivan R. Sasselli, and co-workers (DOI: 10.1002/advs.202507946 ). Advanced Science, Volume 13, Issue 2, 9 January 2026.

Multi‐Instably Mechanical Systems for Computing‐Storing Functions (Adv. Sci. 2/2026)

Multi‐Instably Mechanical Systems Multi‐instably mechanical systems with the integrated functions of scientific computing, logical operations and data storage. In their Research Article (DOI: 10.1002/advs.202510880, Pengcheng Jiao, Qianyun Zhang, and co‐workers demonstrate the mechanical systems with the integrated functions of solving fourth‐order ordinary differential equations (ODEs) and logical operations by digital logic gates in the computation module, while mechanically saving the computing results in the storage module. As a result, this study opens a promising path to expand mechanical computing systems from separate function to multifunctionality. Multi-Instably Mechanical Systems Multi-instably mechanical systems with the integrated functions of scientific computing, logical operations and data storage. In their Research Article (DOI: 10.1002/advs.202510880, Pengcheng Jiao, Qianyun Zhang, and co-workers demonstrate the mechanical systems with the integrated functions of solving fourth-order ordinary differential equations (ODEs) and logical operations by digital logic gates in the computation module, while mechanically saving the computing results in the storage module. As a result, this study opens a promising path to expand mechanical computing systems from separate function to multifunctionality. Advanced Science, Volume 13, Issue 2, 9 January 2026.

Single Cell and Spatial Transcriptomics Define a Proinflammatory and Profibrotic Niche After Kidney Injury (Adv. Sci. 2/2026)

Proinflammatory and Profibrotic Niche After Kidney Injury On this cover, layered terraces represent kidney spatial layers, with circular niches in the outer medulla where blooming water hyacinths symbolize tenascin C. These flowers attract apple snails as macrophages, depicting how niche‐specific microenvironments drive inflammation and fibrosis revealed by single‐cell and spatial transcriptomics profiling in the Research Article by Li Li, Haiyan Fu, Youhua Liu, and co‐workers (DOI: 10.1002/advs.202503691). Proinflammatory and Profibrotic Niche After Kidney Injury On this cover, layered terraces represent kidney spatial layers, with circular niches in the outer medulla where blooming water hyacinths symbolize tenascin C. These flowers attract apple snails as macrophages, depicting how niche-specific microenvironments drive inflammation and fibrosis revealed by single-cell and spatial transcriptomics profiling in the Research Article by Li Li, Haiyan Fu, Youhua Liu, and co-workers (DOI: 10.1002/advs.202503691 ). Advanced Science, Volume 13, Issue 2, 9 January 2026.

CRISPLD2 Attenuates Intervertebral Disc Degeneration by Suppressing Oxidative Stress‐Induced Ferroptosis through the miR‐548I‐IL17A Axis

This study identifies CRISPLD2 as a key protector against IVDD. By regulating ferroptosis through the CRISPLD2–miR‐548I–IL17A axis, CRISPLD2 maintains NPCs homeostasis and reduces oxidative stress. Restoring CRISPLD2 expression effectively alleviates disc degeneration and highlights a promising therapeutic strategy for discogenic low back pain. ABSTRACT Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, yet its molecular mechanisms remain unclear. We identified CRISPLD2 (cysteine‐rich secretory protein LCCL domain‐containing 2) as a critical regulator of nucleus pulposus cells (NPCs) homeostasis during IVDD. Single‐cell transcriptomic analysis (scRNA‐seq) revealed degenerative NPCs subsets enriched in iron metabolism and lipid peroxidation. CRISPLD2 knockdown in NPCs led to disrupted redox balance, elevated lipid peroxides, and excessive iron accumulation, promoting oxidative stress‐induced ferroptosis and disc degeneration. Mechanistically, we identified a CRISPLD2‐miR‐548I‐IL17A axis that governs ferroptotic cell death in IVDD, where CRISPLD2 deficiency was associated with reduced miR‐548I expression, accompanied by subsequent upregulation of IL17A, thereby amplifying inflammatory and oxidative stress responses. In vivo, CRISPLD2 knockdown induced spontaneous IVDD and increased pain sensitivity, while restoration of CRISPLD2 or inhibition of IL17A alleviated ferroptosis and improved NPCs survival. Adeno‐associated virus (AAV)‐mediated overexpression of CRISPLD2 successfully alleviated IVDD in lumbar spine instability and needle‐puncture models, reducing oxidative stress‐induced ferroptosis and restoring disc integrity. These findings highlight the critical role of CRISPLD2 in regulating oxidative stress‐induced ferroptosis in IVDD and suggest that targeting the CRISPLD2‐miR‐548I‐IL17A axis may provide a novel therapeutic strategy for preventing disc degeneration and alleviating discogenic pain. This study identifies CRISPLD2 as a key protector against IVDD. By regulating ferroptosis through the CRISPLD2–miR-548I–IL17A axis, CRISPLD2 maintains NPCs homeostasis and reduces oxidative stress. Restoring CRISPLD2 expression effectively alleviates disc degeneration and highlights a promising therapeutic strategy for discogenic low back pain. ABSTRACT Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain, yet its molecular mechanisms remain unclear. We identified CRISPLD2 (cysteine-rich secretory protein LCCL domain-containing 2) as a critical regulator of nucleus pulposus cells (NPCs) homeostasis during IVDD. Single-cell transcriptomic analysis (scRNA-seq) revealed degenerative NPCs subsets enriched in iron metabolism and lipid peroxidation. CRISPLD2 knockdown in NPCs led to disrupted redox balance, elevated lipid peroxides, and excessive iron accumulation, promoting oxidative stress-induced ferroptosis and disc degeneration. Mechanistically, we identified a CRISPLD2-miR-548I-IL17A axis that governs ferroptotic cell death in IVDD, where CRISPLD2 deficiency was associated with reduced miR-548I expression, accompanied by subsequent upregulation of IL17A, thereby amplifying inflammatory and oxidative stress responses. In vivo, CRISPLD2 knockdown induced spontaneous IVDD and increased pain sensitivity, while restoration of CRISPLD2 or inhibition of IL17A alleviated ferroptosis and improved NPCs survival. Adeno-associated virus (AAV)-mediated overexpression of CRISPLD2 successfully alleviated IVDD in lumbar spine instability and needle-puncture models, reducing oxidative stress-induced ferroptosis and restoring disc integrity. These findings highlight the critical role of CRISPLD2 in regulating oxidative stress-induced ferroptosis in IVDD and suggest that targeting the CRISPLD2-miR-548I-IL17A axis may provide a novel therapeutic strategy for preventing disc degeneration and alleviating discogenic pain. Advanced Science, EarlyView.

Immunoaffinity‐Mimetic Assembly of Peptide‐Aptamer Conjugates and Stem Cell‐Derived Exosomes into Hierarchical Microgels for Spinal Cord Injury Repair

Inspired by antibody‐antigen binding, this study develops an unprecedented immunoaffinity‐mimetic assembly strategy, with Peptide‐AptCD63 conjugates acting as antibody surrogates binding CD63 epitopes on mesenchymal stem cell‐derived exosomes. This creates a hierarchical microstructure intended to synergistically integrate antioxidative and anti‐inflammatory strategies with neuroregenerative processes to enhance spinal cord injury repair. ABSTRACT Mesenchymal stem cell‐derived exosomes (MSC‐Exo) containing various paracrine mediators have recently been recognized to promote functional recovery of spinal cord injury (SCI). However, their biomedical applications are hindered by limited possibilities for specific integration within the delivery systems. In this study, inspired by antibody‐antigen binding, we present an unprecedented assembly strategy that leverages immunoaffinity‐mimetic interactions of peptide‐aptamer (Peptide‐AptCD63) conjugates targeting CD63 markers on MSC‐Exo, yielding a hierarchical microstructure to enhance SCI repair. The conjugate, serving as the microgel scaffold, is synthesized by grafting azide‐modified AptCD63 onto poly(propargyl cysteine‐co‐γ‐propargyl‐L‐glutamate). It exhibits excellent antioxidant capability to mitigate oxidative stress and immune responses at the injury site. In addition, this conjugate constrains the tethered MSC‐Exo within the lesion site during administration, yet its nuclease susceptibility allows for the release of MSC‐Exo to promote the proliferation and migration of neural stem cells and to direct their differentiation into neurons rather than astrocytes. These synergistic effects ultimately enhance neuroregeneration, thereby promoting the motor function recovery of SCI mice. Our work represents a pioneering effort in harnessing the specificity of immunoaffinity‐mimetic interactions between aptamers and biomacromolecules for the high‐performance assembly of chemically vulnerable biologics, facilitating widespread applications across materials science and life science. Inspired by antibody-antigen binding, this study develops an unprecedented immunoaffinity-mimetic assembly strategy, with Peptide-Apt CD63 conjugates acting as antibody surrogates binding CD63 epitopes on mesenchymal stem cell-derived exosomes. This creates a hierarchical microstructure intended to synergistically integrate antioxidative and anti-inflammatory strategies with neuroregenerative processes to enhance spinal cord injury repair. ABSTRACT Mesenchymal stem cell-derived exosomes (MSC-Exo) containing various paracrine mediators have recently been recognized to promote functional recovery of spinal cord injury (SCI). However, their biomedical applications are hindered by limited possibilities for specific integration within the delivery systems. In this study, inspired by antibody-antigen binding, we present an unprecedented assembly strategy that leverages immunoaffinity-mimetic interactions of peptide-aptamer (Peptide-Apt CD63 ) conjugates targeting CD63 markers on MSC-Exo, yielding a hierarchical microstructure to enhance SCI repair. The conjugate, serving as the microgel scaffold, is synthesized by grafting azide-modified Apt CD63 onto poly(propargyl cysteine- co -γ-propargyl- L -glutamate). It exhibits excellent antioxidant capability to mitigate oxidative stress and immune responses at the injury site. In addition, this conjugate constrains the tethered MSC-Exo within the lesion site during administration, yet its nuclease susceptibility allows for the release of MSC-Exo to promote the proliferation and migration of neural stem cells and to direct their differentiation into neurons rather than astrocytes. These synergistic effects ultimately enhance neuroregeneration, thereby promoting the motor function recovery of SCI mice. Our work represents a pioneering effort in harnessing the specificity of immunoaffinity-mimetic interactions between aptamers and biomacromolecules for the high-performance assembly of chemically vulnerable biologics, facilitating widespread applications across materials science and life science. Advanced Science, EarlyView.

PTG‐Dependent Glycogen Metabolic Dysfunction Drives Impaired Adipose Browning: A Novel Mechanism Linking PM2.5 to Metabolic Disorders

This study provides the first evidence that PM2.5 impairs iWAT browning via PTG‐mediated glycogen metabolism disruption, which is initiated by ADRB3 inhibition and subsequently triggers VEGFB upregulation. It thereby delineates the ADRB3‐PTG‐VEGFB axis as central to PM2.5‐induced metabolic dysfunction and identifies adipose glycogen metabolism as a novel therapeutic target against environmental metabolic disruption. ABSTRACT Fine particulate matter (PM2.5) contributes to metabolic dysfunction, but its effects on adipose tissue browning remain unclear. Here, we showed that PM2.5 exposure inhibited inguinal white adipose tissue (iWAT) browning by downregulating protein targeting to glycogen (PTG), disrupting glycogen homeostasis. PTG overexpression in iWAT restored glycogen metabolism, thermogenesis, and mitochondrial function, reversing PM2.5‐induced impairment in iWAT browning and metabolic disorders. Mechanistically, PTG negatively regulated vascular endothelial growth factor B (VEGFB), and VEGFB knockdown rescued browning. Activation of β3‐adrenergic receptor (ADRB3) mitigated PM2.5’s effects by restoring PTG and normalizing VEGFB, defining the ADRB3‐PTG‐VEGFB axis as central to PM2.5‐induced metabolic dysfunction. Our findings identify adipose glycogen metabolism as a target for countering environmental metabolic disruption. This study provides the first evidence that PM 2.5 impairs iWAT browning via PTG-mediated glycogen metabolism disruption, which is initiated by ADRB3 inhibition and subsequently triggers VEGFB upregulation. It thereby delineates the ADRB3-PTG-VEGFB axis as central to PM 2.5 -induced metabolic dysfunction and identifies adipose glycogen metabolism as a novel therapeutic target against environmental metabolic disruption. ABSTRACT Fine particulate matter (PM 2.5 ) contributes to metabolic dysfunction, but its effects on adipose tissue browning remain unclear. Here, we showed that PM 2.5 exposure inhibited inguinal white adipose tissue (iWAT) browning by downregulating protein targeting to glycogen (PTG), disrupting glycogen homeostasis. PTG overexpression in iWAT restored glycogen metabolism, thermogenesis, and mitochondrial function, reversing PM 2.5 -induced impairment in iWAT browning and metabolic disorders. Mechanistically, PTG negatively regulated vascular endothelial growth factor B (VEGFB), and VEGFB knockdown rescued browning. Activation of β3-adrenergic receptor (ADRB3) mitigated PM 2.5 ’s effects by restoring PTG and normalizing VEGFB, defining the ADRB3-PTG-VEGFB axis as central to PM 2.5 -induced metabolic dysfunction. Our findings identify adipose glycogen metabolism as a target for countering environmental metabolic disruption. Advanced Science, EarlyView.

Hepatocyte BPGM Induces RET Lactylation and Macrophage Reprogramming to Promote Tumorigenesis in Hepatocellular Carcinoma

Mechanistic schematic diagram.BPGM promotes the expression level of RET by increasing the lactylation of RET‐K549 and inhibiting its ubiquitination levels in HCC cells. Furthermore, BPGM in HCC cells could also promote M2 polarization in macrophages through lactate secretion. Both of the mechanisms could promote the progression of HCC. ABSTRACT Aerobic glycolysis is a hallmark of cancer, yet the role of the key glycolytic enzyme bisphosphoglycerate mutase (BPGM) in hepatocellular carcinoma (HCC) progression remains unclear. Here, clinical sample analyses revealed that BPGM expression was upregulated in HCC tissues and associated with poor prognosis. Hepatocyte‐specific Bpgm knockout significantly attenuated DEN‐induced HCC development in mice. Spatial transcriptomics and single‐cell RNA sequencing revealed that hepatocyte‐specific Bpgm knockout reduced the monocyte/macrophage infiltration and decreased M2 polarization of tumor‐associated macrophages. Additionally, BPGM overexpression promoted the proliferation and migration of HCC cells and enhanced intracellular lactate accumulation. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) identified ret proto‐oncogene (RET) as a downstream effector that mediated the effects of BPGM on HCC cells. BPGM promoted P300‐mediated lactylation of RET at lysine 549 (K549), which competitively inhibited its ubiquitination, thereby preventing RET protein degradation and enhancing its stability. BPGM in HCC cells also induced both histone lactylation and M2 polarization of macrophages by lactate secretion. This study revealed that BPGM in hepatocytes could enhance RET expression via increasing its lactylation in malignant cells and promote M2 polarization of macrophages, both of which contributed to HCC progression. These findings established that BPGM could act as a potential therapeutic target for HCC. Mechanistic schematic diagram.BPGM promotes the expression level of RET by increasing the lactylation of RET -K549 and inhibiting its ubiquitination levels in HCC cells. Furthermore, BPGM in HCC cells could also promote M2 polarization in macrophages through lactate secretion. Both of the mechanisms could promote the progression of HCC. ABSTRACT Aerobic glycolysis is a hallmark of cancer, yet the role of the key glycolytic enzyme bisphosphoglycerate mutase (BPGM) in hepatocellular carcinoma (HCC) progression remains unclear. Here, clinical sample analyses revealed that BPGM expression was upregulated in HCC tissues and associated with poor prognosis. Hepatocyte-specific Bpgm knockout significantly attenuated DEN-induced HCC development in mice. Spatial transcriptomics and single-cell RNA sequencing revealed that hepatocyte-specific Bpgm knockout reduced the monocyte/macrophage infiltration and decreased M2 polarization of tumor-associated macrophages. Additionally, BPGM overexpression promoted the proliferation and migration of HCC cells and enhanced intracellular lactate accumulation. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified ret proto-oncogene (RET) as a downstream effector that mediated the effects of BPGM on HCC cells. BPGM promoted P300-mediated lactylation of RET at lysine 549 (K549), which competitively inhibited its ubiquitination, thereby preventing RET protein degradation and enhancing its stability. BPGM in HCC cells also induced both histone lactylation and M2 polarization of macrophages by lactate secretion. This study revealed that BPGM in hepatocytes could enhance RET expression via increasing its lactylation in malignant cells and promote M2 polarization of macrophages, both of which contributed to HCC progression. These findings established that BPGM could act as a potential therapeutic target for HCC. Advanced Science, EarlyView.