HCP Network – Latest Medical Journals, Research Articles & Clinical Updates

Nanoscale Decoupling of Carrier–Phonon Transport in Carbon Nanotube–Halide Perovskite Heterostructures

Heterostructures of highly conductive single‐walled carbon nanotubes with low conductivity hybrid perovskites break the trade‐off between electrical and thermal conductivity. This design boosts electrical conductivity while significantly lowering thermal conductivity. Abstract In conventional semiconductors, electrical and thermal conductivity are typically coupled, posing a challenge in optimizing both simultaneously. Overcoming this inherent trade‐off enables strategies for advancing electronic applications. Herein, a strategy is demonstrated to decouple electrical and thermal conductivity trade‐off by creating heterostructures of highly conductive single‐walled carbon nanotubes (SWCNTs) coated with low conductivity hybrid perovskites. Coating SWCNTs with methylammonium lead iodide perovskite results in an enhancement in electrical conductivity (408–1266 S cm−1) due to p‐type doping followed by a threefold decrease of the in‐plane thermal conductivity (3.3–1 W m−1 K−1), compared to pristine SWCNTs. Molecular dynamics simulations uncover phonon boundary scattering at the SWCNT/perovskite interface as well as localization of methylammonium‐related and softening of the Pb─I‐related phonon modes in methylammonium lead iodide perovskite decreasing the thermal conductivity. Heterostructures of highly conductive single-walled carbon nanotubes with low conductivity hybrid perovskites break the trade-off between electrical and thermal conductivity. This design boosts electrical conductivity while significantly lowering thermal conductivity. Abstract In conventional semiconductors, electrical and thermal conductivity are typically coupled, posing a challenge in optimizing both simultaneously. Overcoming this inherent trade-off enables strategies for advancing electronic applications. Herein, a strategy is demonstrated to decouple electrical and thermal conductivity trade-off by creating heterostructures of highly conductive single-walled carbon nanotubes (SWCNTs) coated with low conductivity hybrid perovskites. Coating SWCNTs with methylammonium lead iodide perovskite results in an enhancement in electrical conductivity (408–1266 S cm −1 ) due to p-type doping followed by a threefold decrease of the in-plane thermal conductivity (3.3–1 W m −1 K −1 ), compared to pristine SWCNTs. Molecular dynamics simulations uncover phonon boundary scattering at the SWCNT/perovskite interface as well as localization of methylammonium-related and softening of the Pb─I-related phonon modes in methylammonium lead iodide perovskite decreasing the thermal conductivity. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Succinic Acid‐Induced Macrophage Endocytosis Promotes Extracellular Vesicle‐Based Integrin Beta1 Transfer Accelerating Fibroblast Activation and Sepsis‐Associated Pulmonary Fibrosis

Lipopolysaccharide (LPS) stimulates the production of succinic acid in lung tissue, which promotes macrophages endocytosis and the formation of multivesicular bodies (MVBs). These MVBs release profibrotic extracellular vesicles (EVs), facilitating the transfer of integrin beta1 (ITGβ1) transfer and subsequently activating fibroblasts, thereby contributing to the development of sepsis‐associated pulmonary fibrosis (SAPF). Abstract Sepsis‐associated pulmonary fibrosis (SAPF) is a life‐threatening condition driven by persistent fibroblast activation and excessive extracellular matrix (ECM) deposition. While metabolic reprogramming, profibrotic extracellular vesicles (EVs), and integrin activation are implicated in pulmonary fibrosis, their interplay remains unclear. This study reveals that succinic acid, a product of glycometabolic reprogramming, promotes macrophage‐mediated endocytosis, driving the release of profibrotic EVs. These EVs transfer integrin beta1 (ITGβ1) from macrophages to fibroblasts, activating fibroblasts and advancing SAPF. Through Single‐cell RNA sequencing (scRNA‐seq), proteomics, immunofluorescence, and electron microscopy, the critical role of EV‐mediated ITGβ1 transfer in macrophage‐fibroblast communication is identified. Knockdown of ITGβ1 or Alix, a mediator of multivesicular bodies (MVBs) biogenesis, inhibited profibrotic EVs formation and alleviated SAPF. These findings highlight a novel mechanism in that the transfer ITGβ1 via EVs plays a critical role in macrophage‐fibroblast communication, representing a novel mechanism underlying SAPF. Targeting EV‐mediated ITGβ1 transfer can provide a promising therapeutic strategy to alleviate the progression of SAPF. Lipopolysaccharide (LPS) stimulates the production of succinic acid in lung tissue, which promotes macrophages endocytosis and the formation of multivesicular bodies (MVBs). These MVBs release profibrotic extracellular vesicles (EVs), facilitating the transfer of integrin beta1 (ITGβ1) transfer and subsequently activating fibroblasts, thereby contributing to the development of sepsis-associated pulmonary fibrosis (SAPF). Abstract Sepsis-associated pulmonary fibrosis (SAPF) is a life-threatening condition driven by persistent fibroblast activation and excessive extracellular matrix (ECM) deposition. While metabolic reprogramming, profibrotic extracellular vesicles (EVs), and integrin activation are implicated in pulmonary fibrosis, their interplay remains unclear. This study reveals that succinic acid, a product of glycometabolic reprogramming, promotes macrophage-mediated endocytosis, driving the release of profibrotic EVs. These EVs transfer integrin beta1 (ITGβ1) from macrophages to fibroblasts, activating fibroblasts and advancing SAPF. Through Single-cell RNA sequencing (scRNA-seq), proteomics, immunofluorescence, and electron microscopy, the critical role of EV-mediated ITGβ1 transfer in macrophage-fibroblast communication is identified. Knockdown of ITGβ1 or Alix, a mediator of multivesicular bodies (MVBs) biogenesis, inhibited profibrotic EVs formation and alleviated SAPF. These findings highlight a novel mechanism in that the transfer ITGβ1 via EVs plays a critical role in macrophage-fibroblast communication, representing a novel mechanism underlying SAPF. Targeting EV-mediated ITGβ1 transfer can provide a promising therapeutic strategy to alleviate the progression of SAPF. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Sono‐Controllable Janus Hydrogel Platform for Sequential Tumor Eradication and Bone Regeneration in Metastatic Breast Cancer

Sequential tumor eradication and bone regeneration remain a significant challenge for patients with breast cancer bone metastases. This study develops a novel Janus hydrogel platform, which can achieve tumor elimination and bone repair under the action of different ultrasound frequencies. Moreover, the sustained‐release oxygen can improve the hypoxic microenvironment for synergistic enhancement of efficacy. Abstract Bone metastases occur in 60%–75% of patients with metastatic breast cancer, reducing survival rates and compromising quality of life. Innovative treatments are urgently needed to sequentially eradicate tumor cells and promote bone regeneration. In this study, a novel Janus hydrogel platform (GA@CaMP) is developed for encapsulating the sonosensitive composite nanomaterial MHP, which enables gene expression regulation, along with oxygen‐releasing CaO2 NPs. The platform's therapeutic efficacy is achieved through two distinct mechanisms: high‐concentration ROS, activated under specific ultrasonic conditions, synergizes with the upregulation of ZBP1 expression to co‐activate the necroptotic pathway, inducing tumor cell death and effectively eliminating residual cancer cells. Subsequently, low‐concentration ROS stimulates osteogenic gene expression, promoting bone regeneration in affected areas. The incorporation of CaO2 NPs further enhances therapeutic outcomes through continuous oxygen release, which improves the local hypoxic microenvironment and consequently promotes more effective tumor eradication and bone regeneration. This multifunctional Janus hydrogel system demonstrates remarkable efficacy in tumor clearance and bone defect repair, representing a significant advancement in the comprehensive treatment of bone metastatic breast cancer. The platform's dual functionality and therapeutic precision position it as a promising strategy for holistic breast cancer management, with substantial potential for clinical translation and application in cancer therapy. Sequential tumor eradication and bone regeneration remain a significant challenge for patients with breast cancer bone metastases. This study develops a novel Janus hydrogel platform, which can achieve tumor elimination and bone repair under the action of different ultrasound frequencies. Moreover, the sustained-release oxygen can improve the hypoxic microenvironment for synergistic enhancement of efficacy. Abstract Bone metastases occur in 60%–75% of patients with metastatic breast cancer, reducing survival rates and compromising quality of life. Innovative treatments are urgently needed to sequentially eradicate tumor cells and promote bone regeneration. In this study, a novel Janus hydrogel platform (GA@CaMP) is developed for encapsulating the sonosensitive composite nanomaterial MHP, which enables gene expression regulation, along with oxygen-releasing CaO 2 NPs. The platform's therapeutic efficacy is achieved through two distinct mechanisms: high-concentration ROS, activated under specific ultrasonic conditions, synergizes with the upregulation of ZBP1 expression to co-activate the necroptotic pathway, inducing tumor cell death and effectively eliminating residual cancer cells. Subsequently, low-concentration ROS stimulates osteogenic gene expression, promoting bone regeneration in affected areas. The incorporation of CaO 2 NPs further enhances therapeutic outcomes through continuous oxygen release, which improves the local hypoxic microenvironment and consequently promotes more effective tumor eradication and bone regeneration. This multifunctional Janus hydrogel system demonstrates remarkable efficacy in tumor clearance and bone defect repair, representing a significant advancement in the comprehensive treatment of bone metastatic breast cancer. The platform's dual functionality and therapeutic precision position it as a promising strategy for holistic breast cancer management, with substantial potential for clinical translation and application in cancer therapy. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Homogeneous FACsPbI3 Films via Sequential Deposition for Efficient and Stable Perovskite Solar Cells

A compositional homogeneous perovskite is achieved by constructing a δ‐phase perovskite in the PbI2 film by predepositing the cesium source before PbI2 deposition and facilitating the uniform vertical distribution of FA and Cs cations. The compositional homogeneous perovskite solar cells achieve a higher champion PCE of 24.59%, compared to 22.96% for the inhomogeneous perovskite device. Abstract Despite significant advancements in the power conversion efficiency (PCE) of FAPbI3‐based perovskite solar cells (PSCs), their commercialization remains hindered by stability issues. These challenges arise primarily from the phase transition of the α‐phase to the δ‐phase under operation. Alloying FAPbI3 with Cs to form FA‐Cs perovskite (FACsPbI3) emerged as a promising approach to enhance phase and thermal stability. In this study, it is demonstrated that adding a Cs source to the PbI2 solution promotes the formation of a structurally stable α‐phase in the PbI2 film. This stabilization reduces cation diffusion but leads to Cs accumulation at the surface of the perovskite layer. To address this issue, a δ‐phase perovskite in the PbI2 film by predepositing the Cs source before PbI2 deposition is constructed. This approach facilitates the uniform vertical distribution of FA and Cs cations, resulting in a homogeneous perovskite (h‐perovskite) device. The h‐perovskite device achieves a higher PCE of 24.59%, compared to 22.96% for the inhomogeneous perovskite (i‐perovskite) device. Operando GIWAXS measurements reveal that the h‐perovskite exhibits a slower degradation rate than the i‐perovskite during device operation. This difference is attributed to the formation of the δ‐phase and a stronger crystal lattice contraction observed in the i‐perovskite during the operando measurements. A compositional homogeneous perovskite is achieved by constructing a δ-phase perovskite in the PbI 2 film by predepositing the cesium source before PbI 2 deposition and facilitating the uniform vertical distribution of FA and Cs cations. The compositional homogeneous perovskite solar cells achieve a higher champion PCE of 24.59%, compared to 22.96% for the inhomogeneous perovskite device. Abstract Despite significant advancements in the power conversion efficiency (PCE) of FAPbI 3 -based perovskite solar cells (PSCs), their commercialization remains hindered by stability issues. These challenges arise primarily from the phase transition of the α-phase to the δ-phase under operation. Alloying FAPbI 3 with Cs to form FA-Cs perovskite (FACsPbI 3 ) emerged as a promising approach to enhance phase and thermal stability. In this study, it is demonstrated that adding a Cs source to the PbI 2 solution promotes the formation of a structurally stable α-phase in the PbI 2 film. This stabilization reduces cation diffusion but leads to Cs accumulation at the surface of the perovskite layer. To address this issue, a δ-phase perovskite in the PbI 2 film by predepositing the Cs source before PbI 2 deposition is constructed. This approach facilitates the uniform vertical distribution of FA and Cs cations, resulting in a homogeneous perovskite (h-perovskite) device. The h-perovskite device achieves a higher PCE of 24.59%, compared to 22.96% for the inhomogeneous perovskite (i-perovskite) device. Operando GIWAXS measurements reveal that the h-perovskite exhibits a slower degradation rate than the i-perovskite during device operation. This difference is attributed to the formation of the δ-phase and a stronger crystal lattice contraction observed in the i-perovskite during the operando measurements. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Substrate‐Controlled Response Coefficients in Thin Films

Many material‐specific coefficients, which relate external stimuli and functional responses, are constants governed by atomic vibrations. This work demonstrates the concept of controlling such response coefficients by deformations, or strain, through strain‐induced changes in atomic vibrations. As a proof of concept, the dependence of the Curie constant on substrate‐imposed strain in SrTiO3 films is theoretically predicted and experimentally validated. Abstract To obtain materials with desired properties, material compositions are primarily altered, whereas thin films offer additional unique avenues. By combining state‐of‐the‐art first‐principles calculations and experimental investigations of thin films of strontium titanate as an exemplary representative of a broad class of perovskite oxides and the extensive family of ferroelectrics, a novel approach is presented to achieving superior material responses to external stimuli. The findings reveal that substrate‐imposed deformations, or strains, significantly alter the frequencies and magnitudes of atomic vibrations in thin films. Consequently, material‐specific response‐stimulus coefficients can become strain‐dependent. The strain‐dependent Curie constant, which characterizes the dielectric response to thermal stimuli, is theoretically justified and experimentally validated. Given that atomic vibrations fundamentally govern various response coefficients in a wide range of materials, and that thin films are typically deformed by substrates, it is anticipated that unprecedented responses can be generally attained through substrate‐induced control of atomic vibrations in thin films. Many material-specific coefficients, which relate external stimuli and functional responses, are constants governed by atomic vibrations. This work demonstrates the concept of controlling such response coefficients by deformations, or strain, through strain-induced changes in atomic vibrations. As a proof of concept, the dependence of the Curie constant on substrate-imposed strain in SrTiO 3 films is theoretically predicted and experimentally validated. Abstract To obtain materials with desired properties, material compositions are primarily altered, whereas thin films offer additional unique avenues. By combining state-of-the-art first-principles calculations and experimental investigations of thin films of strontium titanate as an exemplary representative of a broad class of perovskite oxides and the extensive family of ferroelectrics, a novel approach is presented to achieving superior material responses to external stimuli. The findings reveal that substrate-imposed deformations, or strains, significantly alter the frequencies and magnitudes of atomic vibrations in thin films. Consequently, material-specific response-stimulus coefficients can become strain-dependent. The strain-dependent Curie constant, which characterizes the dielectric response to thermal stimuli, is theoretically justified and experimentally validated. Given that atomic vibrations fundamentally govern various response coefficients in a wide range of materials, and that thin films are typically deformed by substrates, it is anticipated that unprecedented responses can be generally attained through substrate-induced control of atomic vibrations in thin films. Advanced Science, Volume 12, Issue 43, November 20, 2025.

An Automated Lab‐On‐A‐Chip Approach for Pollen Tube Growth Manipulation in a Controlled Chemical Environment

Here, a microfluidic‐based robotic lab‐on‐a‐chip (LoC) device is presented for automated, continuous‐flow investigation and manipulation of single pollen tube growth under precisely controlled chemical gradients. This closed‐loop system streamlines data collection and analysis while enhancing experimental precision compared to manual methods, highlighting the transformative potential of robotic laboratory automation for miniaturized, cost‐effective single‐cell research. Abstract Laboratory automation is successfully implemented across a wide range of applications, from space exploration to oceanic research, facilitating data collection and analysis while improving precision in biological and medical fields. The future of robotic laboratory automation is closely tied to advancements in miniaturization. Thus, automation of lab‐on‐a‐chip (LoC) systems–integrating complex laboratory tasks onto a small chip–holds great potential for scientific research, including the study of model organisms and cells. Here, an automated continuous‐flow‐based LoC device designed to investigate and manipulate the growth of pollen tubes (PTs)–fastest‐growing cells in nature–within controlled chemical environments is presented. The automated LoC approach allows for the generation of tailored chemical gradients (e.g., of Ca2+) around the PT tip, offering unprecedented precision and efficiency in the manipulation of PT growth when compared to manual experiments. Besides advancing the experimental methodology by providing more precise information on the response of PTs to Ca2+ concentration gradients, the developed closed‐loop approach with simultaneous data recording and processing reduces the time and costs associated with experiments. This underscores the great potential of robotic laboratory automation for streamlining data collection and analysis, paving the way for more efficient and precise scientific research. Here, a microfluidic-based robotic lab-on-a-chip (LoC) device is presented for automated, continuous-flow investigation and manipulation of single pollen tube growth under precisely controlled chemical gradients. This closed-loop system streamlines data collection and analysis while enhancing experimental precision compared to manual methods, highlighting the transformative potential of robotic laboratory automation for miniaturized, cost-effective single-cell research. Abstract Laboratory automation is successfully implemented across a wide range of applications, from space exploration to oceanic research, facilitating data collection and analysis while improving precision in biological and medical fields. The future of robotic laboratory automation is closely tied to advancements in miniaturization. Thus, automation of lab-on-a-chip (LoC) systems–integrating complex laboratory tasks onto a small chip–holds great potential for scientific research, including the study of model organisms and cells. Here, an automated continuous-flow-based LoC device designed to investigate and manipulate the growth of pollen tubes (PTs)–fastest-growing cells in nature–within controlled chemical environments is presented. The automated LoC approach allows for the generation of tailored chemical gradients (e.g., of Ca 2+ ) around the PT tip, offering unprecedented precision and efficiency in the manipulation of PT growth when compared to manual experiments. Besides advancing the experimental methodology by providing more precise information on the response of PTs to Ca 2+ concentration gradients, the developed closed-loop approach with simultaneous data recording and processing reduces the time and costs associated with experiments. This underscores the great potential of robotic laboratory automation for streamlining data collection and analysis, paving the way for more efficient and precise scientific research. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Local p‐ and n‐Type Doping of an Oxide Semiconductor via Electric‐Field‐Driven Defect Migration

Local acceptor and donor doping is achieved in a semiconducting oxide by controlled splitting of oxygen interstitial‐vacancy pairs under applied d.c. voltage. The separated oxygen defects are demonstrated to form interstitial‐rich (p‐type) and vacancy‐rich (n‐type) regions, comparable to dipolar npn‐junctions, enabling transient functionalization. Abstract Layered oxides exhibit high ionic mobility and chemical flexibility, attracting interest as cathode materials for lithium‐ion batteries and the pairing of hydrogen production and carbon capture. Recently, layered oxides emerged as highly tunable semiconductors. For example, by introducing anti‐Frenkel defects, the electronic hopping conductance in hexagonal manganites is increased locally by orders of magnitude. Here, local acceptor and donor doping in Er(Mn,Ti)O3 is demonstrated, facilitated by the controlled splitting of anti‐Frenkel defects under applied d.c. voltage. By combining density functional theory calculations, scanning probe microscopy, atom probe tomography, and scanning transmission electron microscopy, it is shown that the oxygen defects can readily be moved through the layered crystal structure, leading to nano‐sized interstitial‐rich (p‐type) and vacancy‐rich (n‐type) regions. The resulting pattern is comparable to dipolar npn‐junctions and stable on the timescale of days. These findings reveal the possibility of temporarily functionalizing oxide semiconductors at the nanoscale, giving additional opportunities for the field of oxide electronics and the development of transient electronics in general. Local acceptor and donor doping is achieved in a semiconducting oxide by controlled splitting of oxygen interstitial-vacancy pairs under applied d.c. voltage. The separated oxygen defects are demonstrated to form interstitial-rich (p-type) and vacancy-rich (n-type) regions, comparable to dipolar npn-junctions, enabling transient functionalization. Abstract Layered oxides exhibit high ionic mobility and chemical flexibility, attracting interest as cathode materials for lithium-ion batteries and the pairing of hydrogen production and carbon capture. Recently, layered oxides emerged as highly tunable semiconductors. For example, by introducing anti-Frenkel defects, the electronic hopping conductance in hexagonal manganites is increased locally by orders of magnitude. Here, local acceptor and donor doping in Er(Mn,Ti)O 3 is demonstrated, facilitated by the controlled splitting of anti-Frenkel defects under applied d.c. voltage. By combining density functional theory calculations, scanning probe microscopy, atom probe tomography, and scanning transmission electron microscopy, it is shown that the oxygen defects can readily be moved through the layered crystal structure, leading to nano-sized interstitial-rich (p-type) and vacancy-rich (n-type) regions. The resulting pattern is comparable to dipolar npn-junctions and stable on the timescale of days. These findings reveal the possibility of temporarily functionalizing oxide semiconductors at the nanoscale, giving additional opportunities for the field of oxide electronics and the development of transient electronics in general. Advanced Science, Volume 12, Issue 43, November 20, 2025.

T2T Genomes Unveil Centromere Architecture and Adaptive Divergence in Large Yellow Croaker (Larimichthys crocea)

This study presents telomere‐to‐telomere genome assemblies for two populations of Larimichthys crocea. We identified centromere‐specific tandem repeats invaded by LTR/ERV1 retrotransposons, unique 5S rRNA enrichment patterns, and population‐specific structural variants. Comparative genomic analyses further reveal distinct adaptive mechanisms in the MYD and DQ populations, potentially driven by their respective environmental conditions.‐. Abstract The large yellow croaker (Larimichthys crocea) is a key aquaculture species, yet gaps in high‐quality genomes hinder studies of centromeric and adaptive evolution. This study presents two telomere‐to‐telomere (T2T), gapless genomes from the Min‐Yuedong (MYD) and Daiqu (DQ) populations, which diverged 4.18 million years ago. The centromeres are characterized by a 42 bp tandem repeat (Cen‐42) and invasions by endogenous retrovirus 1 (ERV1) of long terminal repeat (LTR) elements. Both populations exhibit transcriptional activity in centromeric regions, but display significant divergence in gene number and composition, likely driven by rapid population expansion and selective pressure. In addition, 5S ribosomal RNA genes form ultra‐large tandem repeat clusters in the short‐arm regions of more than 10 chromosomes. The T2T genome assemblies resolve previously unassembled regions, identifying 533 and 351 new genes in T2T‐MYD and T2T‐DQ, respectively. Four population‐specific structural variations, located in pla2g4a, eno2, ptprb, and itrp3 are identified. Comparative genomic analyses highlight distinct adaptive features between the two populations, including differences in metabolic efficiency, arachidonic acid metabolism, chemosensasory function, and circadian rhythm. Collectively, these findings deepen the understanding of L. crocea evolution and provide valuable genomic resources for its conservation and breeding. This study presents telomere-to-telomere genome assemblies for two populations of Larimichthys crocea. We identified centromere-specific tandem repeats invaded by LTR/ERV1 retrotransposons, unique 5S rRNA enrichment patterns, and population-specific structural variants. Comparative genomic analyses further reveal distinct adaptive mechanisms in the MYD and DQ populations, potentially driven by their respective environmental conditions.-. Abstract The large yellow croaker ( Larimichthys crocea ) is a key aquaculture species, yet gaps in high-quality genomes hinder studies of centromeric and adaptive evolution. This study presents two telomere-to-telomere (T2T), gapless genomes from the Min-Yuedong (MYD) and Daiqu (DQ) populations, which diverged 4.18 million years ago. The centromeres are characterized by a 42 bp tandem repeat (Cen-42) and invasions by endogenous retrovirus 1 (ERV1) of long terminal repeat (LTR) elements. Both populations exhibit transcriptional activity in centromeric regions, but display significant divergence in gene number and composition, likely driven by rapid population expansion and selective pressure. In addition, 5S ribosomal RNA genes form ultra-large tandem repeat clusters in the short-arm regions of more than 10 chromosomes. The T2T genome assemblies resolve previously unassembled regions, identifying 533 and 351 new genes in T2T-MYD and T2T-DQ, respectively. Four population-specific structural variations, located in pla2g4a, eno2, ptprb, and itrp3 are identified. Comparative genomic analyses highlight distinct adaptive features between the two populations, including differences in metabolic efficiency, arachidonic acid metabolism, chemosensasory function, and circadian rhythm. Collectively, these findings deepen the understanding of L. crocea evolution and provide valuable genomic resources for its conservation and breeding. Advanced Science, Volume 12, Issue 43, November 20, 2025.

Human Brain Cell‐Type‐Specific Aging Clocks Based on Single‐Nuclei Transcriptomics

Muralidharan and colleagues develop cell‐type‐specific transcriptomic aging clocks using single‐nucleus RNA sequencing of human post mortem prefrontal cortex samples. These clocks accurately predict age and identify distinct aging trajectories in specific brain cell types. Their method also detects accelerated aging in Alzheimer's disease and schizophrenia, offering insight into differential brain aging across health and disease. Abstract Aging is the primary risk factor for most neurodegenerative diseases, yet the cell‐type‐specific progression of brain aging remains poorly understood. Here, human cell‐type‐specific transcriptomic aging clocks are developed using high‐quality single‐nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18–94 years, encompassing 73,941 high‐quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single‐nucleus RNA‐sequencing datasets, underscoring their broad applicability. Notably, cell‐type‐specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell‐type‐specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases. Muralidharan and colleagues develop cell-type-specific transcriptomic aging clocks using single-nucleus RNA sequencing of human post mortem prefrontal cortex samples. These clocks accurately predict age and identify distinct aging trajectories in specific brain cell types. Their method also detects accelerated aging in Alzheimer's disease and schizophrenia, offering insight into differential brain aging across health and disease. Abstract Aging is the primary risk factor for most neurodegenerative diseases, yet the cell-type-specific progression of brain aging remains poorly understood. Here, human cell-type-specific transcriptomic aging clocks are developed using high-quality single-nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18–94 years, encompassing 73,941 high-quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single-nucleus RNA-sequencing datasets, underscoring their broad applicability. Notably, cell-type-specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell-type-specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases. Advanced Science, Volume 12, Issue 43, November 20, 2025.

A Redox‐Active and Electroactive Hydrogel Enabled by an Integrated PEDOT@PMOF Nanofiller for Post‐Infarct Myocardial Repair

An integrated nanoparticle PEDOT@PMOF is constructed as a redox‐active nanozyme and electroactive nanofiller in a cell‐affinity hydrogel platform for acute MI treatment. It is demonstrated that MOF‐based nanozymes have good catalytic ability, and the incorporation of PEDOT increases the conductivity. This work provides a promising strategy to combine ROS‐scavenging and electrical coupling reconstruction therapies for future applications. Abstract Injury and apoptosis of cardiomyocytes (CMs) lead to the excessive accumulation of reactive oxygen species (ROS) within the infarcted region, which affects the viability of healthy CMs in the border zone and contributes to the progressive enlargement of the infarct area. The subsequent replacement of necrotic myocardium with fibrotic tissue disrupts normal electrophysiological conduction pathways. This study develops a multifunctional hydrogel, TAlg/PEDOT@PMOF, incorporating an integrated PEDOT@PMOF nanofiller designed to simultaneously scavenge ROS and restore electrical coupling following myocardial infarction (MI). The ROS‐neutralizing capability of the nanofiller stems from the manganese porphyrin, which closely emulates the catalytically active site of native antioxidant enzymes. To increase electrical conductivity, the conductive polymer PEDOT is immobilized onto the MOF structure via a polydopamine (PDA) adhesion layer. Furthermore, the hydrogel network is functionalized with cell‐adhesion peptides, enabling a synergistic enhancement of ROS clearance and electrical signal transmission by the nanofiller at both the cellular and tissue scales. This dual functionality is evidenced by improved cytoprotection under oxidative stress, enhanced calcium transient in cardiomyocytes, restoration of cardiac function, and reduced susceptibility to arrhythmia. These results establish an effective strategy for engineering an integrated enzyme‐mimicking system and highlight a practical and innovative approach for future MI therapy. An integrated nanoparticle PEDOT@PMOF is constructed as a redox-active nanozyme and electroactive nanofiller in a cell-affinity hydrogel platform for acute MI treatment. It is demonstrated that MOF-based nanozymes have good catalytic ability, and the incorporation of PEDOT increases the conductivity. This work provides a promising strategy to combine ROS-scavenging and electrical coupling reconstruction therapies for future applications. Abstract Injury and apoptosis of cardiomyocytes (CMs) lead to the excessive accumulation of reactive oxygen species (ROS) within the infarcted region, which affects the viability of healthy CMs in the border zone and contributes to the progressive enlargement of the infarct area. The subsequent replacement of necrotic myocardium with fibrotic tissue disrupts normal electrophysiological conduction pathways. This study develops a multifunctional hydrogel, TAlg/PEDOT@PMOF, incorporating an integrated PEDOT@PMOF nanofiller designed to simultaneously scavenge ROS and restore electrical coupling following myocardial infarction (MI). The ROS-neutralizing capability of the nanofiller stems from the manganese porphyrin, which closely emulates the catalytically active site of native antioxidant enzymes. To increase electrical conductivity, the conductive polymer PEDOT is immobilized onto the MOF structure via a polydopamine (PDA) adhesion layer. Furthermore, the hydrogel network is functionalized with cell-adhesion peptides, enabling a synergistic enhancement of ROS clearance and electrical signal transmission by the nanofiller at both the cellular and tissue scales. This dual functionality is evidenced by improved cytoprotection under oxidative stress, enhanced calcium transient in cardiomyocytes, restoration of cardiac function, and reduced susceptibility to arrhythmia. These results establish an effective strategy for engineering an integrated enzyme-mimicking system and highlight a practical and innovative approach for future MI therapy. Advanced Science, Volume 12, Issue 43, November 20, 2025.