Search Medical Journals & Research Articles

CRISPR‐MI and scRNA‐Seq Reveal TREM2's Function in Monocyte Infiltration and Macrophage Apoptosis During Abdominal Aortic Aneurysm Development

A method is developed for conducting genome‐wide CRISPR/Cas9 screening of monocyte infiltration in vivo (CRISPR‐MI) that is easily adaptable across a variety of disease models. Through the combination of CRISPR‐MI and scRNA‐Seq, this study discovers that Trem2 is a key regulator of early monocyte infiltration in abdominal aortic aneurysm (AAA). Abstract Abdominal aortic aneurysm (AAA) is a life‐threatening aortic disease without effective medication. The infiltration of monocytes into the aortic wall is critical for AAA development, but the genes and pathways regulating this process remain to be elucidated. A novel method is developed for in vivo genome‐wide CRISPR/Cas9 screening of monocyte infiltration (CRISPR‐MI). By combining CRISPR‐MI with single‐cell RNA sequencing (scRNA‐Seq), this study finds that Triggering receptor expressed on myeloid cells 2 (Trem2) is a negative regulator of monocyte infiltration into the aortic wall in early AAA induction. Trem2 knockout (KO) increases the expression of adhesion molecules, chemotactic receptors, and cytokines in monocytes. Trem2 KO promotes monocyte adhesion and migration in vitro and increases monocyte infiltration into the aortic wall in vivo. However, Trem2 KO attenuates AAA development because of prominent macrophage death at the late stage. In conclusion, CRISPR‐MI is a powerful tool for studying genes underlying monocyte infiltration in disease conditions in vivo. These findings reveal a dichotomous role of Trem2 in monocyte recruitment and macrophage survival during AAA. A method is developed for conducting genome-wide CRISPR/Cas9 screening of monocyte infiltration in vivo (CRISPR-MI) that is easily adaptable across a variety of disease models. Through the combination of CRISPR-MI and scRNA-Seq, this study discovers that Trem2 is a key regulator of early monocyte infiltration in abdominal aortic aneurysm (AAA). Abstract Abdominal aortic aneurysm (AAA) is a life-threatening aortic disease without effective medication. The infiltration of monocytes into the aortic wall is critical for AAA development, but the genes and pathways regulating this process remain to be elucidated. A novel method is developed for in vivo genome-wide CRISPR/Cas9 screening of monocyte infiltration (CRISPR-MI). By combining CRISPR-MI with single-cell RNA sequencing (scRNA-Seq), this study finds that Triggering receptor expressed on myeloid cells 2 ( Trem2) is a negative regulator of monocyte infiltration into the aortic wall in early AAA induction. Trem2 knockout (KO) increases the expression of adhesion molecules, chemotactic receptors, and cytokines in monocytes. Trem2 KO promotes monocyte adhesion and migration in vitro and increases monocyte infiltration into the aortic wall in vivo. However, Trem2 KO attenuates AAA development because of prominent macrophage death at the late stage. In conclusion, CRISPR-MI is a powerful tool for studying genes underlying monocyte infiltration in disease conditions in vivo. These findings reveal a dichotomous role of Trem2 in monocyte recruitment and macrophage survival during AAA. Advanced Science, Volume 12, Issue 48, December 29, 2025.

SERS‐AI‐LUA‐Driven Salivary Diagnosis of Head and Neck Cancer Using Graphene‐Assisted Plasmonic Nanocorals

The developed graphene‐assisted plasmonic nanocoral platform enables sensitive, label‐free surface‐enhanced Raman scattering analysis of salivary metabolites for head and neck cancer (HNC) detection. When combined with machine learning classification and nonnegative least squares‐based spectral deconvolution, this approach achieves 98% diagnostic accuracy in distinguishing HNC patients from healthy controls. Furthermore, the method identifies 15 potential biomarkers consistent with clinical findings, establishing a powerful framework for artificial intelligence‐integrated, noninvasive cancer diagnostics using saliva. Abstract The early detection of head and neck cancer (HNC) remains an important challenge owing to the lack of reliable noninvasive biomarkers. This study introduces a graphene‐assisted plasmonic nanocoral platform coupled with an artificial intelligence‐linear unmixing algorithm for diagnosing HNC from saliva and identifying associated metabolic biomarkers. The nanocoral structures, formed via a spontaneous gold growth mechanism on graphene templates, exhibit strong plasmonic enhancement and selective adsorption of volatile metabolites. Raman signals acquired from the saliva of HNC patients and healthy individuals are analyzed using a logistic regression model, achieving 98% classification accuracy. To identify potential metabolic biomarkers, candidate metabolites are initially selected based on spectral similarity using the Pearson correlation coefficient. Subsequently, the nonnegative least squares method is applied to refine this selection and extract the final set of biomarker candidates. This approach identifies 15 potential metabolic biomarkers, and their clinical relevance is corroborated through comparison with the findings of previous clinical studies. This study not only introduces a highly sensitive, noninvasive diagnostic platform for HNC but also establishes a robust framework for Raman‐based biomarker discovery, with potential applicability that warrants evaluation in other biofluid‐based disease models in future studies. The developed graphene-assisted plasmonic nanocoral platform enables sensitive, label-free surface-enhanced Raman scattering analysis of salivary metabolites for head and neck cancer (HNC) detection. When combined with machine learning classification and nonnegative least squares-based spectral deconvolution, this approach achieves 98% diagnostic accuracy in distinguishing HNC patients from healthy controls. Furthermore, the method identifies 15 potential biomarkers consistent with clinical findings, establishing a powerful framework for artificial intelligence-integrated, noninvasive cancer diagnostics using saliva. Abstract The early detection of head and neck cancer (HNC) remains an important challenge owing to the lack of reliable noninvasive biomarkers. This study introduces a graphene-assisted plasmonic nanocoral platform coupled with an artificial intelligence-linear unmixing algorithm for diagnosing HNC from saliva and identifying associated metabolic biomarkers. The nanocoral structures, formed via a spontaneous gold growth mechanism on graphene templates, exhibit strong plasmonic enhancement and selective adsorption of volatile metabolites. Raman signals acquired from the saliva of HNC patients and healthy individuals are analyzed using a logistic regression model, achieving 98% classification accuracy. To identify potential metabolic biomarkers, candidate metabolites are initially selected based on spectral similarity using the Pearson correlation coefficient. Subsequently, the nonnegative least squares method is applied to refine this selection and extract the final set of biomarker candidates. This approach identifies 15 potential metabolic biomarkers, and their clinical relevance is corroborated through comparison with the findings of previous clinical studies. This study not only introduces a highly sensitive, noninvasive diagnostic platform for HNC but also establishes a robust framework for Raman-based biomarker discovery, with potential applicability that warrants evaluation in other biofluid-based disease models in future studies. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Osmotically Tunable Microdroplets Enable Amplification‐Free CRISPR Detection of Gene Doping

A novel amplification‐free clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein (CRISPR/Cas) 12a assay is integrated with osmotically shrinkable double emulsion droplets for the rapid and ultrasensitive detection of gene doping. Controlled droplet shrinkage concentrates cleaved reporters, significantly enhancing signal intensity and achieving a 25‐fold improved detection limit, independent of nucleic acid amplification. Abstract Gene doping is an increasing challenge in sports, demanding highly sensitive and specific detection tools beyond the limitations of the current amplification‐dependent methods. Here, an innovative amplification‐free clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein (CRISPR/Cas) 12a assay integrated with osmotically tunable double emulsion (DE) droplets is reported for rapid and ultrasensitive gene doping detection. Target DNA and CRISPR/Cas12a complexes are encapsulated within DE droplets, where osmotic shrinkage rapidly concentrates the reaction components, thereby enhancing the fluorescent signal intensity without nucleic acid amplification. This platform enables the detection of the human erythropoietin (hEPO) gene at unprecedented attomolar levels within 30 min, achieving a 25‐fold improvement in sensitivity compared with that of nonshrinkable formats. Notably, the assay demonstrated a robust and specific performance in complex serum samples with minimal matrix interference. This novel approach offers a rapid, reliable, and inherently contamination‐free solution for gene doping surveillance with broad potential for versatile amplification‐free nucleic acid diagnostics. A novel amplification-free clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) 12a assay is integrated with osmotically shrinkable double emulsion droplets for the rapid and ultrasensitive detection of gene doping. Controlled droplet shrinkage concentrates cleaved reporters, significantly enhancing signal intensity and achieving a 25-fold improved detection limit, independent of nucleic acid amplification. Abstract Gene doping is an increasing challenge in sports, demanding highly sensitive and specific detection tools beyond the limitations of the current amplification-dependent methods. Here, an innovative amplification-free clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) 12a assay integrated with osmotically tunable double emulsion (DE) droplets is reported for rapid and ultrasensitive gene doping detection. Target DNA and CRISPR/Cas12a complexes are encapsulated within DE droplets, where osmotic shrinkage rapidly concentrates the reaction components, thereby enhancing the fluorescent signal intensity without nucleic acid amplification. This platform enables the detection of the human erythropoietin ( hEPO ) gene at unprecedented attomolar levels within 30 min, achieving a 25-fold improvement in sensitivity compared with that of nonshrinkable formats. Notably, the assay demonstrated a robust and specific performance in complex serum samples with minimal matrix interference. This novel approach offers a rapid, reliable, and inherently contamination-free solution for gene doping surveillance with broad potential for versatile amplification-free nucleic acid diagnostics. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Boosting Electrochemical Capacitive of Ultrathin Shower‐Pouf Birnessite‐Type MnO2 for Porous High‐Mass‐Loading Energy Storage Device

Ultrathin Shower‐pouf Birnessite‐type MnO2 (thickness: ~3 nm) has been fabricated via the specific adsorption of fluoride ions on the (001) crystal plane of birnessite. By constructing an electrically conductive network and optimizing electrode slurry concentration, the electrode mass loading can be substantially improved. These electrodes also exhibit excellent capacitive properties, thereby being suitable for high‐mass‐loading energy storage devices. Abstract High‐mass‐loading electrodes are critical for the economic viability and practicability of energy storage devices. Here, shower‐pouf‐like birnessite (SPB) with dense‐core‐free nanostructures are synthesized via a cost‐effective strategy, which significantly reduces the content of electrochemical dead mass caused by insufficient ion diffusion. Ascribed to the F− (from NH4F) adsorbed on the (001) crystal plane of birnessite, the thickness of ultrathin birnessite films is regulated to ≈3 nm, providing abundant electrochemical active sites. By constructing high‐speed electronic transfer routes with conductive carbon black (CCB) and carbon nanotubes (CNTs), an SPB/CCB/CNTs electrode delivers a high capacitance of 278.6 F g−1 with an optimal high mass loading of 15.3 mg cm−2. Based on the optimized slurry, the power‐law b‐values, Ohmic resistance and cycling stability can be improved dramatically with increasing mass loading. Hence, a high‐mass‐loading asymmetric supercapacitor, assembled by SPB/CCB/CNTs nanostructure and hierarchical porous carbon composites (HPC/CCB/CNTs), delivers a capacitance of 1.75 F cm−2 and a record areal energy density of 0.97 mWh cm−2 (39.6 Wh kg−1). Moreover, A PV‐SC (photovoltaic‐supercapacitor) system driven mechanical vehicle achieves a travel distance of 4.8 m after being charged for 60 s in sunlight, highlighting the practical application prospect of SPB based high‐mass‐loading electrodes. Ultrathin Shower-pouf Birnessite-type MnO 2 (thickness: ~3 nm) has been fabricated via the specific adsorption of fluoride ions on the (001) crystal plane of birnessite. By constructing an electrically conductive network and optimizing electrode slurry concentration, the electrode mass loading can be substantially improved. These electrodes also exhibit excellent capacitive properties, thereby being suitable for high-mass-loading energy storage devices. Abstract High-mass-loading electrodes are critical for the economic viability and practicability of energy storage devices. Here, shower-pouf-like birnessite (SPB) with dense-core-free nanostructures are synthesized via a cost-effective strategy, which significantly reduces the content of electrochemical dead mass caused by insufficient ion diffusion. Ascribed to the F − (from NH 4 F) adsorbed on the (001) crystal plane of birnessite, the thickness of ultrathin birnessite films is regulated to ≈3 nm, providing abundant electrochemical active sites. By constructing high-speed electronic transfer routes with conductive carbon black (CCB) and carbon nanotubes (CNTs), an SPB/CCB/CNTs electrode delivers a high capacitance of 278.6 F g −1 with an optimal high mass loading of 15.3 mg cm −2. Based on the optimized slurry, the power-law b -values, Ohmic resistance and cycling stability can be improved dramatically with increasing mass loading. Hence, a high-mass-loading asymmetric supercapacitor, assembled by SPB/CCB/CNTs nanostructure and hierarchical porous carbon composites (HPC/CCB/CNTs), delivers a capacitance of 1.75 F cm −2 and a record areal energy density of 0.97 mWh cm −2 (39.6 Wh kg −1 ). Moreover, A PV-SC (photovoltaic-supercapacitor) system driven mechanical vehicle achieves a travel distance of 4.8 m after being charged for 60 s in sunlight, highlighting the practical application prospect of SPB based high-mass-loading electrodes. Advanced Science, Volume 12, Issue 48, December 29, 2025.

RNA G‐Quadruplex RIBOTAC‐Mediated Targeted Degradation of lncRNA TERRA

This study introduces a selective RNA degradation strategy targeting long noncoding RNA (lncRNA) TERRA, upregulated in ALT (alternative lengthening of telomeres) cancer cells. Using ribonuclease‐targeting chimeras (RIBOTACs), RNase L is recruited to catalytically degrade TERRA, uncovering a novel approach to affect a disease associated lncRNA in ALT‐driven cancers. Abstract Long noncoding RNAs (lncRNAs) regulate gene expression and play crucial roles in development and disease, including cancer. One important but still poorly understood lncRNA is TERRA (telomeric repeat‐containing RNA), transcribed from telomeres and essential for telomere maintenance, genome stability, and cellular aging. TERRA adopts two structural features,R‐loops and G‐quadruplexes (G4s), that drive its biological activity. Its dysregulation is linked to telomere dysfunction and is prominent in Alternative Lengthening of Telomeres (ALT) cancers, where TERRA is highly upregulated and promotes telomere recombination. Here, first‐in‐class small molecules targeting TERRA using RIBOTAC (Ribonuclease‐Targeting Chimera) technology is developed. These compounds selectively bind TERRA's G4 structures and recruit RNase L, inducing its degradation while sparing DNA G4s and other G4 RNAs. This selectivity results from ternary complex formation with RNase L and the repetitive G4 motifs enriched in TERRA. TERRA‐RIBOTACs in HeLa and U2OS cells, the latter representing an ALT cancer model, are evaluated. TERRA degradation, particularly at 7p, 13q, 15q, and 20q loci, impairs telomere function and reduces colony formation. Manipulating lncRNAs like TERRA with chemical tools opens new avenues for drug development and deepens the understanding of RNA‐based regulation in cancer biology. This study introduces a selective RNA degradation strategy targeting long noncoding RNA (lncRNA) TERRA, upregulated in ALT (alternative lengthening of telomeres) cancer cells. Using ribonuclease-targeting chimeras (RIBOTACs), RNase L is recruited to catalytically degrade TERRA, uncovering a novel approach to affect a disease associated lncRNA in ALT-driven cancers. Abstract Long noncoding RNAs (lncRNAs) regulate gene expression and play crucial roles in development and disease, including cancer. One important but still poorly understood lncRNA is TERRA (telomeric repeat-containing RNA), transcribed from telomeres and essential for telomere maintenance, genome stability, and cellular aging. TERRA adopts two structural features,R-loops and G-quadruplexes (G4s), that drive its biological activity. Its dysregulation is linked to telomere dysfunction and is prominent in Alternative Lengthening of Telomeres (ALT) cancers, where TERRA is highly upregulated and promotes telomere recombination. Here, first-in-class small molecules targeting TERRA using RIBOTAC (Ribonuclease-Targeting Chimera) technology is developed. These compounds selectively bind TERRA's G4 structures and recruit RNase L, inducing its degradation while sparing DNA G4s and other G4 RNAs. This selectivity results from ternary complex formation with RNase L and the repetitive G4 motifs enriched in TERRA. TERRA-RIBOTACs in HeLa and U2OS cells, the latter representing an ALT cancer model, are evaluated. TERRA degradation, particularly at 7p, 13q, 15q, and 20q loci, impairs telomere function and reduces colony formation. Manipulating lncRNAs like TERRA with chemical tools opens new avenues for drug development and deepens the understanding of RNA-based regulation in cancer biology. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Abrupt and Reversible Stretching in an Azobenzene Single Crystal via Thermal Phase Transition

Crystals of azobenzene compounds exhibit abrupt and reversible stretching and shrinking in response to thermal and photo stimulation. The single‐crystal‐to‐single‐crystal phase transition between two polymorphs involving reorientation of CH–π hydrogen interactions are demonstrated. Furthermore, the abrupt photoinduced stretching of the crystals is used to trigger microparticle transportation. Abstract Mechanically responsive crystals are promising for actuators and microrobotics; however, achieving large reversible deformation with high durability remains challenging. Herein, A single‐component azobenzene crystal is reported to exhibit an abrupt and reversible stretching of over 8% along its long axis, driven by a thermally induced single‐crystal‐to‐single‐crystal phase transition. Single‐crystal X‐ray diffraction revealed a significant change in molecular packing distance along the long axis accompanied by the reorientation of CH–π interactions, leading to large macroscopic stretching/shrinking. Furthermore, visible light (435 nm) induced rapid, localized, and reversible stretching of the crystal via the photothermal effect, enabling the remote control of microparticle motion. This study reveals a rare combination of large anisotropic deformation, reversibility, and light responsiveness in a single‐component organic crystal, offering a new molecular platform for advancing micro‐energy conversion and soft robotics. Crystals of azobenzene compounds exhibit abrupt and reversible stretching and shrinking in response to thermal and photo stimulation. The single-crystal-to-single-crystal phase transition between two polymorphs involving reorientation of CH–π hydrogen interactions are demonstrated. Furthermore, the abrupt photoinduced stretching of the crystals is used to trigger microparticle transportation. Abstract Mechanically responsive crystals are promising for actuators and microrobotics; however, achieving large reversible deformation with high durability remains challenging. Herein, A single-component azobenzene crystal is reported to exhibit an abrupt and reversible stretching of over 8% along its long axis, driven by a thermally induced single-crystal-to-single-crystal phase transition. Single-crystal X-ray diffraction revealed a significant change in molecular packing distance along the long axis accompanied by the reorientation of CH–π interactions, leading to large macroscopic stretching/shrinking. Furthermore, visible light (435 nm) induced rapid, localized, and reversible stretching of the crystal via the photothermal effect, enabling the remote control of microparticle motion. This study reveals a rare combination of large anisotropic deformation, reversibility, and light responsiveness in a single-component organic crystal, offering a new molecular platform for advancing micro-energy conversion and soft robotics. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Synergistic Electrocatalytic N2 Reduction over Asymmetric Heteronuclear Dual Ru‐Fe Sites

A heteronuclear Ru‐Fe dual atom catalyst with asymmetryic coordination environment anchored on N,S‐codoped Ti3C2Tx nanosheet is reported. The asymmetric dual Ru‐Fe sites breaks the scaling relationship and synergistically improve eNRR efficiency. Abstract The scaling relationship limit poses a significant challenge in single‐atom catalysts (SACs) for reactions involving multi‐intermediate interactions, such as the electrocatalytic nitrogen reduction reaction (eNRR) for ammonia synthesis. To overcome this limitation, a heteronuclear dual Ru‐Fe sites on N,S‐codoped Ti3C2Tx nanosheet (referred to as Fe1‐N^S‐Ru1/Ti3C2Tx) with precisely designed asymmetric coordination for eNRR is developed. Advanced characterizations verify the unique asymmetric coordination structure where Ru and Fe atoms are individually coordinated to N and S atoms, respectively, with the two metal centers interconnected via bridging N and S atoms. This catalyst achieves remarkable eNRR performance with an NH3 yield rate of 32.8 µg h−1 mg−1cat at −0.55 V and 47.1% Faradaic efficiency at −0.25 V, surpassing its homonuclear analogues by 3.2‐ and 2.3‐fold in activity and ≈3.0‐fold in selectivity. Experimental and theoretical studies reveal a synergistic mechanism, in which Ru sites effectively dissociate H2O to supply protons while the adjacent Fe sites selectively activate N2, effectively decoupling proton supply from N2 activation but also benefiting the formation of key intermediate *NNH. Additionally, the electronic interaction between Ru and Fe sites also lowers the energy barrier of the rate‐determining step, thereby significantly enhancing catalytic activity and selectivity. A heteronuclear Ru-Fe dual atom catalyst with asymmetryic coordination environment anchored on N,S-codoped Ti 3 C 2 T x nanosheet is reported. The asymmetric dual Ru-Fe sites breaks the scaling relationship and synergistically improve eNRR efficiency. Abstract The scaling relationship limit poses a significant challenge in single-atom catalysts (SACs) for reactions involving multi-intermediate interactions, such as the electrocatalytic nitrogen reduction reaction (eNRR) for ammonia synthesis. To overcome this limitation, a heteronuclear dual Ru-Fe sites on N,S-codoped Ti 3 C 2 T x nanosheet (referred to as Fe 1 -N^S-Ru 1 /Ti 3 C 2 T x ) with precisely designed asymmetric coordination for eNRR is developed. Advanced characterizations verify the unique asymmetric coordination structure where Ru and Fe atoms are individually coordinated to N and S atoms, respectively, with the two metal centers interconnected via bridging N and S atoms. This catalyst achieves remarkable eNRR performance with an NH 3 yield rate of 32.8 µg h −1 mg −1 cat at −0.55 V and 47.1% Faradaic efficiency at −0.25 V, surpassing its homonuclear analogues by 3.2- and 2.3-fold in activity and ≈3.0-fold in selectivity. Experimental and theoretical studies reveal a synergistic mechanism, in which Ru sites effectively dissociate H 2 O to supply protons while the adjacent Fe sites selectively activate N 2, effectively decoupling proton supply from N 2 activation but also benefiting the formation of key intermediate * NNH. Additionally, the electronic interaction between Ru and Fe sites also lowers the energy barrier of the rate-determining step, thereby significantly enhancing catalytic activity and selectivity. Advanced Science, Volume 12, Issue 48, December 29, 2025.

MnO2 Nanosponge‐Accelerated Cas12a Trans‐Cleavage: Breaking the Kinetic Barrier for In Vivo RNA Imaging

A Cas12a@MnO2 nanosponge (hMNS) nanoprobe is engineered to overcome the intracellular delivery and kinetic barrier of the conventional CRISPR/Cas12a system via GSH‐responsive release and Mn2⁺‐enhanced trans‐cleavage. It enables preamplification‐free detection of mRNA with single‐cell sensitivity, differentiation of mRNA expression between breast cancer tissues and their healthy counterparts, and real‐time tracking of mRNA dynamics in living cells. Abstract CRISPR/Cas12a system has emerged as a promising tool for in vitro biosensing, but its in vivo applications are hindered by its inefficient intracellular delivery and suboptimal trans‐cleavage kinetics. To address these challenges, a Cas12a@MnO2 nanosponge (hMNS) nanoprobe is constructed, in which hMNS as both a degradable carrier and an accelerator of CRISPR/Cas12a system for efficient imaging of RNA in living cells. The Cas12a@hMNS nanoprobe is obtained via a one‐step co‐assembly process. It not only facilitates synchronous cellular uptake and glutathione (GSH)‐responsive release of CRISPR/Cas12a components, but also supplies adequate Mn2+ cofactors to improve the trans‐cleavage activity of Cas12a. This dual‐function probe can break the kinetic barrier of conventional CRISPR/Cas12a systems due to its unique characteristics of effective cellular internalization, rapid intracellular release, and accelerated signal gain, enabling sensitive detection of mRNA down to 63.6 pM without pre‐amplification. Moreover, the Cas12a@hMNS nanoprobe can profile endogenous mRNA at the single‐cell level, discriminate breast cancer tissues from healthy counterparts, and real‐time visualize mRNA dynamics in living cells with exceptional spatiotemporal precision. Importantly, the elongation‐blocked (EB) activator‐modulated CRISPR/Cas12a system can be extended to detect various intracellular biomarkers, holding promising applications in clinical diagnosis, treatment, and surveillance. A Cas12a@MnO 2 nanosponge (hMNS) nanoprobe is engineered to overcome the intracellular delivery and kinetic barrier of the conventional CRISPR/Cas12a system via GSH-responsive release and Mn 2 ⁺-enhanced trans -cleavage. It enables preamplification-free detection of mRNA with single-cell sensitivity, differentiation of mRNA expression between breast cancer tissues and their healthy counterparts, and real-time tracking of mRNA dynamics in living cells. Abstract CRISPR/Cas12a system has emerged as a promising tool for in vitro biosensing, but its in vivo applications are hindered by its inefficient intracellular delivery and suboptimal trans -cleavage kinetics. To address these challenges, a Cas12a@MnO 2 nanosponge (hMNS) nanoprobe is constructed, in which hMNS as both a degradable carrier and an accelerator of CRISPR/Cas12a system for efficient imaging of RNA in living cells. The Cas12a@hMNS nanoprobe is obtained via a one-step co-assembly process. It not only facilitates synchronous cellular uptake and glutathione (GSH)-responsive release of CRISPR/Cas12a components, but also supplies adequate Mn 2+ cofactors to improve the trans -cleavage activity of Cas12a. This dual-function probe can break the kinetic barrier of conventional CRISPR/Cas12a systems due to its unique characteristics of effective cellular internalization, rapid intracellular release, and accelerated signal gain, enabling sensitive detection of mRNA down to 63.6 pM without pre-amplification. Moreover, the Cas12a@hMNS nanoprobe can profile endogenous mRNA at the single-cell level, discriminate breast cancer tissues from healthy counterparts, and real-time visualize mRNA dynamics in living cells with exceptional spatiotemporal precision. Importantly, the elongation-blocked (EB) activator-modulated CRISPR/Cas12a system can be extended to detect various intracellular biomarkers, holding promising applications in clinical diagnosis, treatment, and surveillance. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Mechanism of Carbon Diffusion and Phase‐Transition‐Induced FCC‐TiC Formation via Hot Pressing

A solid‐state diffusion bonding steel‐titanium interface is designed, revealing the formation of continuous micro–nano‐sized FCC‐TiC grains at the interface. Carbon atoms occupying the octahedral interstice in the FCC‐TiC lattice are directly observed. The study shows that FCC‐TiC formation is driven by carbon diffusion and titanium phase transformation, providing new insights into atomic‐scale regulation of titanium carbide. Abstract Titanium carbide (TiC), which typically forms at the solid‐state diffusion interface in steel–titanium (Ti) composite structures, significantly influences steel–Ti interface bonding. However, the atomic‐level formation mechanism of this carbide remains unclear. Herein, the TiC crystal structure and formation mechanism are investigated through experiments involving TA2 pure Ti and 45# carbon steel under solid‐state diffusion conditions. Analysis of the solid‐state diffusion behavior between the steel and Ti, based on selected area electron diffraction, reveals the formation of a continuous micro–nano TiC layer with a balanced (FCC) crystal structure on the substrate near the Ti side of the interface. Using the integrated differential phase contrast technique, occupation of the octahedral interstices in the FCC‐TiC lattice by carbon (C) atoms is confirmed for the first time. Additionally, it is suggested that C diffusion and phase transformation jointly induce the FCC‐TiC crystal phase transformation under hot‐pressing conditions. Finally, the atomic‐scale TiC formation mechanism is elucidated. The findings of this study may guide the design and development of high‐performance materials with unique properties for aerospace equipment manufacturing. A solid-state diffusion bonding steel-titanium interface is designed, revealing the formation of continuous micro–nano-sized FCC-TiC grains at the interface. Carbon atoms occupying the octahedral interstice in the FCC-TiC lattice are directly observed. The study shows that FCC-TiC formation is driven by carbon diffusion and titanium phase transformation, providing new insights into atomic-scale regulation of titanium carbide. Abstract Titanium carbide (TiC), which typically forms at the solid-state diffusion interface in steel–titanium (Ti) composite structures, significantly influences steel–Ti interface bonding. However, the atomic-level formation mechanism of this carbide remains unclear. Herein, the TiC crystal structure and formation mechanism are investigated through experiments involving TA2 pure Ti and 45# carbon steel under solid-state diffusion conditions. Analysis of the solid-state diffusion behavior between the steel and Ti, based on selected area electron diffraction, reveals the formation of a continuous micro–nano TiC layer with a balanced (FCC) crystal structure on the substrate near the Ti side of the interface. Using the integrated differential phase contrast technique, occupation of the octahedral interstices in the FCC-TiC lattice by carbon (C) atoms is confirmed for the first time. Additionally, it is suggested that C diffusion and phase transformation jointly induce the FCC-TiC crystal phase transformation under hot-pressing conditions. Finally, the atomic-scale TiC formation mechanism is elucidated. The findings of this study may guide the design and development of high-performance materials with unique properties for aerospace equipment manufacturing. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Intelligent Sensing: The Emerging Integration of Machine Learning and Soft Sensors Based on Hydrogels and Ionogels

By integrating with machine learning (ML), hydrogel‐ and ionogel‐based soft sensors are gaining human brain‐like capabilities to perceive, learn, and predict. This review summarizes their advances, focusing on ML‐powered applications such as handwriting/gesture/object/motion/speech recognition, health monitoring, food detection, and beyond. This integration is accelerating development in human‐machine interfaces, healthcare, and soft robotics. Abstract Intelligent sensing means the capability of systems to perceive, learn, analyze, and predict based on external stimuli, mimicking the cognitive functions of the human brain. With the assistance of machine learning algorithms for data processing, soft sensors made from hydrogels and ionogels possess intelligent sensing abilities. Here, the recent advances of hydrogel‐ and ionogel‐based soft sensors are comprehensively investigated and summarized, with a specific focus on machine learning‐implemented applications, including handwriting/gesture/object/motion/speech recognition, health monitoring, food detection, and beyond. With current limitations and future perspectives discussed, the fusion of the two is envisioned that can accelerate the development of intelligent sensing in the areas of human‐machine interface (HMI), health care, and soft robotics. By integrating with machine learning (ML), hydrogel- and ionogel-based soft sensors are gaining human brain-like capabilities to perceive, learn, and predict. This review summarizes their advances, focusing on ML-powered applications such as handwriting/gesture/object/motion/speech recognition, health monitoring, food detection, and beyond. This integration is accelerating development in human-machine interfaces, healthcare, and soft robotics. Abstract Intelligent sensing means the capability of systems to perceive, learn, analyze, and predict based on external stimuli, mimicking the cognitive functions of the human brain. With the assistance of machine learning algorithms for data processing, soft sensors made from hydrogels and ionogels possess intelligent sensing abilities. Here, the recent advances of hydrogel- and ionogel-based soft sensors are comprehensively investigated and summarized, with a specific focus on machine learning-implemented applications, including handwriting/gesture/object/motion/speech recognition, health monitoring, food detection, and beyond. With current limitations and future perspectives discussed, the fusion of the two is envisioned that can accelerate the development of intelligent sensing in the areas of human-machine interface (HMI), health care, and soft robotics. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Nanomedicines Against Mitochondrial Dysfunction‐Induced Metabolic Diseases

Mitochondrial dysfunction is central to metabolic diseases. Nanomedicine offers transformative approaches for restoring function via targeted delivery, responsive release, and multimodal therapy. This review outlines the pathological basis, nanocarrier design, organelle‐specific targeting, recent advances, and future clinical translation challenges. Abstract Mitochondrial dysfunction is a common pathology for metabolic diseases such as obesity, diabetes, non‐alcoholic fatty liver disease, atherosclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD). Nanomedicines provide a revolutionary strategy for mitochondrial function repair. They can realize targeted delivery, responsive release, and integration of multimodal therapies through nanotechnology and engineering and overcome limitations of traditional therapeutic methods, such as insufficient targeting, low bioavailability, and toxic side effects. In this article, the pathological characteristics of mitochondria are first introduced, and the relationship between mitochondrial dysfunction and metabolic diseases are illustrated. Structural features and design strategies of nanomedicines targeting mitochondrial dysfunction are summarized, with particular elaboration on targeting strategies and response mechanisms for diseased organs and subcellular organelles such as the liver, adipose tissue, atherosclerotic plaques, the brain, and mitochondria. The application and clinical translation of nanomedicines in obesity, atherosclerosis, diabetes, non‐alcoholic fatty liver disease (NAFLD), and brain metabolic disorders are detailed. This article is concluded with a summary and outlook of the current research status, challenges, and future development directions. Mitochondrial dysfunction is central to metabolic diseases. Nanomedicine offers transformative approaches for restoring function via targeted delivery, responsive release, and multimodal therapy. This review outlines the pathological basis, nanocarrier design, organelle-specific targeting, recent advances, and future clinical translation challenges. Abstract Mitochondrial dysfunction is a common pathology for metabolic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, Alzheimer's disease (AD), and Parkinson's disease (PD). Nanomedicines provide a revolutionary strategy for mitochondrial function repair. They can realize targeted delivery, responsive release, and integration of multimodal therapies through nanotechnology and engineering and overcome limitations of traditional therapeutic methods, such as insufficient targeting, low bioavailability, and toxic side effects. In this article, the pathological characteristics of mitochondria are first introduced, and the relationship between mitochondrial dysfunction and metabolic diseases are illustrated. Structural features and design strategies of nanomedicines targeting mitochondrial dysfunction are summarized, with particular elaboration on targeting strategies and response mechanisms for diseased organs and subcellular organelles such as the liver, adipose tissue, atherosclerotic plaques, the brain, and mitochondria. The application and clinical translation of nanomedicines in obesity, atherosclerosis, diabetes, non-alcoholic fatty liver disease (NAFLD), and brain metabolic disorders are detailed. This article is concluded with a summary and outlook of the current research status, challenges, and future development directions. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Review on Cathode‐Electrolyte Interphase for Stabilizing Interfaces in Solid‐State Lithium Batteries

The cathode‐electrolyte interphase in solid‐state batteries faces new issues due to the solid nature of the electrolyte, including poor self‐repair of CEI, insufficient interface passivation, physical contact loss, and inferior lithium ion transport kinetics. These issues is examined from a broader perspective, promoting the proposal of a generalized CEI to solid‐state batteries. Abstract Solid‐state lithium batteries (SSLBs) hold great promise for improving battery safety and achieving higher energy density. Nevertheless, the matching diversity between solid‐state electrolytes (SEs) and the paired high‐voltage cathodes complicate to understand the formation and failure mechanisms of cathode‐electrolyte interphase (CEI). Furthermore, the structural degradation of cathodes and the electrochemical decomposition of SEs during cycling continuously reconfigure the CEI and alter the CEI composition and structure, adding further complexity to its analysis. The limited understanding of these processes hinders the development of effective strategies to address persistent cathode‐electrolyte interfacial issues (e.g., high interfacial impedance and contact loss) that shorten SSLB lifetime. A prerequisite for overcoming these challenges is to establish a comprehensive knowledge of CEI properties, which remains elusive and is often underestimated. Therefore, this review provides a comprehensive overview of the mechanisms governing CEI formation and failure, elucidating the complex nature of the interphase. Key challenges related to interfacial stability are discussed in detail, along with corresponding strategies for CEI regulation. Innovatively, an expanded conceptual CEI framework is proposed based on recent advances, facilitating a deeper understanding of CEI properties. Finally, forward‐looking perspectives are provided for designing stable CEIs and further advancing SSLB technology. The cathode-electrolyte interphase in solid-state batteries faces new issues due to the solid nature of the electrolyte, including poor self-repair of CEI, insufficient interface passivation, physical contact loss, and inferior lithium ion transport kinetics. These issues is examined from a broader perspective, promoting the proposal of a generalized CEI to solid-state batteries. Abstract Solid-state lithium batteries (SSLBs) hold great promise for improving battery safety and achieving higher energy density. Nevertheless, the matching diversity between solid-state electrolytes (SEs) and the paired high-voltage cathodes complicate to understand the formation and failure mechanisms of cathode-electrolyte interphase (CEI). Furthermore, the structural degradation of cathodes and the electrochemical decomposition of SEs during cycling continuously reconfigure the CEI and alter the CEI composition and structure, adding further complexity to its analysis. The limited understanding of these processes hinders the development of effective strategies to address persistent cathode-electrolyte interfacial issues (e.g., high interfacial impedance and contact loss) that shorten SSLB lifetime. A prerequisite for overcoming these challenges is to establish a comprehensive knowledge of CEI properties, which remains elusive and is often underestimated. Therefore, this review provides a comprehensive overview of the mechanisms governing CEI formation and failure, elucidating the complex nature of the interphase. Key challenges related to interfacial stability are discussed in detail, along with corresponding strategies for CEI regulation. Innovatively, an expanded conceptual CEI framework is proposed based on recent advances, facilitating a deeper understanding of CEI properties. Finally, forward-looking perspectives are provided for designing stable CEIs and further advancing SSLB technology. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Recent Advances in Lithium Ion/Lithium Metal Hybrid Anodes: from Design Principles to Practical Applications

Lithium‐graphite hybrid anodes offer a promising solution to the challenges of lithium metal anodes, such as dendrite growth and instability. By combining graphite's stable framework with lithium's high capacity, these anodes enable controlled plating and enhance safety. This review examines their design principles, mechanistic insights, and compatible electrolytes, connecting fundamental research to practical applications for next‐generation high‐energy batteries. Abstract Lithium metal is widely regarded as the ultimate anode material for next‐generation high‐energy‐density batteries due to its exceptional theoretical specific capacity (3860 mA h g−1) and low redox potential (−3.04 V vs standard hydrogen electrode). However, its practical application is hindered by low Coulombic efficiency, rapid capacity degradation, and severe safety risks caused by uncontrolled dendrite growth, substantial volume variations, and unstable solid electrolyte interphase formation. To address these limitations, an emerging paradigm involves the strategic integration of lithium metal with porous graphite or graphitized carbon hosts, forming lithium‐ion/lithium‐metal hybrid anodes. Such hybrid architectures utilize the synergistic advantages of both materials: graphite provides a mechanically robust, conductive framework with a well‐defined structure to regulate Li plating/stripping processes, while Li metal delivers unparalleled capacity. This review systematically summarizes recent breakthroughs in mechanistic understanding, configuration designs, and electrolyte engineering that optimize the performance of hybrid anodes for high‐energy lithium metal batteries. A critical analysis of the interfacial stabilization and the influence of electrolyte composition in improving cycling stability is conducted. Finally, a concise conclusion and prospective outlook regarding current challenges and future research opportunities in the material design and the development of compatible electrolyte systems of hybrid anode systems are proposed. Lithium-graphite hybrid anodes offer a promising solution to the challenges of lithium metal anodes, such as dendrite growth and instability. By combining graphite's stable framework with lithium's high capacity, these anodes enable controlled plating and enhance safety. This review examines their design principles, mechanistic insights, and compatible electrolytes, connecting fundamental research to practical applications for next-generation high-energy batteries. Abstract Lithium metal is widely regarded as the ultimate anode material for next-generation high-energy-density batteries due to its exceptional theoretical specific capacity (3860 mA h g −1 ) and low redox potential (−3.04 V vs standard hydrogen electrode). However, its practical application is hindered by low Coulombic efficiency, rapid capacity degradation, and severe safety risks caused by uncontrolled dendrite growth, substantial volume variations, and unstable solid electrolyte interphase formation. To address these limitations, an emerging paradigm involves the strategic integration of lithium metal with porous graphite or graphitized carbon hosts, forming lithium-ion/lithium-metal hybrid anodes. Such hybrid architectures utilize the synergistic advantages of both materials: graphite provides a mechanically robust, conductive framework with a well-defined structure to regulate Li plating/stripping processes, while Li metal delivers unparalleled capacity. This review systematically summarizes recent breakthroughs in mechanistic understanding, configuration designs, and electrolyte engineering that optimize the performance of hybrid anodes for high-energy lithium metal batteries. A critical analysis of the interfacial stabilization and the influence of electrolyte composition in improving cycling stability is conducted. Finally, a concise conclusion and prospective outlook regarding current challenges and future research opportunities in the material design and the development of compatible electrolyte systems of hybrid anode systems are proposed. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Recent Progress in Solid‐State Lithium Batteries through Cathode Microstructure Engineering

Solid‐state batteries offer transformative advancements in energy density and safety, yet they are still in the early stages of development and face significant technical challenges. Here recent advancements in cathode are explored emphasizing the challenges of developing efficient cathode/electrolyte interfaces. It delves into advancements in coating techniques, composition adjustment, cathode processing, and structural design methodologies. Abstract A high‐performance cathode is necessary to realize the great potentials of solid‐state batteries such as high energy density and long cycle life. It is also needed to validate electrolyte performance, which is lacking. Currently, cathodes for solid‐state batteries are thinner and have lower cathode active material content than their lithium‐ion battery counterpart, resulting from insufficient conductivity and limiting the battery energy density. This review article provides an overview of recent development in cathode microstructures and their impact on battery properties, including compatibility between cathode and electrolyte, cathode architecture design, interface engineering, correlation between material properties, cathode processing approaches, and performance, as well as the advanced characterization methods used to understand the above correlations. Some perspectives on future development are shared including utilizing in situ and operando characterization tools to better understand dynamic evolution of the cathode/electrolyte interface, adapting artificial intelligence and machine learning to design and optimize cathode structures. The article is aimed to promote research interest on cathode development and advance solid‐state battery technologies. Solid-state batteries offer transformative advancements in energy density and safety, yet they are still in the early stages of development and face significant technical challenges. Here recent advancements in cathode are explored emphasizing the challenges of developing efficient cathode/electrolyte interfaces. It delves into advancements in coating techniques, composition adjustment, cathode processing, and structural design methodologies. Abstract A high-performance cathode is necessary to realize the great potentials of solid-state batteries such as high energy density and long cycle life. It is also needed to validate electrolyte performance, which is lacking. Currently, cathodes for solid-state batteries are thinner and have lower cathode active material content than their lithium-ion battery counterpart, resulting from insufficient conductivity and limiting the battery energy density. This review article provides an overview of recent development in cathode microstructures and their impact on battery properties, including compatibility between cathode and electrolyte, cathode architecture design, interface engineering, correlation between material properties, cathode processing approaches, and performance, as well as the advanced characterization methods used to understand the above correlations. Some perspectives on future development are shared including utilizing in situ and operando characterization tools to better understand dynamic evolution of the cathode/electrolyte interface, adapting artificial intelligence and machine learning to design and optimize cathode structures. The article is aimed to promote research interest on cathode development and advance solid-state battery technologies. Advanced Science, Volume 12, Issue 48, December 29, 2025.

Hepatic KLF9 Deficiency Inhibits Dehydroepiandrosterone (DHEA)‐Induced Polycystic Ovary Syndrome via Liver‐Ovary Axis (Adv. Sci. 48/2025)

Androgen Homeostasis In their Research Article (DOI: 10.1002/advs.202508240), Rong Hu, Yongsheng Chang, Yaolin Zhang, Heng Fan, and co‐workers demonstrate that the liver plays a key role about androgen homeostasis in the development of DHEA‐induced PCOS. KLF9 is required for the conversion of DHEA to DHT in hepatocytes. The image shows the liver origin T and DHT circulate to the ovary, leading to infertility. The upper island represents the liver and the under island represents the ovary. Androgen Homeostasis In their Research Article (DOI: 10.1002/advs.202508240 ), Rong Hu, Yongsheng Chang, Yaolin Zhang, Heng Fan, and co-workers demonstrate that the liver plays a key role about androgen homeostasis in the development of DHEA-induced PCOS. KLF9 is required for the conversion of DHEA to DHT in hepatocytes. The image shows the liver origin T and DHT circulate to the ovary, leading to infertility. The upper island represents the liver and the under island represents the ovary. Advanced Science, Volume 12, Issue 48, December 29, 2025.