In this work, a red-emissive fluorescent probe CouS-CN based on a thiophene-coumarin scaffold was developed for the detection of SO2. The probe exhibits high sensitivity, broad applicability, strong anti-interference performance, and good stability toward various ions. Due to low cytotoxicity, CouS-CN was successfully applied for the fluorescence imaging of exogenous SO2 in living HeLa cells.
Hydrogen production from plastic waste via pyrolysis-reforming offers a compelling route toward sustainable energy, yet it is hindered by three major bottlenecks: inefficient C-C/C-H bond activation of the dominant C1-C4 hydrocarbons in plastic pyrolysis gas, severe Ni sintering, and carbon deposition. Although oxygen vacancies (Ov) are recognized as potential solutions for mitigating surface carbon deposition, conventional catalysts suffer from thermodynamic limitations in Ov formation. Here, we design a La2Ce2O7 pyrochlore carrier that exhibits a negative formation energy for Ov, thereby driving spontaneous Ov formation. XRD confirms a single-phase pyrochlore structure in La2Ce2O7, distinct from non-pyrochlore reference carriers (La2O3 + CeO2, La2O3, CeO2). EPR and DFT calculations further verify that only the La2Ce2O7 pyrochlore thermodynamically favors massive Ov formation, yielding the highest Ov concentration among all carriers. Moreover, H2-TPR, in-situ XPS and TEM reveal that a moderate metal-support interaction in the 3wt%Ni/La2Ce2O7-R catalyst leads to a high surface Ni0 concentration. During a 50 h pyrolysis-gas reforming test, the 3wt%Ni/La2Ce2O7-R catalyst delivered a H2 yield of 34.2% and a C1-C4 conversion of 89.5%, with only 1.4% CH4 and 0.9% C2-C4 remaining, and a carbon accumulation of merely 0.21 mmol∙g−1. We attribute the enhanced catalytic activity to the synergy between abundant Ov and highly dispersed metallic Ni0 sites. These mechanistic insights provide a design paradigm for plastic-to-H2 technologies and contribute to the broader green-energy transition.
Osteosarcoma (OS) presents formidable challenges due to its aggressive progression and resistance to conventional therapies. Recent advancements in multimodal strategies, such as combining gene therapy with mild-temperature photothermal therapy (mPTT), referred to as GT-mPTT, have shown promise in enhancing therapeutic efficacy while minimizing side effects. However, current systems face limitations in therapeutic response, efficiency, and biosafety. Herein, we report a reactive oxygen species (ROS)-responsive polymeric amphiphile for imaging-guided combinational GT-mPTT therapy, achieving a high-efficiency antitumor performance against OS. This polymer incorporates guanidine-functionalized units for effective gene condensation and near-infrared II (NIR-II) active dyes for efficient photothermal conversion. The system exhibits charge reversal under elevated intratumoral ROS levels, promoting gene release, and achieves controlled mild hyperthermia under NIR-II irradiation, enhancing cellular uptake and enabling effective mPTT. The GT-mPTT combination therapy, guided by dual NIR-II fluorescence and photothermal imaging, demonstrated significant therapeutic outcomes in vitro and in vivo. These include pronounced tumor cell apoptosis, substantial tumor size reduction, and mitigation of osteolysis in OS-bearing mouse models, all while maintaining excellent biosafety and negligible systemic toxicity. This work shows the potential of responsive polymeric platforms with integrated multimodal therapeutic and imaging capabilities as a robust foundation for advancing precision therapies against OS.
Artificial mitochondrial transplantation (AMT) holds great promise for reprogramming cellular metabolism and restoring cell function. Its clinical translation, however, relies on access to mitochondria that are both of high purity and metabolically active, requirements that current isolation techniques struggle to meet. Conventional differential centrifugation (DC) method yields heterogeneous and low-activity mitochondria, whereas magnetic bead (MB)-based immuno-isolation leaves non-biodegradable beads permanently attached. Herein, we present a Light-Activated Mitochondrial Isolation (LAMI) platform comprising programmable mitochondria-targeting MBs and a photo-responsive release mechanism for the selective, efficient, and non-destructive extraction of high-quality mitochondria. LAMI employs magnetic nanoparticles decorated with a branched, modular probe architecture that supports systematic variation in mitochondria-targeting ligand type, ligand density, and optical tracking elements. Incorporation of a photo-cleavable linker allows on-demand, mild, and reagent-free release of captured mitochondria. Compared with DC method, LAMI produces mitochondria with markedly improved purity, structural integrity, and functionality. In an ischemia-reperfusion injury (IRI) model, LAMI-isolated mitochondria-based AMT exhibits superior therapeutic performance. Together, LAMI provides a non-destructive, efficient, and versatile mitochondrial isolation strategy that overcomes long-standing limitations of current methods, offering a robust platform to advance AMT and its future biomedical applications.
Abstract Efficiently sieving C 2 H 2 from CO 2 remains a significant challenge due to their similar molecular sizes and physical properties. To address this issue, we developed a novel strategy for selectively sieving C 2 H 2 from CO 2 by functionalizing metal–organic frameworks (MOFs) with imidazole‐based ionic liquids (ILs). The constructed model material, MIL‐101‐Cr‐EMImCl (EMImCl = 1‐ethyl‐3‐methylimidazolium chloride), exhibits both a high C 2 H 2 capacity (94.2 cm 3 g −1 at 298 K and 1.0 bar) and outstanding C 2 H 2 IAST selectivity over CO 2 (2.43), which are 1.7 and 1.5 times higher than those of the control (MIL‐101‐Cr), respectively. This highlights the critical role of IMIL functionalization in enhancing the C 2 H 2 /CO 2 separation performance of MOFs. This work not only positions the IL‐functionalized MIL‐101‐Cr‐EMImCl as a promising candidate for efficient C 2 H 2 /CO 2 separation, but also introduces a novel strategy for developing advanced C 2 H 2 /CO 2 separation adsorbents through the incorporation of ILs into porous materials.
Glioblastoma multiforme (GBM), the most aggressive and lethal type of brain cancer, is a considerable threat to human health. Conventional therapeutic modalities fail to yield satisfactory outcomes; therefore, a more effective intervention strategy is urgently required. Ferroptosis, a novel type of cell death, has potential for GBM therapy. However, its efficacy is substantially compromised by the tumor-intrinsic anti-ferroptosis defense system. Moreover, approaches that trigger ferroptosis by modulating a single target are insufficient. Thus, it is imperative to simultaneously inhibit anti-ferroptotic regulators to overcome compensatory pathways and achieve robust tumor eradication. Therefore, in the present study, a multifunctional nanoplatform, hollow mesoporous manganese dioxide (H-MnO2)-hemin-leflunomide@membrane (MHL@M), is proposed and fabricated. GBM cell membrane coating enables blood-brain barrier (BBB) penetrating and tumor-targeting properties. H-MnO2 consumes the overexpressed GSH in the tumor microenvironment (TME), and as derived Mn2+ converts H2O2 into more toxic •OH, resulting in a chemodynamic therapy (CDT) effect. Hemin downregulates glutathione peroxidase 4 (GPX4), and leflunomide inhibits dihydroorotate dehydrogenase (DHODH), which synergistically triggers ferroptosis. Both in vitro and in vivo results demonstrate that MHL@M has excellent tumor-targeting, TME-responsive, and ferroptosis activation capacities. This study provides a solid foundation for the development of ferroptosis-based therapeutic strategies for GBM.
Covalent organic frameworks (COFs) exhibit significant potential for photocatalysis. Nevertheless, the relationship between their structural units and optoelectronic and photocatalytic properties remains largely unclear. This study systematically investigates the modulation mechanisms underlying the optoelectronic and photocatalytic properties of thiazole-based COFs using density functional theory (DFT) and time-dependent DFT (TDDFT). A series of eight thiazole-based COFs with varied donor-acceptor (D-A) building block units was examined. We focus on the effects of heteroatom incorporation, it-bridge structural modifications, and symmetry control on photocatalytic properties and charge separation behaviors. We demonstrate that integrating strong D-A pairs with conjugated it-bridges (e.g., imine or cyanovinyl) markedly promotes charge separation, achieving a high CT% of 78.9 % and a low exciton binding energy of -0.3 eV for BTH-series COFs. This molecular strategy thereby narrows the band gap to 1.9 eV and concurrently broadens the absorption edge to 604.3 nm. According to these insights, we proposed an integrated molecular design strategy including heteroatom doping, optimized D-A unit level, it-bridge engineering, and multivariate parameter optimization to achieve narrow bandgaps, high photon absorption, and exceptional charge separation. This work provides theoretical guidance and a structural foundation for the development of high-performance COF-based photocatalysts.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a global public health challenge. Rapid and accurate diagnostic methods are critical for effective TB control. In recent years, serological diagnosis has attracted growing attention with the continuous identification of novel biomarkers, owing to its simplicity, rapid turnaround, and cost-effectiveness, particularly for the diagnosis of extrapulmonary TB (EPTB) and in individuals who test negative by sputum culture and rapid molecular assays. In this review, we summarize current biomarkers used in TB serodiagnosis, discuss the integration of advanced diagnostic technologies, and highlight their potential to improve TB diagnosis across diverse clinical settings.
Deep-seated tumors are difficult to treat because of their location, conventional treatment resistance, and limited light penetration during photothermal therapy (PTT). Interstitial PTT with "inside-out" laser irradiation using optical fibers (OFs) offers a promising solution. This study proposes a drug-device integrated platform assisted by a puncture needle combining stimuli-responsive hydrogels with a spherical-tip polymer OF (SPOF) to overcome dual challenges: Inadequate photothermal agent retention and insufficient optical penetration. The injectable thermosensitive hydrogel (SW8@Gel), composed of Pluronic F127 and aza-boron-dipyrromethene-derived SW8 nanoparticles, rapidly undergoes sol-gel transition at 38°C, facilitating localized and sustained delivery of the photothermal agent. The flexible low-bending-loss SPOF emits 360° divergent near-infrared II (1064 nm) light from its spherical tip, allowing single-fiber illumination of deep-seated tumors (penetration >10 cm) in complex biological environments. Integrating these components enables depth-adaptive tumor ablation. Compared to other methods, the SPOF/SW8@Gel combination demonstrates the lowest frequency and shortest duration for PTT of deep-seated tumors and achieves superior efficacy, with a 90% tumor regression rate in mice models and no off-target damage due to enhanced heating uniformity and reduced systemic toxicity. This platform offers a transformative clinically viable solution for precise ablation of deep malignancies, bridging advanced photonics and targeted oncotherapy.
Tumor hypoxia, a hallmark feature of solid malignancies, significantly compromises the therapeutic efficacy of oxygen-dependent photodynamic therapy (PDT). The development of hypoxia-alleviating nanoplatforms integrating PDT with complementary treatment modalities represents a promising strategy for enhanced cancer therapy. In this study, we developed multifunctional metal-phenolic network nanoparticles (VAF@TA-Fe) through co-encapsulation of verteporfin (VER) and atovaquone (ATO), a mitochondrial respiration inhibitor, to integrate enhanced PDT with chemodynamic therapy (CDT) within a unified nanoplatform. The incorporation of ATO enables VAF@TA-Fe to significantly suppress cellular oxygen consumption by inhibiting the mitochondrial electron transport chain, thereby potentiating VER-mediated 1O2 generation and substantially improving PDT efficacy against hypoxic tumors. Furthermore, the Fe3+ released from VAF@TA-Fe effectively catalyze the conversion of tumor-associated hydrogen peroxide into highly cytotoxic hydroxyl radicals (center dot OH) through tannic acid-enhanced Fenton reactions within the tumor microenvironment. Ultimately, the coordinated PDT/CDT therapeutic action enabled by VAF@TA-Fe nanoplatforms achieves significant growth suppression in triplenegative breast cancer models. In conclusion, this study provides a novel strategy for enhancing PDT efficacy and demonstrates the therapeutic potential of combined PDT/CDT in tumor treatment.
Therapeutic nucleic acids hold great promise for cancer therapy but face intrinsic hurdles, including poor in vivo stability, short circulatory half-life, and suboptimal cellular internalization. Herein, we engineered a hypoxia-degradable nanogel (NGNN) using a sulfonated azobenzene-derived crosslinker (HPM) via radical copolymerization—its sulfonated moiety enhances water solubility, facilitating uniform polymerization and nanogel formation. Distinct from traditional carriers, NGNN enables hypoxia-specific degradation and on-demand siRNA/ASO release in the tumor microenvironment (TME), with ultrahigh loading capacity to preclude leakage. Notably, its cationic surface coordinated with HPM's sulfonated moiety mediates synergistic cellular uptake and endosomal escape, maximizing payload bioactivity. Tumor targeting is achieved via enhanced permeability and retention (EPR) effect, and HPM-driven hypoxia responsiveness ensures superior tumor retention over GSH-degradable controls (NGSS). In vitro, MDM2-ASO@NGNN abrogated MDM2 expression, upregulated p53, and reduced cell viability by 82.1%. Strikingly, two systemic doses of MDM2-ASO@NGNN elicited 90.5% tumor growth inhibition in a 14-day murine model, outperforming NGSS and free ASO with negligible toxicity. This HPM-based platform overcomes nucleic acid delivery bottlenecks, offering a precision strategy for tumor-targeted gene therapy.
Mitochondrial Ca2+(mito-Ca2+) interference, an effective mitochondria destruction strategy in cancer treatment, suffers from precise self-protective Ca2+ metabolic autoregulation by Ca2+ channels. Direct regulation of Ca2+ channels-mediated mito-Ca2 + metabolic autonomy will overcome this obstacle for advanced Ca2+ interference therapy. Here, we engineer a novel meta-phenolic nanocluster (TCMH) by self-assembly of polyphenols encapsulating mitochondrial calcium uniporter (MCU) modulators (mitofusin 1 siRNA (siMFN1), H2S donor) and Ca2+ via metal-phenolic coordination. After cellular internalization, the acid-responsive disassembly of TCMH triggers the release of its' payloads. TCMH promotes a rapid surge in mito-Ca2+ via synergistic MCU activation by siMFN1-mediated mitochondrial fusion suppression and released H2S. Furthermore, integrating with H2S-mediated reactive oxygen species (ROS) enrichment, this Ca2+-based TCMH forms a self-amplifying ROS-Ca2 + positive feedback loop to sensitize mitochondrial apoptosis. TCMH potently benefits robust antitumor therapeutics in both oral squamous cell carcinoma orthotopic and patient-derived xenograft models. Together, a powerful MCU-mediated mito-Ca2+ metabolic autonomy modulation tactic is highlighted here to optimize precise tumor Ca2+ interference therapy.
Cell-free protein synthesis (CFPS) is an in vitro platform that enables rapid protein production using cell extracts, energy sources, and genetic templates. Owing to its fast response, elimination of cell culture, open reaction environment, lyophilization compatibility, and high programmability, CFPS has emerged as a versatile engine for diagnostic sensing. Recent advances have integrated CFPS with modular genetic circuits, CRISPR-based detection, isothermal amplification, and portable formats such as paper-based devices and microfluidic chips, enabling sensitive and specific detection of viral nucleic acids, pathogen antigens, and small-molecule targets. These platforms further support multiplexed and point-of-care testing, substantially reducing assay time, cost, and infrastructure requirements. Despite remaining challenges in biosensor design for novel targets, analytical sensitivity in complex samples, batch-to-batch reproducibility, and clinical translation, continued engineering optimization is rapidly improving CFPS performance and robustness. This review summarizes the fundamental principles of CFPS, its major technological platforms, recent progress in diagnostic applications, and key challenges and opportunities for future development.
Monitoring and regulating the functions of mitochondria holds significant research value for disease management. Small molecule fluorescent probes, due to their various advantages including noninvasiveness, superior sensitivity, and real-time feedback, have emerged as powerful tools for studying the structure and function of mitochondria. Until now, numerous fluorescent probes based on various mitochondrial targeting strategies and multiple response mechanisms have been reported. Therefore, we herein summarize the typical response mechanism of the fluorescent probes, including photoinduced electron transfer (PET), Förster resonance energy transfer (FRET), intramolecular charge transfer (ICT), etc. In addition, the strategies for mitochondria-targeting probes, such as triphenylphosphonium, pyridinium, rhodamine derivatives, and indolium derivatives, are also concluded. Specially, the mitochondria-targeting probes developed in recent years are highlighted carefully according to the analytes, including probes responding to enzymes, reactive oxygen species, viscosity, etc. At last, a detailed outlook for designing high-performance small molecule fluorescent probes is provided.
The cellular stress response is a fundamental process across all domains of life, reflecting the dynamic interaction between an organism and its environment. Fluctuations in phenotype provide a visual representation of this interaction. Repeated stress events lead to the formation of a “cell stress pulse (CSP)”, where the peak stimulation time (tp) corresponds to the maximum expression of beneficial phenotypes. The capture of this peak can be leveraged for biomedical applications by exploiting the cells' optimal beneficial phenotypic state at this stage. In this study, we introduced ultrafast-responsive Cu²⁺ fluorogenic probes (CU1 and CU2) and tyrosinase fluorogenic probes (TY1 and TY2) for successfully identifying the peak time during CSP processes by monitoring these two phenotypic changes. Thus, ultrafast fluorogenic probes could be promising tools for confirming peak stimulation time.
Urgent demand for point-of-care testing (POCT) in the fields of biomedicine, environmental monitoring, and food safety has driven the rapid development of biosensors. With its significant advantages of low cost, strong portability, and ease of use, paper-based biosensors have become an ideal platform. Metal-organic frameworks (MOFs), with their high specific surface area, tunable structure, and designable functions, provide a key breakthrough for paper functionalization to meet the growing demands of various applications. This article systematically summarizes recent advances in MOFs integrated paper-based biosensors for POCT. It begins by outlining the types of paper-based devices and MOFs, as well as strategies for functionalizing MOFs onto paper substrates. Subsequently, the design principles and signal amplification mechanisms of MOFs integrated paper-based biosensors are discussed separately under different signal reading methods. Furthermore, it demonstrates the potential applications of such biosensors in detecting disease biomarkers, monitoring environmental pollutants, and ensuring food safety. Ultimately, the current challenges in stability, large-scale production, and applicability to real samples are summarized. It is envisioned that incorporating artificial intelligence and machine learning technologies into MOFs integrated paper-based biosensors will further enhance their performance and advance the development of intelligent platforms for POCT.
Recent advances have highlighted olefin-linked triazine-based covalent organic frameworks (NKCOFs) as promising photocatalysts for hydrogen evolution, due to their intrinsic donor-acceptor architectures providing an ideal platform for manipulating charge separation and transfer behavior. However, a systematic molecular-level understanding of how donor-acceptor (D-A) architectures and it-conjugation length cooperatively modulate the photoelectric properties in COFs remains elusive, particularly regarding structure-property relationships. In this work, we investigated the photoelectric properties of three NKCOFs with varying it-conjugated lengths using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations. Our findings revealed that the D-it-A configuration in olefin-linked NKCOFs facilitates charge transfer within it-*it* transitions, driven by their symmetric electronic structures. The introduction of cyano groups and it-conjugated units (such as olefins and benzene rings) enhances the planarity of NKCOFs, promoting charge separation and transfer during photocatalysis. The extension of the it-conjugated building blocks caused a redshift in absorption spectra and narrows the HOMO-LUMO gap, optimizing light-harvesting in the visible range. Crucially, we identified an optimal it-conjugated length in NKCOFs that influences the charge separation efficiency. Through hole-electron analysis, we confirmed that charge delocalization decreases with extended it-conjugated chains, while local excitation characteristics (14 %) become more pronounced. Several quantitative parameters further demonstrate NKCOF-113's superior charge transfer capability (Sr = 0.77 a.u., D = 0.28 & Aring;, CT = 0.14 e, t = -0.60 & Aring;) among the three NKCOFs. This work established a quantitative relationship between it-conjugated length, polarity, and planarity, offering a strategy approach for design COFs toward solar energy conversion (e.g., H2 evolution) and environmental remediation.