Myocardial ischemia/reperfusion injury (MI/RI) is driven by a cascade of pathological events, including oxidative stress and the activation of novel cell death pathways such as ferroptosis. The stage-specific shift in dominant cell death modalities coupled with the inherently low bioavailability of conventional therapeutics in the rhythmically contracting heart critically constrain the efficacy of single-target interventions. Here, we developed a spatiotemporally controllable “therapeutic relay” strategy based on a metal–phenolic network-hybridized liposomal system (MP@T NPs). During the early reperfusion phase, the tannic acid–cerium (TA–Ce) network shell exhibits reactive oxygen species (ROS) scavenging and anti-inflammatory activities, thereby effectively mitigating apoptosis and autophagy-associated cell death. Concurrently, its high affinity for collagen ensures the prolonged and targeted retention of the nanoparticles at the injury site. Upon the initiation of ferroptosis, ultrasound (US) irradiation subsequently induces the phase transition and vaporization of perfluoropentane (PFP), triggering the on-demand release of the arachidonate lipoxygenase (ALOX) inhibitor ML351 to precisely suppress ferroptotic cell death. This sequential action inhibits ferroptosis by downregulating ACSL4 and upregulating GPX4, thereby attenuating lipid peroxidation and restoring mitochondrial function in H9c2 cells. In the MI/RI rat model, MP@T NPs reduced ROS levels and iron deposition, suppressed inflammation, and restored the ejection fraction and fractional shortening. This novel, noninvasively regulated therapeutic platform enables temporally precise intervention in the key pathological cascades of MI/RI, offering a promising multitarget approach for enhancing myocardial salvage and functional recovery.

Sonogenetics is an emerging technology for precise biological modulation. It utilizes ultrasound waves for remote, noninvasive, and spatiotemporally precise functional intervention in target cells genetically engineered for acoustic sensitivity. This review systematically summarizes the three core components comprising sonogenetics: sound-responsive agents for modulating cellular functions, highly efficient vectors for targeted gene delivery, and ultrasound emitters with optimized parameters. Furthermore, we delineate optimization strategies for these components and propose a standardized workflow for sonogenetic operations. This review proposes strategies to accelerate the transformation process of sonogenetics by analyzing current limitations in regulatory efficiency and clinical safety. Finally, this review discusses the existing technical challenges and transformation bottlenecks, and points out the promising directions of future research.

Apoptosis resistance, the severely immunosuppressive tumor microenvironment (TME), and the self-adaptive survival mechanisms of tumor cells significantly impair the efficacy of tumor therapies, driving us to seek more effective antitumor therapeutics that can induce devastative tumor death modalities. Herein, we present a biomineralized bacterial outer membrane vesicles-based nanocomposite (Gd-ZIF@OMV@DC661) designed to activate pyroptotic dualism while simultaneously blocking the pyroptotic checkpoint. Upon internalization by tumor cells, the nanocomposite undergoes acid-responsive degradation, releasing Zn2+, Gd3+, DC661 (a potent autophagy and lysosomal function inhibitor), and exposing OMVs with pyroptotic performance. Cellular oxidative stress induced by Zn2+ and Gd3+, in conjunction with lipopolysaccharide (LPS) presented by the outer membrane vesicles (OMVs), activates both caspase-1-dependent canonical and caspase-11-dependent non-canonical pyroptotic pathways. To counteract the tumor’s adaptive autophagic mechanisms—known as a pyroptotic checkpoint to suppress pyroptosis, the released DC661 inhibited tumor autophagy, deactivated pyroptotic actuators, amplified tumor pyroptosis, and simultaneously induced lysosomal cell death by causing lysosomal lipid peroxidation, thereby inducing robust immunogenic cell death. The consequent release of damage-associated molecular patterns (DAMPs) and tumor-associated antigens (TAAs) facilitates dendritic cell (DC) maturation and T-cell activation, driving a potent adaptive immune response. Furthermore, the presence of Gd³⁺ allows for real-time tumor tracking via T1-weighted magnetic resonance imaging. Overall, this study presents a multifunctional, theranostic nanoplatform that integrates dual pyroptosis, lysosomal cell death, and immune activation, offering a promising strategy for immune-silent solid tumor treatment.

Uveal melanoma (UM), the most prevalent primary intraocular malignancy in adults, is characterized by high metastatic potential, with no therapies shown to improve overall survival. This underscores the critical need for exploring new treatment approaches. Ferroptosis has become a promising therapeutic approach in cancer therapy. However, metabolic reprogramming of tumor cells frequently upregulates antioxidative defense by enhancing antioxidant synthesis, thus constraining the effectiveness of ferroptosis. In this study, we have developed a pH/near-infrared (NIR)-responsive nanoplatform that co-loads ferric ions and the hypoxia-inducible factor-1 (HIF-1) inhibitor acriflavine (ACF), aiming to potentiate iron-based ferrotherapy through modulation of glucose metabolism. Upon release, ferric ions are reduced intracellularly to ferrous ions by glutathione (GSH). The resultant ferrous ions subsequently catalyze Fenton reactions that produce hydroxyl radicals (•OH), ultimately triggering ferroptosis. Concurrently, HIF-1-mediated metabolic reprogramming is suppressed by ACF. The resulting inhibition of glycolysis and the pentose phosphate pathway curtailed ATP and NADPH supply, resulting in impairment of the GSH/glutathione peroxidase 4 defense system and thus enhancing tumor susceptibility to ferroptosis. In addition, the excellent NIR absorption efficiency of MPDA enables photoacoustic imaging-guided treatment monitoring as well as efficient photothermal therapy (PTT). The PTT further enhanced drug release and accelerated the Fenton reaction, resulting in a cascade amplification of therapeutic efficacy against UM. Collectively, our study establishes a synergistic therapeutic strategy that integrates glycometabolism-intervention-enhanced ferroptosis with PTT, presenting a powerful and versatile approach for UM treatment.

Venous thromboembolism (VTE) remains a critical clinical challenge due to limitations in conventional therapies, including poor thrombus targeting, inadequate imaging, and bleeding risks. This study develops nanoparticles composed of polylactic-co-glycolic acid, perfluoropentane, ferric oxide, and a macrophage membrane (designated as PLGA-PFP-Fe3O4-MO NPs) for targeted thrombolysis and dual-modal imaging. The NPs integrate macrophage membrane coating to enhance immune evasion and thrombus targeting, a perfluoropentane core enabling phase-change capabilities under low-intensity focused ultrasound (LIFU), and Fe3O4 for magnetic targeting and photoacoustic imaging. Evaluations in vitro and in a rat deep vein thrombosis model demonstrate superior thrombolytic efficacy, imaging performance, and long-term safety. The NPs reduce residual thrombus area to 15.57%, outperforming urokinase at 30.25% and low-molecular-weight heparin, while restoring venous blood flow and eliminating pulmonary embolism incidence. Long-term safety assessments over 28 days confirm no systemic toxicity or organ damage. LIFU-triggered phase transitions enable contrast-enhanced ultrasound imaging with prolonged durability exceeding 8 min surpassing SonoVue, and high-resolution photoacoustic localization. These findings establish PLGA-PFP-Fe3O4-MO as a multifunctional platform for precise VTE management, offering non-invasive thrombolysis, real-time imaging guidance, and robust biosafety for clinical translation.

Collagen IV-targeted phase-change nanoparticles enable precise ultrasound staging of early liver fibrosis.

Abstract Background Pathological intraplaque neovascularization, vascular leakage, and fibrous cap thinning contribute to vulnerable atherosclerotic plaque rupture. Platelet- derived growth factor-BB (PDGF-BB) has been shown to promote pericyte recruitment, thereby stabilizing the microvascular structure, and to induce phenotypic modulation of vascular smooth muscle cells (VSMCs), which enhances fibrous cap thickness and reinforces plaque stability. Nevertheless, systemic protein delivery is limited by rapid clearance and potential off-target effects. Methods We developed PDGF-BB mRNA-loaded lipid nanoparticle–poly(lactic-co- glycolic acid) nanobubble complexes (LNPmRNA@PLGA) and used low-intensity focused ultrasound (LIFU) to enhance plaque-targeted delivery. Cellular uptake, PDGF- BB expression, vascular mural-cell responses, plaque histology, hemodynamics, and proteomic changes were evaluated in vitro and in ApoE −/− Fbn1 C1041G+/− mice. Results LIFU enhanced nanocomplex uptake and PDGF-BB expression, promoted vascular smooth muscle cell proliferation, migration, and phenotypic switching, and increased pericyte coverage. In vivo, LIFU plus LNPmRNA@PLGA reduced the plaque vulnerability index by 78.2% and the neovascularization area by 67.3% compared with controls, while increasing collagen deposition and improving carotid hemodynamics. Conclusions LIFU-responsive delivery of PDGF-BB mRNA stabilized vulnerable plaques by promoting neovessel maturation and strengthening the fibrous cap. This strategy provides a spatially controlled framework for therapeutic remodeling of high-risk atherosclerotic plaques. Research Perspective What New Question Does This Study Raise? Can spatially controlled PDGF-BB mRNA delivery simultaneously mature intraplaque neovessels and reinforce the fibrous cap without the systemic effects associated with recombinant PDGF-BB? What Question Should Be Addressed Next? Future studies should define the therapeutic window, durability, and long-term safety of LIFU-triggered PDGF-BB mRNA delivery in large-animal models that more closely reproduce human plaque rupture.

This study develops a novel multifunctional nanoplatform, modified polyethylene glycol-bismuth trioxide (mPEG-Bi2O3), synthesized via vacuum ball milling followed by ultrasonic liquid-phase exfoliation and surface PEGylation, to enhance the synergistic effects of sonodynamic therapy (SDT) and radiotherapy (RT). Characterization revealed that mPEG-Bi2O3 exhibits a thin-layered nanosheet structure (hydrodynamic size: 239.28 ± 4.32 nm; lattice spacing: 0.29 nm) and a zeta potential of -33.64 ± 0.80 mV. Notably, the nanoplatform demonstrated exceptional colloidal stability in physiologically relevant media, maintaining consistent size and surface charge over 7 d in serum-containing medium, which confirms the effectiveness of the PEG coating for biomedical applications. XPS analysis confirmed a mixed Bi3+/Bi5+ oxidation state, and deconvolution of the O 1s spectrum quantified the oxygen vacancy content at 11.02%, confirming a defect-rich structure. Successful PEG grafting was verified by Fourier transform infrared spectroscopy and quantified by thermogravimetric analysis, showing a grafting content of ~13.59 wt %. Under low-intensity focused ultrasound (LIFU), mPEG-Bi2O3 significantly enhanced reactive oxygen species generation, leading to a marked reduction in intracellular glutathione levels. In vitro cytotoxicity studies demonstrated favorable selectivity, with lower toxicity toward normal endothelial cells compared to 4T1 cancer cells, and the combination of mPEG-Bi2O3 and LIFU induced apoptosis in 4T1 cells. In vivo studies showed that intravenous administration of mPEG-Bi2O3 in tumor-bearing mice resulted in peak tumor accumulation at 24 h (0.17 ± 0.03 %ID/g), correlating with a significant 87.82% ± 4.77% reduction in tumor volume after 14 d of treatment when combined with LIFU and RT (10 Gy), superior to dual-modality treatments. Immune profiling indicated enhanced dendritic cell maturation, increased tumor-infiltrating CD8+ T cells, and reduced regulatory T cells, demonstrating immune microenvironment remodeling. Collectively, mPEG-Bi2O3 presents a surface-engineered strategy for potent SDT-RT synergy with demonstrated biosafety, showing promising potential for solid tumor treatment.

Background : Retinal neovascularization remains a leading cause of visual loss in retinal disorders, with key pathological features including endothelial cell overgrowth, ROS-driven fibrosis, and alterations in the extracellular matrix. YAP1, a transcription factor that regulates both cell proliferation and fibrotic responses, has emerged as an attractive target for intervention. Verteporfin, a well-known YAP1 inhibitor, was formerly used as a first-line therapy for retinal neovascularization, but the ophthalmic verteporfin formulation has been discontinued, and no currently available treatment offers both anti-angiogenic and anti-fibrotic activities. To solve this problem, we designed a hybrid nanoparticle system (cRGD/siYAP/MEL) capable of crossing ocular barriers and delivering YAP1-siRNA specifically to sites of pathological neovascularization. In addition, we examined whether this delivery platform could modulate the behavior of retinal-resident immune cells. Results : The cRGD/siYAP/MEL nanoparticles displayed favorable physicochemical properties, including appropriate size and surface charge, along with strong specificity for retinal neovascularization. In cellular assays, treatment with these nanoparticles led to marked suppression of YAP1 and its downstream effectors VEGF, CTGF, and Nrf2. This suppression correlated with reduced endothelial cell proliferation and diminished fibrotic changes. Mechanistic investigations further indicated that the nanoparticles facilitated the clearance of damaged mitochondria via restoration of mitophagic flux, resulting in lowered intracellular ROS levels. As a consequence, the secretion of inflammatory cytokines by vascular endothelial cells declined, which in turn lessened the inflammatory burden on the extracellular microenvironment and resident microglia. Collectively, these events contributed to the alleviation of fibrosis and the re-establishment of retinal homeostasis. Conclusion : By restoring mitophagic flux and reducing ROS generation, the cRGD/siYAP/MEL hybrid nanoparticles effectively suppress pathological vascular proliferation and fibrotic progression in the retina. Moreover, the system is found to influence the phenotype of retinal microglia, further supporting tissue recovery. Given its combined ability to home to inflamed tissues and traverse the retinal barrier, this nanoparticle platform holds considerable promise as a siRNA delivery vehicle for the treatment of neovascular retinal diseases.

Reactive oxygen species (ROS)-mediated tumor therapy, which induces oxidative stress damage for precise oncolysis, represents a novel antitumor strategy. However, the overexpression of glutathione (GSH) in the tumor microenvironment (TME) forms a strong antioxidant barrier, rapidly scavenging ROS and repairing oxidative damage, thus limiting the efficacy of conventional ROS-based therapies. Metal nanosonosensitizers, activated by ultrasound and penetrating deeply into the TME, offer a promising solution when combined with glutaminase1 (GLS1) inhibitors to overcome GSH-mediated defenses. This study innovatively constructs a biomimetic metal nanosonosensitizer, CRIM, with a copper sulfide as core, encapsulating IR780 and IPN60090, coated with tumor cell membranes. CRIM specifically accumulates in tumor cell mitochondria, where ultrasound activation triggers efficient ROS generation while depleting GSH levels by direct consumption and indirect synthesis. This synergistic GSH depletion disrupts the tumor antioxidant system, sustaining ROS accumulation and triggering a ROS storm. The "ROS generation-GSH depletion-exacerbated oxidative stress" feedback loop induces immunogenic cell death (ICD). Additionally, copper ion released from CRIM induces cuproptosis, synergizing with ROS-mediated cytotoxicity to enhance therapeutic efficacy. This approach triggers a ROS storm via multi-pathway synergy, induces comprehensive tumor destruction, and activates systemic immunity, thereby unleashing a potent antitumor force and offering a new direction for cancer treatment.

Rotator cuff tear is a prevalent musculoskeletal condition. The complex soft-to-hard transition at the tendon-bone interface (TBI) makes the healing process more challenging than in homogeneous tissues. In this study, low-intensity pulsed ultrasound (LIPUS), a non-invasive modality for bone repair, was employed as an external stimulus in combination with tissue engineering. A composite scaffold, designated as BMP-2/bFGF@GM-PLA, was developed by incorporating a gelatin-methacryloyl (GM) hydrogel loaded with bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) into polylactic acid (PLA) electrospun fibers. Under LIPUS stimulation, the BMP-2/bFGF@GM-PLA scaffold effectively promotes migration, osteogenic and tenogenic differentiation of the bone marrow mesenchymal stem cells through synergistic mechanical and chemical cues. In vivo, the combined system of BMP-2/bFGF@GM-PLA implantation and post-operative LIPUS treatments significantly enhances healing in rat models of rotator cuff tear, as evidenced by enhanced biomechanical properties, accelerated bone defect repair and improved histological structure of the TBI. This study proposes a novel approach that combines LIPUS stimulus with acoustic-responsive biomaterial scaffolds, thereby coordinating mechanical and chemical cues to facilitate rotator cuff healing.

Photodynamic therapy (PDT) is a promising cancer treatment, yet its efficacy is often compromised by tumor hypoxia and limited immune activation. Here, we developed a multifunctional photosynthetic nanoplatform (PnanoCB) derived from Microcystis wesenbergii to alleviate hypoxia, enhance reactive oxygen species (ROS)-mediated tumor cell killing, and activate antitumor immunity. The cyanobacteria were restructured into protoplast-derived vesicles, retaining photosynthetic capacity and chlorophyll, and functionalized with a Matrix metalloproteinase-2 (MMP-2)-cleavable anti-PD-L1 peptide via a pH-sensitive pH low insertion peptide (pHLIP) linker for tumor-targeted immune checkpoint blockade. Upon red light irradiation, PnanoCB efficiently generated oxygen in situ, overcoming hypoxia and significantly amplifying PDT-induced ROS production. Combining PnanoCB with a fasting-mimicking diet (FMD) further improved tumor accumulation and therapeutic efficacy. The combination of PnanoCB, light irradiation, and FMD achieved the most potent tumor inhibition in a 4T1 breast cancer model and effectively prevented tumor recurrence in a rechallenge model, without detectable toxicity to major organs. Overall, PnanoCB significantly alleviates hypoxia, promotes immunogenic cell death, and triggers robust dendritic cell (DC) maturation through stimulator of interferon genes (STING) pathway activation. This study demonstrates a strategy integrating photosynthetic oxygen generation, photodynamic immunotherapy, and metabolic intervention to remodel the tumor microenvironment and elicit robust systemic antitumor immunity.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by recurrent mucosal inflammation and ulceration. Since managing UC remains challenging due to frequent therapeutic resistance and relapse, there is a pressing need for new strategies that target the underlying disease mechanisms to achieve long-term remission. Recent studies have highlighted the functional heterogeneity of intestinal goblet cells (GCs) beyond their classical role in mucus secretion. The goblet cell-associated passages (GAPs) have been identified as a luminal antigen delivery to lamina propria immune cells. Excessive GAP opening contributes to barrier dysfunction and mucosal inflammation, suggesting that GAPs are a promising therapeutic target. In this study, we designed a chondroitin sulfate-coated cerium nanoplatform (CS/CeO₂) loaded with the BAPTA-AM (BA) to stabilize the barrier function in colon. Briefly, BA was used to suppress excessive GAPs opening during the early stage of colitis, thereby alleviating abnormal immune activation. At the same time, CeO₂ served as a carrier to restrict the free diffusion of BA. Meanwhile, CS enabled efficient targeting of ulcerative lesions, allowing CeO₂ to fully exert its reactive oxygen species (ROS)-scavenging and CT imaging capabilities. Upon oral administration, BA-CS/CeO₂ successfully inhibited aberrant GAPs opening in DSS-induced colitis mice and enhanced intestinal barrier integrity, with restoration of mucus layer thickness and epithelial tight junctions, alongside reduced immune cell infiltration. Overall, this work leverages GC heterogeneity to re-establish intestinal barrier homeostasis, offering a promising nanotherapeutic strategy for UC through GAPs regulation, ROS scavenging, and CT monitoring.

The maintenance of intracellular calcium ion (Ca2 +) homeostasis plays a pivotal role in regulating both cellular survival and immunoregulatory pathways. However, achieving safe and precise manipulation of these messenger ions to engineer next-generation antitumor immunotherapies remains a formidable challenge. Here, we reveal an organelle crosstalk paradigm that harnesses innate Ca2+ dynamics to drive calcipoptosis-mediated antitumor immunity, bypassing the limitations of conventional exogenous calcium-dependent strategies. A modular peptide-programmed nanoagonist was designed to activate self-supplied calcium influx between Ca2+-rich and Ca2+-sensitive organelles by inducing endoplasmic reticulum stress and opening mitochondrial calcium transport channels under ultrasound irradiation. Moreover, the targeted dysfunction of dual-organelles leads to the activation of the caspase-dependent apoptotic pathway and the release of a cascade of damage-associated molecular patterns to promote dendritic cell maturation and cytotoxic T-cell infiltration. Additionally, Ca2+ dysregulation polarizes macrophages into a pro-inflammatory phenotype and stiffens cancer cells to establish biochemical and mechanical immunosurveillance. The nanoagonist demonstrated potent ablation of primary tumors and suppression of metastatic growth in breast and liver cancer models. Overall, this work enables customizable subcellular bioenergetic disruption without systemic toxicity risks, which pioneers a translatable strategy that redefines the frontier of calcium-based immunotherapy.

Retinal neovascularization is closely linked to retinal inflammation. Microglia, the resident immune cells of the retina and the primary responders to inflammatory stimuli, play a central role in pathological retinal vascular remodeling, including aberrant neovascularization and increased vascular tortuosity. High-mobility group box 1 (HMGB1), a ubiquitously expressed DNA-binding protein, functions as a damage-associated molecular pattern and has been shown to drive microglial polarization toward the pro-inflammatory M1 phenotype. Whereas M1 microglia exacerbate inflammatory responses, M2 microglia exhibit anti-inflammatory and tissue-repair functions. Accordingly, inhibition of HMGB1 to induce metabolic reprogramming of microglia may promote the transition from the M1 to the M2 phenotype. In this study, we adopted a targeted therapeutic strategy aimed at modulating the M1/M2 polarization balance of microglia to attenuate retinal inflammation and suppress pathological angiogenesis, thereby offering a potential treatment for retinal neovascularization. To achieve this, we engineered a self-assembled nanoparticle delivery system (H-H@MG1) designed to selectively target M1 microglia. These nanoparticles encapsulate the anti-inflammatory flavonoid hesperidin and are functionalized with an M1 microglia-targeting peptide (MG1). In vitro experiments demonstrated that H-H@MG1 efficiently targets M1 microglia, inhibits HMGB1-induced activation of resting microglia, and promotes their polarization toward the M2 phenotype. Furthermore, in vivo studies using an oxygen-induced retinopathy mouse model revealed that H-H@MG1 rebalances M1/M2 microglial polarization within the retina, remodels the retinal immune microenvironment, and significantly reduces the expression of pro-inflammatory cytokines, including IL-6 and TNF-α. Collectively, these effects suppress abnormal retinal vascular remodeling and pathological angiogenesis. Overall, this nanodelivery system effectively reshapes the retinal immune microenvironment and represents a promising therapeutic strategy for the treatment of retinal neovascularization.

Activation of cuproptosis has emerged as a paradigm-shifting therapeutic concept to improve cancer immunotherapy efficacy. Nevertheless, its clinical translation is impeded by the inability of existing delivery systems to achieve spatiotemporally precise copper surges within tumor tissues while minimizing systemic metal toxicity. To address this critical issue, we develop a metallo-drug system (HD-HMCS) featuring NIR-triggered and contractility-mediated co-delivery of copper ions and DOX for precisely tumor-localized induction of cuproptosisimmunotherapy. Upon NIR irradiation, the strong photothermal conversion of hollow mesoporous copper sulfide (HMCS) rapidly raises the local temperature to 40 degrees C, inducing contraction of the PNIPAAm-CS hydrogel shell. The resulting mechanical squeezing force destabilizes the HMCS framework, leading to an instantaneous burst release of the copper-DOX payload. This process induces the downregulation of FDX1 and promotes DLAT oligomerization, thereby enhancing copper-dependent cell death. Furthermore, this approach not only eradicates tumor cells through synergistic cuproptosis and immunogenic cell death (ICD) but also robustly activates systemic antitumor immunity by promoting DC maturation and CD8+ T cell infiltration. Collectively, this work establishes a novel and programmable paradigm for amplifying cuproptosis-immunotherapy, offering a transformative alternative to conventional metal-based nanotherapeutics and a promising synergistic strategy for precision cancer treatment.

Clinical implementation of hydrogen sulfide (H2S) therapy for inflammatory bowel disease (IBD) is hindered by the lack of delivery systems capable of stable, intestine-targeted, and endogenous thiol-independent gas release. To address this, we introduce TB-MnS@S100, a fully synthetic, orally deliverable nanotheranostic platform that decouples H2S release from host biochemistry while enabling real-time imaging. The system comprises a tributyrin-manganese sulfide (TB-MnS) core encapsulated in a pH-responsive Eudragit S100 shell, which remains intact in the upper gastrointestinal tract but dissolves in the alkaline intestinal environment. This platform fully leverages lipases naturally present in vivo-lipase-mediated hydrolysis of tributyrin generates butyrate, whose intracellular metabolism acidifies the local microenvironment, thereby triggering controlled MnS decomposition. This cascade ingeniously exploits endogenous lipase activity to achieve stable and sustained hydrogen sulfide (H2S) release, accompanied by Mn2+ production, providing T1-weighted magnetic resonance imaging (MRI) contrast enhancement without relying on exogenous activators. In a murine model of inflammatory bowel disease induced by dextran sulfate sodium, TB-MnS@S100 achieves synergistic butyrate-H2S therapy, suppressing oxidative stress, downregulating pro-inflammatory cytokines, restoring epithelial tight junction integrity, and rebalancing gut microbiota. The released Mn2+ also enables non-invasive MRI monitoring of inflammation and treatment response, establishing a closed therapeutic-monitoring loop. This work presents an exogenous activator-independent H2S delivery strategy that advances nanotheranostics for IBD by integrating mechanism-guided therapy with real-time imaging.

Sonazoid, a combined blood pool and Kupffer-cell agent, can be specifically phagocytosed by Kupffer cells in the liver, allowing lesion detection and characterization of focal liver lesions (FLLs) at the post-vascular phase, apart from the vascular phase, which is similar to that of other second-generation ultasound (US) contrast agents. Sonazoid contrast-enhanced US (CEUS) is currently approved for use in some Asian countries. With the increasing use of Sonazoid CEUS for FLLs in clinical practice, developing consensus or guidelines to help standardize its use is required. The expert consensus aimed to review recent evidence and make evidence-based recommendations for radiologists and clinicians involved in the management of liver diseases regarding the use of Sonazoid CEUS in the surveillance or detection, characterization of FLLs, CEUS for interventional and intraoperative use, and tumor treatment response evaluation in patients with FLLs. This consensus was conducted without using artificial intelligence tools in accordance with the TITAN Guidelines 2025.

Ferroptosis, an iron-dependent, nonapoptotic form of regulated cell death, has become a new approach for antitumor treatment. However, the insufficient accumulation and poor penetration of ferroptosis inducers deep in tumors greatly limit their therapeutic effects. In this study, we constructed a cascade penetrating metal‒polyphenol ultrasonic molecular probe, Fe3+Cur-PFP@IR780-LIP (FCIPL). The nanoparticles (NPs) can penetrate deep into tumors in a stepwise fashion via specific targeting combined with cavitation effects resulting from acoustic droplet vaporization (ADV) and ultrasound-targeted microbubble destruction (UTMD) technology. Then, the drug can be successfully delivered into the mitochondria of tumor cells under the cascade response of ultrasound and the tumor microenvironment, inducing the ferroptosis domino cascade. The nanoparticles disassemble, releasing the Fenton reaction catalyst Fe2+ and the ferroptosis inducer Cur, which together constitute the ferroptosis ''amplifier,'' promoting the domino-like burst of lipid peroxide (LPO) and triggering ferroptosis. Simultaneously, the sonosensitizer IR780 is activated to induce sonodynamic therapy (SDT). Under the synergistic action of ferroptosis and SDT, a waterfall-like therapeutic effect is produced. In terms of diagnosis, this nanoplatform combines multimodal (ultrasound, photoacoustic, magnetic resonance and fluorescence) imaging to improve the diagnostic performance of anaplastic thyroid cancer (ATC) and provide a visualization strategy for early diagnosis. In this study, the advantages of ultrasound technology are exploited to achieve deep penetration of drugs and overcome the limitations of a single treatment modality, achieve optimal diagnostic and treatment effects, and provide new ideas for integrating ATC diagnosis and treatment.

Objective This research investigated the application of real-time, three-dimensional speckle tracking imaging (RT-3D-STI) to evaluate left atrial (LA) function in individuals suffering from hypertensive heart disease (HHD) and heart failure with preserved ejection fraction (HFpEF).Material and methods This retrospective study included 100 patients with HHD and HFpEF hospitalized from August 2023to June 2024 (HFpEF group). 100 healthy individuals undergoing physical examinations comprised the control group. Patient data were collected, and echocardiography was performed to measure LA diameter (LAD), left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular outflow tract diameter (LVOTd), early diastolic maximum velocity of mitral valve inflow (MVE), late diastolic maximum velocity of mitral valve inflow (MVA), early diastolic and late diastolic velocities of mitral annulus measured by tissue Doppler ultrasound (e' and a'), tricuspid annular plane systolic excursion (TAPSE), and left ventricular ejection fraction (LVEF). The LA images were analyzed using GE software, and the following parameters were measured: L emptying fraction (LAEF), LA emptying volume (LAEV), LAvolume at the onset of contraction (LAVpreA), minimum LA volume (LAVmin), maximum LA volume (LAVmax), LA strain during the reservoir phase (LASr), LA strain during the contraction phase (LASct), and LA strain during the conduit phase (LAScd). ROC curves were adopted to evaluate the diagnostic value of LA parameters for HFpEF, and a Pearson correlation analysis examined the relationship between these parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP).Results Compared with the control group, the blood pressure in the HFpEF group was significantly higher (p<0.05). In the HFpEF group, NT-proBNP concentrations were significantly greater than those observed in the control group (p<0.05). No statistically significant variances were detected in LVEF, LVEDD, LVOTd, TAPSE, MVE, MVA, ratio of E wave velocity to A wave velocity (E / A), a', LAEV, LAVmin, or LAVpreA between the two groups (p>0.05). Compared to the control group, the HFpEF group had dramatically higher LAD, IVST, and LVPWT (p<0.05). The HFpEF group also had lower e', LAEF, LASr, LAScd, and LASct, while E / e', maximum LA volume index (LAV Imax), and LAVmax were higher (p<0.05). LASr was negatively associated with NT-proBNP (r=-0.255, p=0.016), whereas no significant correlation was found among LAScd, LASct, and NT-proBNP (P>0.05).Conclusion LA strain parameters can serve as a non-invasive method for quantitatively assessing LA dysfunction in patients with HFpEF.