搜索结果：ACS pharmacology & translational science

Plasma medicine has emerged as a rapidly emerging interdisciplinary area of research that investigates the interaction of cold atmospheric plasma (CAP) with biological systems. The therapeutic power of CAP relies on the controlled generation of reactive oxygen and nitrogen species (RONS), pulsed electric fields, and ultraviolet radiation, which synergistically enable specific bioactivity. This review summarizes CAP research from the past decade, including in vitro, in vivo, and clinical studies across biomedical applications, and categorizes CAP sources by their distinctive physicochemical properties and associated medical relevance. The discussion highlights that treatment efficacy in wound healing, cancer therapy, and antimicrobial applications is strongly device-dependent, underscoring the critical role of plasma source design in clinical outcomes. CAP demonstrates significant antimicrobial effects, reduces microbial load, and preserves the integrity of healthy tissue. It promotes hemostasis and accelerates wound healing through vascularization, cell proliferation, and microcirculation. In oncology, CAP exhibits selective antitumor effects, including skin cancers and other vertebrate tumor models. Its applications in dentistry reflect its versatility in disinfection and in aiding implantation. Furthermore, CAP can stimulate the growth of stem and cultured cells via nitric oxide-mediated mechanisms. Recent studies have highlighted the potential of CAP in surface modification and transdermal drug delivery. Furthermore, plasma-activated media and solutions have garnered significant interest due to their diverse applications in plasma medicine. The review provides a comprehensive overview of all available literature, facilitating biomedical scientists in their further translational research in this field.

Dopaminergic medication used in disorders like Parkinson's disease (PD) and restless legs syndrome can cause impulsive-compulsive behaviour (ICB), often with strong negative effects on patients' quality of life. This narrative review presents translational evidence on iatrogenic ICB, taking findings from epidemiological, clinical, neuroimaging and preclinical studies into consideration. Epidemiological and clinical studies find dopamine agonists with high D2/3-selectivity to be most strongly linked to ICB. Their effect on ICB has often been shown to be dose-dependent, but the impact of combining different dopaminergic drugs or applying extended-release formulations is less clear. Intervention studies support tapering or replacing dopamine agonists for ICB reduction, whereas no efficacious pharmacotherapy has been identified for ICB treatment specifically. Adequate animal models for mimicking different types of ICB are available, and point, in line with human neuroimaging studies, towards an involvement of striatum and prefrontal cortex in iatrogenic ICB. Overall, complementary research designs have led to profound evidence regarding the occurrence of ICB in PD and establishing methods transferable to other, less-studied patient populations. A combined approach integrating insights from human studies and animal models could contribute to developing dopaminergic drugs with lower ICB risk but also specific pharmacotherapies for impulsivity or compulsivity in the future. Diseases like Parkinson's disease and restless legs syndrome are treated with drugs that affect dopamine activity in the brain. As a side effect, these drugs can lead to a lower impulse control, manifested, for example, as gambling disorder or hypersexuality. This article summarises research on these side effects, collected through a variety of scientific methods. The drug type with the highest risk for behavioural side effects has been identified, but many details remain unclear, especially in patients with other disorders than Parkinson's disease. Results from both human brain imaging and animal models start to reveal brain pathways involved.

Patients with recurrent endometrial or ovarian cancer have poor survival outcomes. We evaluated the clinical efficacy and toxicity of copanlisib [a phosphatidylinositol 3-kinase (PI3K) inhibitor] and niraparib [a poly (ADP-ribose) polymerase inhibitor (PARPi)] in this patient population with translational insights. This was a phase Ib trial. Copanlisib was administered intravenously on days 1, 8, and 15 of a 28-day cycle, and niraparib was given orally once daily. Four dose levels were explored over a dose-limiting toxicity (DLT) window of 28 days. The primary objective was to determine the recommended phase II dose (RP2D) of this combination. Secondary objectives included safety, objective response rate (ORR), and pharmacokinetics. Tumor biopsies were analyzed using reverse phase protein array (RPPA) to identify molecular correlates of response. Thirty patients were enrolled. An RP2D was not established due to DLTs, most commonly a grade 3 maculopapular rash attributed to copanlisib. The ORR was 12.5% (95% confidence interval, 2.8%-33.6%). RPPA was performed on tumors from eight patients. PI3K pathway activity did not correlate with PI3K mutational status. Nineteen proteins were differentially expressed between patients with stable disease and those with progressive disease; many were substrates of Akt (protein kinase B), implicating downstream PI3K signaling in response. The combination of copanlisib and niraparib demonstrated limited tolerability, and the ORR was modest. However, functional proteomic analyses identified candidate biomarkers-particularly Akt pathway substrates-which may inform future strategies to optimize PI3K and PARPi combinations.

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death, with substantial residual risk persisting despite current lipid-lowering, antithrombotic, antihypertensive, weight-management, and anti-inflammatory therapies. This unmet clinical need reflects the multifactorial and heterogeneous nature of ASCVD, which is not fully captured by traditional discovery approaches. Recent advances in large-scale datasets, multi-omics technologies, polygenic risk scores, and artificial intelligence offer unprecedented opportunities to disentangle disease complexity and identify novel therapeutic targets and biomarkers. However, translation into clinically actionable strategies requires robust validation in models that faithfully recapitulate human disease. Conventional two-dimensional cell cultures and standard murine models have provided important mechanistic insights but often fail to reflect human-specific features such as lipid metabolism, hemodynamics, and plaque destabilization. To address these limitations, advanced in vitro and ex vivo platforms are emerging, including induced pluripotent stem cell-derived vascular systems, microphysiological vessel-on-chip devices, vascularized organoids, and ex vivo human tissue models. These systems offer controlled, human-relevant microenvironments for scalable perturbation testing and support personalized therapeutic development. Nevertheless, in vivo models remain essential for capturing systemic physiology, inter-organ crosstalk, and pharmacokinetic and pharmacodynamic responses, underscoring the need for complementary, rather than replacement, use of model systems. In this review, we propose an integrated framework linking data-driven target and biomarker discovery to validation in human-relevant experimental models, supported by selective use of in vivo systems. By aligning multi-omics and AI-based discovery with advanced preclinical platforms, this approach aims to improve translational success and accelerate the development of precision therapies for ASCVD.

Wuzi Yanzong Pill (WZYZP) is a classical Traditional Chinese Medicine (TCM) formula long used for male reproductive disorders, particularly oligoasthenozoospermia (OAT). However, current research is fragmented across formula-level trials, monomer pharmacology, and computational studies, accompanied by inconsistent clinical outcomes and limited translational frameworks. To construct an evidence map linking clinical signals of WZYZP in male infertility to convergent mechanistic networks and actionable research gaps. ACS Publications, Web of Science, PubMed, Elsevier ScienceDirect, SpringerLink, and CNKI were searched from inception to December 2025. A PRISMA-informed screening workflow was applied for evidence mapping (no meta-analysis). Of 1140 records screened, 135 publications were retained: 64 WZYZP intervention studies (56 preclinical; 8 clinical) and 71 mechanistic publications, comprising published in silico analyses (e.g., network pharmacology and molecular docking/molecular dynamics simulations) and single-constituent studies relevant to WZYZP. Clinical studies frequently reported improvements in semen concentration, motility, morphology, and reproductive hormones, but were heterogeneous in formulation sources, diagnostic criteria, comparators, and endpoints. Preclinical interventions consistently indicated enhanced spermatogenesis and testicular function, with pathway convergence on redox and lipid-peroxidation control, mitochondrial bioenergetics, apoptosis modulation (Bcl-2/Bax-caspase axis), inflammatory signaling, blood-testis barrier (BTB) integrity, and hypothalamic-pituitary-gonadal (HPG)-axis/steroidogenesis support. In silico and monomer studies provided hypothesis-generating links between constituent classes and target engagement. The mapped evidence suggests that WZYZP may exert multi-component, multi-target effects for OAT, but translation requires formula standardization and quality control, exposure/PK-informed dosing, biomarker-guided target validation, and adequately powered registered trials with pregnancy/live-birth outcomes. Due to the limited number and variable quality of the included clinical trials, our findings should be interpreted with caution.

Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interplay of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic risk factors. We examined whether the number, components, and complexity of CKM domains influence outcomes and years of life lost (YLL) per death in patients with non-valvular atrial fibrillation (AF) receiving direct oral anticoagulants (DOACs). We included 17 378 AF patients (mean age 76.1 &#xb1; 10.7 years; 40.9% women) on DOACs from a multicentre Taiwanese database (2012-21). Patients were followed until outcomes, death, or study end. Overall, 18.1, 35.1, 32.2, and 14.6% of patients had 0, 1, 2, and 3 CKM domains. Women more often exhibited kidney, metabolic, or combined domains. Clinical risks rose stepwise with domain number; patients with three domains had the highest risks of ischaemic stroke/systemic embolic event/acute coronary syndrome (IS/SEE/ACS) [adjusted hazard ratio (aHR) 1.60, 95% confidence interval (CI) 1.25-2.05], major bleeding (aHR 2.60, 95% CI 2.00-3.38), heart failure hospitalization (aHR 2.83, 95% CI 2.38-3.37), all-cause mortality (aHR 1.80, 95% CI 1.58-2.06), acute kidney injury (aHR 3.42, 95% CI 2.76-4.25), and major adverse renal events (aHR 20.84, 95% CI 14.14-30.71; all P < 0.001). Domain-specific analysis showed kidney involvement conferred the strongest risks (except IS/SEE/ACS), while cardiovascular and metabolic domains were more associated with IS/SEE/ACS. YLL rose with more CKM domains, with females associated with greater reductions, especially in cardiovascular (-10.29 vs. -4.67) and metabolic (-4.98 vs. -0.80) domains (P < 0.001). Increasing CKM burden was associated with progressively worse prognosis and shorter life expectancy in AF patients on DOACs, with more pronounced impacts in women.

Cardiac dysfunction can be aggravated by chemotherapeutic agents, including doxorubicin, through mechanisms involving mitochondrial dysfunction, elevated oxidative stress, suppression of sirtuin (SIRT1/SIRT3) signaling, and activation of apoptotic and ferroptotic pathways. Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, has been demonstrated to possess cardioprotective effects; however, the interplay between sirtuin signaling and ferroptosis in dapagliflozin-mediated cardioprotection under doxorubicin-induced stress remains unclear. In the present study, dapagliflozin restored cellular function in H9c2 cardiomyoblasts exposed to doxorubicin by reducing apoptosis, oxidative stress, and lipid peroxidation, while preserving mitochondrial respiration and glycolytic function. Dapagliflozin reversed doxorubicin-induced downregulation of SIRT1, SIRT3, GPX4, BCL2, OPA1, and PGC1&#x3b1;, and mitigated the upregulation of ACSL4, BAX, and DNM1 at both transcriptional and translational levels. The cardioprotective efficacy of dapagliflozin under cellular stress depends critically on SIRT1/SIRT3 signaling and ferroptosis regulation, as pharmacological inhibition of these sirtuins abolished its protective potentials; conversely, these effects were enhanced by ferroptosis suppression and attenuated by its induction. Furthermore, dapagliflozin-mediated inhibition of ferroptosis downregulated SIRT1/SIRT3 expression, suggesting a potential feedback mechanism under chemotherapeutic stress. Notably, sirtuin inhibition compromised these protective responses despite ferroptosis blockade, highlighting SIRT1/SIRT3 as upstream regulators of dapagliflozin-mediated cardioprotection and underscoring the necessity of sirtuin activity for ferroptosis suppression. Collectively, these findings reveal that dapagliflozin mitigates doxorubicin-induced cardiotoxicity via the coordinated regulation of SIRT1/SIRT3 signaling and ferroptosis pathways, involving key mediators of apoptosis, mitochondrial dynamics, and lipid metabolism.

Rapid platelet inhibition is essential for effective management during emergency percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). However, the oral dosage form of clopidogrel (CLP) commonly used in clinical practice shows a delayed onset due to gastrointestinal absorption, first-pass metabolism, and the requirement for hepatic cytochrome P450 (CYP450)-mediated bioactivation, which limits its applications in urgent scenarios and complicating post-PCI bleeding management. To address these challenges, we developed an intravenous micellar formulation (CLP/PM) using FDA-approved mPEG-PLA copolymers to promote rapid hepatic exposure and metabolic activation. By tuning the PLA chain length, micellar core density and PEG conformation were modulated, thereby influencing protein corona (PC) formation and liver-affinity interactions. Proteomic profiling revealed that micelles with intermediate PLA length selectively recruited liver-affinity apolipoproteins (ApoM, ApoH, ApoA1, and ApoB), which are known ligands of LDLR and SR-BI, while minimizing adsorption of inflammatory and opsonization proteins. The optimized CLP/PM (3.9&#xa0;k) exhibited a hepatotropic-like PC that was associated with hepatocyte-enriched uptake in primary liver cell analyses. In vivo biodistribution showed rapid liver-level signal, and pharmacokinetic studies supported enhanced CYP450-mediated activation, achieving a higher Cmax of the active metabolite and shorter Tmax of 22.5&#xa0;&#xb1;&#xa0;8.2&#xa0;min. This translated into rapid-onset and potent antiplatelet efficacy, as reflected by prolonged bleeding time, diminished platelet reactivity, and reduced thrombus formation. Overall, these findings highlight a structure-corona-function framework for designing micelles that enhance hepatic prodrug bioactivation. By tuning PLA chain length, PC composition can be rationally modulated to optimize hepatic interaction and prodrug activation, providing a translational platform for rapid-onset and reversible platelet inhibition.

Tissue-engineered vascular grafts (TEVGs), particularly small-diameter vascular grafts (SDVGs), continue to face significant clinical challenges such as delayed endothelialization, acute thrombosis, and intimal hyperplasia, which severely compromise long-term patency. Consequently, developing SDVGs with superior antithrombotic properties and efficient endothelial regenerative capacity is of strategic importance for the advancement of cardiovascular therapies. Through the connectivity map (CMap) algorithm screening, prunetin (Pru), a natural flavonoid, was identified as a promising candidate. This study represents the first report of the incorporation of Pru into a functionalized vascular graft. Our findings demonstrate that Pru effectively promotes the proliferation, migration, and maturation of vascular endothelial cells, thereby accelerating graft endothelialization. Moreover, Pru-loaded grafts significantly inhibit calcification and enhance extracellular matrix remodeling, contributing to the improved patency. Transcriptomic and network pharmacology analyses revealed that Pru primarily exerts its effects by inhibiting the NF-&#x3ba;B inflammatory pathway and activating the Nrf2/HO-1 antioxidant signaling axis. This synergistic multipathway regulation restores endothelial function, mitigates cellular dysfunction, and facilitates vascular regeneration. This work establishes a theoretical framework and translational strategy for cardiovascular treatment, demonstrating the potential of Pru as a potent pro-endothelialization agent and providing a strategic direction for the advancement of functionalized SDVGs.

Cancer therapy is often constrained by targeting single pathogenic mechanisms without addressing the complex tumor microenvironment (TME). Here, we introduce FINAL (Fucoidan-docetaxel Immunomodulatory Nanoparticles as an Antitumoral Lancer), a surface-engineered nanoplatform that simultaneously targets P-selectin-expressing cancer cells and tumor-associated macrophages (TAMs). Beyond targeting specificity, fucoidan surface modification provides intrinsic bioactivities that individually modulate both cell types while coordinately reshaping the TME. FINAL achieves dual-cell orchestration through P-selectin-mediated targeting, activating both receptor-dependent signaling pathways and receptor-independent bioactivities of fucoidan and DTX. P-selectin-mediated targeting enhances cellular uptake and disrupts tumor-TAM adhesion, reducing the level of circulating hybrid cell (CHC) formation. Independent of targeting, fucoidan's bioactivity reduces cellular reactive oxygen species in cancer cells, promotes M1 macrophage polarization, and suppresses VEGF-A-mediated angiogenesis. RNA-seq transcriptomic profiling demonstrated that FINAL drives synergistic immune activation pathways while simultaneously repressing tumor progression signatures, providing mechanistic evidence for concurrent tumor-immune dynamics at the molecular level. In triple-negative breast cancer (TNBC) models, this system-level approach achieved breakthrough therapeutic outcomes, including doubling survival duration, suppressing primary tumor growth, inhibiting lung metastasis, and preserving bone marrow hematopoietic function, demonstrating translational potential compared to conventional docetaxel formulations. Importantly, FINAL maintained therapeutic benefits while reducing systemic toxicity, establishing an optimal balance between antitumor efficacy and safety. The rationally designed fucoidan nanobio interface establishes FINAL as a versatile platform for P-selectin-expressing diseases for next-generation immunochemotherapy agents with broad translational potential across multiple cancer types.

Spinal cord injury (SCI) is a debilitating disorder characterized by intricate pathological processes that result in severe motor and sensory deficits. Existing therapeutic approaches remain insufficient to achieve comprehensive functional restoration, indicating the necessity of alternative treatment strategies. In this study, an advanced nanoparticle-based drug delivery system was established using extracellular vesicles (EVs) modified with a matrix metalloproteinase (MMP)-responsive peptide, ACPP, to achieve the targeted delivery of paclitaxel (PTX). The ACPP-EVs@PTX formulation integrates the drug loading capacity of EVs, the lesion-targeting capability conferred by ACPP, and the neuroprotective properties of PTX. Enhanced accumulation of PTX at the SCI lesion site was achieved, accompanied by a reduction in the off-target distribution. Both in vitro and in vivo experiments demonstrated marked therapeutic efficacy of ACPP-EVs@PTX through modulation of the SCI microenvironment, including stimulation of angiogenesis, attenuation of inflammatory responses, alleviation of oxidative stress, and promotion of axonal regeneration. In addition, the activation of PINK1-Parkin-mediated mitophagy was observed, leading to improved mitochondrial function and enhanced neuronal repair. Behavioral evaluations further confirmed significant recovery of neurological function, supporting the translational potential of this multitarget, synergistic therapeutic strategy. Collectively, this work establishes an integrated therapeutic strategy for spinal cord repair and supports its translational potential.

Ischemic heart disease is a leading cause of death worldwide. While percutaneous coronary intervention (PCI) restores blood flow in acute coronary syndrome (ACS), reperfusion injury exacerbates myocardial damage, contributing to heart failure (HF). Preemptive administration of a cardioprotective agent could help counter the imminent proinflammatory insult of PCI and reperfusion. Administering BT2, a small-molecule MAPK kinase/extracellular signal-regulated kinase inhibitor, 24&#xa0;hours before and during ischemia in rats before reperfusion reduced infarct size by ~70% and preserved cardiac function 24&#xa0;hours and 2 weeks postinjury. BT2 prevented adverse left ventricular remodeling and scarring. Single nucleus RNA sequencing (snRNA-seq) and bulk RNA-seq revealed that BT2 modulated genes associated with inflammation, fibrosis, and matrix production, especially within macrophages and myofibroblasts. BT2 suppressed macrophage and neutrophil infiltration. BT2 reduced the expression of genes in rodent hearts predictive of HF in patients with ACS, including many encoding cytokines, inflammasome components, and damage-associated molecular patterns. BT2 is a small molecule that can prevent myocardial ischemia-reperfusion injury, improve heart function, reduce cardiac fibrosis, and favorably modulate multiple key genes and biological processes in rats prognostic of HF when delivered before reperfusion. This strategy could be evaluated with high-risk unstable angina/non-ST-segment elevation myocardial infarction patients or those having an elective PCI.

Sarcopenia, a progressive skeletal muscle disorder marked by loss of mass and function, presents growing societal challenges due to limited therapeutic options. Here, we identify mitochondrial dysfunction and oxidative stress as central drivers of sarcopenia through integrated bioinformatics and clinical validation. To address this pathophysiology, we engineer a muscle-targeted nanocomposite (BP-PEG-MOTS-c, BM) combining mitochondrial-derived peptide MOTS-c with antioxidant black phosphorus nanosheets (BP). BM exhibits dual functionality: MOTS-c restores mitochondrial function, while BP synergistically amplifies ROS scavenging capacity. In cellular and murine models with age-related sarcopenia, BM treatment alleviates muscle dysfunction and muscle loss, concurrently normalizing mitochondrial function and reducing lipid peroxidation. Mechanistic profiling via RNA-seq reveals BM's activation of PI3K/AKT/Nrf2 and suppression of ROS/p38 MAPK signaling pathway, mediating antioxidant responses and maintenance of mitochondrial homeostasis. The nanocomposite demonstrats superior biocompatibility in toxicity assays, outperforming conventional delivery systems. Our findings establish that BM has been established as a promising mitochondrial redox modulator with translational potential for sarcopenia and related age-associated pathologies.

Atherosclerosis (AS) is a key pathological basis causing major cardiovascular diseases. Its proinflammatory microenvironment, characterized by aggregated inflammatory macrophages, excessive reactive oxygen species, and deficient phagocytosis, plays a pivotal role in driving AS pathogenesis. However, given the complexity of the microenvironment inside atherosclerotic plaques, developing highly effective and comprehensive nanoplatforms for precise diagnosis, efficient therapy, and reliable prognostic evaluation remains a major challenge. Herein, we construct a biomimetic nanomodulator (FeMn/Cur@CM) with responsive T1-T2 dual-modal magnetic resonance imaging (MRI) and multifaceted regulation functionalities of the plaque microenvironment for visualized treatment of AS. Coated with a macrophage membrane, curcumin-loaded FeMn/Cur@CM nanoparticles achieve prolonged circulation and specific targeting of inflammatory plaques. Diagnostically, FeMn/Cur@CM functions as a microenvironment-responsive dual-modal MRI contrast agent, amplifying T1-T2 signals in plaques. Therapeutically, FeMn/Cur@CM multifacetedly modulates the plaque microenvironment by alleviating oxidative stress, neutralizing protons, promoting macrophage reprogramming, and restoring macrophage efferocytosis. As a result, the integrated theranostic platform demonstrates remarkable plaque regression and simultaneously realizes real-time visualization of lesion progression via dual-modal MRI, providing precise diagnosis of plaque milieu. Through inflammation-targeted intervention coupled with real-time imaging feedback, this biomimetic nanomodulator establishes a promising strategy for the precise treatment of inflammatory vascular diseases, offering translational potential for AS management.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition characterized by impaired sociability, repetitive behaviors, and communication deficits. Animal models have been instrumental in elucidating the mechanisms underlying ASD, with prenatal exposure to valproic acid (VPA) being one of the most widely validated approaches. However, most studies rely on intraperitoneal administration, which poorly reflects human exposure. Here, we investigated the effects of oral prenatal VPA exposure in Wistar rats, focusing on behavioral outcomes, biochemical alterations, and sex-dependent differences. Pregnant females received VPA (500 mg/kg) by gavage on gestational days 11-13, and offspring were monitored from neonatal to juvenile stages. VPA-exposed pups exhibited delayed physical maturation, including postponed eye opening, tooth eruption, and locomotor development, along with reduced body weight gain. In the juvenile phase, VPA impaired sociability, reduced exploratory activity, and increased repetitive self-grooming. Importantly, behavioral effects were sex-specific: males showed more pronounced deficits in social interaction, whereas females exhibited stronger stereotyped and anxiety-like behaviors. Biochemical assays revealed elevated malondialdehyde (MDA) and nitrite levels, consistent with oxidative and nitrosative stress, especially in the hippocampus and PFC. Additionally, VPA-exposed females showed a marked reduction in hippocampal glutathione (GSH), while males exhibited increased glutamate and &#x3b3;-aminobutyric acid (GABA) levels in the PFC, indicating disrupted excitatory/inhibitory balance. Collectively, our findings demonstrate that oral VPA administration induces autism-like phenotypes and region-specific neurochemical alterations in a sex-dependent manner. This study reinforces the translational validity of the oral VPA model and identifies oxidative stress and neurotransmitter imbalance as potential biomarkers for ASD pathophysiology and therapeutic intervention.

Bacterial infections associated with biofilm formation hinder wound healing via enhanced antibiotic resistance and impaired tissue repair. Herein, we fabricated dandelion herb-derived carbon dots (DH-CDs) through a green solvothermal-extraction method, developing a biocompatible antimicrobial agent with synergistic wound healing potential. Physicochemical characterization showed that DH-CDs are quasi-spherical (4.87 nm), partially graphitized nanoparticles with abundant surface functional groups and pH-responsive charge-switching capability. In vitro studies demonstrated that DH-CDs exhibit broad-spectrum antibacterial activity against S. aureus and E. coli, with minimum inhibitory concentrations (MICs) of 62.5 &#x3bc;g/mL at pH 7.4 and 31.25 &#x3bc;g/mL at pH 5.5. The antibacterial effect is mediated by a multimodal mechanism involving electrostatically driven bacterial membrane disruption, energy metabolism inhibition, intracellular reactive oxygen species (ROS) generation, and antioxidant enzyme inactivation. Moreover, DH-CDs achieve complete disruption of mature S. aureus biofilms at 300 &#x3bc;g/mL. Notably, DH-CDs possess excellent biocompatibility, with a 10% hemolysis concentration (HC10) exceeding 4000 &#x3bc;g/mL and over 95% viability of NIH 3T3 fibroblasts at 2000 &#x3bc;g/mL. A unique dual ROS-modulating capability was identified that DH-CDs generate excessive ROS to eradicate bacteria while scavenging deleterious ROS in mammalian cells, thereby preserving redox homeostasis. In vivo evaluations in a murine S. aureus-infected full-thickness wound model demonstrated that DH-CDs significantly accelerate wound closure by promoting re-epithelialization, granulation tissue maturation, collagen deposition, and hair follicle regeneration, outperforming a commercial wound healing spray. Collectively, DH-CDs integrate green synthesis, pH-responsive antibacterial/antibiofilm activity, dual ROS regulation, and biocompatibility, representing a promising translational candidate for bacteria-infected wounds and a paradigm for multifunctional biomass-derived nanomaterials.

A central obstacle in cancer immunotherapy is the "cold" tumor, characterized by limited immune infiltration, which renders it largely unresponsive to treatment. Tertiary lymphoid structures (TLS), functioning as ectopic immune niches, can convert these cold tumors into "hot" ones by supporting antigen presentation, lymphocyte activation, and coordinated immune responses. Therefore, strategies to induce TLS formation hold significant therapeutic promise. Recent studies have explored a range of biomaterial systems designed to orchestrate the formation of TLS within the tumor microenvironment. This encompasses synthetic biomaterial platforms (nanocarriers, stimulus-responsive hydrogels, programmable 3D scaffolds, and mesoporous materials), natural and bioderived systems (organoids and exosomes), as well as emerging bioactive entities (engineered immune cells, oncolytic viruses, and bacteria). This review outlines the cellular composition, maturation process, and immunological functions of TLS, highlights diverse biomaterial platforms facilitating TLS formation, and summarizes translational challenges, including biosafety, standardization, and scalability. Inducible TLS (iTLS) provide a potent means to remodel the tumor immune microenvironment, offering exciting opportunities for advanced cancer immunotherapy.

Cerebral amyloid angiopathy (CAA) is increasingly prevalent, and it is characterized by frequent recurrence and complex etiology. Aberrant ceruloplasmin (Cp) localization at the astrocytic endfeet, coupled with oxidative stress-induced dysregulation of iron regulatory proteins, is a central trigger of the iron dyshomeostasis that drives CAA progression. However, therapeutic strategies that specifically target iron transport regulation in astrocytes remain lacking. Here, we develop lattice-expanded Au/CeO2 with strong antioxidant capacity validated by DFT calculations. Its mesoporous architecture enables the loading of the phospholipase C inhibitor ET-18-OCH3, and further DAG peptide conjugation yields the astrocyte-targeted, biocompatible, and pluripotent nanomedicine DACe@ET. This nanoplatform stabilizes Cp at the astrocytic endfeet and restores the expression of DMT1 and FPN1. By suppressing anomalous Fe2+ influx while promoting efficient efflux and subsequent extracellular oxidation to nontoxic Fe3+, DACe@ET reestablishes a closed-loop Fe2+ export-oxidation system and restores iron homeostasis. In 3 &#xd7; Tg mice, DACe@ET reduces cerebral iron deposition, decreases amyloid-&#x3b2; burden, attenuates neurodegeneration, and improves cognitive performance. This work demonstrates that restoring astrocytic iron trafficking hub function can serve as an effective therapeutic strategy for CAA, highlighting DACe@ET as a promising disease-modifying therapy with potential applicability to other neurological disorders marked by iron dyshomeostasis while establishing a foundation for future translational research.

Pyroptosis has recently emerged as a promising therapeutic strategy owing to its unique advantages in inducing lytic cell death and eliciting immunogenic responses. Moderate induction of pyroptosis not only directly eliminates cancer cells but also activates antitumor immunity through the release of tumor-associated antigens and proinflammatory cytokines. However, most available pyroptosis inducers suffer from poor solubility, instability, and nonspecific biodistribution, which significantly hinder their translational potential. To address these challenges, we developed a pyroptosis-inducing delivery platform based on carboxybetaine zwitterionic nanogels for the efficient encapsulation of celastrol. These zwitterionic nanogels exhibit excellent resistance to protein adsorption and prolonged circulation in vivo. Upon drug release, celastrol promotes mitochondrial reactive oxygen species (ROS) accumulation, activates the caspase-3/GSDME axis, and triggers pyroptosis accompanied by immunogenic signals, including adenosine triphosphate (ATP) secretion, lactate dehydrogenase (LDH) release, and calreticulin (CRT) exposure. When combined with the anti-PD-1 checkpoint blockade, this platform further enhances dendritic cell maturation and antigen presentation, thereby amplifying pyroptosis-driven immune responses. In summary, our study demonstrates an effective strategy for inducing pyroptosis by integrating zwitterionic nanogel-mediated celastrol delivery with immune checkpoint inhibition, providing new insights and potential breakthroughs for cancer immunotherapy.