Real-time monitoring in organ-on-a-chip (OoC) systems is critical for capturing dynamic drug responses, yet standard gold (Au) electrodes utilized in electrical cell-substrate impedance sensing (ECIS) suffer from opacity, high cost, and poor reusability. Here, we report a transparent, robust, and reusable sensing interface based on iridium oxide-modified fluorine-doped tin oxide (IrOx@FTO). By electrodepositing nanostructured IrOx onto FTO, we exploited its pseudocapacitive properties to significantly improve interfacial properties, enhancing sensitivity while preserving optical clarity. We integrated these electrodes into a 128-channel high-throughput platform to monitor HaCaT keratinocytes. The system successfully resolved acute surfactant-induced barrier disruption and differentiated dose-dependent cytotoxic responses to doxorubicin (DOX) with higher precision than bare FTO. Crucially, cycling tests involving repeated culture and cleaning revealed that IrOx@FTO maintains exceptional baseline stability, significantly outperforming gold electrodes which exhibited severe degradation and delamination. This work establishes a scalable, optically compatible, and cost-effective strategy for long-term, multi-modal monitoring in advanced microphysiological systems.

PURPOSE:Emerging evidence suggests rosacea as a recognizable adverse event during dupilumab therapy. This study aimed to investigate the potential association between dupilumab and rosacea using pharmacovigilance data and to characterize the clinical features of dupilumab-associated rosacea (DAR) through a review of reported cases. MATERIALS AND METHODS:We utilized the FDA Adverse Event Reporting System (FAERS) database (2017-2024) to identify disproportionality signals using four methods: Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Information Component (IC), and Empirical Bayesian Geometric Mean (EBGM). To contextualize these findings, we performed a focused narrative review of 8 publications comprising 10 DAR cases with extractable individual data. RESULTS:A significant disproportionality signal was identified across all four methods (ROR 3.873; PRR 3.872; IC 1.865 with IC025 1.653; EBGM 3.642), with reports predominantly in adults and females. In the case review, a consistent phenotype emerged: papulopustules on persistent centrofacial erythema with frequent burning; facial predominance with occasional extension to neck, scalp, or upper trunk; frequent Demodex detection by scraping, KOH, or in vivo imaging; and occasional granulomatous histology. Onset ranged from approximately 2 weeks to 21 months, including one post-discontinuation case. Most patients improved with rosacea-directed therapy (topical ivermectin or metronidazole; anti-inflammatory-dose doxycycline). However, dechallenge or rechallenge patterns and the need for dose-interval extension, temporary interruption, or switching biologic (e.g., lebrikizumab, upadacitinib) in a subset support a drug-related pattern at the reporting level. CONCLUSIONS:DAR represents a distinct clinical entity from dupilumab-associated head and neck dermatitis, which is eczematous and typically responds to antifungals or calcineurin inhibitors. While disproportionality signals indicate association rather than incidence or causality and are subject to reporting bias, clinicians should be aware of this potential adverse event to ensure appropriate management.

Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by epidermal barrier dysfunction and immune dysregulation, yet effective long-term therapies are limited. Although regulated cell death has been linked to AD, the involvement of copper-dependent cell death (cuproptosis) and its therapeutic relevance in AD have not been explored. Herein, we identify aberrant epidermal upregulation of the copper transporter SLC31A1 as a driver of copper overload and cuproptosis in keratinocytes, which in turn promotes GSDMA-dependent pyroptosis through an α-ketoglutarate (α-KG)/H3K9me3 epigenetic mechanism. To target this pathway, we developed a dual-functional microneedle system composed of calcium phosphate nanoparticles delivering Slc31a1 siRNA and embedded within Bletilla striata polysaccharide microneedles (CaP-siSlc31a1@BSP). This platform enables efficient transdermal gene silencing while BSP simultaneously suppresses STAT3/GSDMA signaling and inflammation. In MC903-induced AD-like mice, CaP-siSlc31a1@BSP markedly alleviated skin inflammation, epidermal hyperplasia and pruritus, accompanied by reduced Th2/Th17 responses. Our study reveals a previously unrecognized cuproptosis-pyroptosis axis in AD and establishes SLC31A1 as a promising therapeutic target. The CaP-siSlc31a1@BSP microneedle offers a synergistic drug-gene transdermal strategy with strong potential for AD treatment.

Patulin (PAT) contamination in fruit-derived products poses a significant threat to food safety, necessitating the development of rapid, sensitive, and cost-effective detection strategies. In this study, a novel colorimetric aptasensor was constructed based on Fe3O4 nanozymes and a rationally engineered high-affinity aptamer for PAT detection. A structure-guided strategy combining molecular docking and molecular dynamics simulations (MD) was employed to optimize the aptamer sequence, yielding a truncated variant (APT-63) with enhanced binding affinity (Kd = 15.68 nmol/L) compared to the parental sequence (Kd = 31.94 nmol/L). The sensing mechanism relies on a target-induced “shielding–restoration” effect, where aptamer adsorption inhibits nanozyme activity and subsequent PAT binding restores catalytic activity toward 3,3′,5,5′-Tetramethylbenzidine (TMB) oxidation, generating a measurable signal at 652 nm. Under optimized conditions, the sensor exhibited a wide linear detection range of 2.5–160 ng/mL with a low limit of detection (LOD) of 1.02 ng/mL. The platform demonstrated excellent selectivity against common mycotoxins. In spiked apple and grape juice samples, satisfactory recoveries (93.7–103.8%) and strong agreement with high-performance liquid chromatography (HPLC) results (R2 ≥ 0.9736) were achieved. Compared with existing methods, the proposed sensor offers advantages including simple operation, low cost, and high stability, highlighting its potential for rapid on-site screening of PAT in food safety monitoring.

Achieving environmentally sustainable synthesis of high-quality metal halide perovskite single crystals (MHP-SCs) is critical for advancing next-generation optoelectronic devices. The constrained solvent choices within the green chemistry framework pose a significant challenge to the fine control of crystallization pathways required for the growth of perfect MHP-SCs. Here, we introduce a new paradigm for crystallization control based on steric hindrance engineering using a quantitatively validated green solvent system with high GlaxoSmithKline green solvent scores. We demonstrate that the steric bulkiness of solvent molecules, rather than donor number alone, plays the dominant role in governing the coordination strength between Pb2+ and solvent, thereby regulating precursor complex stability and crystallization kinetics. Finely tuned steric environments promote the unprecedented fast growth of MAPbI3 SCs with a record-low trap density (2.56 × 108 cm-3) and narrowest x-ray diffraction linewidth of 0.00802° (28.9″). These defect-suppressed MAPbI3 SCs enable photodetectors with an ultrahigh specific detectivity of 6.8 × 1013 Jones and x-ray detectors with a low detection limit of 3.6 nGyair s-1. The steric hindrance engineering strategy proves universal across perovskite compositions. This work establishes a sustainable, scalable platform for the growth of high-quality MHP-SCs using quantitatively green solvents.

The low infiltration of pro-inflammatory immune cells and the sustained activation of multiple immunosuppressive signaling pathways in melanoma significantly limit the efficacy of clinical immunotherapy. Therefore, developing an effective immunostimulant with reversing the immunosuppressive tumor microenvironment (TME) is of great significance for improving melanoma immunotherapy. Herein, a degradable metalloimmunostimulant (PurpN/Mn@PEG) is developed for immunotherapy targeting immunosuppressive melanoma. The PurpN/Mn@PEG NPs are fabricated by coordination-driven self-assembly of purpurin and Mn2+, followed by polyethylene glycol (PEG) modification. PurpN/Mn@PEG dissociates in acidic pH and high glutathione TME, releasing PurpN and Mn2+. The nanoparticle exhibits peroxidase-/oxidase-like activity, generating a reactive oxygen species (ROS) storm that induces immunogenic cell death. PurpN/Mn@PEG amplifies ROS via H2O2 production through phenolic oxidation, enhances TNF-α secretion via CCAAT/enhancer-binding protein beta (CEBPB) upregulation, and sensitizes cGAS-STING pathway, synergistically boosting melanoma immunotherapy. In vivo experiments demonstrated that this purpurin-based metalloimmunostimulant exhibits remarkable therapeutic efficacy with an 87.8 % tumor growth inhibition rate in B16-F10 melanoma-bearing mice by activating multiple immune pathways, thereby effectively augmenting melanoma immunotherapy. This study provides an innovative therapeutic strategy that effectively reprograms the immunosuppressive TME to potentiate melanoma immunotherapy.

Early-stage mycosis fungoides (MF) is often an indolent disease with a favourable prognosis, though 25% progress to advanced stages. Patients with ≥10% body surface area (BSA) involvement have a worse prognosis than those with <10%, but the impact of other BSA levels remains unclear. This study aimed to determine whether additional BSA cut-off points higher than 10% provide additional prognostic information. This study included 401 patients with early-stage MF of the Leiden University Medical Centre and a validation cohort of 602 patients from the PROCLIPI database. Different percentages of lesional BSA were analysed both in the total groups and in subgroups of patients with only patch-stage disease or with patch–plaques-stage disease, and correlated with survival. Both cohorts showed a progressive and gradual decline in overall survival (OS) with each 10% increase in BSA, reaching a 5-year OS below 50% (LUMC) or 70% (PROCLIPI) for BSA ≥40%. In both cohorts, patients with a BSA of 10%–39% had a significantly worse OS than those with a BSA of less than 10%, but a significantly better OS than those with ≥40%. These differences in OS were only found in patients with patches and plaques and not in patients with only patches. An additional cut-off point of 40% involved BSA has prognostic significance in patients with early patch/plaque-stage MF and may be included in future updates of the clinical staging system. In these patients, systemic therapies should be considered.

Postoperative tumor management faces persistent challenges, including residual tumor survival, immune suppression, and impaired wound healing. Surgical resection eliminates the primary lesion but simultaneously removes the continuous antigen source required for sustained immune activation, leaving the postoperative microenvironment vulnerable to recurrence and metastasis. Here, a flexible wearable cold-catalytic patch is constructed by integrating thermoelectric nanorods, enzymatic components, and a zwitterionic hydrogel, enabling synergistic immune activation and enhanced tissue repair. Localized cold stimulation triggers thermoelectrocatalytic generation of reactive oxygen and nitrogen species, enabling sustained release of bioactive molecules that promote antigen presentation, amplify inflammatory cytokine secretion, and enhance immune cell infiltration. Concurrently, the thermoelectrical cues and NO signaling produced during cold catalysis stimulate fibroblast migration, angiogenesis, and extracellular matrix remodeling, thereby accelerating postoperative wound closure. In vivo studies demonstrate that this platform effectively suppresses residual tumor proliferation and distant metastasis while markedly improving healing quality. This work reports a unified thermoelectrocatalytic strategy that couples immune cascade activation with enhanced tissue repair, offering a broadly applicable paradigm for next-generation postoperative tumor therapy.

Ultrasound has gained widespread application in the field of transdermal drug delivery (TDD), including dermatological therapy and aesthetic medicine, owing to its non-invasive nature and cost-effectiveness. Despite its widespread use, clinical researchers have largely relied on empirical selection of low-frequency ultrasound (tens to hundreds of kHz) for single-frequency sonophoresis, and a mechanistic understanding of how ultrasound frequency regulates cavitation-from nucleation to bubble collapse-remains lacking, which limits the rational design of ultrasound-based TDD systems. In this study, we proposed a simulation framework that couples Zwart-Gerber-Belamri (ZGB) cavitation model (for nucleation) with Keller-Miksis (K-M) equation (for bubble dynamics), thereby addressing the limitation of existing models that treat nucleation and bubble growth/collapse separately. Using this model, we analyzed the relationship between ultrasound frequency and cavitation effects was analyzed. The results indicate that high-frequency ultrasound can facilitate faster generation of more cavitation nuclei, whereas low-frequency ultrasound is more conducive to the growth and collapse of pre-existing bubbles. Based on these findings, an integrated dual-frequency (400 kHz, 2 MHz) ultrasound transducer (iDFUT) was designed and fabricated to enhance the efficacy of dermatological treatments. Both in vitro and in vivo studies confirmed that this device significantly improves drug delivery efficiency. The proposed theoretical model, dual-frequency transducer design, and experimental validation form an integrated framework that directly links cavitation mechanisms to device optimization and therapeutic efficacy, offering a reliable technical reference for the rational development of ultrasound-mediated TDD systems.

Clinicians typically avoid antibiotics use during immunotherapy due to concerns about reduced efficacy. However, cancer patients requiring antibiotics postoperatively or for infections urgently need options that provide antimicrobial coverage while potentially enhancing, rather than impairing, immunotherapy. Restoring ferroptosis susceptibility represents a promising strategy to overcome immunotherapy resistance, yet the role of antibiotics in modulating ferroptosis and interacting with immunotherapy remains unexplored. In this study, we screened 96 FDA-approved antibiotics across seven pharmacological classes and identified the macrolide kitasamycin as a specific and potent ferroptosis sensitizer in vitro and in vivo. Mechanistically, kitasamycin competitively bound to HUWE1, inhibiting its E3 ubiquitin ligase activity, which stabilized NCOA4 and activated the NCOA4-FTH1 ferritinophagy axis. Single-cell transcriptomics, flow cytometry, and multiplex immunohistochemistry revealed that kitasamycin induced immunogenic ferroptosis and reshaped anti-tumor T-cell immunity. Critically, kitasamycin potentiated immune checkpoint blockade (ICB)-mediated ferroptosis and overcame ICB resistance across multiple preclinical melanoma models, including B16F10 subcutaneous tumors, BRAF-PTEN-driven spontaneous tumors, and human sourced peripheral blood mononuclear cells (HsPBMCs)-humanized mouse models. Clinically, a high NCOA4, low HUWE1 signature correlated with ferroptosis activation, increased T-cell infiltration, and improved survival in ICB-treated patients, suggesting its potential as a predictive biomarker. Our findings positioned kitasamycin as a promising adjunct to immunotherapy for cancer patients requiring concurrent antibiotic therapy.Abbreviations: FTH1: ferritin heavy chain 1; ICB: immune checkpoint blockade; IFNG: interferon gamma; mIHC: multiplex immunohistochemistry; scRNA-seq: single-cell RNA sequencing.

Atopic dermatitis (AD) is a chronic inflammatory disorder driven by complex neuro‑immune interactions beyond classical immune dysregulation. Previous reviews have largely focused on local peripheral neuro‑immune circuits mediating itch and inflammation, but they have not provided an integrative framework connecting peripheral, systemic, and psychological axes. Here, we propose a “multi‑axial neuro‑immune regulatory network” unifying cutaneous, central, and gut–brain–skin pathways to explain the systemic and psychosomatic nature of AD. We highlight neuroplastic remodeling, psycho-neuro-immunologic mechanisms, and therapeutic innovations that target these intertwined axes. This conceptual framework extends beyond prior literature by positioning AD as a dynamic neuro‑immune disorder rather than a purely epithelial or allergic disease.

The expansion and pathogenic differentiation of intermediate monocytes (IMs) are critical yet poorly understood events in psoriasis pathogenesis. Here, we identify the transcription factor PU.1 (encoded by SPI1) as a master regulator driving IM-mediated psoriasiform inflammation. Single-cell RNA sequencing and flow cytometry of peripheral blood mononuclear cells revealed expansion of IMs in psoriasis patients, with PU.1 uncovered as its specific regulator. Myeloid-specific ablation of Spi1 in mice ameliorated imiquimod-induced psoriasiform dermatitis. Mechanistically, PU.1 promoted IMs differentiation into pro-inflammatory M1 macrophages by transcriptionally upregulating Dectin-1, thereby activating the SYK/NF-κB pathway. We further discovered that the clinical-stage bromodomain and extra-terminal domain inhibitor NHWD-870 effectively suppressed PU.1 expression. Oral administration of NHWD-870 demonstrated potent efficacy in murine psoriasis models by disrupting this PU.1-dependent IMs differentiation. Our findings establish PU.1 as a novel therapeutic target for psoriasis and propose that pharmacologic inhibition of PU.1 represents a promising treatment strategy.

Insufficient infiltration or dysfunction of lymphocytes in the tumor immune microenvironment is considered to be a contributing factor to poor immunotherapy outcomes in solid tumors. Necroptosis, a form of immunogenic cell death, has attracted increasing interest because of its unique role in regulating tumor immune responses. CL-387785, a third-generation EGFR inhibitor, has been reported to inhibit tumors by regulating the cell cycle and inducing apoptosis; however, the underlying mechanisms remain unclear. In this study, we demonstrated that CL-387785 effectively suppressed the malignant phenotype of melanoma and lung cancer and confirmed that cancer cells undergo necroptosis, as evidenced by morphological and protein-level analyses. Further in vivo and in vitro experiments revealed that CL-387785 enhances tumor cell killing by immune cells by inducing CD80 expression on the tumor cell surface, thereby increasing CD8+ T lymphocyte function. Detailed mechanistic studies indicated that CL-387785 targets TRADD, recruiting RIPK1 to induce necroptosis in tumor cells, with subsequent nuclear translocation of NF-κB, which regulates CD80 transcription. In conclusion, our findings indicate that CL-387785 induces necroptosis in tumor cells via the TRADD/RIPK1/NF-κB/CD80 signaling pathway, thereby sensitizing tumors to anti-PD-1 therapy. These results suggest that CL-387785 is a promising candidate for increasing tumor immunotherapy efficacy.

Recent spatially resolved, multi-omic, and functional studies have advanced understanding of the intratumoral microbiota (ITM), shifting attention from microbial detection in tumors to how microbial localization and host-cell interactions influence cancer phenotypes and therapeutic outcomes. In this review, we first trace the historical development of the field and synthesize current evidence on routes of microbial colonization, pan-cancer heterogeneity, and the spatial organization of ITM. We then discuss how ITM directly affects genomic stability, signaling pathways, metabolism, and cellular plasticity of cancer cells, while indirectly shaping tumor evolution through its effects on immune and stromal components within the tumor microenvironment (TME). We further assess the role of ITM in anticancer therapy, explicitly distinguishing mechanisms supported by direct evidence in tumors from those inferred primarily from gut microbiota-driven systemic effects. In addition, we summarize emerging strategies to target or exploit ITM, including antibiotics, phage strategy, engineered strategy and related microbiota-modulating interventions. Finally, we highlight the major challenges that continue to constrain the field, particularly low microbial biomass, contamination, limited spatial resolution, and insufficient in vivo functional validation. Together, these considerations position ITM as a context-dependent component of tumor ecosystems with potential relevance to tumor progression, therapeutic stratification, and biomarker development, while defining priorities for more rigorous and clinically actionable research.

Postoperative tumor management faces persistent challenges, including residual tumor survival, immune suppression, and impaired wound healing. Surgical resection eliminates the primary lesion but simultaneously removes the continuous antigen source required for sustained immune activation, leaving the postoperative microenvironment vulnerable to recurrence and metastasis. Here, a flexible wearable cold-catalytic patch is constructed by integrating thermoelectric nanorods, enzymatic components, and a zwitterionic hydrogel, enabling synergistic immune activation and enhanced tissue repair. Localized cold stimulation triggers thermoelectrocatalytic generation of reactive oxygen and nitrogen species, enabling sustained release of bioactive molecules that promote antigen presentation, amplify inflammatory cytokine secretion, and enhance immune cell infiltration. Concurrently, the thermoelectrical cues and NO signaling produced during cold catalysis stimulate fibroblast migration, angiogenesis, and extracellular matrix remodeling, thereby accelerating postoperative wound closure. In vivo studies demonstrate that this platform effectively suppresses residual tumor proliferation and distant metastasis while markedly improving healing quality. This work reports a unified thermoelectrocatalytic strategy that couples immune cascade activation with enhanced tissue repair, offering a broadly applicable paradigm for next-generation postoperative tumor therapy.

Infectious bronchitis virus (IBV) is a coronavirus that naturally infects chickens and causes damage to multiple tissues and organs, including the respiratory tract. Vaccination remains the primary method for preventing and controlling infectious bronchitis (IB). Progress toward cell-based, attenuated live vaccines has been hindered by IBV's poor replication in vitro. In previous work, we utilized the rH120 strain as the parental strain and domesticated it to derive the IBV strain HV80, which replicates efficiently in Vero cells. Using reverse genetics, we then constructed its infectious clone, rHV80. To assess its potential as a cell-adapted attenuated live vaccine, we evaluated the immunogenicity of the rHV80 strain in 1-day-old SPF chicks. We found that the strain elicits a robust immune response after immunization or infection. However, serial passage broadened the strain's tissue tropism. Compared with the parental strain, the rHV80 strain infects additional tissues, including the pectoralis, heart, and testis. It produces brain lesions that lead to neurological signs and late-stage mortality in chicks, compromising its safety as a live attenuated vaccine. This study shows that using in vitro cell-adapted strains of IBV as seed material for live attenuated vaccines can pose safety risks. Meanwhile, the results offer a theoretical foundation for the rational development of live attenuated IBV vaccines.

Herein, a novel tyrosinase probe (SCy-tyr) was developed to overcome the limitations of poor selectivity and low activation efficiency, providing a new tool for precise imaging and surgical resection of melanoma.

Dysregulation of thymic T cell development compromises immune homeostasis and can lead to leukemic transformation, but the molecular mechanisms linking developmental signals, proliferative cues, and leukemogenesis remain incompletely understood. Here, we integrate deubiquitinase library screening and publicly available single-cell RNA sequencing to analyze mouse and human thymocytes. We find the deubiquitinase USP10 to be expressed in thymocytes, and also elevated in peripheral blood from patients with T-cell acute lymphoblastic leukemia (T-ALL) compared to healthy controls; by contrast, T cell-specific USP10 deficiency blocks mouse thymocyte proliferation and differentiation. Mechanistically, USP10 interacts with SOX4, de-ubiquitinating and protecting SOX4 from degradation to promote thymocyte proliferation, with SOX4 overexpression restoring thymocyte differentiation in USP10-deficient mice. Lastly, MYC induces Usp10 expression, and pharmacologic inhibition of USP10 delays MYC-driven leukemogenesis in a mouse leukemia model. Our results thus identify USP10 as coordinator of developmental signals and oncogenic processes in thymocytes, and implicate USP10 as a potential target for T-ALL therapy.