Near-infrared fluorescence (NIRF) can deliver high-contrast, video-rate, non-contact imaging of tumor-targeted contrast agents with the potential to guide surgeries excising solid tumors. However, it has been met with skepticism for wide-margin excision due to sensitivity and resolution limitations at depths larger than ~ 5 mm in tissue. To address this limitation, fast-sweep photoacoustic-ultrasound (PAUS) imaging is proposed to complement NIRF. In an exploratory in vitro feasibility study using dark-red bovine muscle tissue, we observed that PAUS scanning can identify tozuleristide, a clinical stage investigational imaging agent, at a concentration of 20 µM from the background at depths estimated to be of up to ~ 34 mm, highly extending the capabilities of NIRF alone. The capability of spectroscopic PAUS imaging was tested by direct injection of 20 µM tozuleristide into bovine muscle tissue at a depth of ~ 8 mm. Experimental results demonstrate that multi-point laser fluence compensation and strong clutter suppression enabled by the unique capabilities of the fast-sweep approach greatly improve spectroscopic accuracy and the PA detection limit and strongly reduce image artifacts. Thus, the complementary NIRF-PAUS approach can be promising for comprehensive pre- (with PA) and intra- (with NIRF) operative solid tumor detection and wide-margin excision in optically guided solid tumor surgery.
Complex tissue architecture is achieved through multiple rounds of morphological transitions. Here, we analyzed cellular flows and tissue mechanics during avian skin development by employing chicken and transgenic quail skin explant models. We demonstrate how novel cellular flows initiate chemo-mechanical circuits that guide epithelial protrusion, folding, invagination, and spatial cell fate specification. During initial feather bud formation, stiff dermal condensates protrude vertically from the locally softened epithelial sheet. As the bud elongates, it stretches the epithelial cells at the base, thus mechanically activating YAP, which causes the epithelial sheet to fold downward and form a stiff cylindrical wall that invaginates into the skin. This stiff epithelial tongue is essential for the compaction and formation of the tightly packed dermal papillae. These topological transformational events are mechanically interconnected, and the completion of one circuit initiates the next. In contrast, during scale development, the rigid epithelial sheet restricts dermal cell flows, preventing further topological transformation. Based on these findings, we developed a topological transformation model describing how this process enabled the evolution of feather follicles from scales.
Accurate detection of KRAS codon mutations is essential for precision oncology in colorectal cancer (CRC), yet conventional liquid biopsy methods often lack sufficient sensitivity for rare ctDNA variants, particularly in early diseases. We developed a three-dimensional (3D) plasmonic KRAS microarray integrating blocked recombinase polymerase amplification with plasmon-enhanced fluorescence. Quencher-modified blocking probes suppress wild-type DNA while selectively enabling mutant signal amplification. A single primer-probe set per codon allows comprehensive detection of all substitutions within KRAS codons 12/13, 61, and 146. The platform achieved detection down to 1 fM by direct hybridization and 100 zM after blocked amplification, exceeding conventional PCR and next-generation sequencing sensitivity. Codon-level specificity was validated in CRC cell lines, with distinct signals for each mutation. Clinical analysis of 58 patients showed 100% concordance between tissue, plasma, and urine in mutation-positive malignant cases when sufficient input was available, indicating accurate reflection of tumor profiles. In benign tumors, detection was rare despite tissue mutations, likely due to limited ctDNA release.This plasmonic microarray enables ultra-sensitive, specific, and non-invasive detection, supporting early diagnosis, minimal residual disease monitoring, and longitudinal CRC management.
Systemic administration of glucocorticoids (GCs) has immunosuppressive effects that involve the upregulation of the transcription factor TSC22D3 in dendritic cells (DCs), thereby reducing their capacity for antigen presentation to T lymphocytes. Recently, we found that this effect is not mediated by direct action on the GC receptor in DCs but rather involves an indirect signaling circuitry. Indeed, GCs act on the GC receptor expressed by many cell types to cause the upregulation and release of the tissue hormone DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein). DBI/ACBP, which is an inhibitor of macroautophagy/autophagy, then acts on the benzodiazepine-binding site of the gamma-aminobutyric acid type A receptor (GABAAR) to elicit the upregulation of TSC22D3. The indirect, DBI/ACBP-dependent upregulation of TSC22D3 by GCs is observed both in vivo (mice) and in vitro, in murine splenocytes and bone marrow-derived DCs, as well as in human peripheral blood mononuclear cells and monocyte-derived DCs. Inhibition of human mixed lymphocyte reactions (confronting DCs and lymphocytes from distinct donors) by DCs is reduced by DBI/ACBP neutralizing antibodies. Similarly, the suppression of antitumor immune responses (elicited by vaccination with dying cancer cells, immunogenic chemotherapy or PDCD1/PD-1 blockade) by GCs is reversed by DBI/ACBP neutralization. Epistatic experiments indicate that knockout of Tsc22d3 in DCs and inhibition of DBI/ACBP act on the pathway to reverse GC-mediated inhibition of cancer immunosurveillance. Of note, the benzodiazepine diazepam restores GC-induced immunosuppression when DBI/ACBP is inhibited. Altogether, these findings support a role for the DBI/ACBP-GABAAR system in immunosuppression by GCs.
Xianling Cifang Formula (XLCF) is a specialized Traditional Chinese Medicine prescription for metastatic breast cancer (BC) at Longhua Hospital, though its material basis remains unclear. This study aimed to comprehensively identify XLCF ingredients and its lung-entering components using ultraperformance liquid chromatography-high-resolution mass spectrometry. A total of 493 components were identified from XLCF. In lung tissues of BALB/c mice treated with XLCF, 78 absorbable components were detected, including terpenes, flavonoids, phenylpropanoids, carbohydrates, and alkaloids. Flavonoids and terpenes were particularly abundant and may represent key substances contributing to XLCF's inhibitory effects on pulmonary metastasis. Notably, nine components overlapped with 122 previously identified blood-entering components, including icariin, zederone, and D-salicin. Among these, icariin was the most abundant component detected in the lung and is expected to be a key active constituent for treating BC pulmonary metastasis. This comprehensive characterization provides a foundation for further mechanistic research.
The infiltration and cytotoxicity of T lymphocytes are critical for cancer immunotherapy efficacy; however, the behavior of these immune cells has not been thoroughly investigated. Herein, a Tumor-Immune-On-Chip is established using cells acquired from the tissues of a patient with colorectal cancer to monitor T lymphocytes. Through the Tumor-Immune-On-Chip, the interaction between tumor spheroid and either T lymphocytes expanded from tumors (tumor-infiltrating lymphocytes; TILs) or lymph nodes (lymph node-derived lymphocytes; LN T cells) are investigated. Although initial 24-h analysis showed no statistical differences, extended 48-h observation revealed a significant deviation in T cell-mediated cell death signals between TILs and LN T cells. TILs demonstrated more potent cytotoxic effects than LN T cells after 48 h. The number of tumor-infiltrating CD3+ cells and cleaved caspase-3 expression levels were 4- and 2.1-fold higher, respectively, in TIL co-cultures compared to LN T cell co-cultures. Therefore, this proof-of-concept platform allows us to explore the patient-specific tumor-immune microenvironment, focusing on different types of T lymphocytes and establishing methodology for future clinical applications. ClinicalTrial.gov identifier: NCT02589496.
Non-surgical treatment of the aging lower face remains a therapeutic challenge. Tissue Micro-Coring Technology (MCT) is a novel technology that permits the non-surgical removal of skin as micro-cores, tightening skin and inducing collagen and elastin. To evaluate safety and efficacy of MCT for the treatment of the aging lower face. This retrospective, single-site study assessed outcomes for subjects treated with MCT. Assessments included the change from baseline in Lemperle Wrinkle Severity Scale (LWSS) assessed for the nasolabial folds (NLF), marionette lines, lip lines, and global esthetic improvement scale (I-GAIS). A total of 10 patients met the study criteria. Mean (SD) I-GAIS was 1.7 (0.36), and mean (SD) change from baseline in LWSS for NLF, marionette lines, and lip lines were 1.1 (0.46), 1.3 (0.3), and 0.6 (0.35), respectively. Most subjects had some improvement in LWSS across all three treatment areas, with many experiencing > 1-point improvements. Limitations include the retrospective study design, small study population, and single-sex population. In the real-world setting, MCT leads to improvements in global appearance and wrinkle severity. MCT is an effective alternative to injectable fillers for the treatment of nasolabial fold and marionette and perioral lines.
Cytokine-mediated cross-talk between immune cells and fibroblasts is a driver of excessive ECM accumulation during fibrosis. In this study, we used a 3D in vitro model of a connective tissue to discern the roles of three pro-inflammatory cytokines; TNF-α, IL-18 and IL-1β, alone, and in combination with TGF-β1 to simulate the fibrotic environment. Ring-shaped tissues were formed by seeding human fibroblasts into circular molds of agarose, wherein the cells self-assembled, formed a 3D tissue and synthesized de novo a collagen-rich ECM. Cytokine treated tissues were analyzed at days 7 and 14 by histology and measured for thickness, collagen, DNA and strength and stiffness by tensile testing. Despite their pro-inflammatory nature, none of the cytokines increased collagen alone or in combination with TGF-β1. TNF-α and IL-1β reduced collagen, tissue strength and stiffness, and altered tissue morphology. When combined with TGF-β1, TNF-α and IL-1β counteracted TGF-β1-mediated increases in collagen, strength, and stiffness. In contrast, IL-18 had minimal effects alone or when combined with TGF-β1. These data suggest that IL-18 has no effect on fibroblast activation, whereas TNF-α and IL-1β may modulate TGF-β1's effects. This 3D model of a human collagen-rich tissue can help define cytokine-mediated cross-talk between immune cells and fibroblasts.
Cross-study inconsistencies in autism spectrum disorder (ASD) blood microRNA biomarker studies suggest that methodological heterogeneity may substantially limit reproducibility. We conducted an exploratory meta-analysis of publicly available ASD blood miRNA datasets from the Gene Expression Omnibus, applying rigorous inclusion criteria and standardized analytical protocols. Three datasets were included (GSE89596, GSE67979, GSE222046) comprising 614 miRNAs across 90 participants (45 ASD, 45 controls). Random-effects meta-analysis was performed using Hedges' g effect sizes, with comprehensive heterogeneity assessment and leave-one-dataset-out cross-validation. No miRNAs survived multiple testing correction (Benjamini-Hochberg FDR < 0.05), though seven candidate signals showed consistent evidence with unadjusted p < 0.01 and large effect sizes. These candidates demonstrated near-zero between-study heterogeneity and consistent directionality across validation analyses. Potential age-related and platform-related differences were observed, with near-zero correlation between adult and pediatric effect sizes (Kendall's τ = -0.022); however, these two sources of variability were fully confounded in the available data and could not be separated. Some miRNAs exhibited extreme between-study variability (I² > 80%), indicating substantial methodological differences. Cross-validation revealed that excluding the single adult dataset reduced sign consistency from 89.9% to 68.9%. Our findings suggest that age-related and methodological factors, including technical platform differences, may contribute to limited reproducibility in ASD blood miRNA research, and that blood-derived signals should be interpreted as potentially reflecting peripheral physiological states rather than central disease mechanisms. A supplementary cross-tissue analysis using post-mortem prefrontal cortex data (GSE59286; n = 45) provided direct empirical support for this interpretation: the majority of blood candidate miRNAs showed no corresponding expression in brain tissue, with only hsa-miR-29c-5p demonstrating directional concordance across both tissues. These findings suggest that age stratification, platform harmonization, and cross-tissue validation should be considered essential prerequisites for reliable ASD miRNA biomarker discovery, rather than optional refinements.
Decellularized extracellular matrix (dECM) hydrogels are attractive biomaterials for tissue engineering due to their intrinsic tissue-specific characteristics and the complex three-dimensional microarchitecture of the original tissue. However, their limited mechanical stability in vitro hinders practical applications. In this study, we engineered porcine heart-derived dECM hydrogels reinforced with the transition metal compound potassium tetrachloroplatinate(II) (K2PtCl4). The incorporation of K2PtCl4 accelerated gelation and enhanced the structural stability of the hydrogels through coordination bonding between Pt ions and functional groups within dECM. Rheological analysis revealed concentration-dependent improvements in storage modulus, highlighting the tunable viscoelastic properties of the composites. X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FT-IR) confirmed the formation of Pt-dECM coordination molecular networks, while the native morphology of dECM was verified by scanning electron microscopy (SEM). Furthermore, the biocompatibility and functionality of cell spheroids prepared with metal/dECM hydrogel complex were validated, which exhibited stable morphology, high viability, and expressed E-cadherin-mediated cell-cell junctions within Pt-dECM hydrogels. These findings demonstrate that transition metal complexation effectively improves the mechanical and biological functionality of dECM hydrogels, thereby providing a versatile platform for 3D cell culture and regenerative medicine.
This study investigates the identification of Benign Prostatic Hyperplasia (BPH) through a deep learning-based analysis of RGB prostate histopathological images. Adaptive Contrast Limited Adaptive Histogram Equalization (CLAHE) is selectively applied to the L-channel in the LAB color space to enhance tissue visibility while preserving chromatic fidelity. At the architectural level, Convolutional Neural Networks (CNNs) are integrated with Bidirectional Long Short-Term Memory (BiLSTM) layers, enhanced further through spatial and temporal attention mechanisms. This hybrid design facilitates both localized pattern recognition and the modeling of long-range contextual dependencies across tissue regions. To mitigate class imbalance and prevent overfitting, the training regime incorporates two key strategies: an adaptive focal loss function and a comprehensive image augmentation protocol. The proposed model achieved an AUC of 0.7220 on the validation set and an AUC of 0.73 on the test set. While the precision for normal tissue classification remained high, the recall for BPH detection highlighted the need for improvement in sensitivity. The proposed CNN-BiLSTM-Attention architecture demonstrates potential as a diagnostic aid in digital pathology, offering interpretable insights and forming a foundation for enhancing histological classification systems. Future work will focus on improving recall performance for BPH detection and expanding the architecture to support multi-class prostate disease grading frameworks. This study utilizes an RGB histopathological dataset consisting of 176 prostate images, each appropriately annotated. The model demonstrates moderate classification performance and a moderate true-positive rate for detecting Normal samples. The model, however, has a low sensitivity in the detection of the cases of BPH as indicated by the relatively low recall values.
The repair of postoperative abdominal hernias remains a challenge to this day, even though the surgery is sterile. Wound infection is a problem, which is exacerbated by the comorbidity of the patient population. The incorporation of foreign material always carries a risk of infection. In the event of wound infection, the possibility of hernia recurrence is 0.2-8%, while if the mesh also needs to be removed, the probability of recurrence is over 30%. Compared to open wound treatment, negative pressure therapy is more effective in promoting wound healing and preserving the implanted mesh. In our study, we analyze the cases of a total of 30 patients who underwent onlay mesh abdominal hernia surgery between 2015 and 2023, during which wound dehiscence occurred. In all cases, wound exudate culture and negative pressure wound therapy were performed. In 15 patients, swab samples were taken, while in the other 15, swab, sponge, and tissue roller samples were taken. Swab samples mainly revealed skin flora, which was Gram-positive in 71% of cases. The results of the tissue roller and sponge swab cultures showed Gram-negative pathogens in 50% of cases. The sponge swab and tissue roller cultures provided additional information on the bacterial load. Negative pressure wound therapy meant that the mesh did not need to be removed. During negative pressure wound therapy, cultures taken using multiple methods also helped in the selection of antibiotics. Vacuum therapy used for mesh removal reduces bacterial load and accelerates granulation. Hernia recurrence and mesh removal are significantly reduced. Orv Hetil. 2026; 167(18): 714-721. Bevezetés: A posztoperatív hasi hegsérvek helyreállítása a mai napig kihívást jelent, annak ellenére, hogy steril műtétről van szó. Gondot jelent a sebfertőzés, amelyhez hozzájárul a betegpopuláció komorbiditása is. Idegen anyag beépítése mindig magában hordozza a fertőzés kockázatát. Sebfertőzés esetén a sérvkiújulás lehetősége 0,2–8%, míg ha a hálót is el kell távolítani, a kiújulás valószínűsége már 30% fölött van. A nyitott sebkezeléssel szemben a negatív nyomású terápia hatékonyabban segíti a sebgyógyulást és a beépített háló megmentését. Anyag és módszer: Tanulmányunkban összesen 30 beteg esetét elemezzük, akik 2015 és 2023 között estek át olyan ’onlay’ hálós hasfali sérvműtéten, amelynél sebgennyedés lépett fel. Mindegyik esetben sebváladék-tenyésztést és negatív nyomású sebkezelést végeztünk. 15 betegnél pálcás, míg a másik 15-nél pálcás, szivacsmintás és szövethengeres mintavétel történt. A pálcás mintavételek eredménye főleg bőrflórát mutatott ki, amely 71%-ban Gram-pozitív kórokozó volt. A szövethengeres és szivacsmintás tenyésztések eredményei már 50%-ban mutattak ki Gram-negatív kórokozókat. Eredmények: A szivacsmintás és szövethengeres tenyésztések többletinformációt hordoztak a bakteriális terhelésre vonatkozóan. A negatív nyomású sebkezelés hatására a háló eltávolítására nem volt szükség. Következtetés: A negatív nyomású sebkezelés során az antibiotikumválasztásban is segítséget nyújtott a többféleképpen levett tenyésztés. A hálómentés céljából alkalmazott vákuumkezeléssel a bakteriális terheltség csökken, és a granuláció mértéke felgyorsul. A sérvkiújulás és a háló eltávolítása jelentősen mérséklődik. Orv Hetil. 2026; 167(18): 714–721.
IL-11, a novel target for drug development, has been associated with several fibroinflammatory diseases including thyroid eye disease (TED), where it plays an important role in signaling to stromal cells activating multiple intracellular pathways. In TED patient tissue, IL-11 is elevated and stimulates multiple effects important in disease progression, including the production of proinflammatory cytokines, hyaluronic acid (HA) and fibrotic markers. LASN01, a potent antibody to IL-11 receptor, inhibits these effects and is a potential therapeutic agent for TED. Teprotumumab, an antibody to IGF-1 receptor, inhibits HA production and adipogenesis and is effective in reduction of proptosis. Activation of the IGF-1 and IL-11 pathways in TED tissue induces the expression of fibroinflammatory genes regulated by LASN01 and lipid biosynthetic genes regulated by Teprotumumab. Clinical studies show that LASN01 is well tolerated and in a placebo-controlled phase II trial in TED, LASN01 resulted in a statistically significant resolution of clinical activity score (CAS) in 88% of treated patients (p = 0.028), but had lesser effects on proptosis. The data supports the importance of IL-11 biology in fibroinflammatory disease and that IL-11 receptor is a pharmacologically active target for drug development.
Lipofuscin is an autofluorescent material that accrues in brain tissues with age and in Neuronal Ceroid Lipofuscinosis (NCL), a neurodegenerative disease with pediatric onset. The distribution, composition, and organellar origin of lipofuscin have remained unclear despite its widespread presence in aged tissues and involvement in neurodegeneration. Here, we elucidate lipofuscin composition in mouse and human brain and assemble a reference neuroanatomical atlas of lipofuscin accumulation with age and NCL (Type 1; CLN1) progression across 425 fine brain regions. We identify a primary role of the lysosomal-mitochondrial axis in the formation of lipofuscin pathology via multimodal mass spectrometry, ultrastructural analyses, and assays of cellular and enzymatic metabolism. We find the protein and lipid composition of lipofuscin in the aged and CLN1 brain to be remarkably similar. Dissection of implicated molecular pathways reveals protein S-acylation and unsaturated lipid homeostasis as central processes involved in lipofuscin deposition during aging and CLN1. Notably, > 95% of lipofuscin resident proteins can be S-acylated and many are substrates of the enzyme PPT1, validating a seminal hypothesis that CLN1 lipofuscin contains these lipid-modified proteins. Further, we discover deficient de-S-acylation is correlated with lipofuscin load in healthy aging, as the specific de-S-acylation enzyme activity of PPT1 is found to decline with advancing age. Finally, we identify lipid metabolite biomarkers of lipofuscin, including long-chain polyunsaturated fatty acids, bis(monoacylglycerol)phosphate (BMP), and oxidized phosphatidylethanolamine (OxPE) lipid species. Overall, we provide a comprehensive redefinition of lipofuscin neuropathology and a resource for studying aging, lysosomal storage disorders, and neurodegeneration.
Neutrophil extracellular traps (NETs) play a critical role in amplifying intestinal inflammation in ulcerative colitis (UC). Clostridium butyricum (CB) has shown anti-inflammatory effects in gastrointestinal diseases; however, its impact on NETs formation and related molecular mechanisms remains unclear. UC was induced in C57BL/6 mice by DSS, followed by CB and/or PMA administration. Colonic injury was assessed by colon length measurement, histopathology, and histological scoring. NETs formation was determined by immunofluorescence staining of Ly6G and citrullinated histone H3 (Cit-H3), and serum myeloperoxidase (MPO)/Cit-H3 levels were quantified by ELISA. In vitro, NETs release was induced in neutrophils by PMA with or without CB supernatant (CBS) administration. RNA-seq and qRT-PCR/Western blot analyses were used to explore underlying signaling pathways. IL-17A knockdown via siRNA was conducted to validate mechanistic involvement. CB significantly alleviated DSS-induced colitis, evidenced by reduced colon shortening, lower colon mass, and improved mucosal architecture. CB markedly suppressed NETs formation in both colonic tissue and serum. Comparative transcriptomics indicated that CBS suppresses NETs formation primarily through modulation of the IL-17 signaling pathway. DSS-induced colitis and PMA stimulation markedly increased the expression of IL-17A, IL-17RA, and p-p65 and elevated pro-inflammatory cytokines (IL-1β and TNF-α), while reducing the anti-inflammatory cytokine IL-10. CB or CBS treatment significantly reversed these pathological changes in both colon tissues and neutrophils. Importantly, IL-17A knockdown significantly reduced PMA-induced activation of the IL-17A/IL-17RA/NF-κB, and CBS treatment further enhanced these inhibitory effects under IL-17A-deficient conditions. CB protects against DSS-induced colitis by suppressing IL-17A/IL-17RA/NF-κB-mediated NETs formation in neutrophils. IL-17A knockdown confirmed IL-17A as a critical upstream regulator of NETs, establishing the IL-17A-NETs axis as a central mechanistic target of CB.
Chagas disease (ChD) and Type 2 diabetes (T2D) originate from distinct etiological processes -infectious and metabolic, respectively- yet both share a chronic inflammatory and metabolic imbalance that profoundly impacts immune-endocrine homeostasis. Persistent Trypanosoma cruzi infection in ChD induces sustained immune activation, altered adrenal steroid balance, and tissue remodeling, whereas T2D is characterized by metabolic inflammation, oxidative stress, and insulin resistance. When these two conditions coexist, their overlapping inflammatory, metabolic, and endocrine circuits may act synergistically, amplifying metabolic toxicity, immune exhaustion, and premature immunosenescence. In addition, this comorbidity thus represents the convergence of pathogen-driven and metabolism-driven inflammation, resulting in a disrupted neuroendocrine-immune dialogue and heightened susceptibility to tissue damage, particularly in the heart. Understanding the mechanistic basis of this interplay is crucial, as it highlights shared pathogenic pathways and potential molecular targets for integrated therapeutic interventions. Altogether, recognizing ChD+T2D coexistence as a mechanistic rather than merely epidemiological association provides new insights into the links between chronic infection, metabolic dysfunction, and immune aging-offering a conceptual framework for future studies aimed at restoring immune-metabolic balance and improving disease outcomes, particularly cardiac damage.
The occipital interhemispheric transtentorial approach (OITT) is widely used for accessing lesions in the pineal region. Although reports are scarce, this approach can also be successfully applied to superior cerebellar lesions, involving the quadrangular lobule. We describe the OITT approach for cerebellar quadrangular lobe lesions, providing relevant anatomy, surgical technique, and key technical considerations. Gross total resection can be achieved while preserving normal brain tissue and functionOITT is a safe and low-morbidity route for lesions within the cerebellar quadrangular lobe, as it uses a natural anatomical corridor, avoids manipulation of eloquent areas, and minimizes injury to normal brain tissue.
Immunoglobulin A (IgA) nephropathy (IgAN) is a common clinical autoimmune disease, and the regulatory mechanism of Histone deacetylase 9 (HDAC9) in IgAN remains unclear. This study aims to elucidate the therapeutic value and potential mechanisms of HDAC9 in IgA nephropathy, offering potential new targets for clinical intervention and further research. An adeno-associated virus 9 (AAV9)-shHDAC9 vector was constructed and investigated the protective effect of HDAC9 knockdown in IgAN mouse. Transcriptome sequencing of renal tissues from IgAN mice was conducted, and immune infiltration analysis was quantified using transcriptomic data analyzed through the CIBERSORT deconvolution algorithm. Flow cytometry was employed to assess the expression of Th17 cell, B cell, and macrophage markers in the kidney tissues of IgAN mice. In vivo animal experiments indicate that HDAC9 knockdown ameliorates renal injury and suppresses the immune system to reduce inflammation in IgAN mice. Transcriptome sequencing results suggest that HDAC9 knockdown may exert therapeutic effects on IgAN by regulating immune-inflammatory responses. Through immune infiltration analysis and single-cell data, we found that HDAC9 may modulate immune cells, particularly T cells, B cells, and macrophages. Flow cytometry further confirmed that HDAC9 knockdown effectively inhibits Th17 cell and B cell activation, as well as macrophage polarization towards the M2 phenotype in IgAN mice. The graphical abstract of this study is shown in Fig. 1. HDAC9 knockdown modulates immune responses and alleviates pathological damage in IgAN mice. HDAC9 may serve as a potential therapeutic target for IgAN.
Arthritis has become a widespread global health issue with the aging population. Wearable transdermal drug delivery offers a promising treatment with high bioavailability and sustained drug concentrations. However, current technologies struggle with issues such as high cost, low comfort, risk of infection, or tissue pain and damage. Here, we present a breathable, stretchable electroporation patch (BSEP) that seamlessly integrates the traditional drug patch with electroporation-enhanced transdermal drug delivery technology in a low-cost manner. Conductive ink was patterned and deposited onto a breathable and stretchable non-woven fabric substrate using screen printing. A unique serpentine interdigitated design for stretchable electrodes was adopted to precisely localize the electric field within the superficial layers of the skin, reducing voltage in deep tissues by >50% and minimizing potential damage. Cytotoxicity tests and histological analyses confirmed the biocompatibility and safety of the materials and device. Finally, animal experiments validated the effectiveness of the BSEP in enhancing drug delivery, achieving a two-threefold increase in skin penetration compared to the control group. These findings collectively suggest that the developed BSEP holds significant promise for transdermal drug delivery applications.