Strong near-infrared-II (NIR-II, 1000-1700 nm) absorbers with high photothermal efficiency are highly desirable for deep-tissue photoacoustic imaging and photothermal therapy. However, donor-acceptor (D-A) molecular design strategies that simultaneously achieve structural robustness and intense NIR-II absorption remain scarce. Herein, we demonstrate that single-boron coordination can be implemented on the intrinsically strong acceptor [1,2,5]thiadiazolo[3,4-g]quinoxaline (TQ), an unachieved regime by previously reported boron-engineered strategies, which have typically been based on weaker electron-deficient acceptors. Single intramolecular N -> B-N coordination converts TQ into an even stronger electron-deficient motif than the widely used benzobis(thiadiazole) (BBT) acceptor. Through donor engineering and planarity modulation, the resulting borylated TQ derivative, BLD3, exhibits intense NIR-II absorption with a high molar extinction coefficient (epsilon > 3 & times; 10(4) M--(1) cm(-)(1)) around 1000 nm in toluene. Featuring an ultrafast nonradiative decay of 2.1 ps, BLD3 nanoparticles (NPs) show a high photothermal conversion efficiency of 68% under 1060 nm laser irradiation, as well as a robust photoacoustic (PA) output under 1064 nm excitation. Combining excellent photo/thermal stability, favorable tumor accumulation, and good biocompatibility, BLD3 NPs enable effective NIR-II PA imaging-guided photothermal therapy with pronounced tumor ablation. This work expands the library of strong acceptors for boron-coordination chemistry, providing a general platform for constructing powerful electron-deficient building blocks and high-performance NIR-II phototheranostic materials.

Refractory colonic lesions, including ulcerative colitis and chemotherapy-induced colitis, represent significant clinical challenges. Patchouli alcohol (PA) and pogostone (PT) are the main pharmacological ingredients of patchouli volatile oil (PO), widely used for treating gastrointestinal tract disorders. PA and PT exhibit promising therapeutic effects on colonic lesions, such as immunoregulation and mucosal barrier repair, but with poor stability and low water solubility. It is a challenge of colon-specific delivery of PA and PT. In this work, we developed a layer-by-layer silk fibroin microparticle system (SF@COS) coated by chito-oligosaccharide. The microparticles exhibited a mean diameter of 3.1 mu m and a zeta potential of +8.6 mV. Encapsulation efficiencies reached 80.8% for PA and 74.7% for PT, benefiting from hydrophobic interactions between the amphiphilic SF beta-sheet structure and the lipophilic drugs. In addition, chito-oligosaccharide coating on the thus-formed SF microparticles can electrostatically bind with mucins for adhesion and is selectively degraded by colon-specific beta-glucosidase and microbiota. The SF@COS microparticles demonstrated superior colon-targeted retention and significantly attenuated body weight loss and colon shortening in DSS-induced mice. Therapeutic outcomes were associated with the downregulation of pro-inflammatory cytokines (TNF-alpha and IL-6) and the restoration of tightjunction proteins (ZO-1 and Occludin), and recovery of mucosal barrier function. Moreover, the microparticles also effectively reduced chemotherapy-induced apoptosis of colonic epithelial cells. Our strategy provides an effective and safe treatment for refractory colonic lesions (e.g., UC and chemotherapy-induced colitis).

Micro-expression recognition (MER) is challenged by a brief duration, low intensity, and heterogeneous spatial frequency patterns. This study introduces a novel MER architecture that reduces computational cost by fine-tuning a large feature extraction model with LoRA, while integrating frequency-domain transformation and graph-based temporal modeling to minimize preprocessing requirements. A Spatial Frequency Adaptive (SFA) module decomposes high- and low-frequency information with dynamic weighting to enhance sensitivity to subtle facial texture variations. A Dynamic Graph Attention Temporal (DGAT) network models video frames as a graph, combining Graph Attention Networks and LSTM with frequency-guided attention for temporal feature fusion. Experiments on the SAMM, CASME II, and SMIC datasets demonstrate superior performance over existing methods. On the SAMM 5-class setting, the proposed approach achieves an unweighted F1 score (UF1) of 81.16% and an unweighted average recall (UAR) of 85.37%, outperforming the next best method by 0.96% and 2.27%, respectively.

Biological agents are the cornerstone of first-line treatment for inflammatory bowel disease. However, approximately 33

Objective: Colitis-associated colorectal cancer (CAC) poses a significant clinical challenge due to its poor prognosis and difficulty in distinguishing malignancy from inflammation with current imaging methods. This study aims to evaluate a multimodal endoscopic imaging system combining optical coherence tomography (OCT), ultrasonography (US), and near-infrared fluorescence (NIRF) to improve the detection of CAC. Methods: The proposed imaging system integrates OCT, US, with NIRF imaging enhanced through the administration of BSA-ICG nanocomplexes. The NIRF component enables visualization of capillary networks within the intestinal wall, while OCT and US assess morphological changes during CAC progression. The system applied in a CAC mice model to monitor both vascular and structural changes from inflammation to tumor formation. Results: The system successfully detected early morphological and vascular changes associated with CAC, including alterations in capillary networks, tissue thickening, and tumor formation. Fluorescence imaging provided high-resolution visualization of the smallest capillaries in the colon, while OCT and US offered valuable insights into the progression from inflammation to malignancy. Conclusion: The system shows strong potential for early and accurate detection of CAC by simultaneously visualizing vascular and morphological changes in vivo. This approach enables dynamic monitoring of disease progression and offers valuable insights into the inflammatory mechanisms underlying carcinogenesis. Significance: This study presents an imaging technique that could improve early diagnosis of CAC, ultimately leading to better clinical outcomes. By enhancing our ability to detect tumor-related changes at an early stage, this multimodal system may help guide therapeutic interventions and improve patient management.

Vascular calcification is a major feature of cardiovascular disease, but mechanistic studies are limited by slow and variable animal models and by ex vivo systems that insufficiently reflect physiological flow. Here, we established an ex vivo vascular calcification perfusion system and compared perfusion with static culture using an in vivo rabbit abdominal aortic calcification model as a pathological reference. Low serum combined with interleukin-17A rapidly induced vascular calcification within 7 days. Under normal culture conditions, the perfusion system preserved endothelial and smooth muscle integrity over 7 days. Static culture produced marked edge effects, excessive mineralization, and increased osteogenic marker expression, whereas perfusion maintained a more moderate calcification phenotype that more closely resembled the in vivo reference. These findings support this model as a biologically relevant and controllable platform for studying vascular calcification mechanisms and evaluating potential interventions.

Aim: Multidrug resistance (MDR) often arises from lysosomal sequestration of chemotherapeutics. This study aims to design and evaluate lysosome-targeting membrane-intercalating conjugated oligoelectrolytes (MICOEs) for their potential to reverse MDR via dual-mode lysosomal membrane disruption, and to identify the most effective candidate. Methods: Three MICOEs featuring a pyridothiadiazole-thienothiophene-pyridothiadiazole (PTTP) conjugated backbone with quaternary ammonium-terminated 4-, 6-, and 8-carbon alkyl chains at both ends (PTTP-DC4, PTTP-DC6, PTTP-DC8) were synthesized and characterized. Their photophysical properties, cellular uptake, and sublocalization were assessed in doxorubicin (DOX)-resistant Michigan Cancer Foundation-7/adriamycin-resistant (MCF-7/ADR) cells. Lysosomal integrity and contents release were evaluated via acridine orange and cathepsin B assays. Proteomic analysis was performed to uncover mechanisms. The combinational effect of PTTP-DC6 and DOX was tested in drug-resistant two-dimensional (2D) and three-dimensional (3D) cell models. Results: Among PTTP-DCns (where n = 4, 6, and 8, corresponding to PTTP-DC4, PTTP-DC6, and PTTP-DC8), PTTP-DC6 showed optimal lysosomal accumulation and induced lysosomal membrane permeabilization (LMP) through both physical membrane interaction and light-triggered reactive oxygen species generation. Proteomic analysis revealed significant enrichment of pathways associated with oxidative stress and lysosomal dysfunction. Pretreatment with PTTP-DC6 at low doses, particularly under mild light irradiation, significantly enhanced DOX sensitivity in resistant 2D monolayers and 3D spheroid models. Conclusion: PTTP-DC6 overcomes MDR by dual-mode LMP induction, providing a simple strategy to resensitize resistant cancers to conventional chemotherapy.

BackgroundAccumulating evidence has identified the gut microbiota as a critical regulator of biological processes such as immune homeostasis, and its dysbiosis has been implicated in the pathogenesis of numerous diseases. Current strategies for modulating the gut microbiota remain limited by several challenges: low colonization efficiency (probiotics), interindividual variability in host response (prebiotics), and safety concerns (antibiotics).MethodsWe investigated the effects of a physically processed, additive-free purified water (Koishio water, KW) on gut microbiota composition and basal inflammatory status in healthy mice.ResultsFirst, KW drinking significantly increased the diversity and richness of the gut microbiota of the mice, including increased abundance of Verrocomicrobiota and decreased abundance of Proteobacteria; Second, KW drinking significantly increased the abundance of several beneficial genera of the gut bacterium (Akkermansia, Faecalibaculum, Ligilactobacillus, and Muribaculum) and significantly decreased the abundance of several harmful genera of the gut bacterium (Clostridioides, Citrobacter, Escherichia-Shigella, and Clostridium Innocuum group); and third, functional prediction suggested enrichment of microbial pathways related to mucosal barrier integrity, host metabolic regulation, and antioxidative capacity. Moreover, KW significantly decreased the basal level of three major pro-inflammatory factors, including IL-1β, IL-6, and TNF-α, which are widely recognized as biomarkers of subclinical low-grade chronic inflammation.ConclusionThese findings demonstrate that KW, characterized by affordability, safety, and suitability for daily consumption, may serve as a novel non-pharmacological intervention to beneficially modulate gut microbiota composition and reduce basal inflammatory levels under non-pathological conditions.

Ligand-receptor pair analysis, a key aspect of cell-to-cell interactions, is vital for understanding physiological and pathological processes in organisms. However, most analytical tools fail to incorporate spatial in situ information, resulting in false positive predictions. Spatial transcriptomics, which integrates gene expression data with cellular localization, has emerged as a powerful method for inferring cell-cell interactions. Co-localization analysis using spatial transcriptomic data enables the identification of cell candidates with potential interactions, significantly enhancing ligand-receptor pair analysis and improving predictive accuracy. This review explores the data types and computational approaches for co-localization analysis, along with its specific applications in identifying ligand-receptor pairs within the tumor microenvironment, based on a systematic literature search. Additionally, it examines the future prospects of co-localization analysis in the discovery of therapeutic targets and its role in advancing precision medicine. In summary, co-localization analysis aids in uncovering novel ligand-receptor pairs, supports the identification of new disease targets, and contributes to the development of clinical precision medicine, with the integration of artificial intelligence further enhancing analysis accuracy.

Bigel, formed by high-speed shearing of hydrogel and oleogel, is suited to deliver both lipophilic and hydrophilic active compounds. Patchouli oil and paeoniflorin, despite their potential in treating ulcerative colitis, face challenges due to patchouli oil's poor aqueous solubility and paeoniflorin's high solubility but low permeability. In this study, we developed an oral colon-targeted bigel system to co-deliver patchouli oil and paeoniflorin for treating ulcerative colitis. Patchouli oil served as both a therapeutic agent and an oil phase (excipient). The bigel system enhanced mechanical stability, prolonging retention at the colon and enabling effective colon-targeted drug delivery. Compared to oleogel, bigel significantly alleviated symptoms in DSS-induced colitis in mice, reduced inflammatory cytokine release, repaired intestinal mucosal damage, and regulated immune cell populations in the gut. The combination of patchouli oil and paeoniflorin in the bigel exerted a synergistic effect on ulcerative colitis treatment. This work underscores the efficacy of bigel in delivering a combination of hydrophilic and lipophilic drugs, offering a novel strategy for enhanced drug delivery in ulcerative colitis. It also provides a delivery platform technology for volatile oils.

The concurrence of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) presents a therapeutic challenge, often necessitating liver transplantation in severe cases. Paeoniflorin (PAE), known for its immunomodulatory and anti-inflammatory properties but with very high-water solubility and low permeability, is formulated into a paeoniflorin/phospholipid complex microemulsion (PAE-ME) to enhance its delivery in this study. It demonstrated the PAE-ME's macrophage-regulating ability to repolarize the pro-inflammatory M1 subtype to the anti-inflammatory M2 type and reduce inflammatory cytokine release. In a PSC-IBD mouse model, PAE-ME alleviated the symptoms and regulated bile acid balance. Given the close connection and crosstalk between the liver and intestine, PAE-ME yielded a synergistic therapeutic effect on both the liver and intestinal lesions. These findings suggest a promising translational approach for complex comorbidities by acting on the liver-gut axis.

[This corrects the article DOI: 10.3389/fphar.2025.1526952.].

Gastrointestinal tract toxicity represents a serious adverse effect of chemotherapy, leading to reduced quality of life and survival. For instance, irinotecan (CPT-11) usually causes severe gastrointestinal toxicity, with a lack of effective therapeutic interventions, making treatment often unsustainable. Therefore, development of an effective and safe therapy is crucial for improving chemotherapy efficacy and the patients’ quality of life. In this work, we developed a novel approach involving the helical-shaped cyanobacterium microalgae, Spirulina platensis (SP), to carry the bornyl acetate (BA)-loaded chitosan nanoparticles to enhance drug retention in the small intestine. We demonstrated the protection effect of BA against chemotherapy-induced intestinal injury using an epithelial cell model. In a mouse model, orally administered BA-ChNPs@SP accumulated in the small intestine and attenuated inflammation by reducing dsDNA release and oxidative stress. This was concomitant with the restoration of the intestinal barrier and modulation of the immune microenvironment. This work suggests the promise of the microalgae-carrying nanomedicine strategy for treatment of intestinal diseases, emphasizing its potential in addressing chemotherapy-induced gastrointestinal complications.

As a novel approach to killing bacteria, photodynamic therapy holds great potential in antibacterial treatment. However, the majority of traditional photosensitizers exhibit relatively low reactive oxygen species (ROS) quantum yield. Therefore, it is essential to develop photosensitizers with high ROS quantum yield to effectively kill bacteria. Herein, we propose a molecular design approach to enhance the spin-orbit coupling (SOC) and improve the ROS quantum yield by introducing carbonyl groups into a donor-acceptor (D-A) system. In the meantime, we also introduced membrane-anchoring functional groups to the photosensitizer to anchor on the bacterial surface for improved antibacterial treatment. In this design, two D-A photosensitizers (CTI-1-anchor and CTI-2-anchor) were synthesized by linking membrane-anchoring functional groups to carbazole and indanedione derivatives. Notably, the resulting CTI-1-anchor exhibited a significantly enhanced ROS generation capability, and its ROS quantum yield can reach 87%. Moreover, the CTI-1-anchor demonstrated superior antibacterial performance against Gram-positive bacteria (S. aureus) and Gram-negative bacteria (E. coli). The antibacterial efficacy of CTI-1-anchor reached 97.7% and 73.4% for S. aureus and E. coli, respectively. This study is expected to inspire further molecular designs of photosensitizers, ultimately contributing to the development of efficient antibacterial therapy.

Journal of the European Academy of Dermatology and VenereologyEarly View LETTER TO THE EDITOR Exploring Th17-related inflammation in AP1B1-associated KIDAR syndrome and potential therapeutic implications of secukinumab Chaolan Pan, Chaolan Pan Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHongsong Ge, Hongsong Ge Department of Dermatology, Anhui Provincial Children's Hospital, Hefei, ChinaSearch for more papers by this authorLuyao Zheng, Luyao Zheng Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorQiaoyu Cao, Qiaoyu Cao Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaSearch for more papers by this authorCheng Zhang, Cheng Zhang orcid.org/0000-0002-7735-7839 Department of Dermatology, Anhui Provincial Children's Hospital, Hefei, ChinaSearch for more papers by this authorYumeng Wang, Yumeng Wang orcid.org/0000-0002-5298-3171 Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorAnqi Zhao, Anqi Zhao Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorWei He, Wei He Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaSearch for more papers by this authorGuofang Li, Guofang Li Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHaifei Liu, Haifei Liu orcid.org/0000-0002-6954-5899 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorYijun Yang, Yijun Yang orcid.org/0000-0003-4974-8012 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorRuoqu Wei, Ruoqu Wei orcid.org/0000-0001-8818-4534 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHaoyu Wang, Haoyu Wang orcid.org/0000-0003-3075-7840 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorYidong Tan, Yidong Tan Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorBing Wang, Bing Wang Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorWenjie Cheng, Wenjie Cheng Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorZhe Sun, Zhe Sun Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorXiaoxiao Wang, Corresponding Author Xiaoxiao Wang [email protected] Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Correspondence Ming Li, Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai, China. Email: [email protected] Xiaoxiao Wang, Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Email: [email protected]Search for more papers by this authorMing Li, Corresponding Author Ming Li [email protected] orcid.org/0000-0003-3053-2756 Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Correspondence Ming Li, Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai, China. Email: [email protected] Xiaoxiao Wang, Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Email: [email protected]Search for more papers by this author Chaolan Pan, Chaolan Pan Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHongsong Ge, Hongsong Ge Department of Dermatology, Anhui Provincial Children's Hospital, Hefei, ChinaSearch for more papers by this authorLuyao Zheng, Luyao Zheng Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorQiaoyu Cao, Qiaoyu Cao Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaSearch for more papers by this authorCheng Zhang, Cheng Zhang orcid.org/0000-0002-7735-7839 Department of Dermatology, Anhui Provincial Children's Hospital, Hefei, ChinaSearch for more papers by this authorYumeng Wang, Yumeng Wang orcid.org/0000-0002-5298-3171 Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorAnqi Zhao, Anqi Zhao Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorWei He, Wei He Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaSearch for more papers by this authorGuofang Li, Guofang Li Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHaifei Liu, Haifei Liu orcid.org/0000-0002-6954-5899 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorYijun Yang, Yijun Yang orcid.org/0000-0003-4974-8012 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorRuoqu Wei, Ruoqu Wei orcid.org/0000-0001-8818-4534 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorHaoyu Wang, Haoyu Wang orcid.org/0000-0003-3075-7840 Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorYidong Tan, Yidong Tan Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorBing Wang, Bing Wang Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorWenjie Cheng, Wenjie Cheng Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorZhe Sun, Zhe Sun Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Institute of Dermatology, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaSearch for more papers by this authorXiaoxiao Wang, Corresponding Author Xiaoxiao Wang [email protected] Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Correspondence Ming Li, Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai, China. Email: [email protected] Xiaoxiao Wang, Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Email: [email protected]Search for more papers by this authorMing Li, Corresponding Author Ming Li [email protected] orcid.org/0000-0003-3053-2756 Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China Correspondence Ming Li, Department of Dermatology, Children's Hospital of Fudan University, National Children's Medical Center, 399 Wanyuan Road, Shanghai, China. Email: [email protected] Xiaoxiao Wang, Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. Email: [email protected]Search for more papers by this author First published: 20 April 2024 https://doi.org/10.1111/jdv.20033 Chaolan Pan and Hongsong Ge contribute equally to this paper. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Open Research DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request. REFERENCES 1Gan Y, McGraw TE, Rodriguez-Boulan E. The epithelial-specific adaptor AP1B mediates post-endocytic recycling to the basolateral membrane. Nat Cell Biol. 2002; 4(8): 605–609. 10.1038/ncb827 CASPubMedWeb of Science®Google Scholar 2Fölsch H. 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Ferroptosis has emerged as a promising therapeutic approach for glioma. However, its efficacy is often compromised by the activated GPX4-reduced glutathione (GSH) system and the poor brain delivery efficiency of ferroptosis inducers. Therefore, suppression of the GPX4-GSH axis to induce the accumulation of lipid peroxides becomes an essential strategy to augment ferroptosis. In this study, we present a metalloimmunological strategy to target the GPX4-GSH axis by inhibiting the cystine/glutamate antiporter system (system Xc-) and glutathione synthesis. To achieve this, we developed a complex of diethyldithiocarbamate (DDC) chelated with copper and ferrous ions (DDC/Cu-Fe) to trigger T-cell immune responses in the tumor microenvironment, as well as to inhibit tumor-associated macrophages, thereby alleviating immunosuppression. To enhance brain delivery, the DDC/Cu-Fe complex was encapsulated into a hybrid albumin and lactoferrin nanoparticle (Alb/LF NP), targeting the nutrient transporters (e.g., LRP-1 and SPARC) overexpressed in the blood-brain barrier (BBB) and glioma cells. The Alb/LF NP effectively promoted the brain accumulation of DDC/Cu-Fe, synergistically induced ferroptosis in glioma cells and activated anticancer immunity, thereby prolonging the survival of glioma-bearing mice. The nanoformulation of DDC/Cu-Fe provides a promising strategy that combines ferroptosis and metalloimmunology for glioma treatment.

The limited therapeutic efficacy of oral medications against ulcerative colitis (UC) is attributed to inadequate drug exposure to inflammation site in the colon. To address this challenge, we developed a pH-triggered oral hydrogel microsphere system composed of alginate/silk fibroin (Alg/SF) using zinc ions (Zn2+) as a crosslink agent for colon-targeted delivery. This system, with moderate gelation toughness, can protect the anti-inflammatory drug bornyl acetate (BA) from gastric degradation, ensuring its delivery to the colon. SF effectively shields the microspheres during passage through the small intestine and then facilitates rapid drug release upon reaching the colon. We evaluated the efficacy of this strategy in murine models of both acute and chronic colitis, demonstrating its significant capacity to attenuate pro-inflammatory cytokine secretion, enhance intestinal barrier restitution, and modulate immune cell responses for effective amelioration of colitis-associated symptoms. Upon oral administration of microspheres, their therapeutic efficacy against both acute and chronic UC is demonstrated to be superior to that of a widely used clinical drug, 5-aminosalicylic acid. Overall, the oral hydrogel microspheres offer a promising approach to enhance the therapeutic outcomes of small molecule drug against UC.

Despite that the current anti-hyperuricemia drugs can effectively reduce uric acid (UA) levels, imprecise medication dosage or uncontrolled lowering of UA levels may result in undesired effects. To address this issue, a closed-loop cascade strategy based on a biocompatible network composite, NW-FPNP/uricase (UOX), is proposed for on-demand regulation of UA levels. NW-FPNP/UOX is constructed by encapsulation of UOX) as UA-responsive element and FPNP, a nanoparticle of phenylboronic acid modified xanthine oxidase (XOD) inhibitor febuxostat, as H2O2-sensitive element with AMP/Gd3+ network. It interrelates the UA metabolization and generation processes into a closed loop of cascade reactions involving UOX-catalyzed UA metabolization and H2O2 generation, H2O2-triggered febuxostat regeneration and XOD inhibition, and XOD-catalyzed UA generation. Through UA level-dependent auto-adjustment of XOD activity, specially 6% at 600 x 10-6 m UA compared to 82% at 100 x 10-6 m, UA levels can be regulated to an appropriate range through dynamically balancing UA metabolization and generation. This biocompatible on-demand UA regulation system prevents the overdose of UA-lowering medications and avoids hypouricemia in hyperuricemia treatment, demonstrating great potential in intelligent UA level management. This work also introduces a new concept of a closed-loop cascade strategy for on-demand regulation of biochemical indicators within specific thresholds.

Boronic acid based optical continuous glucose monitoring systems (CGMs) hold promise for long-term glucose monitoring. However, these sensors suffer drifts induced inaccuracy and external calibration. One of the reasons is the denature of boronic acid structures and optical reporters. To solve this problem, a dual-mode glucose sensing method with auto-recalibration capabilities is developed using glucose-selective diboronic acid molecule (DBA) and optical reporter alizarin red S (ARS). DBA binds ARS at a 1:2 ratio and produces distinct changes in both the absorbance (Abs) and the fluorescence (FL) spectra of ARS. Through competitive binding with DBA, glucose induces a compensatory shift in both Abs and FL signals. The two signals were demonstrated to be strongly correlated and were combined to build Abs-FL-glucose 3D calibration curves for glucose determination. The mapping relationship of two signals drift closely with both changes of DBA and ARS concentration. By ascertain the right mapping relationship, the two strongly correlated signals can alert undesirable degradation of sensing components, identify the correct calibration curve, and accurately predict glucose concentration without external calibration. The introduction and adoption of the auto-recalibrating dual-mode sensing strategy could constitute a useful development in the pursuit of next generation long-term calibration-free CGM and wearable sensors technologies with superior precision.