Abstract Pancreatic cancer (PaCa) patients have a low rate of curative resection and a high frequency of relapse. Exosomes from plasma can carry molecules such as proteins, DNAs, mRNAs, and noncoding RNAs; among these molecules, those that are differentially expressed may be novel diagnostic biomarkers for PaCa. To obtain PaCa‐associated exosomal RNA signatures, we employed whole‐transcriptome sequencing of plasma exosomes from PaCa patients and found that a total of 1522 mRNAs and 23 circular RNAs (circRNAs) were differentially expressed in plasma exosomes from PaCa patients. Five circRNAs (hsa_circ_0000690, hsa_circ_0002130, hsa_circ_0037096, hsa_circ_0000976, and hsa_circ_0001821) were overexpressed, which was consistent with the expression levels of their host genes (integrin subunit alpha L [ITGAL], complement C3 [C3], proprotein convertase subtilisin/kexin type 6 [PCSK6], hippocalcin‐like 1 [HPCAL1], and Pvt1 oncogene (nonprotein coding) [PVT1]) in the plasma exosomes from PaCa patients. Furthermore, hsa_circ_0000976, hsa_circ_0002130, and hsa_circ_0037096 were verified to be highly expressed in the plasma of PaCa patients by qRT‐PCR analyses. The areas under the curve (AUCs) of hsa_circ_0000976, hsa_circ_0002130, hsa_circ_0037096, and carbohydrate antigen 19‐9 (CA19‐9) were 0.851, 0.675, 0.696, and 0.843, respectively, and the combination of hsa_circ_0000976 with CA19‐9 significantly increased the AUC to 0.914. Collectively, our findings underscore that hsa_circ_0000976, hsa_circ_0002130, and hsa_circ_0037096 can serve as novel biomarkers and potential therapeutic targets for PaCa and that differential circRNAs may present an enormous opportunity in PaCa diagnostics.

Abstract Hepatocellular carcinoma (HCC) often arises from liver cirrhosis, yet real‐time, noninvasive monitoring of immune escape during this transition remains limited. We developed a multifunctional biomimetic nanoprobe (ICGB@Apt) by conjugating a programmed death‐ligand 1 (PD‐L1)–specific DNA aptamer (selected via Cell–SELEX) onto an indocyanine green/BMS‐684 polymer, enabling in vivo imaging and immune modulation. In CCl 4 ‐induced mouse models progressing from cirrhosis to HCC and in complementary in vitro 3D co‐culture systems, ICGB@Apt preferentially accumulated in tumor tissue, dynamically visualized PD‐L1, and mitigated disease progression. The probe enhanced CD8 + T‐cell activity (IFN‐γ and granzyme B), reduced fibrosis and tumor burden, and outperformed non‐aptamer controls (Apt+ICG or ICGB alone). Knockdown experiments and RNA‐seq highlighted the centrality of the programmed death‐1 (PD‐1)/PD‐L1 axis; immune deconvolution implicated CD8 + T cells, follicular helper T cells, and M0 macrophages in the cirrhosis‐to‐cancer shift. The nanoprobes showed favorable biocompatibility and enabled longitudinal tracking of primary and metastatic lesions. Together, these findings establish ICGB@Apt as a PD‐L1–targeted platform that simultaneously monitors and counteracts immune escape, offering translational potential for early detection and immunotherapy guidance in HCC.

Abstract Bladder cancer exhibits considerable heterogeneity, posing challenges for prognosis and treatment. In this study, we utilized an integrated approach involving single‐cell RNA sequencing and the Cancer Genome Atlas dataset analysis, combined with in vitro functional assays, to identify key genes associated with bladder cancer progression. A novel three‐gene signature was identified and validated for its prognostic relevance in independent patient samples. Among these genes, FAM3B emerged as the most significant driver, consistently overexpressed in high‐risk patients and strongly associated with poor survival outcomes. Functional assays in bladder cancer cell lines demonstrated that FAM3B promotes cell proliferation, clonogenicity, migration, and invasion. Additionally, the three‐gene signature showed a significant correlation with advanced tumor grade and stage, highlighting its potential utility for clinical risk stratification and personalized treatment strategies. These findings not only enhance our understanding of bladder cancer biology but also underscore the therapeutic potential of targeting FAM3B and the three‐gene signature as prognostic biomarkers.

Abstract Despite the availability of antiviral drugs and vaccines, respiratory viral infections remain a serious global health burden. To identify novel therapeutic candidates, we performed metabolomic profiling comparing serum from patients infected with influenza or SARS‐CoV‐2 with healthy individuals. This analysis identified sphinganine‐phosphate (SA) as a potential protective metabolite. In a murine model of influenza infection, SA treatment significantly reduced viral load and attenuated inflammatory responses. Further mechanistic studies, including both in vivo and in vitro experiments, demonstrated that SA enhances antiviral immunity by promoting the proliferation and activation of CD8 + T cells and boosting the production of interferon‐γ and tumor necrosis factor‐α. This effect is mediated through the inhibition of suppressor of cytokine signaling 1 and subsequent activation of the Janus kinase 1/signal transducer and activator of transcription 1 signaling pathway. Our study reveals, for the first time, that SA promotes CD8 + T cell‐mediated immunity against influenza infection, providing important insights for the development of novel therapeutic strategies.

Abstract Bony materials are biogenic composites of protein fibers and mineral that create hierarchical structures. In the case of teeth, dentin is the main component and similar to other bones, it contains porosity at multiple length scales. It is traversed by micron‐sized hollow channels known as dentinal tubules, essential for temperature and pain sensation. Tubule density and thus porosity vary throughout the macroscopic three‐dimensional (3D) structure, with porosity increasing toward the pulp. The different densities in teeth are easily revealed non‐destructively in 3D by X‐ray imaging using computer tomography (CT). Yet elemental composition analysis is more difficult to obtain from within the centimeter‐sized heterogeneous bulk material. We describe an approach of merging CT measurements of healthy, intact bovine teeth with micro‐X‐ray fluorescence (micro‐XRF) images of matching serially sectioned slices. Through the combination of multi‐resolution quantitative CT measurements with elemental mass fraction derivation, gradients in density and element distributions such as calcium (Ca), phosphorus (P), and zinc (Zn) are revealed across entire teeth in 3D. While the main constituents (Ca and P) are homogeneously distributed in the matrix, Zn concentration increases significantly and exponentially toward the pulp. We find an inverse association between dentin tissue density and Zn concentration localizing this element in or around tubules. Our data serve as a quantitative reference for density and Zn mass fractions in healthy, neither carious nor hypermineralized dentin, as a basis for comparisons across species in health and disease states.

Abstract Protein sensors are key tools for infectious disease diagnosis and monitoring. The medical diagnostics field is now rapidly identifying key protein markers for the detection of a range of conditions, from early cancer development through to assessment of dementia risk a decade prior to symptoms onset. Many point‐of‐use diagnostic tools form part of standard protocols for small molecule sensing in healthcare, including glucose and ketone body sensors. Label‐free optical biosensors have emerged as reliable detection tools that provide high versatility and adaptability to detect a broad range of target analytes. Herein, we combined nanoporous anodic alumina (NAA) photonic chip technology with tailor‐engineered “nanobodies”—recombinant variable domains of heavy‐chain‐only antibodies—to achieve high affinity binding to human serum albumin (HSA). We monitored dynamic shifts in the optical fingerprint of nanobody‐conjugated NAA platforms in real time when these were exposed to target proteins, through reflectometric interference spectroscopy (RIfS). We performed a comprehensive characterization of the sensing performance, where binding mechanisms were elucidated through kinetic profiles. The nanobody‐conjugated NAA protein sensor demonstrated good affinity, selectivity, and sensitivity toward HSA. Our analysis revealed a sensitivity of 27.3 ± 3.2 nm µM −1 and low limit of detection of 16.3 ± 1.6 µM, which are well‐below the ranges for diagnosis of medical conditions such as nephrotic syndrome. The obtained results revealed that the RIfS‐based protein sensor integrated with nanobody‐modified NAA has promising potential to develop point‐of‐care platforms for clinical diagnosis of diseases.

Abstract Photodynamic therapy (PDT) holds promise for tumor ablation, but the clinical translation of photosensitizers, such as chlorin e6 (Ce6), is limited by poor aqueous solubility, low bioavailability, and insufficient tumor selectivity. To address these limitations, we constructed a nanobody–photosensitizer conjugate (NPC) by covalently linking Ce6 to a variable heavy‐chain domain targeting Nectin‐4, a clinically relevant tumor biomarker. Cell‐based assays demonstrated that NPC exhibited markedly enhanced aqueous solubility, efficient cellular uptake, and strong Nectin‐4‐dependent binding compared with free Ce6. Upon light activation, NPC generated abundant reactive oxygen species (ROS), triggered lysosomal disruption, and induced apoptosis and immunogenic cell death. In xenograft mouse models, NPC displayed prolonged circulation, rapid and selective tumor‐specific accumulation, and potent PDT to inhibit tumor growth, whereas free Ce6 displayed weak tumor retention and limited therapeutic benefit. Importantly, NPC treatment caused no measurable systemic toxicity or body weight loss during repeated administration. Collectively, these findings demonstrate that nanobody conjugation can overcome key pharmacological limitations of conventional photosensitizers by improving solubility, tumor targeting, and therapeutic index. NPC, thus, represents a promising next‐generation PDT agent with potential for tumor‐selective and clinically translatable phototherapy.