tbuckley/cabot-search huggingface dataset:
Injectable cellular vesicle-based bone meal for inflammatory bone defect repair through restoring immune homeostasis
Authors: Yu-Yue Zhao, Qian-Fang Meng, Hao Cui, Wei Liu, Yan Chen, Zhou Lan, Hao Chen, Dan-Dan Ma, Lang Rao, Guang-Tao Yu
Journal: Theranostics (2025)

Rationale: Immune homeostasis microenvironment of bone regeneration is especially important for inflammatory-derived bone defect repair. The two key influencing factors for achieving ideal bone regeneration are the balance between inflammatory cells represented by T cells and anti-inflammatory cells represented by MDSCs, and the dynamic balance between osteoblasts and osteoclasts. Methods: Herein, an injectable thermosensitive bone meal was designed with Pluronic F127 hydrogel loading myeloid-derived suppressive cells (MDSCs) membrane vesicles coated nano-hydroxyapatite (F127/nHA/MDSCs-MV, abbreviated as F127/nHAM) for periodontitis-derived bone defect repair. Results: The proteomics revealed F127/nHAM were able to catalyze the production of adenosine from ATP depend on CD73 and CD39. In vitro and in vivo assays further showed that F127/nHAM inhibited the proliferation and function of T cells by component MDSCs-MV, exerting an anti-inflammatory role. Subsequently, the RNA-sequencing and confirmation experiments revealed that F127/nHAM inhibiting the differentiation of macrophages into osteoclasts through down-regulating the secretion of CCL2 and CCL5. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that F127/nHAM had an outstanding anti-inflammatory and bone regeneration promoting properties, restoring immune homeostasis. Conclusion: This biomimetic and multifunctional bone meal opens new avenues for inflammatory-derived bone defect repair and future clinical application.
Nanocatalytic system releases overloaded zinc ions and ROS to induce Znproptosis and interrupt cell cycle through inhibiting Akt/mTOR pathway
Authors: Zi-Yue Xi, Chuan-Yong Fan, Ying-Ying Jiang, Xin-Ran Xi, Gan-Yu Nie, Shuang Zhu, Jun-Jie Zhang, Lu Xu
Journal: Theranostics (2025)

Background: Traditional programmed cell death, including ferroptosis, cuproptosis, and apoptosis, has demonstrated excellent anti-tumor effects and declared their complete mechanisms, however, the zinc ion-mediated tumor inhibiting mechanisms remain insufficiently explored. In this study, a self-generated oxygen nanocatalytic system (ZnO@COF@EM, ZCE) was developed to stimulate cascade amplified effect (CAE) of reactive oxygen species (ROS) generation leading to Znproptosis. The underlying Znproptosis mechanism to disrupt mitochondrial (Mito) metabolism was also investigated. Methods: Specifically, the principle of Znproptosis caused by accumulated zinc and ROS, which served as key factors, was declared through western blot analysis and genetic testing. The mechanism of generated ROS (·OH and 1O2) under NIR irradiation by ZCE was detected by UV scanning curves, confocal laser scanning microscopy (CLSM) images, and density functional analysis. The injury condition of Fe-S protein of mitochondria metabolism, which triggered Znproptosis with FDX2/LIAS pathway by zinc and ROS, was examined by PCR test and MTT assay. Notably, a Mito-targeting strategy for ZCE was proposed by using molecular docking technology, wherein Zn2+ was recognized by zinc finger proteins (ZFPs) with the Mito. Results: ZCE, along with CAE, produced abundant ROS (2.42-time more than control group). At the quantum chemical level, the CAE mechanism was associated with a narrower highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) gap and increased electronic energy motion within ZCE, which prolonged the excited triplet state (ETS). At the gene level, Znproptosis was achieved by regulating FDX2 and ZIP7 proteins to damage Fe-S protein. The cell cycle was interrupted by Chk2/Cdc25C/Cdc2 and Chk2/p21/Cyclin B1 pathways, leading to the arrest of G1/S and G2/M phases of the cell cycle and inhibition of the Akt/mTOR signaling pathway. Moreover, Znproptosis induced by overloading zinc ions and ROS resulted in a significant antitumor effect (up to 83.81%). Conclusion: Hence, the research reveals a detailed Znproptosis mechanism in nanocatalytic system. Through regulating FDX2/LIAS pathway, Znproptosis could improve the death rate of mitochondria by decreasing the production of Fe-S protein, contributing to advancements in the field of antitumor therapy.
Microglial Lcn2 knockout enhances chronic intracerebral hemorrhage recovery by restoring myelin and reducing inflammation
Authors: Li Wang, Lei Zhang, Kai Wang, Jun He, Liang Yuan, Yangang Wang, Weihao Lv, Zehan Zhang, Yuan Feng, Hongchen Zhang, Min Zhang, Rui Lv, Ya-Nan Dou, Xiaowei Fei, Jialiang Wei
Journal: Theranostics (2025)

Rationale: Damage to white matter and myelin poses a significant challenge to neurological recovery in the chronic phase of intracerebral hemorrhage (ICH). The repair of myelin damage post-ICH largely depends on the activation and differentiation of oligodendrocyte precursor cells (OPCs) into oligodendrocytes, a process that is significantly influenced by the inflammatory microenvironment. Lipocalin-2 (Lcn2) regulate phenotypic transformation of microglia and thus modulates inflammation. However, the exact role of Lcn2 in facilitating myelin recovery during the chronic phase of ICH remains to be fully understood. Methods: To create the ICH model, autologous blood from male C57BL/6 and Lcn2fl/flCx3cr1Cre mice was utilized. Behavioral tests were conducted to evaluate neurological recovery. The differentiation of OPCs and extent of myelin recovery were assessed using OPC and myelin markers. A multi-factor inflammatory chip was employed to investigate potential molecular regulatory mechanisms. Additionally, the Lcn2 inhibitor ZINC-94/89 was administered to explore its potential in targeting Lcn2 for enhancing myelin recovery during the chronic phase of ICH. Results: Knocking out Lcn2 in microglia significantly improved behavioral performance in chronic ICH mice, reduced inflammatory response, and enhanced myelin recovery. Both in vivo and in vitro experiments confirmed that Lcn2 knockout promoted microglia transformation to the M2 phenotype and enhanced OPCs differentiation. Mechanistically, Lcn2 knockout might affect Gdf-1 secretion in BV2 cells by modulating the JAK/STAT signaling pathway. Treatment with JAK inhibitors decreased Gdf-1 expression in BV2 cells, inhibiting OPCs migration and differentiation. Additionally, phosphorylation of Stat3 at Thr705 plays a critical role in enhancing Gdf-1 transcription and translation. Administration of the Lcn2 inhibitor ZINC-94/89 significantly improved behavioral performance, reduced inflammatory response, and promoted myelin recovery in chronic ICH mice. Conclusions: Lcn2 is crucial for myelin recovery in the chronic phase of ICH by modulating microglial phenotypes, thereby enhancing the migration and differentiation of OPCs. Administering an Lcn2 inhibitor early on could serve as a novel and effective strategy to boost recovery during this phase.
Deciphering single-cell landscape unravels cell-type-specific functional roles of RNA m<sup>6</sup>A modification in atherosclerosis
Authors: Xiaorui Ping, Xiaoyun Liang, Wenlu Xing, Saiqi Wang, Fengcongzhe Gong, Yaqi Cheng, Songqi Duan, Xueqi Lv, Xueying Li, Tianli Zhang, Chunxiao Chen, Yuxin Zhang, Chengzhu Yuan, Shangyu Liu, Gang Liu, Baofa Sun
Journal: Theranostics (2025)

Background: Atherosclerosis is a chronic inflammatory disease that is the major cause of mortality worldwide. Although several studies have assessed the function of m6A (N6-methyladenosine) modification in atherosclerosis, its regulatory mechanism at the single-cell level remains unclear. This study provides a comprehensive single-cell atlas of m6A modification regulating cell-type-specific functions in atherosclerosis. Methods: We analyzed single-cell sequencing data derived from atherosclerosis patients to elucidate the influence of m6A modification on diverse cell types. We demonstrated the potential regulatory functions of m6A regulators across various cell types and key transcription factors involved. Furthermore, we discovered m6A regulators mediated intercellular communication in important biological processes. In vitro experiments were conducted to further investigate the effects of ALKBH5, WTAP and METTL3 on atherosclerosis. Results: ALKBH5 upregulated in endothelial cells induced cell proliferation and migration involved in sprouting angiogenesis. In smooth muscle cells, upregulation of WTAP enhanced proliferation, migration and phenotypic transformation. Upregulation of METTL3 and YTHDF2 promoted macrophage activation and differentiation. Furthermore, we identified abnormally activated transcription factors could regulate m6A regulators in a cell-type-specific manner. Moreover, we revealed that m6A regulators were implicated in dysregulated intercellular communication in atherosclerosis. And a series of experimental validations supported the conclusion that m6A regulators exert cell-type-specific regulatory functions. Conclusion: Our study provided evidence for the roles of ALKBH5, WTAP and METTL3 in orchestrating atherosclerotic cell-type-specific functions, representing promising targets for precision medicine.
Vine-inspired zinc-ion modified black phosphorus coating accelerates bone tissue infiltration of 3D printed scaffolds
Authors: Dan Li, Danni Dai, Jianrong Wang, Yan Wang, Yujia Tian, Chao Zhang
Journal: Theranostics (2025)

Rationale: In the reconstruction of diabetic bone defects, 3D-printed scaffolds often encounter the challenge of limited and delayed tissue ingrowth in their central regions, which is critical for successful osseointegration and prognostic outcomes. Hyperglycemia induces endothelial apoptosis and impedes angiogenesis, thus inhibiting osteogenic differentiation of bone marrow stem cells (BMSCs). Methods: Drawing inspiration from the growth pattern of vines, we developed a Zn@BP/Si coating on the 3D-printed titanium scaffold to promote the coupling of angiogenesis and osteogenesis. This coating was achieved by Zn2+-modified black phosphorus (BP), which not only enhances the stability and photothermal properties of BP, but also prevents endothelial apoptosis. The effectiveness of Zn@BP/Si in the reconstruction of diabetic bone defects was investigated in rat model of diabetic femoral defect. Its effect on osteogenesis-angiogenesis coupling has also been explored in BMSCs and HUVECs. Results: Zn@BP/Si regulated mitochondrial dynamics and provided motivation for cell adhesion and migration, just like the climbing of vines. Notably, the regulation of enzymatic activity plays a crucial role in its inhibition of excessive mitochondrial fission. The results demonstrate that the Zn@BP/Si promotes the growth of "vascular vines" and ameliorates the angiogenic and osteogenic inhibition in diabetes. Conclusions: The study reveals the potential of bio-inspired Zn@BP/Si coating in angiogenesis-osteogenesis coupling and the treatment of diabetic bone defects.
GLSP mitigates vascular aging by promoting Sirt7-mediated Keap1 deacetylation and Keap1-Nrf2 dissociation
Authors: Yanfei Cheng, Guobin Zheng, Heming Huang, Jingyu Ni, Yun Zhao, Yuting Sun, Yingxin Chang, Shangjing Liu, Feng He, Dan Li, Yuying Guo, Yaodong Miao, Mengxin Xu, Dongyue Wang, Yunsha Zhang, Yunqing Hua, Shu Yang, Guanwei Fan, Chuanrui Ma
Journal: Theranostics (2025)

Background and Purpose: Vascular aging is a prior marker of human aging and a significant contributor to atherosclerosis and vascular calcification. However, there are limited pharmacological options available to mitigate vascular aging. Thus, understanding the mechanisms underlying vascular aging and age-related atherosclerosis and vascular calcification is crucial. This study investigates the targets of vascular aging and elucidates the role and mechanisms of Ganoderma lucidum spore powder (GLSP) in mitigating vascular aging and aging-associated atherosclerosis as well as vascular calcification. Methods: The anti-vascular aging effects of GLSP was determined in aged C57BL/6J mice and the targets of GLSP was identified through transcriptome sequencing. Additionally, the protective effects of GLSP on the aged vasculature were assessed by examining atherosclerosis in apoE-/- mice and vascular calcification in VD3 and nicotine-induced mice. In vitro, the protective effects of GLSP triterpenes against vascular aging and calcification was determined in vascular smooth muscle cells (VSMCs). Results: GLSP exerted anti-vascular aging effects by regulating the cell cycle and senescence-associated secretory phenotype (SASP), mitigating DNA damage, reducing oxidative stress, improving mitochondrial function and modulating metabolic levels. Furthermore, GLSP improved vascular aging-associated atherosclerosis and vascular calcification in vivo. Mechanistically, RNA sequencing revealed an upregulation of Sirt7 expression after GLSP treatment. Sirt7 inhibitor exacerbated VSMCs senescence and calcification in senescent VSMCs and abolished the anti-senescence and the inhibitory effect of GLSP triterpenes on VSMCs senescence and calcification. Innovatively, we found that Sirt7 interacted with Keap1 and facilitated Keap1 deacetylation, which promoted Keap1-Nrf2 dissociation and consequently enhanced Nrf2 nuclear translocation and activation. Conclusion: GLSP alleviates vascular aging by exerting antioxidant effects through the activation of the Sirt7-Nrf2 axis, providing a promising new strategy for delaying vascular aging, atherosclerosis and vascular calcification.
AMBP protects against aortic valve calcification by inhibiting ERK1/2 and JNK pathways mediated by FHL3
Authors: Chenghu Guo, Xiaoling Liu, Zeyuan Mei, Meiling Chang, Jiaqi Li, Baiqiang Wang, Wei Ji, Meng Zhang, Mei Zhang, Cheng Zhang, Guipeng An
Journal: Theranostics (2025)

Rationale: Calcific aortic valve disease (CAVD) is a progressive disorder characterized by aortic valve (AV) calcification and fibrosis. Despite advances in our understanding of CAVD pathogenesis, no drug has proven effective in preventing AV calcification. The aim of this study was to identify the key pathogenic genes in CAVD and elucidate mechanisms that may guide development of new targeted therapies. Methods: A CAVD model was established in ApoE-/- mice by administering a high-cholesterol diet for 24 weeks. An adeno-associated virus was used to induce alpha-1-microglobulin/bikunin precursor (AMBP) overexpression. RNA sequencing, quantitative real-time polymerase chain reaction, western blotting, immunofluorescence, histopathology, and echocardiography were performed to assess AV function. The mechanism of interaction between AMBP and four-and-a-half LIM domain protein 3 (FHL3) was explored using bioinformatics analyses, co-immunoprecipitation, and AlphaFold3-based simulations of crystal structures. Results: RNA sequencing identified AMBP as a key regulator of CAVD. AMBP was increased in calcified AV from CAVD patients and high cholesterol diet (HCD)-induced ApoE-/- mice. In vivo, AMBP overexpression significantly reduced HCD-induced AV calcification and fibrosis. In vitro, AMBP knockdown elevated osteogenic markers, RUNX2 and OSTERIX, and promoted calcium deposition in valvular interstitial cells induced by osteogenic medium (OM), whereas AMBP overexpression reversed these effects. Mechanistically, AMBP inhibited OM-induced phosphorylation of ERK1/2 (P-ERK1/2) and JNK (P-JNK) by competitively binding to the zinc finger domain of FHL3. This interaction disrupted the protective role of FHL3 in preventing ubiquitin-proteasome-mediated degradation of P-ERK1/2 and P-JNK. P-ERK1/2 and P-JNK inhibitors and agonists confirmed that the protective effects of AMBP against CAVD were mediated via these pathways in vivo and in vitro. Conclusions: AMBP protects valvular interstitial cells from osteoblastic differentiation and calcium deposit accumulation, thereby alleviating AV calcification. This study sheds additional light on the pathogenesis of CAVD and potential new therapeutic approaches.
The role of manganese-based MRI contrast agents for cancer theranostics: Where do we stand in 2025?
Authors: Lingyan Zhang, Shubham Roy, Bing Guo
Journal: Theranostics (2025)

Magnetic resonance imaging (MRI) guidance in the realm of anticancer therapy is crucial to visualize the spread of tumors in deep tissues, accumulate the therapeutics, and trigger them for precise therapy. Recent studies bridge this gap by integrating MRI contrast agents (CAs) with different therapeutic regimes for a better outcome. In this context, manganese-based materials hold great potential owing to their T1/T2 dual-modal MR-relaxation, less toxicity, and other therapeutic capabilities such as chemodynamic therapy, immunotherapy, etc., which have gained increasing interest among researchers and medical professionals. This work offers a timely update on the last three years for Mn-based MRI-guided theranostic applications, including chemodynamic therapy, chemotherapy, photo therapies, sonodynamic therapy, and radiotherapy against cancer. Further, several combinatory therapies and surgical intersections have also been summarized in the light of MRI guidance. The design rationale of these Mn-based agents has been discussed to understand the existing challenges and plausible outcomes shortly. Herein, we deep dive into the stimulus-based probes including pH, temperature, etc. to show the unexplored potential of Mn-complexes in this domain. This state-of-the-art review will guide innovations in Mn-based CAs to expedite safer anticancer theranostic modules for clinical translation.
Artificial intelligence in chronic kidney disease management: a scoping review
Authors: Charumathi Sabanayagam, Riswana Banu, Cynthia Lim, Yih Chung Tham, Ching-Yu Cheng, Gavin Tan, Elif Ekinci, Bin Sheng, Gareth McKay, Jonathan E Shaw, Kunihiro Matsushita, Navdeep Tangri, Jason Choo, Tien Y Wong
Journal: Theranostics (2025)

Rationale: Chronic kidney disease (CKD) is a major public health problem worldwide associated with cardiovascular disease, renal failure, and mortality. To effectively address this growing burden, innovative solutions to management are urgently required. We conducted a scoping review to identify key use cases in which artificial intelligence (AI) could be leveraged for improving management of CKD. Additionally, we examined the challenges faced by AI in CKD management, proposed potential solutions to overcome these barriers. Methods: We reviewed 41 articles published between 2014-2024 which examined various AI techniques including machine learning (ML) and deep learning (DL), unsupervised clustering, digital twin, natural language processing (NLP) and large language models (LLMs) in CKD management. We focused on four areas: early detection, risk stratification and prediction, treatment recommendations and patient care and communication. Results: We identified 41 articles published between 2014-2024 that assessed image-based DL models for early detection (n = 6), ML models for risk stratification and prediction (n = 14) and treatment recommendations (n = 4), and NLP and LLMs for patient care and communication (n = 17). Key challenges in integrating AI models into healthcare include technical issues such as data quality and access, model accuracy, and interpretability, alongside adoption barriers like workflow integration, user training, and regulatory approval. Conclusions: There is tremendous potential of integrating AI into clinical care of CKD patients to enable early detection, prediction, and improved patient outcomes. Collaboration among healthcare providers, researchers, regulators, and industries is crucial to developing robust protocols that ensure compliance with legal standards, while minimizing risks and maintaining patient safety.
Two-plex <i>in vivo</i> molecular imaging in the second near-infrared window for immunotherapeutic response
Authors: Yupeng Sun, Rui Li, Yike Cai, Yan Liu, Peiyuan Wang, Ming Wu, Xiaolong Zhang, Naishun Liao, Cuilin Zhang, Aixian Zheng, Haipo Xu, Rui Zeng, Yongyi Zeng, Xiaolong Liu
Journal: Theranostics (2025)

Tumor-infiltrating CD8+ T cells and programmed death-1 (PD1) levels are critical indicators for tumor immunophenotyping and therapeutic decision-making. Noninvasive optical imaging in the second near infrared window (NIR-II) is particularly well-suited for investigating the biological processes within tumors in live mammals, thanks to its deep-tissue penetration and superior spatiotemporal resolution. However, in vivo NIR-II imaging has primarily been restricted to a single probe at a time. Methods: Herein, we developed a two-plex NIR-II molecular imaging method utilizing the non-overlapping fluorescence emission of indocyanine green (ICG) in the NIR-IIa window (1000-1200 nm) and PbS/CdS core-shell quantum dots (QDs) in the NIR-IIb window (1500-1700 nm). By integrating PD1 aptamer-labeled ICG (ICG-Apt-PD1, targeting PD1) and CD8 aptamer-labeled QDs (QDs@Apt-CD8, targeting CD8+ T cells), our two-plex NIR-II molecular imaging enabled simultaneous and noninvasive monitoring of the number of CD8+ T cells and PD1 levels in tumors. Results: QDs@Apt-CD8 demonstrated the excellent ability for in vivo imaging of tumor infiltrating CD8+ T cells, owing to its strong NIR-IIb luminescence and the high selectivity and specificity. This two-plex in vivo molecular imaging allowed for dynamic monitoring for PD1 levels and the number of CD8+ T cells in tumors. We observed the heterogeneous bio-distributions of PD1 and CD8+ T cells across different tumor types and revealed the tumor immunophenotypes. Moreover, our findings indicated that the low PD1 and high CD8+ T cells levels in tumors predicted a better anti-tumor effect. Conclusions: Such in vivo noninvasive NIR-II molecular imaging would complement ex vivo biopsy-based diagnostic techniques, and it could contribute to developing an in vivo tumor immune-scoring algorithm to offer a more precise prediction for immunotherapeutic response.
Macrophage membrane-functionalized nanotherapeutics for tumor targeted therapy
Authors: Mubassir Khan, Razi Ullah, Guixue Wang, Maoquan Chu
Journal: Theranostics (2025)

Cancer is a multifaceted disease characterized by uncontrollable cell growth. To date, various therapies are employed including conventional chemotherapy, surgery, radiotherapy, and immunotherapies. However, these approaches still present significant limitations. Interestingly, macrophage membranes utilize their innate antigen recognition affinity to facilitate targeted localization to tumor sites with high specificity. As a result, they display distinct characteristics such as avoiding premature leakage, tumor targeting ability, immune evasion, immune system activation, tumor-infiltrating ability, improved cell endocytosis and release payload in tumor-microenvironment. In this paper, the recent advances in macrophage-membrane-encapsulated nanotherapeutics for targeted cancer therapy are presented. We begin by introducing macrophage membrane-encapsulated nanotherapeutics preparation and characterization, followed by cancer immunotherapy such as macrophage polarization, T-cell infiltration, macrophage membrane modification, immunization, and inducing immunological cell death. Lastly, a future perspective is proposed to highlight the limitations of macrophage membrane-encapsulated nanotherapeutics and the possible resolutions toward the clinical transformation of currently developed biomimetic chemotherapies. We believe this review may be beneficial for improving the deep research of macrophage membrane-encapsulated nanotherapeutics for targeted cancer therapy.