Latest Issue

    2026 Year 13 Volume 1 Issue

      RESEARCH

    • Accelerating cartilage regeneration with DNA-SF hydrogel sustained release system-based cartilage organoids AI Introduction

      Introducing research progress in the field of cartilage repair. Experts have developed a DNA-silk fibroin hydrogel sustained-release system (DSRGT) to construct cartilage organoids (COs). This innovative strategy provides solutions to solve prolonged repair cycles and suboptimal outcomes in cartilage repair.
      Cong-Yi Shen, Qi-Rong Zhou, Xiang Wu, Xin-Yu Han, Qin Zhang, Xiao Chen, Yu-Xiao Lai, Long Bai, Ying-Ying Jing, Jian-Hua Wang, Cheng-Long Wang, Zhen Geng, Jia-Can Su
      2026, 13(1): 1-23. DOI: 10.1186/s40779-025-00625-z
      Accelerating cartilage regeneration with DNA-SF hydrogel sustained release system-based cartilage organoids
      Abstract:BackgroundCartilage repair remains a considerable challenge in regenerative medicine. Despite extensive research on biomaterials for cartilage repair in recent years, issues such as prolonged repair cycles and suboptimal outcomes persist. Organoids, miniature three-dimensional (3D) tissue structures derived from the directed differentiation of stem or progenitor cells, mimic the structure and function of natural organs. Therefore, the construction of cartilage organoids (COs) holds great promise as a novel strategy for cartilage repair.MethodsThis study employed a digital light processing system to perform 3D bioprinting of a DNA-silk fibroin(DNA-SF) hydrogel sustained-release system (DSRGT) with bone-marrow mesenchymal stem cells (BMSCs) to con-struct millimeter-scale cerebral organoids. COs at different developmental stages were characterized, and the COs with the best cartilage phenotype were selected for in vivo cartilage repair in a rat articular cartilage defect model.ResultsThis study developed a DSRGT by covalently grafting glucosamine (which promotes cartilage matrix synthe-sis) and TD-198946 (which promotes chondrogenic differentiation) onto a hydrogel using acrylic acid-polyethylene glycol-N-hydroxysuccinimide (AC-PEG-NHS). In vitro, 4-week COs exhibited higher SRY-box transcription factor 9(SOX9), type II collagen (Col II), and aggrecan (ACAN) expression and lower type I collagen (Col I) and type X collagen(Col X) expression, indicating that 4 weeks is the optimal culture duration for hyaline cartilage development. In vivo, the mitogen-activated protein kinase (MAPK) signaling pathway was upregulated in 4-week COs, enabling cartilage repair within 8 weeks. Transcriptomic analysis revealed that cartilage regenerated with 4-week COs presented gene expression profiles resembling those of healthy cartilage.ConclusionsThis study employs DSRGT to construct COs, providing an innovative strategy for the regeneration of cartilage defects.  
      Keywords:Cartilage organoid (COs);Glucosamine;TD-198946;DNA-silk fibroin hydrogel;Chondrogenesis;Cartilage repair   
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      Updated:2026-03-26
    • A new study explores the role of IL-33 in repetitive mild traumatic brain injury (rmTBI). Researchers used an rmTBI mouse model to investigate how IL-33 affects cognitive function and neuroinflammation. The study found that IL-33 enhances microglial phagocytosis and reduces neuronal damage, suggesting it could be a therapeutic target for improving neurological outcomes in rmTBI.
      Ze-Xi Jia, Meng-Tian Guo, Mei-Mei Li, Pan Liao, Bo Yan, Wei Zhang, Fang-Yuan Cheng, Ya-Ru Liu, Zi-Han Zhang, Cheng Wei, Jie Zhou, Fang-Lian Chen, Ping Lei, Xin-Tong Ge
      2026, 13(1): 24-42. DOI: 10.1186/s40779-025-00631-1
      Decreased IL-33 in the brain following repetitive mild traumatic brain injury contributes to cognitive impairment by inhibiting microglial phagocytosis
      Abstract:BackgroundRepetitive mild traumatic brain injury (rmTBI) is a significant risk factor for neurodegeneration, charac-terized by pathological protein deposition and persistent neuroinflammation. Research has observed increased inter-leukin-33 (IL-33) levels in the peripheral blood of patients with rmTBI, suggesting IL-33 may participate in regulating the pathological development of rmTBI. The study aims to elucidate the impact and mechanism of IL-33 in the pro-gression of neuropathology following rmTBI, and to explore its potential as a therapeutic target to improve the neuro-logical outcome.MethodsThe study employed an rmTBI mouse model using the wild-type (WT) and IL-33 knockout mice. Cognitive function was assessed via the Y-maze and Barnes tests. The main cell type expressing IL-33 and its receptor, suppres-sion of tumorigenicity 2 (ST2), was then investigated in the mouse brain through immunofluorescence colocaliza-tion. As the primary neural cell responsible for ST2 expression, microglia were studied in vitro using the BV2 cell line. The effects of lipid droplets (LDs) accumulation and amyloid-beta (Aβ) phagocytosis were measured to elucidate the impact of IL-33 on BV2 cells’ phagocytosis. Additionally, HT22 neuronal apoptosis was assessed by flow cytometry.Finally, the cognitive effects of intranasal administration of IL-33 were evaluated in mice.ResultsIL-33KO mice exhibited pronounced cognitive impairment after rmTBI. In the mouse brain, astrocytes were identified as the primary source of IL-33 secretion, while microglia predominantly expressed ST2. Transcriptome sequencing revealed that IL-33 significantly influenced phagocytosis function. IL-33 mitigated LDs accumulation in BV2 cells and enhanced Aβ phagocytosis in vitro. In addition, the culture medium of BV2 cells with activated IL-33/ST2 signaling reduced HT22 neuronal apoptosis and axonal damage. Furthermore, intranasal administration of IL-33 was observed to be effective in alleviating neurodegeneration and cognitive outcome of rmTBI mice.ConclusionsDysfunction of the IL-33/ST2 axis following rmTBI leads to cognitive dysfunction via impairing microglial phagocytosis capacity and promoting neuronal damage. IL-33 would be a promising therapeutic target for alleviating neurodegeneration following rmTBI.  
      Keywords:Repetitive mild traumatic brain injury (rmTBI);Interleukin-33 (IL-33);Microglia;Cognition   
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      Updated:2026-03-26
    • Clinical information prompt-driven retinal fundus image for brain health evaluation AI Introduction

      A new study introduces its research progress in estimating brain volume through retinal fundus imaging. Experts proposed the CMCR network to elucidate the co-degenerative relationships between the eyes and brain, offering a cost-effective approach for assessing brain health.
      Nuo Tong, Ying Hui, Shui-Ping Gou, Ling-Xi Chen, Xiang-Hong Wang, Shuo-Hua Chen, Jing Li, Xiao-Shuai Li, Yun-Tao Wu, Shou-Ling Wu, Zhen-Chang Wang, Jing Sun, Han Lv
      2026, 13(1): 43-57. DOI: 10.1186/s40779-025-00630-2
      Clinical information prompt-driven retinal fundus image for brain health evaluation
      Abstract:BackgroundBrain volume measurement serves as a critical approach for assessing brain health status. Considering the close biological connection between the eyes and brain, this study aims to investigate the feasibility of estimating brain volume through retinal fundus imaging integrated with clinical metadata, and to offer a cost-effective approach for assessing brain health.MethodsBased on clinical information, retinal fundus images, and neuroimaging data derived from a multicenter, population-based cohort study, the KaiLuan Study, we proposed a cross-modal correlation representation (CMCR)network to elucidate the intricate co-degenerative relationships between the eyes and brain for 755 subjects. Specifi-cally, individual clinical information, which has been followed up for as long as 12 years, was encoded as a prompt to enhance the accuracy of brain volume estimation. Independent internal validation and external validation were performed to assess the robustness of the proposed model. Root mean square error (RMSE), peak signal-to-noise ratio(PSNR), and structural similarity index measure (SSIM) metrics were employed to quantitatively evaluate the quality of synthetic brain images derived from retinal imaging data.ResultsThe proposed framework yielded average RMSE, PSNR, and SSIM values of 98.23, 35.78 dB, and 0.64, respec-tively, which significantly outperformed 5 other methods: multi-channel Variational Autoencoder (mcVAE), Pixel-to-Pixel (Pixel2pixel), transformer-based U-Net (TransUNet), multi-scale transformer network (MT-Net), and residual vision transformer (ResViT). The two- (2D) and three-dimensional (3D) visualization results showed that the shape and texture of the synthetic brain images generated by the proposed method most closely resembled those of actual brain images. Thus, the CMCR framework accurately captured the latent structural correlations between the fundus and the brain. The average difference between predicted and actual brain volumes was 61.36 cm3, with a relative error of 4.54%. When all of the clinical information (including age and sex, daily habits, cardiovascular factors, meta-bolic factors, and inflammatory factors) was encoded, the difference was decreased to 53.89 cm3, with a relative error of 3.98%. Based on the synthesized brain MR images from retinal fundus images, the volumes of brain tissues could be estimated with high accuracy.ConclusionsThis study provides an innovative, accurate, and cost-effective approach to characterize brain health status through readily accessible retinal fundus images.  
      Keywords:Retinal fundus image;Brain volume;Brain health;magnetic resonance imaging;Deep learning;Eye and brain connection   
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      Updated:2026-03-26
    • Clinical-transcriptomic classification of lumbar disc degeneration enhanced by machine learning AI Introduction

      A new study introduces significant research progress in the field of lumbar disc degeneration (LDD). Experts identified four distinct molecular subtypes of LDD using clinical features. This breakthrough could facilitate precise diagnostics and guide personalized treatment strategies for LDD.
      Huai-Jian Jin, Peng Lin, Xiao-Yuan Ma, Sha Huang, Liang Zhang, Ou Hu, Yang-Yang Li, Ying-Bo Wang, Jun Zhu, Bo Hu, Jun-Gang Pu, Qin Qin, Pu-Lin Yan, Bing Liu, Yu Lan, Lin Chen, Yang-Li Xie, Jian He, Yi-Bo Gan, Peng Liu
      2026, 13(1): 58-77. DOI: 10.1186/s40779-025-00637-9
      Clinical-transcriptomic classification of lumbar disc degeneration enhanced by machine learning
      Abstract:BackgroundLumbar disc degeneration (LDD) displays considerable heterogeneity in terms of clinical features and pathological changes. However, researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features. This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.MethodsOne hundred and twenty-two nucleus pulposus (NP) tissues from 108 patients were consecutively collected for bulk RNA sequencing (RNA-seq). An unsupervised clustering method was employed to analyze the bulk RNA matrix. Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix (ECM) dysregulation. The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets. Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved. Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.ResultsLDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling: C1 with collagenesis, C2 with ossification, C3 with low chondrogenesis, and C4 with fibrogenesis. Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1; NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes; Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis; Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α (TNF-α). Furthermore, the random forest diagnostic prediction model was proven to have a robust performance [area under the receiver operating characteristic (ROC) curve: 0.9312; accuracy: 0.84] in stratifying the molecular subtypes of LDD based on 12 clinical features.ConclusionsOur study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features. The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.  
      Keywords:Lumbar disc degeneration (LDD);Molecular classification;Machine learning;diagnosis;Transcriptome;RNA sequencing (RNA-seq)   
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      Updated:2026-03-26

      REVIEW

    • Metal-based nanomedicines for cancer theranostics AI Introduction

      Metal-based nanomedicines introduce research progress in cancer diagnosis and treatment. Experts have explored the use of these nanomaterials, which offer solutions to address the challenges posed by cancer cell heterogeneity and invasiveness.
      Hai-Jia Yu, Jian-Hua Liu, Wei Liu, Rui Niu, Bin Zhang, Yuan Xiong, Yang Liu, Ying-Hui Wang, Hong-Jie Zhang
      2026, 13(1): 78-128. DOI: 10.1186/s40779-025-00627-x
      Metal-based nanomedicines for cancer theranostics
      Abstract:The heterogeneity and invasiveness of cancer cells pose serious challenges in cancer diagnosis and treatment. Advancements and innovations in metal-based nanomedicines provide novel avenues for addressing these challenges. Metal-based nanomedicines possess unique physicochemical properties that enable their interaction with living organisms, thereby inducing complex biological responses. These nanomaterials have been extensively used to enhance the contrast and sensitivity of cancer imaging and to amplify the distinction between cancerous and healthy tissues. Moreover, these nanomaterials can effectively combat a wide spectrum of cancers through various methods, including drug delivery, radiotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), biocatalytic therapy, ion interference therapy (IIT), and immunotherapy. Currently, there is still a need for a comprehensive summary on the metal-based nanomaterials for cancer diagnosis and treatment. Herein, we present a systematic and complete overview of action mechanisms and the applications of metal-based nanomaterials in cancer theranostics. A summary of common strategies for synthesizing and modifying metal-based nanomedicines is presented, and their biosafety is analyzed. Then, the latest developments in their applications for cancer imaging and anticancer treatment are provided. Finally, the key technical challenges and reasonable perspectives of metal-based nanomedicines for cancer theranostics in clinical applications are discussed.  
      Keywords:Metal-based nanomedicines;Synthesis strategy;Computed tomography imaging;Nuclear imaging;magnetic resonance imaging;Fluorescence imaging;Photoacoustic imaging;Drug-delivery;Phototherapy;Catalytic therapy;Ion interference therapy;Immunotherapy   
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      Updated:2026-03-26
    • Healing of tendon-related diseases: insights from macrophage regulation AI Introduction

      A new review introduces research progress in tendon-related diseases (TRDs). Experts explored the dual role of macrophages in TRDs, either promoting healing or amplifying inflammation. This research provides novel insights for designing biomaterials-based targeted delivery systems to accelerate the regeneration process.
      Ren-Qiang Chen, Peng-Ju Liu, Shuai Li, Hong-Pu He, Dan-Mei Li, Guang-Xun Yuan, Xiang-Yu Du, Jing-Yue Su, Zhen-Han Deng, Jian Xu
      2026, 13(1): 129-158. DOI: 10.1186/s40779-025-00635-x
      Healing of tendon-related diseases: insights from macrophage regulation
      Abstract:Tendon-related diseases (TRDs) are increasingly common in the current aging society and impose a significant burden on patients. Despite therapeutic advances, the pathophysiology of TRDs remains poorly understood, hindering effective clinical management. The macrophages are highly plastic immune cells involved in the maintenance of in vivo homeostasis and the injury-healing process. Their dual role in TRDs has been widely investigated, either promoting tenogenic and chondrogenic differentiation or amplifying inflammatory response, underscoring their therapeutic potential for TRDs treatment. Therefore, the review aims to summarize the roles of macrophages in the healing of TRDs, characterized by limited regenerative capacity, and examine strategies for the modulation of macrophage phenotypes to accelerate the regeneration process. Finally, we review applications involving macrophage modulation within the context of tissue engineering of TRDs, providing novel insights for the design of biomaterials-based targeted delivery systems.  
      Keywords:Tendon;Tendon-bone interface (TBI);Tendon-related diseases (TRDs);macrophages;Tissue engineering   
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      Updated:2026-03-26
    • A new study explores the use of dexamethasone to prevent acute altitude illnesses during rapid high-altitude ascents. Researchers found it effective at altitudes above 4000 m with doses of 8−16 mg/d. Further trials are needed to optimize its application.
      Johannes Burtscher, Hannes Gatterer, Beth A. Beidleman, Martin Burtscher
      2026, 13(1): 159-168. DOI: 10.1186/s40779-025-00634-y
      Dexamethasone for prevention of AMS, HACE, and HAPE and for limiting impairment of performance after rapid ascent to high altitude: a narrative review
      Abstract:Acute exposure to high altitude can cause acute altitude illnesses and is associated with impaired cognitive and physical performance. The most effective preventive strategies currently recommended include environmental acclimatization (slow ascent and/or pre-acclimatization) or pharmacological support of acclimatization using acetazolamide. However, these strategies are not practical for high-altitude exposures that require rapid and unplanned ascent, high physical and mental performance, such as rescue missions or military operations. Dexamethasone and other modulators of the glucocorticoid system take effect quickly and are effective alternatives for preventing acute altitude illnesses when rapidly ascending to high altitudes. As the efficacy of dexamethasone in preventing acute mountain illnesses remains controversial, a review of existing studies on the use of dexamethasone for the prevention of acute mountain sickness was conducted, aiming to determine the best strategy. Possible mechanisms of protection against acute altitude illnesses are discussed based on the results of clinical trials. The data indicate that dexamethasone is most effective at altitudes above 4000 m at doses of 8−16 mg/d. Appropriately designed and powered trials are needed to obtain more evidence-based results on the dosage and timing of dexamethasone administration, and to provide optimized recommendations for the application of this powerful pharmacological tool.  
      Keywords:Altitude illnesses;prevention;dexamethasone;Emergency;Rescue mission;military operation   
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      Updated:2026-03-26

      LETTER TO THE EDITOR

    • Extracellular BAG3 is elevated in early diffuse systemic sclerosis AI Introduction

      In the latest research, expert xx has made significant strides in the field of xxx. By establishing the xx system, they have provided solutions to solve xx problems, opening up new directions for future research and laying a foundation for the construction of the xx system.
      Paul Freedman, Margot De Marco, Alessandra Rosati, Liberato Marzullo, Nicoletta Del Papa, Maria Caterina Turco, Steven O’Reilly
      2026, 13(1): 169-172. DOI: 10.1186/s40779-025-00628-w
      Extracellular BAG3 is elevated in early diffuse systemic sclerosis
      Keywords:Systemic sclerosis;Bcl-2 associated athanogene-3 (BAG3);cytokine;Lung disease;Stimulator of interferon genes (STING)   
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