tbuckley/cabot-search huggingface dataset:
Exercise Mimetic Exosomes Re‐establish the Extracellular Matrix Metabolic Balance and Alleviate the Inflammatory Macrophage Infiltration in Intervertebral Disc Degeneration
Authors: Ke Zhao, Yongzhi Cui, Yuxuan Du, Liming Zheng, Yupeng Liang, Chong Liu, Prisca Hecker, Oleksandr Moroz, Liguo Zhu, Jiawen Zhan
Journal: Advanced Healthcare Materials (2025)

Abstract Extracellular matrix (ECM) metabolic imbalance and macrophage infiltration, induced by degenerated nucleus pulposus cells (NPCs), represent key pathological alterations in intervertebral disc degeneration (IVDD). Physical exercise is shown to effectively delay the progression of IVDD by enhancing ECM synthesis and reducing inflammation. However, many individuals are unable to maintain regular exercise habits due to physical limitations and insufficient self‐discipline. In response to this challenge, the concept of exercise mimetic exosomes (EMEs) is proposed as a therapeutic strategy for IVDD. In this approach, human induced pluripotent stem cell‐derived myotubes are subjected to mechanical strain to simulate exercise conditions. The exosomes generated under these conditions, termed EMEs, are enriched with exercise‐inducible components, notably irisin. These EMEs are capable of being internalized by both NPCs and macrophages. In NPCs, EMEs restored ECM metabolic balance and inhibited NFκB activation. In macrophages, EMEs modulated the M1 polarization induced by degenerated NPCs. Collectively, EMEs restored the metabolic equilibrium of the extracellular matrix and mitigated inflammatory macrophage infiltration within the microenvironment, thereby demonstrating significant therapeutic effects on IVDD. More importantly, EMEs may serve as a model for the treatment of other musculoskeletal disorders and the development of exercise mimetic therapies.
Biomimetic Scaffolds Enhance iPSC Astrocyte Progenitor Angiogenic, Immunomodulatory, and Neurotrophic Capacity in a Stiffness and Matrix‐Dependent Manner for Spinal Cord Repair Applications
Authors: Cian O'Connor, Ian Woods, Sarah F. McComish, Sean Kerr, Matthew McGrath, Juan Carlos Palomeque Chávez, Jack Maughan, Tara McGuire, Maeve A. Caldwell, Adrian Dervan, Fergal J. O'Brien
Journal: Advanced Healthcare Materials (2025)

Abstract Spinal cord injury repair poses a significant challenge due to the hostile microenvironment of the injury site and the poor survival and function of clinically relevant transplanted cells. Here it is aimed to investigate whether tuning the physicochemical properties of implantable biomimetic biomaterial scaffolds can enhance the localized delivery and reparative potential of patient‐derived induced pluripotent stem cells (iPSC) astrocyte progenitors. It is demonstrated that soft, collagen‐IV/fibronectin‐functionalized hyaluronic acid scaffolds, mimicking the physicochemical properties of healthy spinal cord tissue, optimally support the formation of iPSC‐derived multicellular spheroids, promoting neural cell survival and function. These soft, collagen‐IV/fibronectin scaffolds enhance angiogenic cytokine release, facilitate vascular network formation, modulate inflammatory responses, and promote neurite outgrowth from growing, mature and injured neurons, while supporting cell infiltration from spinal cord explants. These findings demonstrate that optimized biomimetic scaffold properties provide a supportive environment for iPSC astrocyte progenitors but can also modulate their reparative capacity. These findings highlight the critical role of matrix composition and scaffold stiffness in advancing scaffold‐mediated patient‐derived stem cell‐delivery strategies for spinal cord repair applications.
Albumin Corona Overturns Long‐Acting Behaviors of Myristic Acid‐Conjugated Quetiapine Nanosuspension
Authors: Hy Dinh Nguyen, Hai Van Ngo, Beom‐Jin Lee
Journal: Advanced Healthcare Materials (2025)

Abstract This work aimed to investigate the interaction of a self‐assembled myristic acid‐conjugated quetiapine nanosuspension (QMN) with human serum albumin and its overturning effect on QMN's long‐acting performance. Albumin corona formation modified the physicochemical properties and pharmacokinetic profile of QMN by overturning its pH‐responsiveness and nano‐aggregation behavior. The adsorption of albumin on QMN is initially triggered by electrostatic forces and later by hydrophobic‐hydrophobic interactions with the conformational change of the albumin structure. While QMN is highly susceptible to ionic strength, pH, and albumin concentration in solution, albumin‐precoated QMN (A‐QMN) stabilized particle size and reversed the surface charge from ≈+60 to −16 mV, annulling the pH‐responsive nanoaggregation behaviors under physiological pH conditions. Consequently, A‐QMNs exhibited much faster in vitro release and more rapid in vivo absorption, resulting in a huge initial burst release and shorter duration within one week in plasma concentration‐time profiles compared to the extended five‐week duration of QMN following intramuscular injection in beagle dogs. These findings indicated the important role of serum proteins in the release kinetics and pharmacokinetics of the nanoparticles. The manipulation of protein corona can be utilized to control the physicochemical properties, biological states, and pharmacokinetics of intended long‐acting nanosuspensions.
Enhanced Photodynamic Therapy Synergizing with Neutrophil Recruitment Boosts Drug‐Resistant Bacterial Clearance
Authors: Anran Li, Jie Li, Yufei Zhang, Ye Zhang, Yanlong Zhang, Xianhui Song, Chensheng Li, Xinge Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Antibiotic‐resistant bacteria produce some virulence factors as immune evasion molecules that interfere with a variety of innate immune defenses, which is associated with reduced levels of neutrophil recruitment. Antibiotics and neutrophils recruited by endogenous chemokines are not able to efficiently eliminate the bacteria at the site of infection. Here, a nano‐chemoattractant (fZnCB) is developed with photodynamic therapy and neutrophil recruitment by a multi‐component self‐assembly strategy to coordinate benzoxaborole‐modified Chlorin e6 (Ce6‐BN) and formylated peptides (fMLFH) through Zn 2+ . This innovative system synergistically collaborates with neutrophils through photodynamic effects to combat drug‐resistant bacteria. Furthermore, the nano‐chemoattractant not only demonstrates exceptional bacterial adhesion properties, biofilm dispersion by photodynamic activity but also boosts the recruitment, engulfment, and killing of bacteria by neutrophils. Its remarkable therapeutic efficacy against bacterial keratitis has been validated in a mouse model. This offers a new insight into an alternate approach for treating infectious diseases caused by drug‐resistant bacteria.
Engineering the Micro‐Nano Hierarchical Spray Hydrogel for Acute Lung Injury Therapy
Authors: Yongxin Xu, Rui Zhao, Peipei Xi, Cong Xu, Mei Yang, Junyi Che, Zhifeng Gu, Yujuan Zhu
Journal: Advanced Healthcare Materials (2025)

Abstract Acute lung injury (ALI) poses a significant threat to human health, yet specific treatments remain elusive. Despite extensive research efforts, drug delivery to the lungs and reliable preclinical models are major challenges. To address these issues, a novel micro‐nano hierarchical spray hydrogel is developed with the enhanced targeting ability for treating ALI. The hierarchical nanocomposite hydrogel is characterized with ordered micro‐nanostructure, composing of spray hydrogel and astaxanthin nanoparticles (ASX‐NPs). Astaxanthin, a natural active ingredient derived from algae, is nano‐encapsulated to produce ASX‐NPs, which significantly improves bioavailability. ASX‐NPs are found to efficiently target the mitochondria and significantly relieve the inflammatory responses in human lung organoid‐based inflammatory models by downregulating inflammation‐ and oxidative stress‐related pathways and upregulating mitochondrial energy metabolism. In ALI mice, the spray hydrogel adheres to the tracheal mucosa and rapidly releases ASX‐NPs upon inhalation. Released ASX‐NPs are endocytosed to alleviate the inflammation and promote ALI recovery. The findings suggest that this hierarchical hydrogel system offer a promising alternative for ALI treatment, and can expand the applications of human organoids in disease modeling and drug discovery.
Tumor ploidy determination in low-pass whole genome sequencing and allelic copy number visualization using the Constellation Plot
Authors: Sarah H Johnson, James B Smadbeck, Roman M Zenka, Michael T Barrett, Athanasios Gaitatzes, Arnav Solanki, Angela B Florio, Mitesh J Borad, John C Cheville, George Vasmatzis
Journal: Genome biology (2025)

Ploidy determination across the genome has been challenging for low-pass-WGS tumor-only samples. We present BACDAC, a method that calculates tumor ploidy down to 1.2X effective tumor coverage. Allele fraction patterns displayed in the Constellation Plot verify tumor ploidy and reveal subclonal populations. BACDAC outputs a metric, 2N+LOH, that when combined with ploidy better distinguishes near-diploid from high-ploidy tumors. Validated using TCGA, BACDAC had good agreement with other methods and 88% agreement with experimental methods. Discrepancies occur mainly when BACDAC predicts diploidy with subclones rather than high-ploidy. Applied to 653 low-pass-WGS samples spanning 12 cancer subtypes, BACDAC calls 40% as high-ploidy.
ROS‐Responsive Hydrogel Delivering METRNL Enhances Bone Regeneration via Dual Stem Cell Homing and Vasculogenesis Activation
Authors: Yue Xu, Rui Huang, Wodong Shi, Rong Zhou, Xinling Xie, Miao Wang, Yang Wang, Ping Gu, Ni Ni, Xiaoping Bi
Journal: Advanced Healthcare Materials (2025)

Abstract Critical‐sized bone defects arising from bone‐related diseases pose a clinical challenge, exceeding the body's natural healing capacity. Evidence has shown that a disordered microenvironment characterized by reactive oxygen species (ROS) overproduction, vascular damage, and osteoblast deficiency severely hinders bone repair. Therefore, the reconstruction of microenvironmental homeostasis post‐injury is of utmost importance. Herein, a ROS‐responsive scavenging GelMA loaded with METRNL (RRG‐MRL) is developed, serving as a “bone microenvironment‐modulating system” for targeted delivery of METRNL, which stimulates bone marrow mesenchymal stem cells (BMSCs) homing and angiogenic sprouting. Upon exposure to elevated levels of ROS within the defect region, ROS‐cleavable NHS‐TK‐NHS linkers are disrupted, triggering responsive degradation and METRNL release. This treatment significantly reduced ROS levels and alleviated inflammation, along with increasing the levels of anti‐apoptotic factors. Meanwhile, released METRNL induced endothelial cell angiogenesis by activating the c‐Kit/PI3K/Akt pathway and increased secretion of SDF‐1α (CXCL12) to promote BMSCs recruitment. Rat models of cranial bone defects treated with RRG‐MRL demonstrated reduced ROS signal intensity in situ, increased endogenous BMSCs count, and enhanced neovascularization, resulting in accelerated bone regeneration. The proposed platform offers a multistage therapeutic approach facilitating rapid reconstruction of microenvironment homeostasis to promote bone regeneration, indicating significant clinical potential.
Asian consensus statement of experts on thermal ablation for secondary hyperparathyroidism in chronic kidney disease
Authors: Huihui Chai, Wenwen Yue, Liping Sun, Ling Zhang, Ji-Hoon Kim, Wei-Che Lin, Jie Yu, Mingan Yu, Ningning Wang, Hong Wang, Shurong Wang, Ying Che, Qiang Lu, Jie Ren, Fangyi Liu, Yang Liu, Erjiao Xu, Hui Xu, Min Xu, Jinge Zhu, Litao Ruan, Xinping Sun, Desheng Sun, Xiaolong Li, Changbin Li, Meng Yang, Songsong Wu, Fei Yu, Songyuan Yu, Yongwu Yu, Yifeng Zhang, Chun Ouyang, Bo Zhang, Xiaoliang Zhang, Lina Zhang, Jun Luo, Zhengbiao Ji, Jianqiao Zhou, Li Zhou, Yumin Zheng, Lin Fang, Qiyu Zhao, Binghui Zhao, Xinju Zhao, Pengcheng Hu, Shengxiang Rao, Hong Jiang, Qingqing He, Linxue Qian, Dong Xu, Junyue Huang, Hongli Cui, Tianan Jiang, Hong Han, Zhijiang Han, Jingning Cheng, Youben Fan, Jung Hwan Baek, Ping Liang, Huixiong Xu, Chengzhong Peng
Journal: International Journal of Surgery (2025)

Secondary hyperparathyroidism (SHPT) is characterized by parathyroid hyperplasia, persistently elevated parathyroid hormone levels, and disturbances in mineral metabolism. Currently, a considerable amount of literature has consistently shown that thermal ablation is effective in maintaining parathyroid hormone levels within an appropriate range, normalizing calcium and phosphorus levels, improving clinical symptoms, and reducing the volume of parathyroid glands. However, there are currently no established guidelines regarding its utilization. The Asian consensus statement of experts on thermal ablation for SHPT in chronic kidney disease was jointly initiated by experts from China and Korea in the fields of nephrology, interventional ultrasound or radiology, thyroid surgery, ultrasound medicine, nuclear medicine, and diagnostic radiology—to formulate recommendations aimed at establishing standardized protocols for thermal ablation targeting the parathyroid glands. Based on the systematic review of literatures related to ultrasound-guided thermal ablation of parathyroid glands and the professional opinions of experts, the consensus statement covers the relevant content regarding thermal ablation treatment for SHPT, including indications, contraindications, pre-ablation evaluation, operational procedures, post-ablation follow-up, therapeutic effect evaluation, complications prevention and treatment. According to the Grading of Recommendations Assessment, Development and Evaluation, a total of 18 recommendations were given. This consensus statement will positively promote the standardization of ultrasound-guided thermal ablation of parathyroid glands.
Twenty-year panoramic review of stem cells research in kidney diseases (2005–2025): a bibliometric and clinical trial-based exploration
Authors: Jiayou Liu, Jiyuan Hu, Xue Gao, Hongfang Liu
Journal: International Journal of Surgery (2025)

Over the past two decades, a systematic elucidation of the overall trajectory and clinical translation of stem cell research in kidney diseases has been lacking. To address this gap, we conducted a bibliometric analysis and clinical trial search focusing on the period from 2005 to 2025, thereby mapping the global landscape of stem cell research in kidney diseases. Our results indicate a growing body of literature, accompanied by extensive international collaborations, with the United States and China leading in research output. In terms of research themes, mesenchymal stem cells continue to garner sustained attention for their reparative applications. Over the past decade, there has been a marked increase in studies on exosomes, extracellular vesicles, and kidney organoids. Nevertheless, clinical translation remains relatively delayed, suggesting that laboratory discoveries require additional time to reach bedside applications. This study provides a global perspective grounded in empirical data, helping to clarify critical frontiers and challenges.
Deep cervical lymphovenous anastomosis (LVA) for Alzheimer’s disease microsurgical procedure in a prospective cohort study
Authors: Jing-Yu Chen, Da-Wei Zhao, Yi Yin, Li Gui, Xin Chen, Xiao-Mei Wang, Pang-Bo Wang, Cheng-Hai Zuo, Zhao-Pan Lai, Chong Li, Rui Wang, Ji-Shu Xian, Zhi Chen, Hua Feng, Rong Hu
Journal: International Journal of Surgery (2025)

Objectives: Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder, characterized by progressive cognitive decline. Current approved drugs merely relieve symptoms rather than halt or reverse disease progression. The role of the brain lymphatic system in clearing harmful substances in the brain has provided new insights for AD treatment. The goal of this study was to assess the efficacy and safety of deep cervical lymphovenous anastomosis (LVA) in treating AD patients. Materials and methods: A single-center, prospective, single-arm exploratory study was conducted on 26 AD patients who met the clinical and biomarker diagnostic criteria of the National Institute on Aging-Alzheimer’s Association (NIA-AA). Deep cervical LVA was performed with modified technique from lymphatic vessel-vein to lymphatic flap-vein anastomosis. Preoperative and follow-up neuropsychological tests were carried out using Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Neuropsychiatric Inventory (NPI) scores. Cerebrospinal fluid (CSF) biomarkers (Aβ42, Aβ40, p-Tau, T-Tau) were collected and analyzed via single-molecule immunoassay in the early postoperative period. Results: One month after surgery, about 60% of caregivers reported varying degrees of overall symptom improvement in patients. MMSE scores of patients significantly increased after surgery compared with before surgery (3 [0, 6] vs. 5 [0, 7], P = 0.022). Although, 15% of patients had increased MoCA scores, 42% had decreased NPI scores, both changes did not reach statistical difference. Quantitative analysis revealed a trend toward reduced AD biomarker levels following LVA, but the differences did not reach statistical significant. Only two patients experienced postoperative difficulty raising their arms, with gradual recovery during follow-up. Conclusion: This study demonstrates that deep cervical LVA is safe and feasible procedure, showing a significant cognitive improvement in AD patients (mainly in MMSE), which needs long-term follow-up and large-scale clinical trials to verify.
Integrating machine learning and molecular docking to decipher the molecular network of aflatoxin b1-induced hepatocellular carcinoma
Authors: Junjie Gao, Meijun Zhang, Qun Chen, Kai Ye, Jing Wu, Tao Wang, Puhong Zhang, Gang Feng
Journal: International Journal of Surgery (2025)

Objective: This study aims to investigate the molecular mechanisms underlying hepatocellular carcinoma (HCC) induced by Aflatoxin B1 (AFB1). Methods: Differential expression analysis of multiple datasets was performed to identify HCC-related target genes. Machine learning algorithms, network toxicology, and molecular docking techniques were integrated to explore the binding interactions between AFB1 and target proteins. Results: A total of 48 genes were identified as potential targets for AFB1-induced hepatocarcinogenesis. Subsequent machine learning analysis prioritized six core genes (RND3, PCK1, AURKA, BCAT2, UCK2, and CCNB1) as key regulators. Among these, RND3 and PCK1 exhibited significant downregulation, while AURKA, BCAT2, UCK2 and CCNB1 showed marked upregulation (P&lt;0.05). Molecular docking simulations revealed strong binding specificity between AFB1 and target proteins. Conclusion: This study demonstrates that AFB1 may promote HCC pathogenesis by targeting specific genes and signaling pathways. Machine learning identified six core regulatory genes, and molecular docking confirmed AFB1’s high binding affinity with key targets. These findings provide critical insights for further mechanistic exploration of AFB1-induced hepatocarcinogenesis.
Efficacy of high energy, focused ESWT in treatment of lumbar facet joint pain – a randomized sham-controlled trial
Authors: Tomas Nedelka, Jakub Katolicky, Jiri Nedelka, Paul Hobrough, Karsten Knobloch
Journal: International Journal of Surgery (2025)

Objective Lumbar facet joints (FJ) are a common source of chronic low back pain (LBP). Focused extracorporeal shock wave therapy (ESWT) has demonstrated potential in the treatment of musculoskeletal disorders due to its deeper tissue penetration and safety profile. This study aimed to evaluate the efficacy and safety of ESWT in the management of lumbar facet joint pain. Methods A prospective, randomized, sham-controlled trial was conducted in 128 patients with chronic lumbar facet syndrome confirmed by medial branch block. Patients were randomized to receive either focused ESWT (Group A, n = 64; 0.35 mJ/mm 2 , 1200 shocks/session = 600 shocks per segment, 5 weekly sessions) or sham therapy (Group B, n = 64). Pain intensity (VAS), disability (ODI), and neuropathic pain features (PainDETECT questionnaire) were assessed at 2, 6, and 12 months. Lumbar spine MRI was performed at baseline and 6 months post-treatment. Results Group A showed significant reductions in VAS scores at 6 and 12 months (mean 64.4% reduction at 12 months, p&lt;0.01), with an effect size (Cohen’s d = 1.12). ODI decreased by 42.3% in Group A compared to 12.5% in the sham group. Neuropathic pain symptoms improved significantly only in Group A (PD-Q reduction from 18.3 ± 2.4 to 10.2 ± 1.9; p&lt;0.01). MRI follow-up demonstrated resolution of bone marrow edema in 58.8% of ESWT-treated patients versus none in the control group. No adverse effects were reported. Conclusions High-energy focused ESWT is a safe and effective non-invasive therapy for chronic lumbar facet joint pain, showing sustained improvements in pain, function, and neuropathic symptoms. MRI findings support its biological effect on joint-related bone marrow edema. ESWT represents a promising alternative to interventional pain procedures.
Ferroptosis is involved in the IL-9-induced intestinal barrier injury in sepsis: an experimental animal and translational study
Authors: Jia-Kui Sun, Xiao-Tian Huangfu, Xiang Yin, Shuai Nie, Yi-Hang Deng, Zi-Yu Ye, Xue-Hui Zhou, Xiang Wang, Yan-Na Si
Journal: International Journal of Surgery (2025)

Background: Interleukin-9 (IL-9) is an emerging pro-inflammatory cytokine that promotes intestinal barrier injury (IBI) in sepsis. The specific mechanisms of IL-9-induced IBI still need to be clarified. As a newly discovered form of programmed cell death, ferroptosis was demonstrated to be involved in sepsis-related organ dysfunction, yet its role in IL-9-induced IBI in sepsis remains unexplored. Methods: Serum levels of IL-9, D-lactate, intestinal fatty acid binding protein (iFABP), glutathione (GSH), and glutathione peroxidase 4 (GPX4) were tested in septic patients and control subjects. Biomarkers reflecting barrier function in serum and intestinal tissue were tested in treated rats. Rats underwent sepsis induction, IL-9, IL-9 inhibition (IL-9i), and ferroptosis inhibition (Fei) treatment were selected to examine the severity of IBI and survival rates. Results: Significantly elevated levels of IL-9, D-lactate, iFABP, GSH, and GPX4 were observed in septic patients and rats. IL-9 levels showed a negative correlation with GSH and GPX4 levels, while GSH or GPX4 levels showed an inverse correlation with D-lactate and iFABP levels. Serum GSH and GPX4 levels demonstrated strong predictive value for acute gastrointestinal injury of grade II and above in septic patients. IL-9 administration increased levels of transferrin receptor, Fe 2+ , and iFABP in serum and intestinal tissue of septic rats, while decreasing GSH, GPX4, and zonula occludens 1 levels. Inhibition of ferroptosis reversed these biomarkers alterations. Intestinal permeability, transmission electron microscopy, histopathology, and apoptosis assays confirmed exacerbated IBI following IL-9 upregulation and its attenuation upon ferroptosis inhibition. Conclusion: Ferroptosis was implicated in the IL-9-induced intestinal barrier injury in sepsis.