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SEAWATER-CONTAMINATED ULNAR RABBIT BONE DEFECTS REPAIR USING 3D-PRINTED β-TCP/VANCOMYCIN COMPOSITE SCAFFOLDS
No full textBackground: Repairing extensive bone defects following seawater immersion poses a significant challenge for orthopedic surgeons. Recent advancements in three-dimensional (3D) printing technology have demonstrated considerable potential in fabricating scaffolds with optimized morphological structures and superior biological properties. However, the specific characteristics and therapeutic efficacy of 3D-printed nano beta-tricalcium phosphate (β-TCP) scaffolds in the repair of seawater-immersed rabbit ulna bone defects remain inadequately explored. Methods: Nano-β-TCP scaffolds were fabricated via stereo lithography apparatus (SLA) and characterized using scanning electron microscope (SEM), X-ray diffraction, and mechanical testing. Vancomycin-loaded scaffolds were implanted in 18 rats, with drug release profiles monitored over a 56-day period. Thirty-six rabbits were assigned to three groups to assess scaffold performance in 1.5 cm seawater-immersed ulnar defects. Serum tumor necrosis factor-alpha (TNF-α) levels were measured pre-and post-implantation to evaluate inflammatory responses. Bone repair was assessed through X-ray, histological analysis, and micro-computed tomography (micro-CT) scanning. In vitro antibacterial efficacy was also evaluated. Results: The scaffold exhibited a cylindrical porous structure with dimensions of 0.5 cm in both diameter and height. The average pore size was approximately 400 µm, with a porosity of 53 %, and a compressive strength of 170 N. The scaffold demonstrated sustained vancomycin release over 56 days. In vivo, implantation of the scaffolds resulted in a significant reduction in serum TNF-α levels (p < 0.05) and promoted new bone formation compared to controls (p < 0.05). Histological and micro-CT analyses confirmed superior bone repair, with increased expression of osteocalcin (OCN), osteopontin (OPN), and vascular endothelial growth factor (VEGF). The scaffolds exhibited robust antibacterial activity after 72 hours. Conclusions: 3D-printed nano-β-TCP scaffolds offer an effective solution for repairing seawater-immersed bone defects and significantly enhance bone regeneration.link_to_subscribed_fulltex
Deep imaging of LepR+ stromal cells in optically cleared murine bone hemisections
No full textTissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional (3D) architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions. Deciphering the spatial interaction of leptin receptor-expressing (LepR+) stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue. In this study, we introduce an optimized protocol for the 3D analysis of skeletal tissues, enabling the visualization of hematopoietic and stromal cells, especially LepR+ stromal cells, within optically cleared bone hemisections. Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae. The protocol entails tissue fixation, decalcification, and cryosectioning to reveal the marrow cavity. Completed within approximately 12 days, this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals. The bone hemisections are compatible with diverse antibody labeling strategies. Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software, assessing a spectrum of parameters. With proper storage, the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months. This protocol is robust, straightforward to implement, and highly reproducible, offering a valuable tool for tissue architecture and cellular interaction studies.link_to_subscribed_fulltex
Chemically Induced Ferroic-like Phase and Collective Chemotaxis in an Active Swarm
No full textAmplification of weak chemical signals through intracellular cascade networks is crucial for long-range cohesive migration in biological processes, such as embryogenesis and cancer metastasis. While this capability has transformative potential for synthetic systems in precision medicine and adaptive materials, the lack of cascade communication in artificial matter has been a significant barrier. This study demonstrates that a binary active colloid mixture, mediated by a chemical reaction, forms a simple chemical reaction network capable of self-organizing into polarized dynamic swarms, dramatically enhancing chemical amplification. By applying the classical Ising model, we rationalize the self-polarization with increasing chemical activity, drawing an analogy to ferroic materials in the chemically polarized active phase. Under optimal conditions, these “ferrochemical” swarms can amplify weak chemical gradients by over 104 times, resulting in exceptional chemical sensitivity and remarkable long-range collective chemotaxis. As a proof of concept, we demonstrate the application of silver-doped active swarms to enhance antibacterial efficacy, showcasing a chemotactic swarm that effectively combats dental biofilm growth on human teeth.</p
Evaluating log odds of positive lymph nodes as a prognostic tool in differentiated gastric cancer: A retrospective study
No full textBACKGROUND The log odds of positive lymph nodes (LODDS) are correlated with survival outcomes in gastric cancer (GC) patients. However, the prognostic value across different tumor differentiation levels remains unclear. AIM To evaluate the independent prognostic value of LODDS and the stratified predictive efficacy in GC patients with different histologic differentiations. METHODS We conducted a retrospective analysis of 2103 GC patients who underwent radical gastrectomy at Zhejiang Cancer Hospital. The prognostic value of LODDS was compared with that of other lymph node-based metrics, including the pathologic N stage, number of positive lymph nodes, number of total lymph nodes, and lymph node ratio, stratified by tumor differentiation. RESULTS LODDS was identified as an independent prognostic factor for overall survival in moderately to poorly differentiated GC patients. LODDS demonstrated superior predictive accuracy over other lymph node metrics. A nomogram incorporating LODDS, age, carbohydrate antigen (CA) 125, carcinoembryonic antigen, and tumor differentiation showed good predictive accuracy (C-index = 0.703). A higher LODDS was significantly associated with an increased risk of recurrence or metastasis, poorly differentiated tumors, advanced cancer, mucinous gastric adenocarcinoma, nerve invasion, and vascular tumor thrombus. Additionally, LODDS was positively correlated with the tumor markers CA19-9, CA72-4, CA125, and CA242 (all P < 0.05). CONCLUSION LODDS is an independent prognostic indicator for patients with moderately and poorly differentiated GC, and its predictive performance is superior to that of other models
Epstein-Barr virus mRNA vaccine synergizes with NK cells to enhance nasopharyngeal carcinoma eradication in humanized mice
No full textThe close association between nasopharyngeal carcinoma (NPC) and Epstein-Barr virus (EBV) infection highlights the potential of therapeutic vaccination against viral antigens as an attractive immunotherapy for treating EBV+ NPC. Maximizing vaccine efficacy often requires selecting optimal T cell epitopes and incorporating co-treatment strategies. Here, we analyzed genomic mutations of 283 cancer-associated EBV strains and predicted epitopes with broad human leukocyte antigen (HLA) coverage from high-frequency nonsynonymous mutations. A polyepitope mRNA vaccine constructed from the predicted epitopes elicited antigen-specific T cell responses but showed suboptimal efficacy in tumor control in a PBMC-humanized mouse EBV+ NPC model. To enhance treatment efficacy, we developed an optimized system for expanding human natural killer (NK) cells with high purity and cytotoxicity as a co-treatment modality. Combined administration of mRNA vaccine and NK cells synergistically improved therapeutic efficacy by durably suppressing or eradicating NPC tumors in humanized mice. The concurrent treatment could improve the infiltration of both human T cells and NK cells into the tumor microenvironment and boost their effector functions. Our study suggests the combined therapeutic vaccination and NK cell therapy as a potential strategy for treating EBV+ NPC
A battery-free nanofluidic intracellular delivery patch for internal organs
No full textThe targeted delivery of therapeutics to internal organs to, for example, promote healing or apoptosis holds promise in the treatment of numerous diseases1, 2, 3–4. Currently, the prevailing delivery modality relies on the circulation; however, this modality has substantial efficiency, safety and/or controllability limitations5, 6, 7, 8–9. Here we report a battery-free, chipless, soft nanofluidic intracellular delivery (NanoFLUID) patch that provides enhanced and customized delivery of payloads in targeted internal organs. The chipless architecture and the flexible nature of thin functional layers facilitate integration with internal organs. The nanopore–microchannel–microelectrode structure enables safe, efficient and precise electroperforation of the cell membrane, which in turn accelerates intracellular payload transport by approximately 105 times compared with conventional diffusion methods while operating under relatively low-amplitude pulses (20 V). Through evaluations of the NanoFLUID patch in multiple in vivo scenarios, including treatment of breast tumours and acute injury in the liver and modelling tumour development, we validated its efficiency, safety and controllability for organ-targeted delivery. NanoFLUID-mediated in vivo transfection of a gene library also enabled efficient screening of essential drivers of breast cancer metastasis in the lung and liver. Through this approach, DUS2 was identified as a lung-specific metastasis driver. Thus, NanoFLUID represents an innovative bioelectronic platform for the targeted delivery of payloads to internal organs to treat various diseases and to uncover new insights in biology
Multiphase flow simulation in deformable porous media using DEM
No full textpublished_or_final_versionCivil EngineeringDoctoralDoctor of Philosoph
K-pop soft masculinity and gender empowerment : a reception study among Hong Kong fans
No full textpublished_or_final_versionChineseMasterMaster of Philosoph
Adaptive phototactic behaviors and navigation strategies in Chlamydomonas
No full textpublished_or_final_versionMechanical EngineeringDoctoralDoctor of Philosoph
SNPmanifold : detecting single-cell SNV clonality and lineages using binomial variational autoencoder
No full textpublished_or_final_versionBiomedical SciencesMasterMaster of Philosoph