tbuckley/cabot-search huggingface dataset:
Altered zygotic gene expression caused by sperm with <i>Tdrd6</i> variants disrupts early embryonic development
Authors: Zhijie Hu, Yuqi Zhang, Renfei Cai, Qiuju Chen, Haiyan Guo, Danjun Li, Weidong Lin, Hongxi He, Haibo Wu, Yali Liu, Bin Li, Qianwen Xi, Hongyuan Gao, Jian Zhang, Qifeng Lyu, Yanping Kuang, Xuefeng Lu
Journal: MedComm (2025)

Abstract The precise mechanisms behind early embryonic arrest due to sperm‐related factors and the most effective strategies are not yet fully understood. Here, we present two cases of male infertility linked to novel TDRD6 variants, associated with oligoasthenoteratozoospermia (OAT) and early embryonic arrest. To investigate the underlying mechanisms and promising therapeutic approaches, Tdrd6 knock‐in and knock‐out mice were generated. The Tdrd6 variant male mice demonstrated OAT and embryonic arrest, mirroring the clinical observations of our patients. Sperm from both affected individuals and mice exhibited aberrant localization of phospholipase C zeta and oocyte activation deficiency (OAD). The application of artificial oocyte activation (AOA) effectively overcame the infertility caused by the variants, facilitating successful pregnancies and live births in both human and mice. Additionally, our research revealed that OAD influences the expression of multitude of genes at the 2‐pronuclear (2PN) stage, with the Mos gene playing a pivotal role in early embryonic arrest. The injection of Mos mRNA can mitigate this arrest. To our knowledge, this is the first study to show that sperm‐related OAD affects gene expression at the 2PN stage and elucidate how AOA overcomes male factor‐derived embryonic arrest, enabling successful pregnancies and live births.
In Vitro Engineered ECM‐incorporated Hydrogels for Osteochondral Tissue Repair: A Cell‐Free Approach
Authors: Ali Coyle, Aishik Chakraborty, Jiaqi Huang, Yasmeen Shamiya, Wei Luo, Arghya Paul
Journal: Advanced Healthcare Materials (2025)

Prevalence of osteoarthritis has been increasing in aging populations, which has necessitated the use of advanced biomedical treatments. These involve grafts or delivering drug molecules entrapped in scaffolds. However, such treatments often show suboptimal therapeutic effects due to poor half-life and off-target effects of drug molecules. As a countermeasure, a 3D printable robust hydrogel-based tissue-repair platform is developed containing decellularized extracellular matrix (dECM) from differentiated mammalian cells as the therapeutic cargo. Here, pre-osteoblastic and pre-chondrogenic murine cells are differentiated in vitro, decellularized, and incorporated into methacrylated gelatin (GelMA) solutions to form osteogenic (GelO) and chondrogenic (GelC) hydrogels, respectively. Integrating the bioactive dECM from differentiated cell sources allows GelO and GelC to induce differentiation in human adipose-derived stem cells (hASCs) toward osteogenic and chondrogenic lineages. Further, GelO and GelC can be covalently adhered using a carbodiimide coupling reaction, forming a multi-layered hydrogel with potential application as a bioactive osteochondral plug. The designed multi-layered hydrogel can also induce differentiation of hASCs in vitro. In conclusion, the bioactive dECM carrying 3D printed robust hydrogel offers a promising new drug and cell-free therapeutic strategy for bone and cartilage repair and future osteoarthritis management.
A Slimming/Excavating Strategy for Enhanced Intratumoral Penetration of Acid‐Disassemblable NO‐Releasing Nanomedicines
Authors: Lingdong Jiang, Anbang Wu, Lingting Zeng, Bin Zhou, Min Zhao, Mingjian Fan, Zhaokui Jin, Qianjun He
Journal: Advanced Healthcare Materials (2025)

Abstract Poor tumor penetration is the major predicament of nanomedicines that limits their anticancer efficacy. The dense extracellular matrix (ECM) in the tumor is one of the major barriers against the deep penetration of nanomedicines. In this work, a slimming/excavating strategy is proposed for enhanced intratumoral penetration based on an acid‐disassemblable nanomicelles‐assembled nanomedicine and the NO‐mediated degradation of ECM. The nanomedicine is constructed by cross‐linking nanomicelles, which are self‐assembled with two kinds of dendrimers containing phenylboronic acid and lactobionic acid, through borate esterification. In the acidic tumor microenvironment, the pH‐sensitive borate ester bonds among the nanomicelles are hydrolyzed, triggering the disassembly of nanomedicine (≈150 nm) into small nanomicelles (≈25 nm). In response to the intratumoral over‐expressed glutathione (GSH), the NO donor loaded in the nanomicelles produces NO, which mediates the expression of matrix metalloproteinases for the degradation of ECM in the tumor. By collaboration of the disassembling behavior of nanomedicine with the NO‐mediated degradation of ECM, the designed nanomedicine can penetrate a long distance in tumors. The proposed slimming/excavating strategy will provide inspiration for overcoming the challenge of nanomedicines in tumor penetration.
Multifunctional Carbon Dots In Situ Confined Hydrogel for Optical Communication, Drug Delivery, pH Sensing, Nanozymatic Activity, and UV Shielding Applications
Authors: Parham Khoshbakht Marvi, Poushali Das, Arman Jafari, Shiza Hassan, Houman Savoji, Seshasai Srinivasan, Amin Reza Rajabzadeh
Journal: Advanced Healthcare Materials (2025)

Abstract Inspired by the emerging potential of photoluminescent hydrogels, this work unlocks new avenues for advanced biosensing, bioimaging, and drug delivery applications. Carbon quantum dots (CDs) are deemed particularly promising among various optical dyes, for enhancing polymeric networks with superior physical and chemical properties. This study presents the synthesis of CDs derived from Prunella vulgaris , a natural plant resource, through a single‐step hydrothermal process, followed by their uniform integration into hydrogel matrices via an in situ free radical graft polymerization. The resulting CD‐integrated hydrogels exhibit multifunctionality in biomedical applications, featuring a diffusion‐controlled drug release mechanism, permit concurrent delivery of photoluminescent CDs and therapeutic agents, enabling real‐time monitoring over 32 h. In addition, these hydrogels function as a broad‐range optical pH sensor (pH 3–11), provide robust ultraviolet (UV) shielding, and demonstrate nanozyme‐like peroxidase activity. Critically, biocompatibility tests confirm their non‐cytotoxicity toward fibroblast cells, establishing these hydrogels as promising candidates for diverse biomedical applications. These include advanced wound dressings that monitor the healing process and detect infection through pH sensing, and promote healing through the nanozymatic activity, all while maintaining a moist wound microenvironment. These hydrogels demonstrate exceptional suitability for advanced smart drug delivery, effective UV‐blocking, and as innovative platforms for in vivo sensing and bioimaging.
Insulative Compression of Neuronal Tissues on Microelectrode Arrays by Perfluorodecalin Enhances Electrophysiological Measurements
Authors: Tomoya Duenki, Yoshiho Ikeuchi
Journal: Advanced Healthcare Materials (2025)

Abstract Microelectrode array (MEA) techniques provide a powerful method for exploration of neural network dynamics. A critical challenge is to interface 3D neural tissues including neural organoids with the flat MEAs surface, as it is essential to place neurons near to the electrodes for recording weak extracellular signals of neurons. To enhance performance of MEAs, most research have focused on improving their surface treatment, while little attention has been given to improve the tissue‐MEA interactions from the medium side. Here, a strategy is introduced to augment MEA measurements by overlaying perfluorodecalin (PFD), a biocompatible fluorinated solvent, over neural tissues. Laying PFD over cerebral organoids insulates and compresses the tissues on MEA, which significantly enhances electrophysiological recordings. Even subtle signals such as the propagation of action potentials in bundled axons of motor nerve organoids can be detected with the technique. Moreover, PFD stabilizes tissues in acute recordings and its transparency allows optogenetic manipulations. This research highlights the potential of PFD as a tool for refining electrophysiological measurements of in vitro neuronal cultures. This can open new avenues to leverage precision of neuroscientific investigations and expanding the toolkit for in vitro studies of neural function and connectivity.
Regulating Supramolecular Assembly and Disassembly of Chitosan toward Efficiently Antibacterial Lubricous and Biodegradable Hydrogel Urinary Catheters
Authors: Yicheng Guo, Qitong He, Marieh B. Al‐Handawi, Tao Chen, Panče Naumov, Lidong Zhang
Journal: Advanced Healthcare Materials (2025)

Abstract Urinary catheters serve as critical medical devices in clinical practice. However, the currently used urinary catheters lack efficient antibacterial and lubricating properties, often leading to discomfort with patients and even severe urinary infections. Herein, a new strategy of supramolecular assembly and disassembly of chitosan (Cs) is developed that enables efficient antibacterial lubricous and biodegradable hydrogel urinary catheters. Sodium lauryl sulfonate (SLS) is employed to induce supramolecular assembly on the surface of Cs film strips in an aqueous solution, resulting in the formation of hollow hydrogel catheters of Cs@SLS. Subsequent disassembly in a strong alkaline solution eliminates the SLS component, yielding neat Cs hydrogel catheters. The mechanical strength of these catheters reaches 16 MPa, exceeding that of similar devices made of plastics. The Cs hydrogel catheters are endowed with high antibacterial activity, capable of inhibiting the growth of Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Proteus mirabilis(P. mirabilis) on its surface, while these bacteria are found to proliferate rapidly on plastic catheters within 24 h. They also demonstrate excellent lubricity, with a friction coefficient approaching zero, and thus about 13 times lower than that of plastic catheters. In vivo tests further confirm the biodegradability of the catheters, highlighting their strong potential for clinical applications.
Biomimetic Membrane Vesicles Reprogram Microglia Polarization and Remodel the Immunosuppressive Microenvironment of Glioblastoma via PERK/HIF‐1α/Glycolysis Pathway
Authors: Yinghan Guo, Lulu Jin, Zhipeng Shen, Linfeng Fan, Xian Yu, Yirui Kuang, Lingxin Cai, Jiayin Zhou, Zihang Chen, Feng Yan, Jianmin Zhang, Minfeng Tong, Jianlie Yuan, Zhengwei Mao, Gao Chen
Journal: Advanced Healthcare Materials (2025)

Abstract The malignant interaction between tumor cells and immune cells is one of the important reasons for the rapid progression and refractoriness of glioblastoma (GBM). As an essential metabolic center of M2 macrophages, the inhibition of protein kinase RNA‐like endoplasmic reticulum kinase (PERK) leads to the reduction of M2 macrophages. Nevertheless, the restriction of the blood‐brain barrier (BBB) and non‐specific cell targeting hinder the application of PERK inhibitors in GBM. Herein, the optimal NP‐M‐M2pep is developed successfully, which has shown the capacity of BBB penetration and specific targeting of M2 microglia. In addition to inhibiting the polarization of M2 microglia, the administration of iPERK@NP‐M‐M2pep reprogrammed M2 microglia into M1 ones in vitro via PERK/HIF‐1α/glycolysis pathway. Efficient brain accumulation of nanoparticles is achieved after tail vein injection, with effective inhibition of GBM progression after one course of treatment. The glioma‐associated microglia and macrophages (GAM) with M2 type are induced to M1 and the immunosuppressive TME is remodeled by upregulating immunostimulatory cells and downregulating immunosuppressive cells. In summary, the biomimetic membrane vesicles (BMVs) specifically delivered iPERK to GAMs offer an inspiring strategy to reprogram microglia polarization, re‐educate immunosuppressive TME, and inhibit the progression of GBM.
The Printed Path to Healing: Advancing Wound Dressings through Additive Manufacturing
Authors: Joana Galvão Duarte, Ana Paula Piedade, Bruno Sarmento, Filipa Mascarenhas‐Melo
Journal: Advanced Healthcare Materials (2025)

Abstract Wound care challenges healthcare systems worldwide as traditional dressings often fall short in addressing the diverse and complex nature of wound healing. Given conventional treatments limitations, innovative alternatives are urgent. Additive manufacturing (AM) has emerged as a distinct and transformative approach for developing advanced wound dressings, offering unprecedented functionality and customization. Besides exploring the AM processes state‐of‐the‐art, this review comprehensively examines the application of AM to produce cellular‐compatible and bioactive, therapeutic agent delivery, patient‐centric, and responsive dressings. This review distinguishes itself from the published literature by covering a variety of wound types and by summarizing important data, including used materials, process/technology, printing parameters, and findings from in vitro, ex vivo, and in vivo studies. The prospects of AM in enhancing wound healing outcomes are also analyzed in a translational and cost‐effective manner.
Dynamically Assembling Magnetic Nanochains as New Generation of Swarm‐Type Magneto‐Mechanical Nanorobots Affecting Biofilm Integrity
Authors: Slavko Kralj, Charlotte Da Silva, Sebastjan Nemec, Maja Caf, Isabelle Fourquaux, Marie‐Pierre Rols, Muriel Golzio, Alenka Mertelj, Jelena Kolosnjaj‐Tabi
Journal: Advanced Healthcare Materials (2025)

Abstract Bacterial resistance is gaining ground and novel, unconventional strategies are required to improve antibiotic treatments. As a synthetic analog of planktonic bacilli, the natural bacterial swimmers that can penetrate bacterial biofilms, ultra‐short propelling magnetic nanochains are presented as bioinspired magnetic nanorobots, enhancing the antibiotic treatment in biofilm‐forming Staphylococcus epidermidis . Propelling nanochains, activated by a low intensity (&lt;20 mT) and low frequency (&lt;10 Hz) rotating magnetic field (RMF), prompt the otherwise resistant biofilm‐forming bacteria to become sensitive to methicillin, resulting in the killing of 99.99% of bacteria. While magnetic force‐driven spherical magnetic nanoparticles were previously reported as unidirectional biofilm channel diggers, propelling nanochains emerge as second‐generation magnetic nanorobots, which, due to their magnetic core, shape anisotropy, and negative zeta potential, combine magnetic responsiveness, torque‐driven movement, and attractive electrostatic interactions to attach to bacterial aggregates and multi‐directionally protrude throughout the biofilm, indulging mechanical forces. These synergistic effects, in combination with an antibiotic drug, destroy the bacterial extracellular matrix and eradicate the formed biofilm, as confirmed with several complementary techniques.
Silicene‐Based Quantum Dots Nanocomposite Coated Functional UV Protected Textiles With Antibacterial and Antioxidant Properties: A Versatile Solution for Healthcare and Everyday Protection
Authors: Poushali Das, Sayan Ganguly, Parham Khoshbakht Marvi, Shiza Hassan, Masoomeh Sherazee, Mohamed Mahana, Xiaowu (Shirley) Tang, Seshasai Srinivasan, Amin Reza Rajabzadeh
Journal: Advanced Healthcare Materials (2025)

Abstract The predominant adverse health effects in care delivery result from hospital‐acquired (nosocomial) infections, which impose a substantial financial burden on global healthcare systems. Integrating contact‐killing antibacterial action, gas permeability, and antioxidant properties into textile coatings offers a transformative solution, significantly enhancing both medical and everyday protective applications. This study presents an innovative, pollution‐free physical compounding method for creating a fluorescent biopolymer composite embedded with silicene‐based heteroatom‐doped carbon quantum dots for the production of functional textiles. The resulting coated fabric shows superior ultraviolet (UV) protection behavior (UV A and UV B ), thermal stability, breathability, mechanical strength, and antioxidant capabilities as demonstrated by the 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) experiment (&gt;78%) and 2,2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid) ABTS assay (&gt;90%). Rigorous testing against both gram positive and gram negative bacteria confirms that the coated fabric has excellent antibacterial activity. Results from time‐dependent antibacterial assays indicate that the nanocomposite can markedly inhibit bacterial proliferation within a few hours. Molecular dynamics modeling, in conjunction with experimental investigations, is employed to elucidate the intermolecular interactions influencing the components of the treated cotton fabrics. The ongoing research can result in the creation of cost‐effective smart textile substrates aimed at inhibiting microbial contamination in healthcare and medical applications, possibly rendering them commercially viable.
Microwave‐Sintered Nano‐SiC Reinforced 8SiC/Ti‐3Cu Composite: Fabrication, Wear Resistance, Antibacterial Function, and Biocompatibility
Authors: Xin Li, Ying‐Chao Zhao, Dengfeng Yin, Ying Cai, Desheng Xiao, Ming‐Chun Zhao, Cuie Wen, Andrej Atrens
Journal: Advanced Healthcare Materials (2025)

Abstract The significance of biomedical applications of Ti alloys is best emphasized by their widespread utilization as implantable materials, such as internal supports and bone replacements. Ti alloys are sensitive to fretting wear, which leads to the early failure of Ti implants. Improved wear resistance of such implants is essential to ensure a prolonged implant life. Based on the structure‐function‐integrated concept, this work unprecedentedly designs and fabricates an antibacterial 8SiC/Ti‐3Cu composite with improved wear resistance using microwave sintering from pure Ti, Cu, and nano‐SiC powders. For comparison, SiC‐free Ti‐3Cu composite is manufactured under the same conditions using microwave sintering. The addition of 8 vol.% SiC to Ti‐3Cu significantly reduces the porosity and pore size of composites. The 8SiC/Ti‐3Cu shows a Vickers hardness of 353 HV, compressive strength of 803 MPa, elastic modulus of 28.7 GPa, and a significantly increased wear resistance (wear rate decreased by 70% compared to Ti‐3Cu). In addition, 8SiC/Ti‐3Cu exhibits excellent electrochemical corrosion resistance, biocompatibility in relation to MC3T3‐E1 cells, and a bacteriostatic rate over 99% against E. coli . The combination of the wear‐resistant nano‐reinforced SiC and antibacterial Ti 2 Cu in the 8SiC/Ti‐3Cu composite renders it a highly promising implant material.
Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity
Authors: Can Can, Xinyu Yang, Hexiao Jia, Hanyang Wu, Xiaodong Guo, Yihong Wei, Ziting Jia, Wancheng Liu, Amin Zhang, Na He, Hailei Zhang, Daoxin Ma
Journal: Molecular Cancer (2025)

Drug resistance and immune escape continue to contribute to poor prognosis in AML. Increasing evidence suggests that exosomes play a crucial role in AML immune microenvironment. Sanger sequencing, RNase R and fluorescence in situ hybridization were performed to confirm the existence of circ_0006896. The role of circ_0006896 in the progression of AML was assessed by in vitro and in vivo functional experiments. Flow cytometry, RT-qPCR and adoptive T cell-transfer immunotherapy were conducted to assess the function of exosomal circ_0006896 in CD8+ T cell dysfunction. RNA pull-down assay, mass spectrometry, immunofluorescence, co-immunoprecipitation and western blot were performed to identify and confirm the circ_0006896 interacting proteins. CircRNA expression patterns in exosomes differ significantly between AML and controls compared to lncRNAs or mRNAs. A new crucial exosomal circRNA, circ_0006896, is upregulated in both AML cells and exosomes and correlates with the prognosis and relapse of AML. In vitro and in vivo studies suggest that circ_0006896 significantly promotes AML cell proliferation, reduces chemotherapy sensitivity, and more importantly, impairs the efficacy of adoptive T cell-transfer immunotherapy. Mechanistically, circ_0006896 physically interacts with the catalytic domain of histone deacetylase HDAC1, decreasing histone H3 acetylation, and impairing the transcription of genes involved in arachidonic acid metabolism, ultimately inhibiting lipid peroxidation and ferroptosis in AML cells. Exosomal circ_0006896 disrupts CD8+ T cell function by interacting with HDAC1, impairing LEF1 transcription and subsequently decreasing the expression of cytotoxic molecules IFN-γ and Granzyme B. We demonstrate a self-driven progression mediated by exosomal circRNAs and CD8+ T cells, highlighting the potential of targeting circRNAs in AML immunotherapy.
Impact of circulating lymphoma cells at diagnosis on outcomes in patients with newly diagnosed de novo diffuse large B-cell lymphoma
Authors: Sayan Mullick Chowdhury, Subodh Bhatta, Timothy J. Voorhees, Kaitlin Annunzio, David A. Bond, Yazeed Sawalha, Audrey Sigmund, Walter Hanel, Lalit Sehgal, Lapo Alinari, Robert Baiocchi, Kami Maddocks, Beth Christian, Dan Jones, Narendranath Epperla
Journal: Journal of Hematology & Oncology (2025)

Abstract Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma rarely presents with circulating lymphoma cells (CL) at diagnosis. Previous studies were limited by small sample size precluding robust analysis. Hence, we evaluated the prognostic relevance of CL cells in newly diagnosed DLBCL patients. Based on peripheral blood (PB) immunophenotyping, patients were grouped into CL + and CL−. CL was defined as detectable clonally restricted B-cells that matched the actual or expected B-cell immunophenotype of DLBCL. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and diagnosis-to-treatment interval (DTI). Among the 1266 patients with DLBCL, 621 had PB flow at diagnosis, and after excluding patients not meeting eligibility criteria, 588 cases remained. Among these, 85 (15%) were CL + and 503 were CL- (85%). Patients in CL + group were younger (67 vs. 70 years, p = 0.03) with a higher proportion of non-bulky disease (85% vs. 56%, p &lt; 0.0001), normal albumin (79% vs. 54%, p &lt; 0.0001), and MYC/BCL2 and/or BCL6 rearrangements (18% vs. 7%, p = 0.003) compared to the CL − group. Patients with CL at diagnosis had significantly inferior PFS and OS compared with those without CL. After adjusting for factors associated with inferior PFS and OS in univariable analysis, presence of CL remained significantly associated with inferior PFS (HR = 2.04, 95%CI = 1.47–2.84, p &lt; 0.0001) and OS (HR = 1.61, 95%CI = 1.1–2.36, p = 0.01), respectively. There was no significant difference in DTI between the two groups. Given the prognostic relevance associated with presence of CL, clinicians should consider checking PB flow at diagnosis in all newly diagnosed DLBCL patients.