tbuckley/cabot-search huggingface dataset:
A Facile Approach To Develop Ion Pair Micelles Satellited Freshly Derived Neutrophils For Targeted Tumor Therapy
Authors: Garima Sharma, Kwanjira Wangpimool, Jomon George Joy, Ashish Ranjan Sharma, Hyeon Ki Son, Songrae Kim, Hoibin Jeong, Jin‐Chul Kim
Journal: Advanced Healthcare Materials (2025)

Immune cells show enormous potential for targeted nanoparticle delivery due to their intrinsic tumor-homing skills. However, the immune cells can internalize the nanoparticles, leading to cellular functional impairments, degradation of the nanoparticles, and delayed release of drugs from the immune cells. To address these issues, this study introduces an approach for the synthesis of freshly derived neutrophils (NUs)-based nanocarriers system where the NUs are surfaced by dialdehyde alginate-coated self-assembled micelles loaded with mitoxantrone (MIT) and indocyanine green (ICG) (i.e., dA(MI@IPM)s) for stimuli-responsive tumor-targeted therapy. Here, the dA(MI@IPM)s are not internalized by the NUs, but they are anchored on the membrane of the NUs via distearoylphosphatidylethanolamine-polyethylene glycol-polyethylenimine anchors. Owing to the natural recruitment ability of NUs to the tumor microenvironment, NUs-anchored dA(MI@IPM)s accumulation is higher at the tumor site than free dA(MI@IPM)s, where the dA(MI@IPM)s can readily detach from the NUs to get internalized in the tumor cells. The stimuli-responsive dA(MI@IPM)s disassembles inside the cancer cells upon near-infrared irradiation due to the photosensitizing effect of the loaded ICG, releasing MIT and significantly inhibiting tumor growth. This approach is simple and fast to prepare, opening up exciting possibilities for personalized cancer treatment using patient's autologous NUs.
Quantitative Assessment of Microbial Transmission onto Environmental Surfaces Using Thermoresponsive Gelatin Hydrogels as a Finger Mimetic under In Situ‐Mimicking Conditions
Authors: Mihyun Lee, Luzia Wiesli, Frank Schreiber, Angela Ivask, Qun Ren
Journal: Advanced Healthcare Materials (2025)

Surface-mediated transmission of pathogens plays a key role in healthcare-associated infections. However, proper techniques for its quantitative analysis are lacking, making it challenging to develop novel antimicrobial and anti-fouling surfaces to reduce pathogen spread via environmental surfaces. This study demonstrates a gelatin hydrogel-based touch transfer test, the HydroTouch test, to evaluate pathogen transmission on high-touch surfaces under semi-dry conditions. The HydroTouch test employs gelatin as a finger mimetic, facilitating testing with pathogenic bacteria under controlled conditions. The thermoresponsive sol-gel transition of gelatin allows easy recovery and quantification of bacteria before and after testing. The HydroTouch test demonstrates that methicillin-resistant Staphylococcus aureus has a high transmission efficiency of ≈16% onto stainless steel, compared to <3% for Escherichia coli or Pseudomonas aeruginosa. Polyurethane surfaces exhibit strong resistance to bacterial contamination with a transmission efficiency of ≈0.6%, while polytetrafluoroethylene shows a transmission efficiency approximately four times higher than polyurethane. Additionally, quaternary ammonium-based antimicrobial coatings reduce the transmission efficiency of live bacteria on stainless steel to ≈4% of the original level. The HydroTouch test provides a reliable method for assessing pathogen transmission on various surfaces under semi-dry settings, supporting the development of effective antimicrobial, anti-transmission coatings to reduce healthcare-associated infections.
Smart Polymeric 3D Microscaffolds Hosting Spheroids for Neuronal Research via Quantum Metrology
Authors: Beatriz N. L. Costa, Ana Marote, Catarina Barbosa, Jonas Campos, António J. Salgado, Jana B. Nieder
Journal: Advanced Healthcare Materials (2025)

Toward the aim of reducing animal testing, innovative in vitro models are required. Here, this study proposes a novel smart polymeric microscaffold to establish an advanced 3D model of dopaminergic neurons. These scaffolds are fabricated with Ormocomp via Two-Photon Polymerization. The scaffolds are further enhanced by functionalization with fluorescent nanodiamonds (FNDs), which can serve as quantum nanosensors for both magnetic and temperature sensing. The material biocompatibility is tested using two different cell lines, SH-SY5Y and A431, with cell viability over 98%. A total of 69% of the FNDs are grafted on the structure compared to those that remained on the glass surface. Cells are tested with the scaffolds in several microenvironments, and the final assembly required for 3D quantum metrology experiments achieved 91% biocompatibility. Subsequently, embryoid bodies containing dopaminergic neurons, the cell type affected by Parkinson's disease (PD), are integrated with FND-functionalized scaffolds. This 3D model is successfully established, demonstrated by strong interactions between dopaminergic neurons and the scaffold, with the directional growth of neurites along the 3D scaffold. Ultimately, this study have developed a 3D platform that enables the readout of signaling in a model that holds great potential for future PD research.
Bactericidal Hemostatic Sponge: A Point of Care Solution to Combat Traumatic Injury
Authors: Rajib Dey, Riya Mukherjee, Sudip Mukherjee, Jayanta Haldar
Journal: Advanced Healthcare Materials (2025)

Uncontrollable haemorrhage and associated microbial contamination in the battlefield and civilian injuries pose a tremendous threat to healthcare professionals. Such traumatic wounds often necessitate an effective point-of-care solution to prevent the consequent morbidity owing to blood loss or haemorrhage. However, developing superior hemostatic materials with anti-infective properties remains a challenge. To address this, an injectable, cationic dextran-mesoporous silica nanoparticle-based bactericidal hemostatic sponge (BACSTAT) has been developed. A dual crosslinking approach is adopted through in situ covalent cross-linking through photo polymerization and silica nanoparticle-induced non-covalent interactions. This interconnected macroporous BACSTAT sponge has superior fluid absorption properties and fluid-induced rapid shape recovery of the sponge helps to seal the irregularly shaped wound. Furthermore, this sponge can stimulate a coagulation cascade for rapid blood clotting in mice femoral vein incision and liver puncture model. The optimum sponge exhibited potent antibacterial activity against wide-spectrum Gram-positive and Gram-negative pathogens. Notably, it is completely biocompatible with mammalian cells and mice skin. Significantly, this sponge reduces Pseudomonas aeruginosa burden >99% in mice subcutaneous infection model with substantially lessening inflammatory responses in infected tissues. Collectively, the optimized sponge bears immense potential to be developed as point-of-care solution for military and civilian traumatic injury.
<i>Staphylococcus warneri</i> dampens SUMOylation and promotes intestinal inflammation
Authors: Léa Loison, Marion Huré, Benjamin Lefranc, Jérôme Leprince, Christine Bôle-Feysot, Moïse Coëffier, David Ribet
Journal: Gut Microbes (2025)

Gut bacteria play key roles in intestinal physiology, via the secretion of diversified bacterial effectors. Many of these effectors remodel the host proteome, either by altering transcription or by regulating protein post-translational modifications. SUMOylation, a ubiquitin-like post-translational modification playing key roles in intestinal physiology, is a target of gut bacteria. Mutualistic gut bacteria can promote SUMOylation, via the production of short- or branched-chain fatty acids (SCFA/BCFA). In contrast, several pathogenic bacteria were shown to dampen SUMOylation in order to promote infection. Here, we demonstrate that Staphylococcus warneri, a natural member of the human gut microbiota, decreases SUMOylation in intestinal cells. We identify that Warnericin RK, a hemolytic toxin secreted by S. warneri, targets key components of the host SUMOylation machinery, leading to the loss of SUMO-conjugated proteins. We further demonstrate that Warnericin RK promotes inflammation in intestinal and immune cells using both SUMO-dependent and SUMO-independent mechanisms. We finally show that Warnericin RK regulates the expression of genes involved in intestinal tight junctions. Together, these results highlight the diversity of mechanisms used by bacteria from the gut microbiota to manipulate host SUMOylation. They further highlight that changes in gut microbiota composition may impact intestinal inflammation, by altering the equilibrium between bacterial effectors promoting or dampening SUMOylation.
Gastroenteropancreatic Neuroendocrine Tumor Incidence by Sex and Age in the US
Authors: Yazan Abboud, Anand Shah, Riya Sutariya, Vraj P. Shah, Ahmed Al-Khazraji, Paul J. Gaglio, Kaveh Hajifathalian
Journal: JAMA Oncology (2025)

This observational study reports on a comprehensive nationwide evaluation of rising gastroenteropancreatic neuroendocrine tumor incidence in the US from 2001 to 2020.
Vaping—Reply
Authors: Jonathan P. Winickoff, A. Eden Evins, Sharon Levy
Journal: JAMA (2025)

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Novel vaccine strategies to induce respiratory mucosal immunity: advances and implications
Authors: Ming Zhou, Haiqin Xiao, Xinyi Yang, Tong Cheng, Lunzhi Yuan, Ningshao Xia
Journal: MedComm (2025)

Rapid advances in vaccine technology are becoming increasingly important in tackling global health crises caused by respiratory virus infections. While traditional vaccines, primarily administered by intramuscular injection, have proven effective, they often fail to provide the broad upper respiratory tract mucosal immunity, which is urgently needed for first-line control of respiratory viral infections. Furthermore, traditional intramuscular vaccines may not adequately address the immune escape of emerging virus variants. In contrast, respiratory mucosal vaccines developed using the body's mucosal immune response mechanism can simultaneously establish both systemic and mucosal immunity. This dual action effectively allows the respiratory mucosal immune system to function as the first line of defense, preventing infections at the entry points. This review highlights the efficacy of respiratory mucosal vaccines, including innovative delivery methods such as nasal and oral formulations, in enhancing local and systemic immune barriers. Notably, respiratory mucosal vaccines offer potential advantages in protecting against emerging virus variants and maintaining long-term and multidimensional immune memory in the upper respiratory tract. In addition, a combination of intramuscular and respiratory mucosal delivery of vaccines largely improves their coverage and effectiveness, providing valuable insights for future vaccine development and public inoculation strategies.
Vascular endothelial cell injury: causes, molecular mechanisms, and treatments
Authors: Tian Xia, Jiachi Yu, Meng Du, Ximeng Chen, Chengbin Wang, Ruibing Li
Journal: MedComm (2025)

Vascular endothelial cells form a single layer of flat cells that line the inner surface of blood vessels, extending from large vessels to the microvasculature of various organs. These cells are crucial metabolic and endocrine components of the body, playing vital roles in maintaining circulatory stability, regulating vascular tone, and preventing coagulation and thrombosis. Endothelial cell injury is regarded as a pivotal initiating factor in the pathogenesis of various diseases, triggered by multiple factors, including infection, inflammation, and hemodynamic changes, which significantly compromise vascular integrity and function. This review examines the causes, underlying molecular mechanisms, and potential therapeutic approaches for endothelial cell injury, focusing specifically on endothelial damage in cardiac ischemia/reperfusion (I/R) injury, sepsis, and diabetes. It delves into the intricate signaling pathways involved in endothelial cell injury, emphasizing the roles of oxidative stress, mitochondrial dysfunction, inflammatory mediators, and barrier damage. Current treatment strategies-ranging from pharmacological interventions to regenerative approaches and lifestyle modifications-face ongoing challenges and limitations. Overall, this review highlights the importance of understanding endothelial cell injury within the context of various diseases and the necessity for innovative therapeutic methods to improve patient outcomes.
Phase I study of BMS-986299, an NLRP3 agonist, as monotherapy and in combination with nivolumab and ipilimumab in patients with advanced solid tumors
Authors: Blessie E Nelson, Shaun O'Brien, Rahul A Sheth, David S Hong, Aung Naing, Xiaoping Zhang, Amy Xu, Lora Hamuro, Rasika Suryawanshi, Derrick McKinley, Ruslan D Novosiadly, Sarina A Piha-Paul
Journal: Journal for ImmunoTherapy of Cancer (2025)

BMS-986299 is a first-in-class, NOD-, LRR-, and pyrin-domain containing-3 (NLRP3) inflammasome agonist enhancing adaptive immune and T-cell memory responses. This was a phase-I (NCT03444753) study that assessed the safety and tolerability of intra-tumoral BMS-986299 monotherapy (part 1A) and in combination (part 1B) with nivolumab, and ipilimumab in advanced solid tumors. Reported here are single-center results. 36 patients were enrolled, with breast (31%), colorectal (17%), and head and neck (14%) being the more commonly enrolled cancers. Most patients (58%) had received prior immunotherapy. Therapy was well-tolerated, with G1-G2 fever (70%), neutrophilia (36%), and leukocytosis (33%) being the most common treatment-related adverse events with one case of G4 interstitial nephritis and one case of G3 hepatotoxicity and G3 colitis. Intratumoral BMS-986299 monotherapy resulted in dose-dependent increases in systemic exposure with increase in tumor CTLs (67%), CD4+ TILs (63%), along with notable above twofold increases in serum IL-1B, G-CSF and IL-6 at doses above 2000 µg. Systemic BMS-986299 exposure was positively associated with systemic cytokine elevation for G-CSF and IL-6. No antitumor activity was noted in BMS-986299 monotherapy cohort. However, in the combination therapy cohort (BMS-986299+nivolumab+ipilimumab), overall objective response rate was 10%, with confirmed PRs observed in TNBC, hormone receptor-positive, human epidermal growth factor receptor 2 negative breast cancer, and cutaneous squamous cell carcinoma. BMS-986299 in combination with immune checkpoint inhibitors demonstrated manageable toxicities, good tolerability, and promising antitumor activity in certain cancer types. NCT03444753.
Enhancer regulatory networks globally connect non-coding breast cancer loci to cancer genes
Authors: Yihan Wang, Daniel A. Armendariz, Lei Wang, Huan Zhao, Shiqi Xie, Gary C. Hon
Journal: Genome biology (2025)

Genetic studies have associated thousands of enhancers with breast cancer (BC). However, the vast majority have not been functionally characterized. Thus, it remains unclear how BC-associated enhancers contribute to cancer. Here, we perform single-cell CRISPRi screens of 3513 regulatory elements associated with breast cancer to measure the impact of these regions on transcriptional phenotypes. Analysis of > 500,000 single-cell transcriptomes in two breast cancer cell lines shows that perturbation of BC-associated enhancers disrupts breast cancer gene programs. We observe BC-associated enhancers that directly or indirectly regulate the expression of cancer genes. We also find one-to-multiple and multiple-to-one network motifs where enhancers indirectly regulate cancer genes. Notably, multiple BC-associated enhancers indirectly regulate TP53. Comparative studies illustrate subtype specific functions between enhancers in ER + and ER - cells. Finally, we develop the pySpade package to facilitate analysis of single-cell enhancer screens. Overall, we demonstrate that enhancers form regulatory networks that link cancer genes in the genome, providing a more comprehensive understanding of the contribution of enhancers to breast cancer development.
Advances in the understanding and therapeutic manipulation of cancer immune responsiveness: a Society for Immunotherapy of Cancer (SITC) review
Authors: Alessandra Cesano, Ryan Augustin, Luigi Barrea, Davide Bedognetti, Tullia C Bruno, Alberto Carturan, Christian Hammer, Winson S Ho, Jakob Nikolas Kather, Tomas Kirchhoff, Rongze O Lu, Jennifer McQuade, Yana G Najjar, Violena Pietrobon, Marco Ruella, Rhine Shen, Laura Soldati, Christine Spencer, Allison Betof Warner, Sarah Warren, Elad Ziv, Francesco M Marincola
Journal: Journal for ImmunoTherapy of Cancer (2025)

Cancer immunotherapy-including immune checkpoint inhibition (ICI) and adoptive cell therapy (ACT)-has become a standard, potentially curative treatment for a subset of advanced solid and liquid tumors. However, most patients with cancer do not benefit from the rapidly evolving improvements in the understanding of principal mechanisms determining cancer immune responsiveness (CIR); including patient-specific genetically determined and acquired factors, as well as intrinsic cancer cell biology. Though CIR is multifactorial, fundamental concepts are emerging that should be considered for the design of novel therapeutic strategies and related clinical studies. Recent advancements as well as novel approaches to address the limitations of current treatments are discussed here, with a specific focus on ICI and ACT.
Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial
Authors: Zhichao Tan, Yan Wu, Zhengfu Fan, Tian Gao, Sijuan Ding, Liang Han, Suxia Luo, Qingxia Fan, Jianhua Shi, Chujie Bai, Ruifeng Xue, Shu Li, Lu Zhang, Xinyu Wang, Ling Jia, Lixin Zhou, Binlei Liu, Jing Huang, Jiayong Liu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients. Methods This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment. Patients were treated with OH2 at three dose levels (10 6 , 10 7 and 10 8 CCID 50 /mL) as single agent or in combination with a fixed dose of HX008. The primary endpoints were safety and tolerability in phase 1 and objective response rate determined by RECIST (V.1.1) criteria and immune-RECIST in phase 2. Results Between October 20, 2020 and December 30, 2023, 26 patients were enrolled. Seven patients were treated with single-agent OH2 and 19 with HX008 and OH2 combination. No dose-limiting toxicities were observed during the dose escalation. We documented four partial or complete responses in injected lesions, and one partial response in non-injected lesions, which were all from the combination group. Hence, the overall response rate was 0% and 16.7% in the single agent and combination groups, respectively. The duration of response was 3.9–6.5 months. The most frequent treatment-related adverse events (TRAEs) were fever (n=9). Grade 3 or 4 TRAEs were reported in four patients (15.4%). A clear increase in CD8+cell density in the tumor microenvironment was observed in the patients’ post-treatment specimens compared with baseline. Conclusions Intratumoral injection of oncolytic virus OH2 is well tolerable in patients with sarcoma. Further investigation of OH2 with HX008 in select sarcoma subtypes is warranted.
Glut3 overexpression improves environmental glucose uptake and antitumor efficacy of CAR-T cells in solid tumors
Authors: Wenhao Hu, Feng Li, Yue Liang, Shasha Liu, Shumin Wang, Chunyi Shen, Yuyu Zhao, Hui Wang, Yi Zhang
Journal: Journal for ImmunoTherapy of Cancer (2025)

Glucose deprivation inhibits T-cell metabolism and function. Glucose levels are low in the tumor microenvironment of solid tumors and insufficient glucose uptake limits the antitumor response of T cells. Furthermore, glucose restriction can contribute to the failure of chimeric antigen receptor T (CAR-T) cell therapy for solid tumors. However, the impact of glucose restriction remains unknown in CAR-T cell therapy. Glucose transporters were detected and overexpressed in CAR-T cells. The impacts of glucose restriction on CAR-T cells were checked in vitro and in vivo. Glucose restriction significantly decreased CAR-T cell activation, effector function, and expansion. CAR-T cells expressed high levels of the glucose transporter Glut1, which has a low affinity for glucose. Overexpression of Glut1 failed to improve CAR-T cell function under glucose-restricted conditions. In contrast, the function and antitumor potential of CAR-T cells was enhanced by the overexpression of Glut3, which has the highest affinity for glucose among the Glut transporter family and is expressed in minor parts of CAR-T cells. Glut3-overexpressing CAR-T cells demonstrated increased tumoricidal efficacy in multiple xenografts and syngenetic mouse models. Furthermore, Glut3 overexpression activated the PI3K/Akt pathway and increased OXPHOS and mitochondrial fitness. We provide a direct and effective approach to enhance low glucose uptake levels by CAR-T cells and improve their antitumor efficacy against solid tumors.