tbuckley/cabot-search huggingface dataset:
Rescuing Nucleus Pulposus Cells from ROS Toxic Microenvironment via Mitochondria‐Targeted Carbon Dot‐Supported Prussian Blue to Alleviate Intervertebral Disc Degeneration
Authors: Yu Shi, Wenzhen Bu, Dongchuan Chu, Wenzheng Lin, Ke Li, Xueping Huang, Xinglong Wang, Yin Wu, Shang Wu, Dandan Li, Zhuobin Xu, Zhipeng Cao, Hao Chen, Huihui Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Intervertebral disc degeneration (IVDD) is invariably accompanied by excessive accumulation of reactive oxygen species (ROS), resulting in progressive deterioration of mitochondrial function and senescence in nucleus pulposus cells (NPCs). Significantly, the main ROS production site in non‐immune cells is mitochondria, suggesting mitochondria is a feasible therapeutic target to reverse IVDD. Triphenylphosphine (TPP), which is known as mitochondrial‐tropic ligands, is utilized to modify carbon dot‐supported Prussian blue (CD‐PB) to scavenge superfluous intro‐cellular ROS and maintain NPCs at normal redox levels. CD‐PB‐TPP can effectively escape from lysosomal phagocytosis, permitting efficient mitochondrial targeting. After strikingly lessening the ROS in mitochondria via exerting antioxidant enzyme‐like activities, such as superoxide dismutase, and catalase, CD‐PB‐TPP rescues damaged mitochondrial function and NPCs from senescence, catabolism, and inflammatory reaction in vitro. Imaging evaluation and tissue morphology assessment in vivo suggest that disc height index, mean grey values of nucleus pulposus tissue, and histological morphology are significantly improved in the IVDD model after CD‐PB‐TPP is locally performed. In conclusion, this study demonstrates that ROS‐induced mitochondrial dysfunction and senescence of NPCs leads to IVDD and the CD‐PB‐TPP possesses enormous potential to rescue this pathological process through efficient removal of ROS via targeting mitochondria, supplying a neoteric strategy for IVDD treatment.
Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations
Authors: Yuliang L Sun, Erin E Hennessey, Hillary Heins, Ping Yang, Carlos Villacorta-Martin, Julian Kwan, Krithi Gopalan, Marianne James, Andrew Emili, F Sessions Cole, Jennifer A Wambach, Darrell N Kotton
Journal: Journal of Clinical Investigation (2024)

Mutations in ATP-binding cassette A3 (ABCA3), a phospholipid transporter critical for surfactant homeostasis in pulmonary alveolar type II epithelial cells (AEC2s), are the most common genetic causes of childhood interstitial lung disease (chILD). Treatments for patients with pathological variants of ABCA3 mutations are limited, in part due to a lack of understanding of disease pathogenesis resulting from an inability to access primary AEC2s from affected children. Here, we report the generation of AEC2s from affected patient induced pluripotent stem cells (iPSCs) carrying homozygous versions of multiple ABCA3 mutations. We generated syngeneic CRISPR/Cas9 gene-corrected and uncorrected iPSCs and ABCA3-mutant knockin ABCA3:GFP fusion reporter lines for in vitro disease modeling. We observed an expected decreased capacity for surfactant secretion in ABCA3-mutant iPSC-derived AEC2s (iAEC2s), but we also found an unexpected epithelial-intrinsic aberrant phenotype in mutant iAEC2s, presenting as diminished progenitor potential, increased NFκB signaling, and the production of pro-inflammatory cytokines. The ABCA3:GFP fusion reporter permitted mutant-specific, quantifiable characterization of lamellar body size and ABCA3 protein trafficking, functional features that are perturbed depending on ABCA3 mutation type. Our disease model provides a platform for understanding ABCA3 mutation-mediated mechanisms of alveolar epithelial cell dysfunction that may trigger chILD pathogenesis.
Hypomorphic human SEL1L and HRD1 variants uncouple multilayered ER-associated degradation machinery
Authors: Katharine Umphred-Wilson, Stanley Adoro
Journal: Journal of Clinical Investigation (2024)

The suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) complex of the endoplasmic reticulum-associated degradation (ERAD) machinery is a key cellular proteostasis pathway. Although previous studies have shown ERAD as promoting the development and maintenance of many cell types in mice, its importance to human physiology remained undetermined. In two articles in this issue of the JCI, Qi and colleagues describe four biallelic hypomorphic SEL1L and HRD1 variants that were associated with neurodevelopment disorders, locomotor dysfunction, impaired immunity, and premature death in patients. These pathogenic SEL1L-HRD1 variants shine a light on the critical importance of ERAD in humans and pave the way for future studies dissecting ERAD mechanisms in specific cell types.
Modulation of macrophage metabolism as an emerging immunotherapy strategy for cancer
Authors: Corey Dussold, Kaylee Zilinger, Jillyn Turunen, Amy B. Heimberger, Jason Miska
Journal: Journal of Clinical Investigation (2024)

Immunometabolism is a burgeoning field of research that investigates how immune cells harness nutrients to drive their growth and functions. Myeloid cells play a pivotal role in tumor biology, yet their metabolic influence on tumor growth and antitumor immune responses remains inadequately understood. This Review explores the metabolic landscape of tumor-associated macrophages, including the immunoregulatory roles of glucose, fatty acids, glutamine, and arginine, alongside the tools used to perturb their metabolism to promote antitumor immunity. The confounding role of metabolic inhibitors on our interpretation of myeloid metabolic phenotypes will also be discussed. A binary metabolic schema is currently used to describe macrophage immunological phenotypes, characterizing inflammatory M1 phenotypes, as supported by glycolysis, and immunosuppressive M2 phenotypes, as supported by oxidative phosphorylation. However, this classification likely underestimates the variety of states in vivo. Understanding these nuances will be critical when developing interventional metabolic strategies. Future research should focus on refining drug specificity and targeted delivery methods to maximize therapeutic efficacy.
FGFR inhibition augments anti–PD-1 efficacy in murine FGFR3-mutant bladder cancer by abrogating immunosuppression
Authors: Atsushi Okato, Takanobu Utsumi, Michela Ranieri, Xingnan Zheng, Mi Zhou, Luiza D Pereira, Ting Chen, Yuki Kita, Di Wu, Hyesun Hyun, Hyojin Lee, Andrew S Gdowski, John D Raupp, Sean Clark-Garvey, Ujjawal Manocha, Alison Chafitz, Fiona Sherman, Janaye Stephens, Tracy L Rose, Matthew I Milowsky, Sara E Wobker, Jonathan S Serody, Jeffrey S Damrauer, Kwok-Kin Wong, William Y Kim
Journal: Journal of Clinical Investigation (2024)

The combination of targeted therapy with immune checkpoint inhibition (ICI) is an area of intense interest. We studied the interaction of fibroblast growth factor receptor (FGFR) inhibition with ICI in urothelial carcinoma (UC) of the bladder, in which FGFR3 is altered in 50% of cases. Using an FGFR3-driven, Trp53-mutant genetically engineered murine model (UPFL), we demonstrate that UPFL tumors recapitulate the histology and molecular subtype of their FGFR3-altered human counterparts. Additionally, UPFL1 allografts exhibit hyperprogression to ICI associated with an expansion of T regulatory cells (Tregs). Erdafitinib blocked Treg proliferation in vitro, while in vivo ICI-induced Treg expansion was fully abrogated by FGFR inhibition. Combined erdafitinib and ICI resulted in high therapeutic efficacy. In aggregate, our work establishes that, in mice, co-alteration of FGFR3 and Trp53 results in high-grade, non-muscle-invasive UC and presents a previously underappreciated role for FGFR inhibition in blocking ICI-induced Treg expansion.
Covalently grafted human serum albumin coating mitigates the foreign body response against silicone implants in mice
Authors: Xianchi Zhou, Hongye Hao, Yifeng Chen, Wenzhong Cao, Zihao Zhu, Yanwen Ni, Zuolong Liu, Fan Jia, Youxiang Wang, Jian Ji, None Peng Zhang
Journal: Bioactive Materials (2024)

Implantable biomaterials and biosensors are integral components of modern medical systems but often encounter hindrances due to the foreign body response (FBR). Herein, we report an albumin coating strategy aimed at addressing this challenge. Using a facile and scalable silane coupling strategy, human serum albumin (HSA) is covalently grafted to the surface of polydimethylsiloxane (PDMS) implants. This covalently grafted albumin coating remains stable and resistant to displacement by other proteins. Notably, the PDMS with covalently grafted HSA strongly resists the fibrotic capsule formation following a 180-day subcutaneous implantation in C57BL/6 mice. Furthermore, the albumin coating led to reduced recruitment of macrophages and triggered a mild immune activation pattern. Exploration of albumin coatings sourced from various mammalian species has shown that only HSA exhibited a promising anti-FBR effect. The albumin coating method reported here holds the potential to improve and extend the function of silicone-based implants by mitigating the host responses to subcutaneously implanted biomaterials.
Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma
Authors: Justin T Low, Michael C Brown, Zachary J Reitman, Joshua D Bernstock, James M Markert, Gregory K Friedman, Matthew S Waitkus, Michelle L Bowie, David M Ashley
Journal: Journal of Clinical Investigation (2024)

Since the discovery that cGAS/STING recognizes endogenous DNA released from dying cancer cells and induces type I interferon and antitumor T cell responses, efforts to understand and therapeutically target the STING pathway in cancer have ensued. Relative to other cancer types, the glioma immune microenvironment harbors few infiltrating T cells, but abundant tumor-associated myeloid cells, possibly explaining disappointing responses to immune checkpoint blockade therapies in cohorts of patients with glioblastoma. Notably, unlike most extracranial tumors, STING expression is absent in the malignant compartment of gliomas, likely due to methylation of the STING promoter. Nonetheless, several preclinical studies suggest that inducing cGAS/STING signaling in the glioma immune microenvironment could be therapeutically beneficial, and cGAS/STING signaling has been shown to mediate inflammatory and antitumor effects of other modalities either in use or being developed for glioblastoma therapy, including radiation, tumor-treating fields, and oncolytic virotherapy. In this Review, we discuss cGAS/STING signaling in gliomas, its implications for glioma immunobiology, compartment-specific roles for STING signaling in influencing immune surveillance, and efforts to target STING signaling - either directly or indirectly - for antiglioma therapy.
Telomerase mRNA Enhances Human Skin Engraftment for Wound Healing (Adv. Healthcare Mater. 2/2024)
Authors: David F. Chang, Karem A. Court, Rhonda Holgate, Elizabeth A. Davis, Katie A. Bush, Andrew P. Quick, Aldona J. Spiegel, Maham Rahimi, John P. Cooke, Biana Godin
Journal: Advanced Healthcare Materials (2024)

Lipid Nanoparticles In article 2302029 by John P. Cooke, Biana Godin, and co-workers, lipid nanoparticles carrying human telomerase reverse transcriptase mRNA (hTERT-mRNA LNP) are formulated for transfection in human skin cells suspension (hSCS) to improve healing of deep skin wounds. hTERT-mRNA LNP-treated hSCS enhances skin regeneration in a partial-thickness wound model, increasing hSCS engraftment and proliferation, while reducing cellular senescence and DNA damage.
Transdermal Sustained Release Properties and Anti‐Photoaging Efficacy of Liposome‐Thermosensitive Hydrogel System (Adv. Healthcare Mater. 2/2024)
Authors: Sijie Wu, Gaodan Liu, Ping Shao, Xingyu Lin, Jiahao Yu, Hanchi Chen, Huiliang Li, Simin Feng
Journal: Advanced Healthcare Materials (2024)

Liposome Hydrogels In article 2301933 by Ping Shao, Simin Feng, and co-workers, a carboxymethyl-modified chitosan/hyaluronic acid thermosensitive hydrogel dressing with good skin suitability is developed as an innovative solution for sustained transdermal delivery. This dressing, with excellent skin compatibility, incorporates liposomes to combat UVA-induced photoaging. The liposome-hydrogel system acts as a versatile and efficient delivery platform, enabling prolonged and targeted transdermal delivery.
Fn‐HMGB1 Adsorption Behavior Initiates Early Immune Recognition and Subsequent Osteoinduction of Biomaterials (Adv. Healthcare Mater. 2/2024)
Authors: Qin Zhao, Zifan Zhao, Jing Zhang, Yueqi Ni, Simin Ouyang, Haoning Qi, Yiqian Yu, Richard J. Miron, Hua Tang, Yufeng Zhang
Journal: Advanced Healthcare Materials (2024)

Bone Regeneration Article 2301808 by Zifan Zhao, Yufeng Zhang, and co-workers reveals the sequential adsorption of Fn and HMGB1 on biomaterials. The Fn-HMGB1 adsorption and subsequent immune recognition determine the process of biomaterial-mediated bone regeneration. Sequential adsorption of proteins is potentially an important reference for improving bone grafting biomaterials and provides a new way for biomaterials to initiate immune recognition and osteoinduction.
ACP‐Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism (Adv. Healthcare Mater. 2/2024)
Authors: Songzhe Shan, Zhenhang Tang, Kaida Sun, Wenjing Jin, Haihua Pan, Ruikang Tang, Wei Yin, Zhijian Xie, Zhuo Chen, Changyu Shao
Journal: Advanced Healthcare Materials (2024)

Collagen Mineralization The work in article 2302418 by Zhijian Xie, Zhuo Chen, Changyu Shao, and co-workers, confirms for the first time that amorphous calcium phosphate (ACP) particles can directly infiltrate inside fibrils and mediate the phase transformation for collagen mineralization, improving the mechanical properties of the mineralized collagen and significantly promoting dentin remineralization, which provides a new mechanistic understanding of collagen mineralization and a promising strategy for hard tissue.
Ex Vivo Evaluation of Combination Immunotherapy Using Tumor‐Microenvironment‐on‐Chip (Adv. Healthcare Mater. 2/2024)
Authors: Hsuan‐Yu Mu, Chiao‐Min Lin, Li‐An Chu, Ya‐Hui Lin, Ji Li, Chao‐Yu Liu, Hsi‐Chien Huang, Sheng‐Liang Cheng, Tsung‐Ying Lee, Hsin Mei Lee, Hsin‐Min Chen, Yun‐Jen Tsai, Yunching Chen, Jen‐Huang Huang
Journal: Advanced Healthcare Materials (2024)

Drug Screening In article 2302268, Yunching Chen, Jen-Huang Huang, and co-workers introduce a tumor-microenvironment-on-chip that preserves the intricate complexity and heterogeneity of the tumor microenvironment while enabling controlled spatial infiltration of cytotoxic CD8+ T cells over time. This chip not only facilitates real-time monitoring of the dynamic interactions between cancer and immune cells but also holds great promise for advancing drug development and informing clinical decision-making.
Platelet Membrane‐Enclosed Bioorthogonal Catalysis for Combating Dental Caries (Adv. Healthcare Mater. 2/2024)
Authors: Mamata Karmacharya, Sumit Kumar, Yoon Jeong Choi, Yoon‐Kyoung Cho
Journal: Advanced Healthcare Materials (2024)

Nanoreactors Platelet nanoreactors, loaded with supramolecular metal catalysts, enable precise targeting of pathogenic biofilms and localized antibiotic production, effectively eradicating bacteria responsible for dental caries with exceptional biocompatibility. This is demonstrated in article 2302121 by Sumit Kumar, Yoon-Kyoung Cho, and co-workers.
TTN truncation variants produce sarcomere-integrating proteins of uncertain functional significance
Authors: J Travis Hinson, Stuart G Campbell
Journal: Journal of Clinical Investigation (2024)

Titin (TTN) is one of the largest and most complex proteins expressed in humans, and truncation variants are the most prevalent genetic lesion identified in individuals with dilated cardiomyopathy (DCM) or other disorders of impaired cardiac contractility. Two reports in this issue of the JCI shed light on a potential mechanism involving truncated TTN sarcomere integration and the potential for disruption of sarcomere structural integrity. Kellermayer, Tordai, and colleagues confirmed the presence of truncated TTN protein in human DCM samples. McAfee and authors developed a patient-specific TTN antibody to study truncated TTN subcellular localization and to explore its functional consequences. A "poison peptide" mechanism emerges that inspires alternative therapeutic approaches while opening new lines for inquiry, such as the role of haploinsufficiency of full-length TTN protein, mechanisms explaining sarcomere dysfunction, and explanations for variable penetrance.
Evaluation of clinical prediction models (part 2): how to undertake an external validation study
Authors: Richard D Riley, Lucinda Archer, Kym I E Snell, Joie Ensor, Paula Dhiman, Glen P Martin, Laura J Bonnett, Gary S Collins
Journal: BMJ (2024)

External validation studies are an important but often neglected part of prediction model research. In this article, the second in a series on model evaluation, Riley and colleagues explain what an external validation study entails and describe the key steps involved, from establishing a high quality dataset to evaluating a model's predictive performance and clinical usefulness.
Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation
Authors: Henry J. Sutton, Xin Gao, Hannah G. Kelly, Brian J. Parker, Mariah Lofgren, Cherrelle Dacon, Deepyan Chatterjee, Robert A. Seder, Joshua Tan, Azza H. Idris, Teresa Neeman, Ian A. Cockburn
Journal: Immunity (2024)
Discrete prefrontal neuronal circuits determine repeated stress-induced behavioral phenotypes in male mice
Authors: Haiyan Li, Ayako Kawatake-Kuno, Hiromichi Inaba, Yuka Miyake, Yukihiro Itoh, Takatoshi Ueki, Naoya Oishi, Toshiya Murai, Takayoshi Suzuki, Shusaku Uchida
Journal: Neuron (2024)
Dissociable neuronal substrates of visual feature attention and working memory
Authors: Diego Mendoza-Halliday, Haoran Xu, Frederico A.C. Azevedo, Robert Desimone
Journal: Neuron (2024)

Attention and working memory (WM) are distinct cognitive functions, yet given their close interactions, it is often assumed that they share the same neuronal mechanisms. We show that in macaques performing a WM-guided feature attention task, the activity of most neurons in areas middle temporal (MT), medial superior temporal (MST), lateral intraparietal (LIP), and posterior lateral prefrontal cortex (LPFC-p) displays attentional modulation or WM coding and not both. One area thought to play a role in both functions is LPFC-p. To test this, we optogenetically inactivated LPFC-p bilaterally during different task periods. Attention period inactivation reduced attentional modulation in LPFC-p, MST, and LIP neurons and impaired task performance. In contrast, WM period inactivation did not affect attentional modulation or performance and minimally affected WM coding. Our results suggest that feature attention and WM have dissociable neuronal substrates and that LPFC-p plays a critical role in feature attention, but not in WM.
Causal effects of gut microbiota on renal tumor: a Mendelian randomization study
Authors: Fuxun Zhang, Yang Xiong, Bo Zhang
Journal: International Journal of Surgery (2024)

aDepartment of Urology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China bDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China Fuxun Zhang and Yang Xiong contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Urology, Tangdu Hospital, Air Force Medical University, Xi'an, Shaanxi, China. E-mail address: [email protected] (B. Zhang). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
A bacterial sialidase mediates early-life colonization by a pioneering gut commensal
Authors: Ekaterina Buzun, Chia-Yun Hsu, Kristija Sejane, Renee E. Oles, Adriana Vasquez Ayala, Luke R. Loomis, Jiaqi Zhao, Leigh-Ana Rossitto, Dominic M. McGrosso, David J. Gonzalez, Lars Bode, Hiutung Chu
Journal: Cell Host & Microbe (2024)
Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells
Authors: Alberto Sogari, Emanuele Rovera, Gaia Grasso, Elisa Mariella, Nicole Megan Reilly, Simona Lamba, Gianluca Mauri, Erika Durinikova, Pietro Paolo Vitiello, Annalisa Lorenzato, Marco Avolio, Eleonora Piumatti, Emanuela Bonoldi, Maria Costanza Aquilano, Sabrina Arena, Andrea Sartore-Bianchi, Salvatore Siena, Livio Trusolino, Manuela Donalisio, Mariangela Russo, Federica Di Nicolantonio, David Lembo, Alberto Bardelli
Journal: Cell Reports Medicine (2024)

The bacterial genotoxin colibactin promotes colorectal cancer (CRC) tumorigenesis, but systematic assessment of its impact on DNA repair is lacking, and its effect on response to DNA-damaging chemotherapeutics is unknown. We find that CRC cell lines display differential response to colibactin on the basis of homologous recombination (HR) proficiency. Sensitivity to colibactin is induced by inhibition of ATM, which regulates DNA double-strand break repair, and blunted by HR reconstitution. Conversely, CRC cells chronically infected with colibactin develop a tolerant phenotype characterized by restored HR activity. Notably, sensitivity to colibactin correlates with response to irinotecan active metabolite SN38, in both cell lines and patient-derived organoids. Moreover, CRC cells that acquire colibactin tolerance develop cross-resistance to SN38, and a trend toward poorer response to irinotecan is observed in a retrospective cohort of CRCs harboring colibactin genomic island. Our results shed insight into colibactin activity and provide translational evidence on its chemoresistance-promoting role in CRC.
Functional precision oncology for follicular lymphoma with patient-derived xenograft in avian embryos
Authors: Manon Zala, Boris Lipinski, Clélia Costechareyre, Loraine Jarrosson, Romain Teinturier, Edith Julia, Marjorie Lacourrège, Aurélie Verney, Jérôme Guitton, Alexandra Traverse-Glehen, Emmanuel Bachy, Gilles Salles, Sarah Huet, Laurent Genestier, Valérie Castellani, Céline Delloye-Bourgeois, Pierre Sujobert
Journal: Leukemia (2024)
Cancer Metastasis‐on‐a‐Chip for Modeling Metastatic Cascade and Drug Screening
Authors: Anastasia Brooks, Yali Zhang, Jiezhong Chen, Chun‐Xia Zhao
Journal: Advanced Healthcare Materials (2024)

Microfluidic chips are valuable tools for studying intricate cellular and cell-microenvironment interactions. Traditional in vitro cancer models lack accuracy in mimicking the complexities of in vivo tumor microenvironment. However, cancer-metastasis-on-a-chip (CMoC) models combine the advantages of 3D cultures and microfluidic technology, serving as powerful platforms for exploring cancer mechanisms and facilitating drug screening. These chips are able to compartmentalize the metastatic cascade, deepening the understanding of its underlying mechanisms. This article provides an overview of current CMoC models, focusing on distinctive models that simulate invasion, intravasation, circulation, extravasation, and colonization, and their applications in drug screening. Furthermore, challenges faced by CMoC and microfluidic technologies are discussed, while exploring promising future directions in cancer research. The ongoing development and integration of these models into cancer studies are expected to drive transformative advancements in the field.