tbuckley/cabot-search huggingface dataset:
Targeted Cancer Therapy‐on‐A‐Chip
Authors: Heba Abed, Remya Radha, Shabana Anjum, Vinod Paul, Nour AlSawaftah, William G. Pitt, Nureddin Ashammakhi, Ghaleb A. Husseini
Journal: Advanced Healthcare Materials (2024)

Abstract Targeted cancer therapy (TCT) is gaining increased interest because it reduces the risks of adverse side effects by specifically treating tumor cells. TCT testing has traditionally been performed using two‐dimensional (2D) cell culture and animal studies. Organ‐on‐a‐chip (OoC) platforms have been developed to recapitulate cancer in vitro, as cancer‐on‐a‐chip (CoC), and used for chemotherapeutics development and testing. This review explores the use of CoCs to both develop and test TCTs, with a focus on three main aspects, the use of CoCs to identify target biomarkers for TCT development, the use of CoCs to test free, un‐encapsulated TCTs, and the use of CoCs to test encapsulated TCTs. Despite current challenges such as system scaling, and testing externally triggered TCTs, TCToC shows a promising future to serve as a supportive, pre‐clinical platform to expedite TCT development and bench‐to‐bedside translation.
Obesity in Adolescents
Authors: Aaron S. Kelly, Sarah C. Armstrong, Marc P. Michalsky, Claudia K. Fox
Journal: JAMA (2024)

Obesity affects approximately 21% of US adolescents and is associated with insulin resistance, hypertension, dyslipidemia, sleep disorders, depression, and musculoskeletal problems. Obesity during adolescence has also been associated with an increased risk of mortality from cardiovascular disease and type 2 diabetes in adulthood.
Ketogenic diet but not free-sugar restriction alters glucose tolerance, lipid metabolism, peripheral tissue phenotype, and gut microbiome: RCT
Authors: Aaron Hengist, Russell G. Davies, Jean-Philippe Walhin, Jariya Buniam, Lucy H. Merrell, Lucy Rogers, Louise Bradshaw, Alfonso Moreno-Cabañas, Peter J. Rogers, Jeff M. Brunstrom, Leanne Hodson, Luc J.C. van Loon, Wiley Barton, Ciara O’Donovan, Fiona Crispie, Orla O’Sullivan, Paul D. Cotter, Kathryn Proctor, James A. Betts, Françoise Koumanov, Dylan Thompson, Javier T. Gonzalez
Journal: Cell Reports Medicine (2024)

Restricted sugar and ketogenic diets can alter energy balance/metabolism, but decreased energy intake may be compensated by reduced expenditure. In healthy adults, randomization to restricting free sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduces fat mass without changing energy expenditure versus control. Free-sugar restriction minimally affects metabolism or gut microbiome but decreases low-density lipoprotein cholesterol (LDL-C). In contrast, a ketogenic diet decreases glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose and increases apolipoprotein B, C-reactive protein, and postprandial glycerol concentrations. However, despite sustained ketosis, these effects are no longer apparent by week 12, when gut microbial beta diversity is altered, possibly reflective of longer-term adjustments to the ketogenic diet and/or energy balance. These data demonstrate that restricting free sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles, and gut microbiome.
Pain Phenotypes and Pain Multimorbidity Among Medicare Beneficiaries With Cerebral Palsy
Authors: Mark D. Peterson, Kathryn Ashbaugh, Michael O’Leary, Mary Schmidt, Heidi Haapala, Neil Kamdar, Edward A. Hurvitz
Journal: JAMA Neurology (2024)

This cohort study assesses the association of pain phenotypes and pain multimorbidity with cerebral palsy subtypes among Medicare beneficiaries.
Ending Trans Fat—The First-Ever Global Elimination Program for a Noncommunicable Disease Risk Factor
Authors: Lindsay Steele, Elizabeth Drummond, Chizuru Nishida, Rain Yamamoto, Francesco Branca, Cristina Parsons Perez, Lorena Allemandi, Liz Arnanz, Veronica Schoj, Hema S. Khanchandani, Swati Bhardwaj, Renu Garg, Thomas R. Frieden, Laura K. Cobb
Journal: Journal of the American College of Cardiology (2024)

Industrially produced trans fat (iTFA) is a harmful compound created as a substitute for animal and saturated fats. Estimated to cause up to 500,000 deaths per year, it is replaceable. In 2018, Resolve to Save Lives, the World Health Organization (WHO), Global Health Advocacy Incubator, and NCD Alliance partnered to achieve global trans fat elimination. The WHO Director-General called for the elimination of trans fat by 2023 through best practice policies outlined in the WHO REPLACE package. Since the accelerated global efforts in 2018, 43 countries have adopted best practice regulations protecting an additional 3.2 billion people and building momentum toward global elimination. Current coverage will prevent 66% of deaths estimated to be caused each year by trans fat in foods. Despite producing and selling iTFA-free products in many countries, companies continue to sell iTFA-containing products in unregulated markets. Global incentives, accountability mechanisms, and regional policies will help achieve the elimination goal.
Role of the National Institute on Aging in Transforming Aging Research Through Geroscience and Gerotherapeutics—50 Years of Innovation
Authors: John C. Newman, Iman M. Al-Naggar, George A. Kuchel
Journal: JAMA Internal Medicine (2024)

This Viewpoint discusses the role of the National Institute on Aging (NIA) in the fields of geroscience and gerotherapeutics.
Defining neuroblastoma: from origin to precision medicine
Authors: Lourdes Sainero-Alcolado, Tomas Sjöberg Bexelius, Giuseppe Santopolo, Ye Yuan, Judit Liaño-Pons, Marie Arsenian-Henriksson
Journal: Neuro-Oncology (2024)

Neuroblastoma (NB), a heterogenous pediatric tumor of the sympathetic nervous system, is the most common and deadly extracranial solid malignancy diagnosed in infants. Numerous efforts have been invested in understanding its origin and in development of novel curative targeted therapies. Here, we summarize the recent advances in the identification of the cell of origin and the genetic alterations occurring during development that contribute to NB. We discuss current treatment regimens, present and future directions for the identification of novel therapeutic metabolic targets, differentiation agents, as well as personalized combinatory therapies as potential approaches for improving the survival and quality of life of children with NB.
The Possible Earliest Allopolyploidization in Tracheophytes Revealed by Phylotranscriptomics and Morphology of Selaginellaceae
Authors: Jong-Soo Kang, Ji-Gao Yu, Qiao-Ping Xiang, Xian-Chun Zhang
Journal: Molecular Biology and Evolution (2024)

Abstract Selaginellaceae, originated in the Carboniferous and survived the Permian–Triassic mass extinction, is the largest family of lycophyte, which is sister to other tracheophytes. It stands out from tracheophytes by exhibiting extraordinary habitat diversity and lacking polyploidization. The organelle genome-based phylogenies confirmed the monophyly of Selaginella, with six or seven subgenera grouped into two superclades, but the phylogenetic positions of the enigmatic Selaginella sanguinolenta clade remained problematic. Here, we conducted a phylogenomic study on Selaginellaceae utilizing large-scale nuclear gene data from RNA-seq to elucidate the phylogeny and explore the causes of the phylogenetic incongruence of the S. sanguinolenta clade. Our phylogenetic analyses resolved three different positions of the S. sanguinolenta clade, which were supported by the sorted three nuclear gene sets, respectively. The results from the gene flow test, species network inference, and plastome-based phylogeny congruently suggested a probable hybrid origin of the S. sanguinolenta clade involving each common ancestor of the two superclades in Selaginellaceae. The hybrid hypothesis is corroborated by the evidence from rhizophore morphology and spore micromorphology. The chromosome observation and Ks distributions further suggested hybridization accompanied by polyploidization. Divergence time estimation based on independent datasets from nuclear gene sets and plastid genome data congruently inferred that allopolyploidization occurred in the Early Triassic. To our best knowledge, the allopolyploidization in the Mesozoic reported here represents the earliest record of tracheophytes. Our study revealed a unique triad of phylogenetic positions for a hybrid-originated group with comprehensive evidence and proposed a hypothesis for retaining both parental alleles through gene conversion.
An activity-regulated transcriptional program directly drives synaptogenesis
Authors: Callista Yee, Yutong Xiao, Hongwen Chen, Anay R. Reddy, Bing Xu, Taylor N. Medwig-Kinney, Wan Zhang, Alan P. Boyle, Wendy A. Herbst, Yang Kevin Xiang, David Q. Matus, Kang Shen
Journal: Nature Neuroscience (2024)

Abstract Although the molecular composition and architecture of synapses have been widely explored, much less is known about what genetic programs directly activate synaptic gene expression and how they are modulated. Here, using Caenorhabditis elegans dopaminergic neurons, we reveal that EGL-43/MECOM and FOS-1/FOS control an activity-dependent synaptogenesis program. Loss of either factor severely reduces presynaptic protein expression. Both factors bind directly to promoters of synaptic genes and act together with CUT homeobox transcription factors to activate transcription. egl-43 and fos-1 mutually promote each other’s expression, and increasing the binding affinity of FOS-1 to the egl-43 locus results in increased presynaptic protein expression and synaptic function. EGL-43 regulates the expression of multiple transcription factors, including activity-regulated factors and developmental factors that define multiple aspects of dopaminergic identity. Together, we describe a robust genetic program underlying activity-regulated synapse formation during development.
Reference genome sequence and population genomic analysis of peas provide insights into the genetic basis of Mendelian and other agronomic traits
Authors: Na Liu, Xiaolong Lyu, Xueying Zhang, Guwen Zhang, Ziqian Zhang, Xueying Guan, Xiaoyang Chen, Xiaoming Yang, Zhijuan Feng, Qiang Gao, Wanghong Shi, Yayuan Deng, Kuang Sheng, Jinwen Ou, Yumeng Zhu, Bin Wang, Yuanpeng Bu, Mingfang Zhang, Liangsheng Zhang, Ting Zhao, Yaming Gong
Journal: Nature Genetics (2024)
Nucleophosmin 1 promotes mucosal immunity by supporting mitochondrial oxidative phosphorylation and ILC3 activity
Authors: Rongchuan Zhao, Jiao Yang, Yunjiao Zhai, Hong Zhang, Yuanshuai Zhou, Lei Hong, Detian Yuan, Ruilong Xia, Yanxiang Liu, Jinlin Pan, Shaheryar Shafi, Guohua Shi, Ruobing Zhang, Dingsan Luo, Jinyun Yuan, Dejing Pan, Changgeng Peng, Shiyang Li, Minxuan Sun
Journal: Nature Immunology (2024)

Nucleophosmin 1 (NPM1) is commonly mutated in myelodysplastic syndrome (MDS) and acute myeloid leukemia. Concurrent inflammatory bowel diseases (IBD) and MDS are common, indicating a close relationship between IBD and MDS. Here we examined the function of NPM1 in IBD and colitis-associated colorectal cancer (CAC). NPM1 expression was reduced in patients with IBD. Npm1
Screening and Exploring the Application of the Multifunctional Antioxidant Peptides MSWLC and TSWLC
Authors: Mingtao Yu, Yue Wang, Dayang Wang, Hailin Cong, Bing Yu
Journal: Advanced Healthcare Materials (2024)

Abstract In this study, an antioxidant pentapeptide library is created based on antioxidant characteristics. The peptides are then purified and separated using liquid chromatography/mass spectrometry (LC/MS) and time‐of‐flight mass spectrometry (TOF). Chemical evaluations identify four peptides with excellent antioxidant activity. The four peptides undergo biocompatibility testing with L‐929, NIH 3T3, and Hep‐G2 cells. A model of hydrogen peroxide‐induced cellular damage in G2 cells shows the peptides' protective and reparative effects against oxidative damage. Two peptides, MSWLC and TSWLC, which perform best overall, are chosen for further analysis. To explore the peptides' potential multifunctionality, acute liver inflammation, keratitis, and aging models are established in mice. MSWLC and TSWLC demonstrate anti‐inflammatory and anti‐aging properties. An antioxidant emulsion prepared by emulsification is found to be non‐irritant in a mouse skin irritation test. In a mouse model exposed to ultraviolet radiation, the sunscreen exhibits excellent UV protection and antioxidant effects. These peptides possess potent antioxidant properties and multifunctionality, indicating broad application potential.
A Pyroptosis‐Inducing Arsenic(III) Nanomicelle Platform for Synergistic Cancer Immunotherapy
Authors: Xing Wang, Yuqi Tang, Yuanhang Li, Zhengjian Qi
Journal: Advanced Healthcare Materials (2024)

Abstract Immunogenic cell death (ICD) could activate anti‐tumor immune responses, which is highly attractive for improving cancer treatment effectiveness. Here, this work reports a multifunctional arsenic(III) allosteric inhibitor Mech02, which induces excessive accumulation of 1 O 2 through sensitized biocatalytic reactions, leading to cell pyroptosis and amplified ICD effect. After Mech02 is converted to Mech03, it could actualize stronger binding effects on the allosteric pocket of pyruvate kinase M2, further interfering with the anaerobic glycolysis pathway of tumors. The enhanced DNA damage triggered by Mech02 and the pyroptosis of cancer stem cells provide assurance for complete tumor clearance. In vivo experiments prove nanomicelle Mech02‐HA NPs is able to activate immune memory effects and raise the persistence of anti‐tumor immunity. In summary, this study for the first time to introduce the arsenic(III) pharmacophore as an enhanced ICD effect initiator into nitrogen mustard, providing insights for the development of efficient multimodal tumor therapy agents.
Rapid Biofabrication of an Advanced Microphysiological System Mimicking Phenotypical Heterogeneity and Drug Resistance in Glioblastoma
Authors: Sirjana Pun, Anusha Prakash, Dalee Demaree, Daniel Pomeranz Krummel, Giuseppe Sciumè, Soma Sengupta, Riccardo Barrile
Journal: Advanced Healthcare Materials (2024)

Abstract Microphysiological systems (MPSs) reconstitute tissue interfaces and organ functions, presenting a promising alternative to animal models in drug development. However, traditional materials like polydimethylsiloxane (PDMS) often interfere by absorbing hydrophobic molecules, affecting drug testing accuracy. Additive manufacturing, including 3D bioprinting, offers viable solutions. GlioFlow3D, a novel microfluidic platform combining extrusion bioprinting and stereolithography (SLA) is introduced. GlioFlow3D integrates primary human cells and glioblastoma (GBM) lines in hydrogel‐based microchannels mimicking vasculature, within an SLA resin framework using cost‐effective materials. The study introduces a robust protocol to mitigate SLA resin cytotoxicity. Compared to PDMS, GlioFlow3D demonstrated lower small molecule absorption, which is relevant for accurate testing of small molecules like Temozolomide (TMZ). Computational modeling is used to optimize a pumpless setup simulating interstitial fluid flow dynamics in tissues. Co‐culturing GBM with brain endothelial cells in GlioFlow3D showed enhanced CD133 expression and TMZ resistance near vascular interfaces, highlighting spatial drug resistance mechanisms. This PDMS‐free platform promises advanced drug testing, improving preclinical research and personalized therapy by elucidating complex GBM drug resistance mechanisms influenced by the tissue microenvironment.
A Photoactivated Self‐Assembled Nanoreactor for Inducing Cascade‐Amplified Oxidative Stress toward Type I Photodynamic Therapy in Hypoxic Tumors
Authors: Xuan Luo, Qishu Jiao, Shicheng Pei, Shuyao Zhou, Yaxin Zheng, Weiyang Shao, Keming Xu, Wenying Zhong
Journal: Advanced Healthcare Materials (2024)

Abstract Type I photodynamic therapy (PDT) generates reactive oxygen species (ROS) through oxygen‐independent photoreactions, making it a promising method for treating hypoxic tumors. However, the superoxide anion (O 2 ∙ – ) generated usually exhibits a low oxidation capacity, restricting the antitumor efficacy of PDT in clinical practice. Herein, a photoactivated self‐assembled nanoreactor ( 1 ‐NBS@CeO 2 ) is designed through integration of type I PDT and cerium oxide (CeO 2 ) nanozymes for inducing cascade‐amplified oxidative stress in hypoxic tumors. The nanoreactor is constructed though co‐assembly of an amphiphilic peptide ( 1 ‐NBS) and CeO 2 , giving well‐dispersed spherical nanoparticles with enhanced superoxide dismutase (SOD)‐like and peroxidase (POD)‐like activities. Following light irradiation, 1 ‐NBS@CeO 2 undergoes type I photoreactions to generated O 2 ∙ – , which is further catalyzed by the nanoreactors, ultimately forming hypertoxic hydroxyl radical (∙OH) through cascade‐amplified reactions. The PDT treatment using 1 ‐NBS@CeO 2 results in elevation of intracellular ROS and depletion of GSH content in A375 cells, thereby inducing mitochondrial dysfunction and triggering apoptosis and ferroptosis of tumor cells. Importantly, intravenous administration of 1 ‐NBS@CeO 2 alongside light irradiation showcases enhances antitumor efficacy and satisfactory biocompatibility in vivo. Together, the self‐assembled nanoreactor facilitates cascade‐amplified photoreactions for achieving efficacious type I PDT, which holds great promise in developing therapeutic modules towards hypoxic tumors.
Contributions of network structure, chemoarchitecture and diagnostic categories to transitions between cognitive topographies
Authors: Andrea I. Luppi, S. Parker Singleton, Justine Y. Hansen, Keith W. Jamison, Danilo Bzdok, Amy Kuceyeski, Richard F. Betzel, Bratislav Misic
Journal: Nature Biomedical Engineering (2024)

Abstract The mechanisms linking the brain’s network structure to cognitively relevant activation patterns remain largely unknown. Here, by leveraging principles of network control, we show how the architecture of the human connectome shapes transitions between 123 experimentally defined cognitive activation maps (cognitive topographies) from the NeuroSynth meta-analytic database. Specifically, we systematically integrated large-scale multimodal neuroimaging data from functional magnetic resonance imaging, diffusion tractography, cortical morphometry and positron emission tomography to simulate how anatomically guided transitions between cognitive states can be reshaped by neurotransmitter engagement or by changes in cortical thickness. Our model incorporates neurotransmitter-receptor density maps (18 receptors and transporters) and maps of cortical thickness pertaining to a wide range of mental health, neurodegenerative, psychiatric and neurodevelopmental diagnostic categories (17,000 patients and 22,000 controls). The results provide a comprehensive look-up table charting how brain network organization and chemoarchitecture interact to manifest different cognitive topographies, and establish a principled foundation for the systematic identification of ways to promote selective transitions between cognitive topographies.
Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice
Authors: Andrew Octavian Sasmita, Constanze Depp, Taisiia Nazarenko, Ting Sun, Sophie B. Siems, Erinne Cherisse Ong, Yakum B. Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Barbara Morgado, Zoe Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A. Berghoff, Katherine Rose Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo-Branco, Hans-Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus-Armin Nave
Journal: Nature Neuroscience (2024)

Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APP
Primary cilia signaling in astrocytes mediates development and regional-specific functional specification
Authors: Lizheng Wang, Qianqian Guo, Sandesh Acharya, Xiao Zheng, Vanessa Huynh, Brandon Whitmore, Askar Yimit, Mehr Malhotra, Siddharth Chatterji, Nicole Rosin, Elodie Labit, Colten Chipak, Kelsea Gorzo, Jordan Haidey, David A Elliott, Tina Ram, Qingrun Zhang, Hedwich Kuipers, Grant Gordon, Jeff Biernaskie, Jiami Guo
Journal: Nature Neuroscience (2024)
Hibernating/Awakening Nanomotors Promote Highly Efficient Cryopreservation by Limiting Ice Crystals
Authors: Rui Gao, Weixin Wang, Zhongchao Wang, Yapeng Fan, Lin Zhang, Jiahui Sun, Miaofang Hong, Min Pan, Jianming Wu, Qibing Mei, Yini Wang, Lingyan Qiao, Jin Liu, Fei Tong
Journal: Advanced Healthcare Materials (2024)

Abstract The disruptions caused by ice crystal formation during the cryopreservation of cells and tissues can cause cell and tissue damage. Thus, preventing such damage during cryopreservation is an important but challenging goal. Here, a hibernating/awakening nanomotor with magnesium/palladium covering one side of a silica platform (Mg@Pd@SiO 2 ) is proposed. This nanomotor is used in the cultivation of live NCM460 cells to demonstrate a new method to actively limit ice crystal formation and enable highly efficient cryopreservation. Cooling Mg@Pd@SiO 2 in solution releases Mg 2+ /H 2 and promotes the adsorption of H 2 at multiple Pd binding sites on the cell surface to inhibit ice crystal formation and cell/tissue damage; additionally, the Pd adsorbs and stores H 2 to form a hibernating nanomotor. During laser‐mediated heating, the hibernating nanomotor is activated (awakened) and releases H 2 , which further suppresses recrystallization and decreases cell/tissue damage. These hibernating/awakening nanomotors have great potential for promoting highly efficient cryopreservation by inhibiting ice crystal formation.
Phosphorus Dendrimers Co‐deliver Fibronectin and Edaravone for Combined Ischemic Stroke Treatment via Cooperative Modulation of Microglia/Neurons and Vascular Regeneration
Authors: Jie Ma, Mengsi Zhan, Huxiao Sun, Liangyu He, Yu Zou, Tianyu Huang, Andrii Karpus, Jean‐Pierre Majoral, Serge Mignani, Mingwu Shen, Xiangyang Shi
Journal: Advanced Healthcare Materials (2024)

The development of new multi-target combination treatment strategies to tackle ischemic stroke (IS) remains to be challenging. Herein, a proof-of-concept demonstration of an advanced nanomedicine formulation composed of macrophage membrane (MM)-camouflaged phosphorous dendrimer (termed as AK137)/fibronectin (FN) nanocomplexes (NCs) loaded with antioxidant edaravone (EDV) to modulate both microglia and neurons for effective IS therapy is showcased. The created MM@AK137-FN/EDV (M@A-F/E) NCs with a mean size of 260 nm possess good colloidal stability, sustained EDV release kinetics, and desired cytocompatibility. By virtue of MM decoration, the M@A-F/E NCs can cross blood-brain barrier, act on microglia to exert the anti-inflammatory (AK137 and FN) and antioxidative (FN and EDV) effects in vitro for oxidative stress alleviation, microglia M2 polarization, and reduction of pro-inflammatory cytokine secretion, and act on neuron cells to be anti-apoptotic. In a transient middle cerebral artery occlusion rat model, the developed M@A-F/E NCs can exert enhanced antioxidant/anti-inflammatory/anti-apoptotic therapeutic effects to comprehensively regulate the brain microenvironment and promote vascular regeneration to collaboratively restore the blood flow after ischemia-reperfusion. The designed MM-coated NCs composed of all-active ingredients of phosphorous dendrimers, FN, and EDV that can fully regulate the brain inflammatory microenvironment may expand their application scope in other neurodegenerative diseases.