tbuckley/cabot-search huggingface dataset:
Multiple loci for foveolar vision in macaque monkey visual cortex
Authors: Meizhen Qian, Jianbao Wang, Yang Gao, Ming Chen, Yin Liu, Dengfeng Zhou, Haidong D. Lu, Xiaotong Zhang, Jia Ming Hu, Anna Wang Roe
Journal: Nature Neuroscience (2024)

In humans and nonhuman primates, the central 1° of vision is processed by the foveola, a retinal structure that comprises a high density of photoreceptors and is crucial for primate-specific high-acuity vision, color vision and gaze-directed visual attention. Here, we developed high-spatial-resolution ultrahigh-field 7T functional magnetic resonance imaging methods for functional mapping of the foveolar visual cortex in awake monkeys. In the ventral pathway (visual areas V1–V4 and the posterior inferior temporal cortex), viewing of a small foveolar spot elicits a ring of multiple (eight) foveolar representations per hemisphere. This ring surrounds an area called the 'foveolar core', which is populated by millimeter-scale functional domains sensitive to fine stimuli and high spatial frequencies, consistent with foveolar visual acuity, color and achromatic information and motion. Thus, this elaborate rerepresentation of central vision coupled with a previously unknown foveolar core area signifies a cortical specialization for primate foveation behaviors. The retinal foveola in the primate eye is critical for seeing fine details, color, text and faces. Using ultrahigh-field functional magnetic resonance imaging, Qian et al discover that there is a highly specialized cortical brain region for processing foveolar information.
In vivo affinity maturation of the CD4 domains of an HIV-1-entry inhibitor
Authors: Andi Pan, Charles C. Bailey, Tianling Ou, Jinge Xu, Tonia Aristotelous, Xin Liu, Baodan Hu, Gogce Crynen, Nickolas Skamangas, Naomi Bronkema, Mai H. Tran, Huihui Mou, Xia Zhang, Michael D. Alpert, Yiming Yin, Michael Farzan, Wenhui He
Journal: Nature Biomedical Engineering (2024)
Systemic evaluation of various CRISPR/Cas13 orthologs for knockdown of targeted transcripts in plants
Authors: Lu Yu, Jiawei Zou, Amjad Hussain, Ruoyu Jia, Yibo Fan, Jinhang Liu, Xinhui Nie, Xianlong Zhang, Shuangxia Jin
Journal: Genome biology (2024)

CRISPR/Cas13 system, recognized for its compact size and specificity in targeting RNA, is currently employed for RNA degradation. However, the potential of various CRISPR/Cas13 subtypes, particularly concerning the knockdown of endogenous transcripts, remains to be comprehensively characterized in plants. Here we present a full spectrum of editing profiles for seven Cas13 orthologs from five distinct subtypes: VI-A (LwaCas13a), VI-B (PbuCas13b), VI-D (RfxCas13d), VI-X (Cas13x.1 and Cas13x.2), and VI-Y (Cas13y.1 and Cas13y.2). A systematic evaluation of the knockdown effects on two endogenous transcripts (GhCLA and GhPGF in cotton) as well as an RNA virus (TMV in tobacco) reveals that RfxCas13d, Cas13x.1, and Cas13x.2 exhibit enhanced stability with editing efficiencies ranging from 58 to 80%, closely followed by Cas13y.1 and Cas13y.2. Notably, both Cas13x.1 and Cas13y.1 can simultaneously degrade two endogenous transcripts through a tRNA-crRNA cassette approach, achieving editing efficiencies of up to 50%. Furthermore, different Cas13 orthologs enable varying degrees of endogenous transcript knockdown with minimal off-target effects, generating germplasms that exhibit a diverse spectrum of mutant phenotypes. Transgenic tobacco plants show significant reductions in damage, along with mild oxidative stress and minimal accumulation of viral particles after TMV infection. In conclusion, our study presents an efficient and reliable platform for transcriptome editing that holds promise for plant functional research and future crop improvement.
A genome-wide meta-analysis reveals shared and population-specific variants for allergic sensitization
Authors: Emiko Noguchi, Wataru Morii, Haruna Kitazawa, Tomomitsu Hirota, Kyuto Sonehara, Hironori Masuko, Yukinori Okada, Nobuyuki Hizawa
Journal: Journal of Allergy and Clinical Immunology (2024)
Development and evaluation of spirometry reference equations at high altitude
Authors: Yanyan Li, Zhenzhen Xing, Xiangda Zhang, Yanlu Hu, Yanfei Guo
Journal: Pulmonology (2024)

Approximately 400 million people live at high altitudes worldwide, yet reference equations for spirometry in these populations are inadequately documented. This study aims to develop reference equations for spirometry and assess their applicability to residents at altitudes ranging from 2,100 to 4,700 metres above sea level. This extensive cross-sectional study encompassed healthy non-smokers aged 15 years or older living at Xinjiang and Tibet autonomous region, which covered eight high-altitude areas by a multistage stratified sampling procedure. All individuals underwent pre- and post-bronchodilator measurement. We used the Lambda-Mu-Sigma (LMS) method to establish reference equations for various spirometry parameters. We assessed model fit using mean absolute error (MAE), mean absolute percentage error (MAPE), and residual values (standard deviation), relative to established benchmarks such as GLI, ECSC, and NHANES III, to evaluate the applicability of our equations to high-altitude residents. Between June 2015 and August 2016, 3174 healthy subjects were included. The reference equations utilise age and height as independent variables, with improved accuracy achieved through spline functions. Our spirometry reference equations demonstrate minimal MAE, MAPE, and residual values (standard deviation) for most of the analysed spirometry parameters, stratified by gender. Our spirometry reference equations are more applicable to residents of high-altitude regions.
Tumor-intrinsic kinome landscape of pancreatic cancer reveals new therapeutic approaches
Authors: Yi Xu, Xianlu L. Peng, Michael P. East, Ian C. McCabe, Grace C. Stroman, Madison R. Jenner, Priscilla S. Chan, Ashley B. Morrison, Emily C. Shen, Silvia G. Hererra, Chinmaya U. Joisa, Naim U. Rashid, Alina C. Iuga, Shawn M. Gomez, Lisa Miller-Phillips, Stefan Boeck, Volker Heinemann, Michael Haas, Steffen Ormanns, Gary L. Johnson, Jen Jen Yeh
Journal: Cancer Discovery (2024)

We provide a comprehensive tumor-intrinsic kinome landscape that provides a roadmap for the use of kinase inhibitors in PDAC treatment approaches.
The role and mechanism of NAT10‐mediated ac4C modification in tumor development and progression
Authors: Zhuoran Gu, Libin Zou, Xinjian Pan, Yang Yu, Yongqiang Liu, Zhijin Zhang, Ji Liu, Shiyu Mao, Junfeng Zhang, Changcheng Guo, Wei Li, Jiang Geng, Wentao Zhang, Xudong Yao, Bing Shen
Journal: MedComm (2024)

Abstract RNA modification has emerged as a crucial area of research in epigenetics, significantly influencing tumor biology by regulating RNA metabolism. N‐acetyltransferase 10 (NAT10)‐mediated N4‐acetylcytidine (ac4C) modification, the sole known acetylation in eukaryotic RNA, influences cancer pathogenesis and progression. NAT10 is the only writer of ac4C and catalyzes acetyl transfer on targeted RNA, and ac4C helps to improve the stability and translational efficiency of ac4C‐modified RNA. NAT10 is highly expressed and associated with poor prognosis in pan‐cancers. Based on its molecular mechanism and biological functions, ac4C is a central factor in tumorigenesis, tumor progression, drug resistance, and tumor immune escape. Despite the increasing focus on ac4C, the specific regulatory mechanisms of ac4C in cancer remain elusive. The present review thoroughly analyzes the current knowledge on NAT10‐mediated ac4C modification in cancer, highlighting its broad regulatory influence on targeted gene expression and tumor biology. This review also summarizes the limitations and perspectives of current research on NAT10 and ac4C in cancer, to identify new therapeutic targets and advance cancer treatment strategies.
Single‐cell transcriptomic analysis of glioblastoma reveals pericytes contributing to the blood–brain–tumor barrier and tumor progression
Authors: Yuzhe Li, Changwu Wu, Xinmiao Long, Xiangyu Wang, Wei Gao, Kun Deng, Bo Xie, Sen Zhang, Minghua Wu, Qing Liu
Journal: MedComm (2024)

Abstract The blood–brain barrier is often altered in glioblastoma (GBM) creating a blood–brain–tumor barrier (BBTB) composed of pericytes. The BBTB affects chemotherapy efficacy. However, the expression signatures of BBTB‐associated pericytes remain unclear. We aimed to identify BBTB‐associated pericytes in single‐cell RNA sequencing data of GBM using pericyte markers, a normal brain pericyte expression signature, and functional enrichment. We identified parathyroid hormone receptor‐1 (PTH1R) as a potential marker of pericytes associated with BBTB function. These pericytes interact with other cells in GBM mainly through extracellular matrix–integrin signaling pathways. Compared with normal pericytes, pericytes in GBM exhibited upregulation of several ECM genes (including collagen IV and FN1 ), and high expression levels of these genes were associated with a poor prognosis. Cell line experiments showed that PTH1R knockdown in pericytes increased collagen IV and FN1 expression levels. In mice models, the expression levels of PTH1R, collagen IV, and FN1 were consistent with these trends. Evans Blue leakage and IgG detection in the brain tissue suggested a negative correlation between PTH1R expression levels and blood–brain barrier function. Further, a risk model based on differentially expressed genes in PTH1R + pericytes had predictive value for GBM, as validated using independent and in‐house cohorts.
Novel Methods to Assess Tumor Burden and Minimal Residual Disease in Genitourinary Cancers
Authors: Pedro C Barata, Kevin K Zarrabi, Axel Bex, Petros Grivas, Ken Hermann, Michael S Hofman, Roger Li, Antonio Lopez-Beltran, Anwar R Padani, Thomas Powles, Mary-Ellen Taplin, Yohann Loriot
Journal: European Urology (2024)
MOF‐Based Guided Bone Regeneration Membrane for Promoting Osteogenesis by Regulating Bone Microenvironment through Cascade Effects
Authors: Chunyu Liu, Yajuan Xie, Yunfan Zhang, Yuqi Sun, Yuanbo Wang, Bing Han, Xin Jiang, Bo Wang
Journal: Advanced Healthcare Materials (2024)

Abstract Regulation of bone microenvironment (BME) including innate pH values and metal ions affects cellular functions and activities of osteoblasts and osteoclasts, thereby significantly influencing the process of bone regeneration. How to achieve multiple effective regulations of the BME through cascade effects via facile material design and fabrication to significantly facilitate osteogenesis remains a challenge. Herein, a facilely‐designed resorbable guided bone regeneration membrane (PCL/DEX@Ca‐Zol) based on a drug‐loaded metal‐organic framework is reported. Thereinto, calcium ions, zoledronic acid, and dexamethasone embedded in the membrane can be responsively released specifically inside bone defect in an acid‐triggered manner to synergistically regulate BME by neutralization of pH value, enhancement of osteogenic differentiation and mineralization, and inhibition of osteoclasts in one‐go. Along with polycaprolactone as a structural support in the membrane for bone regeneration with fully utilized components of the composite membrane material, enhances bone regeneration with minimized side effects is accordingly achieved with the assistance of effective modulation of BME through multiple cascade effects.
Enhancing the Deformability of the Adjuvant: Achieving Lymph Node Targeted Delivery to Elicit a Long‐Lasting Immune Protection
Authors: Nan Wu, Yuyang Liu, Chunyu Miao, Ziyi Yu, Guanghui Ma, Jie Wu
Journal: Advanced Healthcare Materials (2024)

Abstract A key challenge in vaccine development is to induce an effective and durable immune response. Live virus vaccines induce lifelong antibody responses; however, the immune responses induced by inactivated or subunit vaccines decrease gradually. Activation of the germinal center (GC) reaction, which generates long‐lived plasma cells (LLPCs), is a key mediator of long‐term antibody responses. To enhance the activation of GC, lymph node‐targeted delivery of the vaccine is promoted by enhancing the deformability of the delivery vector. In this study, a double emulsion is designed with strong deformability and containing chitosan nanoparticles (CSNP) in the internal aqueous phase (W NP ) for efficient antigen loading, called W NP /O/W. The flexible oil layer and the internally loaded positively charged particles endow the emulsion with strong deformability, continuously enrich model antigen ovalbumin (OVA) in the lymph nodes, activate germinal center B (GC B) cells and T follicular helper (T FH ) cells, induce LLPCs, and obtain high‐level antibody persistence for more than 5 months, which is significantly better than the traditional oil emulsion adjuvant. Concurrently, it also improves the immune‐protective effect in aged mice. Altogether, these results indicate that W NP /O/W achieves lymph node targeted delivery by strengthening deformability, generating high‐intensity antibody responses, and long‐lasting immune protection.
Liquid Crystal Elastomer for Compression Therapy
Authors: Gaoweiang Dong, Fangchen Zhao, Zongyu Gao, Shengqiang Cai
Journal: Advanced Healthcare Materials (2024)

Abstract Compression therapy is a widely used treatment for various disorders including venous leg ulcers. Traditional methods such as inelastic bandages and elastic stockings, have limitations in maintaining optimal pressure over time. Dynamic therapy devices offer intermittent pressure cycles but are often bulky or rigid. Here liquid crystal elastomer (LCE) is proposed for both static and dynamic compression therapy. Due to the soft elasticity of polydomain LCE, LCE‐based static stocking can maintain consistent pressure over a wide range of leg diameters, permitting the tolerance of stocking application inconsistencies, various limb sizes, and interfacial pressure drop due to leg deswelling. The LCE‐based dynamic stocking consists of monodomain LCEs with reversible thermal actuation, heating elements, and electronics. The dynamic stocking generates intermittent pressure from 20 to 60 mmHg with a slight temperature increase above 33 °C and offers pressure profile programmability. Furthermore, an untethered LCE‐based dynamic compression device on a human leg is demonstrated. Both LCE‐based static and dynamic stockings show minimal stress relaxation and reusability over 1000 cycles, ensuring long‐term use in compression therapy applications.
Nanoformula Design for Inducing Non‐Apoptotic Cell Death Regulation: A Powerful Booster for Cancer Immunotherapy
Authors: Yi Hu, Qing Yu, Xia Li, Juan Wang, Lanping Guo, Luqi Huang, Wenyuan Gao
Journal: Advanced Healthcare Materials (2024)

Abstract Cancer treatment has witnessed revolutionary advancements marked by the emergence of immunotherapy, specifically immune checkpoint blockade (ICB). However, the inherent low immunogenicity of tumor cells and the intricate immunosuppressive network within the tumor microenvironment (TME) pose significant challenges to the further development of immunotherapy. Nanotechnology has ushered in unprecedented opportunities and vast prospects for tumor immunotherapy. Nevertheless, traditional nano‐formulations often rely on inducing apoptosis to kill cancer cells, which encounters the issue of immune silencing, hindering effective tumor immune activation. The non‐apoptotic modes of regulated cell death (RCD), including pyroptosis, ferroptosis, autophagy, necroptosis, and cuproptosis, have gradually garnered attention. These non‐apoptotic cell death pathways can induce effective immunogenic cell death (ICD), enhancing cancer immunotherapy. This review comprehensively explores advanced nano‐formulation design strategies and their applications in enhancing cancer immunotherapy by promoting non‐apoptotic RCD in recent years. It also discusses the potential advantages of these strategies in inducing tumor‐specific non‐apoptotic RCD. By deeply understanding the significance of non‐apoptotic RCD in synergistic cancer immunotherapy, this article provides valuable insights for developing more advanced nano‐delivery systems that can robustly induce highly immunogenic non‐apoptotic modes, offering novel research and development avenues to address the clinical challenges encountered by immunotherapy represented by ICB.
Magnesium‐Impregnated Membrane Promotes Bone Regeneration in Rat Skull Defect by N‐Linked Glycosylation of SPARC via MagT1
Authors: Weisin Chen, Hongwei Lu, Wenhao Yu, Lei Huang, Mengxuan Bian, Ning Wang, Xingdong Xiang, Guokang Mo, Cheng Zhang, Yulin Li, Libo Jiang, Jian Zhang
Journal: Advanced Healthcare Materials (2024)

Abstract Autograft has long been the gold standard for various bone surgeries. Nevertheless, the increasing usage of synthetic implants is taking over the operation rooms due to biosafety and standardized protocols. To fulfill such tremendous needs, a magnesium‐impregnated membrane is devised that steadily releases magnesium ions to stimulate osteogenesis. The compatibility of Magnesium oxide (MgO) particles is enhanced through hydration and grafting, characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). With detailed degradation profiles, an in‐depth investigation of Magnesium transporter 1 (MagT1) for magnesium intake is carried out and engaging in the N‐linked glycosylation by using RNAi and inhibitors. The glycosylation of secreted protein acidic and rich in cysteine (SPARC) affected extracellular secretion and mineral deposition, demonstrated by immunostaining and density‐dependent color‐SEM (DDC‐SEM). Skull defects are treated by implanting magnesium‐impregnated membranes in rats and evaluated them by micro‐CT and histological exams. This study revealed the compatible integration of grafted magnesium hydroxide (g‐MH) particles is the key to functional performance and critical to applicability in vivo; meanwhile, it opens the door to a biological rationale for designing biomimetic materials.
Bioactive Nanoparticle‐Embedded Micro/Nanofibrous Dressing with Improved Angiogenesis and Immunoregulation for Facilitating Burn Wound Healing
Authors: Lerong Yang, Yiyang Wu, Bangqi Yang, Hongjun Huang, Haoqiang He, Siyi Liu, Chanting Huang, Zainen Qin, Li Zheng, Chong Shen, Jinmin Zhao
Journal: Advanced Healthcare Materials (2024)

Abstract In the context of severe burn injuries, the presence of excessive reactive oxygen species (ROS), prolonged microbial infection, and compromised angiogenesis can contribute to the metabolic reprogramming of macrophages, resulting in a dysregulated inflammatory response that hinders the healing process. In this study, cerium oxide nanoparticles (CeNPs) are encapsulated within a silk fibroin‐poly(e‐caprolactone) polymer to create an electrospun PSF/CeNPs nanofiber membrane (PSF/membrane). This membrane is further modified through the addition of an angiopoietin‐1 mimetic peptide, QHREDGS, resulting in the formation of QPSF/CeNPs (QHREDGS modified PSF/CeNPs membrane). In vitro assessments revealed that the QPSF/CeNPs displayed the intended ability to regulate ROS levels, favorable biocompatibility with cells, promoted endothelial cell attachment and growth, exhibited anti‐inflammatory properties through the modulation of macrophage phenotypes from M1 to M2, as well as pro‐angiogenetic and antibacterial effects. In vivo, the membrane dressing demonstrated an acceleration of burn wound healing, promotion of angiogenesis, downregulation of inflammatory factors, and enhancement of collagen deposition. This bioactive membrane dressing shows potential as a clinical therapy for promoting the regeneration of both acute and chronically damaged skin tissue.
Extracellular vesicles: biological mechanisms and emerging therapeutic opportunities in neurodegenerative diseases
Authors: Ling Wang, Xiaoyan Zhang, Ziyi Yang, Binquan Wang, Hongyang Gong, Ke Zhang, Yi Lin, Mingkuan Sun
Journal: Translational Neurodegeneration (2024)

Abstract Extracellular vesicles (EVs) are membrane vesicles originating from different cells within the brain. The pathophysiological role of EVs in neurodegenerative diseases is progressively acknowledged. This field has advanced from basic biological research to essential clinical significance. The capacity to selectively enrich specific subsets of EVs from biofluids via distinctive surface markers has opened new avenues for molecular understandings across various tissues and organs, notably in the brain. In recent years, brain-derived EVs have been extensively investigated as biomarkers, therapeutic targets, and drug-delivery vehicles for neurodegenerative diseases. This review provides a brief overview of the characteristics and physiological functions of the various classes of EVs, focusing on the biological mechanisms by which various types of brain-derived EVs mediate the occurrence and development of neurodegenerative diseases. Concurrently, novel therapeutic approaches and challenges for the use of EVs as delivery vehicles are delineated.
Extending Amyloidosis Diagnosis
Authors: Dilsat Fırat Arslan, Ekin Inal, Emine Göknur Isik, Yasemin Sanli
Journal: Clinical Nuclear Medicine (2024)

Abstract We present a case with systemic amyloidosis secondary to immunoglobulin light-chain amyloidosis (AL amyloidosis), which 18 F-FDG PET/CT and 99m Tc-PYP scintigraphy revealed amyloid deposition in the peritoneum, omentum, and mesentery. AL amyloidosis is characterized by the proliferation of clonal plasma cells and increased production and extracellular accumulation of immunoglobulin light chains, leading to organ malfunction. Even though AL amyloidosis can affect the gastrointestinal system, peritoneal involvement is rarely observed. PET/CT and SPECT/CT images showed moderate to slightly increased tracer uptake in affected organs.
Malignant Phyllodes Tumor With Sphenoid Bone Metastasis Detected on 99mTc-MDP SPECT/CT and 18F-FDG PET/CT
Authors: Ritwik Wakankar, Yamini Dharmashaktu, Akhil Venugopal, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2024)

Abstract Phyllodes tumors (PTs) are rare fibroepithelial tumors accounting for less than 1% of all breast neoplasms. They are malignant in 20% of cases. Only a few cases of malignant PT metastatic to bone have been reported. We report a case of metastatic malignant PT of the breast involving the greater wing of the sphenoid bone and discuss the radiological findings of 99m Tc-methylene diphosphonate skeletal scintigraphy, SPECT/CT, and 18 F-FDG PET/CT. To our knowledge, this is the first time such a case has been reported in literature.
Immune Reconstitution after Allogenic Stem Cell Transplantation in Patients with Myelofibrosis
Authors: Mirko Farina, Marco Chiarini, Sofia Terlizzi, Anna Galvagni, Simona Bernardi, Alessandro Leoni, Enrico Morello, Vera Radici, Gabriele Magliano, Lorenzo Masina, Marco Galli, Federica Re, Virginia Quaresima, Daniele Moratto, Duilio Brugnoni, Michele Malagola, Nicola Polverelli, Domenico Russo
Journal: Blood (2024)
Belumosudil Is Efficacious for the Management of Heavily Pretreated and Prolonged Chronic Graft-Versus-Host Disease: A Retrospective Multi-Center Real-World Study By the Israel Association for Bone Marrow Transplantation and Cellular Therapy
Authors: Ben Varon, Ron Ram, Avichai Shimoni, Batia Avni, Sigal Grisariu, Vered Stavi, Yael Bar-On, Moshe Yeshurun, Ronit Elhasid, Aharon Gefen, Asaf Yanir, Odelia Amit, Dana Yehudai-Ofir, Israel Henig, Tsila Zuckerman
Journal: Blood (2024)
The Impact of the Absolute Lymphocyte Count before Anti-T-Lymphocyte Globulin (ATLG) Administration on Transplant Outcomes in Matched Unrelated Peripheral Blood Stem Cell Allogeneic Stem Cell Transplantation
Authors: Radwan Massoud, Margherita Ursi, Francesco Barbato, Francesco De Felice, Enrico Maffini, Marcello Roberto, Evgeny Klyuchnikov, Claudia Langebrake, Nico Gagelmann, Gabriele Zeck, Christian Niederwieser, Catherina Lück, Dietlinde Janson, Christine Wolschke, Francis A. Ayuk, Nicolaus Kroeger, Francesca Bonifazi
Journal: Blood (2024)