tbuckley/cabot-search huggingface dataset:
Nanoparticles targeting the central circadian clock: Potential applications for neurological disorders
Authors: Marion Le Meur, Jaime Pignatelli, Paolo Blasi, Valle Palomo
Journal: Advanced Drug Delivery Reviews (2025)

Circadian rhythms and their involvement with various human diseases, including neurological disorders, have become an intense area of research for the development of new pharmacological treatments. The location of the circadian clock machinery in the central nervous system makes it challenging to reach molecular targets at therapeutic concentrations. In addition, a timely administration of the therapeutic agents is necessary to efficiently modulate the circadian clock. Thus, the use of nanoparticles in circadian clock dysfunctions may accelerate their clinical translation by addressing these two key challenges: enhancing brain penetration and/or enabling their formulation in chronodelivery systems. This review describes the implications of the circadian clock in neurological pathologies, reviews potential molecular targets and their modulators and suggests how the use of nanoparticle-based formulations could improve their clinical success. Finally, the potential integration of nanoparticles into chronopharmaceutical drug delivery systems will be described.
High-efficiency antioxidant ROS-responsive thermosensitive hydrogel se-PEG-PPG encapsulated Fenofibrate for the treatment of corneal neovascularization
Authors: Kai Fan, Dejun Yang, Xinyi Zhu, Lan Zheng, Yi Han, Jingwei Lin, Zixun Xiang, Yafei Guo, Keyue Tao, Juntong Li, Jia Qu, Yunlong Wu, Huaqiong Li, Cheng Li
Journal: Journal of Controlled Release (2025)
Cerebrospinal fluid proteomics identification of biomarkers for amyloid and tau PET stages
Authors: Zhibo Wang, Yuhan Chen, Katherine Gong, Bote Zhao, Yuye Ning, Meilin Chen, Yan Li, Muhammad Ali, Jigyasha Timsina, Menghan Liu, Carlos Cruchaga, Jianping Jia
Journal: Cell Reports Medicine (2025)

Accurate staging of Alzheimer's disease (AD) pathology is crucial for therapeutic trials and prognosis, but existing fluid biomarkers lack specificity, especially for assessing tau deposition severity, in amyloid-beta (Aβ)-positive patients. We analyze cerebrospinal fluid (CSF) samples from 136 participants in the Alzheimer's Disease Neuroimaging Initiative using more than 6,000 proteins. We apply machine learning to predict AD pathological stages defined by amyloid and tau positron emission tomography (PET). We identify two distinct protein panels: 16 proteins, including neurofilament heavy chain (NEFH) and SPARC-related modular calcium-binding protein 1 (SMOC1), that distinguished Aβ-negative/tau-negative (A-T-) from A+ individuals and nine proteins, such as HCLS1-associated protein X-1 (HAX1) and glucose-6-phosphate isomerase (GPI), that differentiated A+T+ from A+T- stages. These signatures outperform the established CSF biomarkers (area under the curve [AUC]: 0.92 versus 0.67-0.70) and accurately predicted disease progression over a decade. The findings are validated in both internal and external cohorts. These results underscore the potential of proteomic-based signatures to refine AD diagnostic criteria and improve patient stratification in clinical trials.
A reciprocal relationship between markers of genomic DNA damage and alpha-synuclein pathology in dementia with Lewy bodies
Authors: David J. Koss, Olivia Todd, Hariharan Menon, Zoe Anderson, Tamsin Yang, Lucas Findlay, Ben Graham, Pawel Palmowski, Andrew Porter, Nicola Morrice, Lauren Walker, Johannes Attems, Simona S. Ghanem, Omar El-Agnaf, Fiona EN. LeBeau, Daniel Erskine, Tiago F. Outeiro
Journal: Molecular Neurodegeneration (2025)

Abstract Background DNA damage and DNA damage repair (DDR) dysfunction are insults with broad implications for cellular physiology and have been implicated in various neurodegenerative diseases. Alpha-synuclein (aSyn), a pre-synaptic and nuclear protein associated with neurodegenerative disorders known as synucleinopathies, has been associated with DNA double strand break (DSB) repair. However, although nuclear aSyn pathology has been observed in cortical tissue of dementia with Lewy body (DLB) cases, whether such nuclear pathology coincides with the occurrence of DNA damage has not previously been investigated. Moreover, the specific types of DNA damage elevated in DLB cases and the contribution of DNA damage towards Lewy body (LB) formation is unknown. Methods DNA damage and aSyn pathology were assessed in fixed lateral temporal cortex from clinically and neuropathologically confirmed DLB cases and controls, as well as in cortical tissue from young 3-month-old presymptomatic A30P-aSyn mice. Frozen lateral temporal cortex from DLB and control cases was subject to nuclear isolation, western blotting, aSyn seed amplification and proteomic characterisation via mass spectrometry. Results We detected seed-competent nuclear aSyn, and elevated nuclear serine-129 phosphorylation in DLB temporal cortex, alongside the accumulation of DSBs in neuronal and non-neuronal cellular populations. DNA damage was also present in cortical tissue from presymptomatic A30P mice, demonstrating it is an early insult closely associated with pathogenic aSyn. Strikingly, in postmortem DLB tissue, markers of genomic DNA damage-derived cytoplasmic DNA (CytoDNA) were evident within the majority of LBs examined. The observed cellular pathology was consistent with nuclear upregulation of associated DDR proteins, particularly those involved in base excision repair and DSB repair pathways. Conclusions Collectively our study demonstrates the accumulation of seed-competent pathological nuclear associated aSyn, alongside nuclear DNA damage and the potential involvement of DNA damage derived cytoDNA species in cytoplasmic aSyn pathology. Ultimately, our study supports the hypothesis of a reciprocal relationship between aSyn pathology and nuclear DNA damage and highlights a potential underlying role for DNA damage in pathological mechanisms relevant to DLB, as well as other synucleinopathies, opening novel possibilities for diagnosis and treatment.
Quantifying the source-receptor relationships of PM <sub>2.5</sub> pollution and associated health impacts among China, South Korea, and Japan: A dual perspective and an interdisciplinary approach
Authors: Jianzheng Liu, Fei Yao, Hongwen Chen, Hongyan Zhao
Journal: Environmental Health Perspectives (2025)

Transboundary PM2.5 pollution is causing significant environmental conflicts among China, South Korea, and Japan. However, efforts to address these conflicts have been impeded by a lack of a comprehensive understanding of source-receptor relationships of PM2.5 pollution and associated health impacts among these countries.
Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design
Authors: Kevin Groen, Roger Kuratli, Jannik Enkelmann, Sonja Fernbach, Pedro D. Wendel-Garcia, Willy I. Staiger, Marylène Lejeune, Esther Sauras-Colón, Ferran Roche-Campo, Paraskevas Filippidis, Andri Rauch, Irene A. Abela, Karoline Aebi-Popp, Alexia Anagnostopoulos, Manuel Battegay, Enos Bernasconi, Dominique Laurent Braun, Heiner C. Bucher, Alexandra Calmy, Matthias Cavassini, Angela Ciuffi, Günter Dollenmaier, Mattias Egger, Luisa Elzi, Jan Fehr, Jacques Fellay, Hansjakob Furrer, Christoph A. Fux, Huldrych Fritz Günthard, Anna Hachfeld, David Haerry, Barbara Hasse, Hans H. Hirsch, Matthias Hoffmann, Irene Hösli, Michael Huber, David Jackson-Perry, Christian R. Kahlert, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Roger Dimitri Kouyos, Helen Kovari, Katharina Kusejko, Niklaus Labhardt, Karoline Leuzinger, Begogna Martinez de Tejada, Catja Marzolini, Karin Jutta Metzner, Nicolas Müller, Johannes Nemeth, Dunja Nicca, Julia Notter, Paolo Paioni, Giuseppe Pantaleo, Matthieu Perreau, Andri Rauch, Luisa Salazar-Vizcaya, Patrick Schmid, Roberto Speck, Marcel Stöckle, Philip Tarr, Alexandra Trkola, Gilles Wandeler, Maja Weisser, Sabine Yerly, Alexandra Trkola, Huldrych F. Günthard, Roger D. Kouyos, Silvio D. Brugger, Benjamin G. Hale
Journal: The Journal of Experimental Medicine (2025)

Autoantibodies neutralizing type I interferons (IFN-Is; IFNα or IFNω) exacerbate severe viral disease, but specific treatments are unavailable. With footprint profiling, we delineate two dominant IFN-I faces commonly recognized by neutralizing IFN-I autoantibody–containing plasmas from aged individuals with HIV-1 and from individuals with severe COVID-19. These faces overlap with IFN-I regions independently essential for engaging the IFNAR1/IFNAR2 heterodimer, and neutralizing plasmas efficiently block the interaction of IFN-I with both receptor subunits in vitro. In contrast, non-neutralizing autoantibody–containing plasmas limit the interaction of IFN-I with only one receptor subunit and display relatively low IFN-I–binding avidities, thus likely hindering neutralizing function. Iterative engineering of signaling-inert mutant IFN-Is (simIFN-Is) retaining dominant autoantibody targets created potent decoys that prevent IFN-I neutralization by autoantibody-containing plasmas and that restore IFN-I–mediated antiviral activity. Additionally, microparticle-coupled simIFN-Is were effective at depleting IFN-I autoantibodies from plasmas, leaving antiviral antibodies unaffected. Our study reveals mechanisms of action for IFN-I autoantibodies and demonstrates a proof-of-concept strategy to alleviate pathogenic effects.
DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer
Authors: Benjamin B. Morris, Simon Heeke, Yuanxin Xi, Lixia Diao, Qi Wang, Pedro Rocha, Edurne Arriola, Myung Chang Lee, Darren R. Tyson, Kyle Concannon, Kavya Ramkumar, C. Allison Stewart, Robert J. Cardnell, Runsheng Wang, Vito Quaranta, Jing Wang, John V. Heymach, Barzin Y. Nabet, David S. Shames, Carl M. Gay, Lauren A. Byers
Journal: Molecular Cancer (2025)

Abstract Introduction A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes. Methods To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro , and in vivo model systems. We then investigated how DDR regulation is associated with SCLC biology, chemotherapy response, and tumor evolution following therapy. Results Using multi-omic profiling, we demonstrate that SCLC tumors cluster into three DDR phenotypes with unique molecular features. Hallmarks of these DDR clusters include differential expression of DNA repair genes, increased replication stress, and heightened G2/M cell cycle arrest. SCLCs with elevated DDR phenotypes exhibit increased neuroendocrine features and decreased “inflamed” biomarkers, both within and across SCLC subtypes. Clinical analyses demonstrated treatment naive DDR status was associated with different responses to frontline chemotherapy. Using longitudinal liquid biopsies, we found that DDR Intermediate and High tumors exhibited subtype switching and coincident emergence of heterogenous phenotypes following frontline treatment. Conclusions We establish that SCLC can be classified into one of three distinct, clinically relevant DDR clusters. Our data demonstrates that DDR status plays a key role in shaping SCLC phenotypes and may be associated with different chemotherapy responses and patterns of tumor evolution. Future work targeting DDR specific phenotypes will be instrumental in improving patient outcomes.
Case Finding Among and Comprehensive Management of Household Contacts of Persons with Pulmonary Tuberculosis: a Pilot Project — Uganda, 2023–2024
Authors: Denis Mudoola, Pruthu Thekkur, Joseph Nsonga, Ritah Mande, Selma Dar Berger, Stavia Turyahabwe, Simon Muchuro, Proscovia Namuwenge, Moorine Sekadde, Deus Lukoye, Henry Luzze, John Paul Dongo, Anand Date, Riitta A. Dlodlo, Odile Ferroussier-Davis, Macarthur Charles
Journal: MMWR Morbidity and Mortality Weekly Report (2025)

To help achieve the End TB Strategy target of a 90% reduction in tuberculosis (TB) incidence by 2030, member states of the United Nations High-Level Meetings on TB called for improving provision of TB preventive treatment (TPT) for household contacts of persons with TB, who are at increased risk for infection and disease. However, TPT use among household contacts worldwide remained at 21% in 2023. The International Union Against Tuberculosis and Lung Disease, the Uganda Ministry of Health, and CDC piloted a comprehensive approach for increasing case finding and TPT coverage among household contacts of persons with TB. During November 1, 2023-September 30, 2024, a total of 521 index patients with TB disease were registered at six health facilities in Uganda. Home visits to index patients identified 1,913 household contacts, 1,739 (91.0%) of whom underwent TB symptom screening at home; 321 (18.5%) reported TB symptoms. Of 309 (96.3%) persons with TB symptoms who were further evaluated, 284 (91.9%) provided a sputum specimen for laboratory testing, including 270 (84.1% of those with symptoms) who did so during the home visit; 214 (69.3%) underwent chest radiography. Overall, 80 TB cases were diagnosed; in 61 (76.3%) persons, the diagnosis was based on radiographic findings. Among 1,496 HHCs eligible for TPT, 1,239 (82.8%) initiated treatment and 1,178 (95.1%) completed it. Global scale-up of this approach might help reach global TB elimination goals.
Targeting the central and peripheral nervous system to regulate bone homeostasis: mechanisms and potential therapies
Authors: Tong-Zhou Liang, Zhe-Yu Jin, Yue-Jun Lin, Zi-Yi Chen, Ye Li, Jian-Kun Xu, Fan Yang, Ling Qin
Journal: Military Medical Research (2025)

Abstract The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair. Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated, the intimate relationship between the central nervous system and bone remains less understood, yet it has emerged as a hot topic in the bone field. In this review, we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism, either intact or after injury. First, we explored mechanistic studies linking specific brain nuclei with bone homeostasis, including the ventromedial hypothalamus, arcuate nucleus, paraventricular hypothalamic nucleus, amygdala, and locus coeruleus. We then focused on the characteristics of bone innervation and nerve subtypes, such as sensory, sympathetic, and parasympathetic nerves. Moreover, we summarized the molecular features and regulatory functions of these nerves. Finally, we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration. Therefore, considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process, ultimately benefiting future clinical translation.
<i>Notes from the Field:</i> Rhodesiense Human African Trypanosomiasis (Sleeping Sickness) in a Traveler Returning from Zimbabwe — United States, August 2024
Authors: Elizabeth M. Wendt, Farrell A. Tobolowsky, Gerardo Priotto, Jose Ramon Franco, Rebecca Chancey
Journal: MMWR Morbidity and Mortality Weekly Report (2025)
Single-cell profiling of the human endometrium in polycystic ovary syndrome
Authors: Gustaw Eriksson, Congru Li, Tina Gorsek Sparovec, Anja Dekanski, Sara Torstensson, Sanjiv Risal, Claes Ohlsson, Angelica Lindén Hirschberg, Sophie Petropoulos, Qiaolin Deng, Elisabet Stener-Victorin
Journal: Nature Medicine (2025)

Abstract Polycystic ovary syndrome (PCOS) has a negative effect on the receptivity of the endometrium to embryo implantation and increases the risk of miscarriage and endometrial cancer. The cellular and molecular heterogeneity of the endometrium in women with PCOS has not been well studied. Our study presents a comprehensive cellular atlas of the endometrium during the proliferative phase in women with PCOS characterized by overweight and obesity, hyperandrogenism and insulin resistance compared with controls of similar age, weight and body mass index. Analysis of 247,791 isolated endometrial nuclei from 27 biopsies (5 controls and 12 PCOS cases at baseline and 7 after 16 weeks of metformin and 3 after lifestyle intervention) revealed cell-type-specific disease signatures and variations in cellular composition and localization. Samples taken after 16 weeks of metformin treatment and lifestyle management showed extensive recovery of disease-specific endometrial signatures. We linked the specific role of each cell type to clinical features such as hyperandrogenism and insulin resistance, and specific cell types to risk of endometrial and metabolic disease. In addition, potential therapeutic targets such as integrin inhibitors were identified and the role of metformin in restoring endometrial health in patients with PCOS was highlighted. Our findings lay the groundwork to significantly advance the understanding of PCOS-specific endometrial dysfunction for future targeted therapies.
Supercritical Fluid‐Processed Multifunctional Hybrid Decellularized Extracellular Matrix with Chitosan Hydrogel for Improving Photoaged Dermis Microenvironment
Authors: Seol‐Ha Jeong, Jae Jun Kang, Ki‐Myo Kim, Mi hyun lee, Misun Cha, Su Hee Kim, Ji‐Ung Park
Journal: Advanced Healthcare Materials (2025)

Abstract To address the demand for reconstructive procedures in extensive subcutaneous tissue defects and significant dermis matrix loss, vascularized adipose tissue regeneration is essential for maintaining volume after material degradation. Accordingly, a double‐crosslinked hydrogel that combines polyethylene glycol (PEG)‐crosslinked carboxymethyl chitosan (CMC) with a hybrid decellularized extracellular matrix (dECM) is developed. The dECM, sourced from porcine adipose and cardiac tissues, processed using a supercritical fluid technique (scCO 2 ‐EtOH) retains 1.5–5‐fold more angiogenic and adipogenic cytokines than that processed using traditional methods. This hybrid dECM‐based filler demonstrates excellent physical properties and injectability, with injection forces being significantly less than that for crosslinked hyaluronic acid (HA) fillers. Upon incubation at 37 °C, the storage modulus of the fillers increases substantially, eventually enhancing their moldability from additional crosslinking and the thermosensitive nature of collagen. Assessments in a UVB‐induced photoaging mouse model indicate that the material maintains superior shape stability, durability, and supports vascularized tissue regeneration, reduces inflammation, and enhances VEGF expression and ECM maturation more effectively compared with that using other fillers. These promising results suggest that the material can serve as a highly effective multifunctional solution for injectable regenerative medical applications and is well‐suited for potential clinical trials.
Cas12a-knock-in mice for multiplexed genome editing, disease modelling and immune-cell engineering
Authors: Kaiyuan Tang, Liqun Zhou, Xiaolong Tian, Shao-Yu Fang, Erica Vandenbulcke, Andrew Du, Johanna Shen, Hanbing Cao, Jerry Zhou, Krista Chen, Hyunu R. Kim, Zhicheng Luo, Shan Xin, Shawn H. Lin, Daniel Park, Luojia Yang, Yueqi Zhang, Kazushi Suzuki, Medha Majety, Xinyu Ling, Stanley Z. Lam, Ryan D. Chow, Ping Ren, Bo Tao, Keyi Li, Adan Codina, Xiaoyun Dai, Xingbo Shang, Suxia Bai, Timothy Nottoli, Andre Levchenko, Carmen J. Booth, Chen Liu, Rong Fan, Matthew B. Dong, Xiaoyu Zhou, Sidi Chen
Journal: Nature Biomedical Engineering (2025)

The pleiotropic effects of human disease and the complex nature of gene-interaction networks require knock-in mice allowing for multiplexed gene perturbations. Here we describe a series of knock-in mice with a C57BL/6 background and with the conditional or constitutive expression of LbCas12a or of high-fidelity enhanced AsCas12a, which were inserted at the Rosa26 locus. The constitutive expression of Cas12a in the mice did not lead to discernible pathology and enabled efficient multiplexed genome engineering. We used the mice for the retrovirus-based immune-cell engineering of CD4+ and CD8+ T cells, B cells and bone-marrow-derived dendritic cells, for autochthonous cancer modelling through the delivery of multiple CRISPR RNAs as a single array using adeno-associated viruses, and for the targeted genome editing of liver tissue using lipid nanoparticles. We also describe a system for simultaneous dual-gene activation and knockout (DAKO). The Cas12a-knock-in mice and the viral and non-viral delivery vehicles provide a versatile toolkit for ex vivo and in vivo applications in genome editing, disease modelling and immune-cell engineering, and for the deconvolution of complex gene interactions. Knock-in mice conditionally or constitutively expressing Cas12 variants enable a wide range of ex vivo and in vivo applications requiring multiplexed genome engineering.
A Novel pH‐Responsive Baicalein@Chitosan Hydrogel for the Topical Treatment of Herpes Simplex Virus Type 1 Skin Infections: Therapeutic Potential and Mechanisms
Authors: Yuhui Lu, Liying Zhou, Alu Ouyang, Xin Wang, Xiaoyang Wei, Shangping Xing, Feifei Nong, Jinquan Lin, Haotong Wang, Yuan Li, Jie Deng, Yilu Bao, Jie Yang, Ronghua Jin, Zhuo Luo
Journal: Advanced Healthcare Materials (2025)

Abstract Herpes simplex virus type 1 (HSV‐1) is a prevalent human pathogen primarily transmitted through skin‐to‐skin contact. Traditional antiviral drugs like acyclovir (ACV) have limitations due to viral resistance and side effects, necessitating the development of alternative therapeutic strategies. Drug‐loaded hydrogels have emerged as a promising approach for managing various skin infections. Considering the low‐pH microenvironment following HSV‐1 infection, a pH‐responsive baicalein@chitosan (B@C) hydrogel is developed for the topical treatment of HSV‐1 skin infections. This hydrogel is synthesized by incorporating baicalein, a natural flavonoid, into a chitosan matrix modified with 4‐formylphenylboronic acid and protocatechualdehyde to achieve potent anti‐HSV‐1 activity and pH‐responsiveness. In vitro results demonstrated the hydrogel's pH‐dependent inhibitory effect on HSV‐1 infections, including ACV‐resistant strains. Subsequent investigations confirmed its efficacy in multiple murine infection models. Mechanistically, the B@C hydrogel inhibited viral replication by modulating the phosphorylation of inhibitor of nuclear factor kappa‐B kinase subunit beta, promoted collagen synthesis, and decreased reactive oxygen species generation. Ultra‐high‐performance liquid chromatography‐tandem mass spectrometry analysis revealed a sustained release of baicalein from the hydrogel, ensuring long‐term drug retention in HSV‐1‐infected skin tissues. Collectively, these findings suggest that the B@C hydrogel holds significant potential for the therapeutic management of HSV‐1 skin infections.