tbuckley/cabot-search huggingface dataset:
The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk
Authors: Shuyu Li, Ke Wang, Jingni Wu, Yongliang Zhu
Journal: Ageing Research Reviews (2024)

Precisely assessing an individual's immune age is critical for developing targeted aging interventions. Although traditional methods for evaluating biological age, such as the use of cellular senescence markers and physiological indicators, have been widely applied, these methods inherently struggle to capture the full complexity of biological aging. We propose the concept of an 'immunosenescence clock' that evaluates immune system changes on the basis of changes in immune cell abundance and omics data (including transcriptome and proteome data), providing a complementary indicator for understanding age-related physiological transformations. Rather than claiming to definitively measure biological age, this approach can be divided into a biological age prediction clock and a mortality prediction clock. The main function of the biological age prediction clock is to reflect the physiological state through the transcriptome data of peripheral blood mononuclear cells (PBMCs), whereas the mortality prediction clock emphasizes the ability to identify people at high risk of mortality and disease. We hereby present nearly all of the immunosenescence clocks developed to date, as well as their functional differences. Critically, we explicitly acknowledge that no single diagnostic test can exhaustively capture the intricate changes associated with biological aging. Furthermore, as these biological functions are based on the acceleration or delay of immunosenescence, we also summarize the factors that accelerate immunosenescence and the methods for delaying it. A deep understanding of the regulatory mechanisms of immunosenescence can help establish more accurate immune-age models, providing support for personalized longevity interventions and improving quality of life in old age.
The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of colorectal cancer, 2024 update
Authors: Feng Wang, Gong Chen, Zhen Zhang, Ying Yuan, Yi Wang, Yuan‐Hong Gao, Weiqi Sheng, Zixian Wang, Xinxiang Li, Xianglin Yuan, Sanjun Cai, Li Ren, Yunpeng Liu, Jianmin Xu, Yanqiao Zhang, Houjie Liang, Xicheng Wang, Aiping Zhou, Jianming Ying, Guichao Li, Muyan Cai, Gang Ji, Taiyuan Li, Jingyu Wang, Hanguang Hu, Kejun Nan, Liuhong Wang, Suzhan Zhang, Jin Li, Rui‐Hua Xu
Journal: Cancer Communications (2024)

Abstract The 2024 updates of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for the diagnosis and treatment of colorectal cancer emphasize standardizing cancer treatment in China, highlighting the latest advancements in evidence‐based medicine, healthcare resource access, and precision medicine in oncology. These updates address disparities in epidemiological trends, clinicopathological characteristics, tumor biology, treatment approaches, and drug selection for colorectal cancer patients across diverse regions and backgrounds. Key revisions include adjustments to evidence levels for intensive treatment strategies, updates to regimens for deficient mismatch repair (dMMR)/ microsatellite instability‐high (MSI‐H) patients, proficient mismatch repair (pMMR)/ microsatellite stability (MSS) patients who have failed standard therapies, and rectal cancer patients with low recurrence risk. Additionally, recommendations for digital rectal examination and DNA polymerase epsilon ( POLE )/ DNA polymerase delta 1 ( POLD1 ) gene mutation testing have been strengthened. The 2024 CSCO Guidelines are based on both Chinese and international clinical research, as well as expert consensus, ensuring their relevance and applicability in clinical practice, while maintaining a commitment to scientific rigor, impartiality, and timely updates.
Potent painkiller from spider venom antagonizes P2X3 receptors without dysgeusia
Authors: Peter Oparin, Oksana Khokhlova, Aleksandr Cherkashin, Kirill Nadezhdin, Victor Palikov, Yulia Palikova, Yuliya Korolkova, Irina Mosharova, Olga Rogachevskaja, Mikhail Baranov, Ksenia Shaidullova, Elizaveta Ermakova, Vladislav Lushpa, Alexandra Bruter, Alexey Deykin, Elena Ivanova, Yulia Silaeva, Igor Dyachenko, Eduard Bocharov, Guzel Sitdikova, Alexander Andreev-Andrievskiy, Dmitry Poteryaev, Alexander Shuster, Arkady Murashev, Stanislav Kolesnikov, Vasiliy Stepanenko, Eugene Grishin, Alexander Vassilevski
Journal: Molecular Therapy (2024)
Apex1 safeguards genomic stability to ensure a cytopathic T cell fate in autoimmune disease models
Authors: Xiang Xiao, Yong Du, Si Sun, Xiaojun Su, Junji Xing, Guangchuan Wang, Steven M. Elzein, Dawei Zou, Laurie J. Minze, Zhuyun Mao, Rafik M. Ghobrial, Ashton A. Connor, Wenhao Chen, Zhiqiang Zhang, Xian C. Li
Journal: Journal of Clinical Investigation (2024)

T cells have a remarkable capacity to clonally expand, a process that is intricately linked to their effector activities. As vigorously proliferating T cell also incur substantial DNA lesions, how the dividing T cells safeguard their genomic integrity to allow the generation of T effector cells remains largely unknown. Here we report the identification of the apurinic/apyrimidinic endonuclease-1 (Apex1) as an indispensable molecule for the induction of cytopathic T effectors in mouse models. We demonstrate that conditional deletion of Apex1 in T cells results in a remarkable accumulation of baseless DNA sites in the genome of proliferating T cells, which further leads to genomic instability and apoptotic cell death. Consequently, Apex1-deleted T cells fail to acquire any effector features after activation and fail to mediate autoimmune diseases and allergic tissue damages. Detailed mutational analyses pinpoint the importance of its endonuclease domain in the generation of T effector cells. We provide further evidence that inhibiting the base repair activities of Apex1 with chemical inhibitors similarly abrogates the induction of autoimmune diseases. Collectively, our study suggests that Apex1 serves as a gatekeeper for the generation of cytopathic T cells and that therapeutically targeting Apex1 may have important clinical implications in the treatment of autoimmune diseases.
Critical Illness in an Adolescent with Influenza A(H5N1) Virus Infection
Authors: Agatha N Jassem, Ashley Roberts, John Tyson, James E A Zlosnik, Shannon L Russell, Jessica M Caleta, Eric J Eckbo, Ruimin Gao, Taeyo Chestley, Jennifer Grant, Timothy M Uyeki, Natalie A Prystajecky, Chelsea G Himsworth, Elspeth MacBain, Charlene Ranadheera, Lynne Li, Linda M N Hoang, Nathalie Bastien, David M Goldfarb
Journal: New England Journal of Medicine (2024)

Influenza A(H5N1) viruses are an emerging zoonotic threat and have spread widely throughout birds in North America. Recently, influenza A(H5N1) infection led to serious illness in a teenager in Canada.
Resistance to antibody–drug conjugates: A review
Authors: Sijia Li, Xinyu Zhao, Kai Fu, Shuangli Zhu, Can Pan, Chuan Yang, Fang Wang, Kenneth K W To, Liwu Fu
Journal: Acta Pharmaceutica Sinica B (2025)

Antibody-drug conjugates (ADCs) are antitumor drugs composed of monoclonal antibodies and cytotoxic payload covalently coupled by a linker. Currently, 15 ADCs have been clinically approved worldwide. More than 100 clinical trials at different phases are underway to investigate the newly developed ADCs. ADCs represent one of the fastest growing classes of targeted antitumor drugs in oncology drug development. It takes advantage of the specific targeting of tumor-specific antigen by antibodies to deliver cytotoxic chemotherapeutic drugs precisely to tumor cells, thereby producing promising antitumor efficacy and favorable adverse effect profiles. However, emergence of drug resistance has severely hindered the clinical efficacy of ADCs. In this review, we introduce the structure and mechanism of ADCs, describe the development of ADCs, summarized the latest research about the mechanisms of ADC resistance, discussed the strategies to overcome ADCs resistance, and predicted biomarkers for treatment response to ADC, aiming to contribute to the development of ADCs in the future.
USP25 ameliorates vascular remodeling by deubiquitinating FOXO3 and promoting autophagic degradation of FOXO3
Authors: Yanghao Chen, Bozhi Ye, Diyun Xu, Wante Lin, Zimin Fang, Xuefeng Qu, Xue Han, Wu Luo, Chen Chen, Weijian Huang, Hao Zhou, Gaojun Wu, Yi Wang, Guang Liang
Journal: Acta Pharmaceutica Sinica B (2025)

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.
Ginsenoside CK targets PHD2 to prevent platelet adhesion and enhance blood circulation by modifying the three-dimensional arrangement of collagen
Authors: Chuanjing Cheng, Kaixin Liu, Jinling Zhang, Yanqi Han, Tiejun Zhang, Yuanyuan Hou, Gang Bai
Journal: Acta Pharmaceutica Sinica B (2025)

Platelets are indispensable for physiological hemostasis and pathological thrombus formation, and platelet adhesion to endothelial collagen is a critical initial step in thrombus formation, often overlooked in current antiplatelet therapies. This study aims to elucidate how ginsenoside CK enhances hemodynamic circulation, alleviates stasis, and proposes therapeutic mechanisms. Inspired by the effects on improving microcirculatory disturbances in an acute soft tissue injury model, CK was identified as a PHD2 inhibitor, effectively suppressing platelet adhesion to collagen. It was proposed that targeting PHD2 regulates collagen hydroxylation modification, thereby influencing the formation of its three-dimensional structure, reducing the binding affinity between VWF and collagen, and ultimately suppressing thrombotic events. The efficacy of this mechanism was subsequently confirmed through a mouse DIC model, demonstrating the feasibility of CK in alleviating circulatory disorders. It is worth noting that when Phd2 was knocked down in mice's lungs, pulmonary embolism was significantly reduced. Additionally, PHD2 inhibitors approved for other diseases have exhibited similar anti-thrombotic effects. Moreover, when PHD2 inhibitors were combined with aspirin, they more effectively inhibited arterial thrombosis in rats. The findings offer valuable insights into potential targets for developing antiplatelet drugs or expanding therapeutic applications for existing PHD2 inhibitors in treating thrombotic diseases.
Construction of PVA/OHA-Gs@PTMC/PHA double-layer nanofiber flexible scaffold with antibacterial function for tension free rectal in-situ reconstruction
Authors: Bingxu Zhang, Xujian Li, Chuan Jiang, Chuanguang Wang, Haifeng Que, Cheng Zheng, Zhixiao Ji, Xudong Tao, Hongtao Xu, Changcan Shi
Journal: Biomaterials (2024)
Dendritic cells immunotargeted therapy for atherosclerosis
Authors: Zhaohui Li, Yanyan Yang, Jinbao Zong, Bei Zhang, Xiaolu Li, Hongzhao Qi, Tao Yu, Yongxin Li
Journal: Acta Pharmaceutica Sinica B (2025)

Atherosclerosis, a chronic inflammatory disease, is markedly influenced by both immune and inflammatory reactions throughout its progression. Dendritic cells, as pivotal antigen-presenting entities, play a crucial role in the initiation of immune responses and the preservation of immunological homeostasis. Accumulating data indicates that dendritic cells are present in healthy arteries and accumulate significantly in atherosclerotic plaques. Novel immunotherapeutic approaches and vaccination protocols have yielded substantial clinical advancements in managing chronic inflammatory diseases, with dendritic cell-centric modalities emerging for atherosclerotic management. In this review, we delineate the essential functions and underlying mechanisms of dendritic cells and their subsets in the modulation of atherosclerotic inflammation and immune responses. We underscore the immense promise of dendritic cell-based immunotherapeutic strategies, including vaccines and innovative combinations with nanotechnological drug delivery platforms for atherosclerosis treatment. We also discuss the challenges associated with dendritic cell immunotherapy and provide perspectives on the future direction of this field.
STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation
Authors: Chengfei Zhang, Ping Xu, Yongsheng Wang, Xin Chen, Yue Pan, Zhijie Ma, Cheng Wang, Haojun Xu, Guoren Zhou, Feng Zhu, Hongping Xia
Journal: Acta Pharmaceutica Sinica B (2025)

Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.
A retrospective cohort study of the efficacy and safety of oral azvudine versus nirmatrelvir/ritonavir in elderly hospitalized COVID-19 patients aged over 60 years
Authors: Bo Yu, Haiyu Wang, Guangming Li, Junyi Sun, Hong Luo, Mengzhao Yang, Yanyang Zhang, Ruihan Liu, Ming Cheng, Shixi Zhang, Guotao Li, Ling Wang, Guowu Qian, Donghua Zhang, Silin Li, Quancheng Kan, Jiandong Jiang, Zhigang Ren
Journal: Acta Pharmaceutica Sinica B (2025)

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.
Initial antigen encounter determines robust T-cell immunity against SARS-CoV-2 BA.2.86 variant three years later
Authors: Rocío Rubio, Alexei Yavlinsky, Marina Escalera Zamudio, Luis M Molinos-Albert, Carla Martín Pérez, Edwards Pradenas, Mar Canyelles, Cèlia Torres, Cedric Tan, Leo Swadling, Anna Ramírez-Morros, Benjamin Trinité, Josep Vidal-Alaball, Ruth Aguilar, Anna Ruiz-Comellas, Julià Blanco, Lucy van Dorp, François Balloux, Carlota Dobaño, Gemma Moncunill
Journal: Journal of Infection (2024)

We aimed to evaluate the adaptive immune responses' cross-recognition of the hypermutated SARS-CoV-2 BA.2.86 variant and identify the determinants influencing this recognition.
NRP1 instructs IL-17-producing ILC3s to drive colitis progression
Authors: Ying Wang, Jianye Wang, Gaoyu Liu, Xianfu Yi, Jingyi Wu, Hailong Cao, Lijuan Zhang, Pan Zhou, Yong Fan, Ying Yu, Qiang Liu, Zhi Yao, Haitao Wang, Jie Zhou
Journal: Cellular and Molecular Immunology (2025)
Sequential STING and CD40 agonism drives massive expansion of tumor-specific T cells in liposomal peptide vaccines
Authors: Dmitrij Ostroumov, Naomi Benne, Fernando Lozano Vigario, Oscar Escalona-Rayo, Ksenia Dodz, Sarah Sauer, Lena Luisa Suhl, Hans Heiner Wedemeyer, Florian Kühnel, Bram Slütter, Thomas Christian Wirth
Journal: Cellular and Molecular Immunology (2025)

Abstract The clinical use of cancer vaccines is hampered by the low magnitude of induced T-cell responses and the need for repetitive antigen stimulation. Here, we demonstrate that liposomal formulations with incorporated STING agonists are optimally suited to deliver peptide antigens to dendritic cells in vivo and to activate dendritic cells in secondary lymphoid organs. One week after liposomal priming, systemic administration of peptides and a costimulatory agonistic CD40 antibody enables ultrarapid expansion of T cells, resulting in massive expansion of tumor-specific T cells in the peripheral blood two weeks after priming. In the MC-38 colon cancer model, this synthetic prime-boost regimen induces rapid regression and cure of large established subcutaneous cancers via the use of a single tumor-specific neoantigen. These experiments demonstrate the feasibility of liposome-based heterologous vaccination regimens to increase the therapeutic efficacy of peptide vaccines in the context of immunogenic adjuvants and costimulatory booster immunizations. Our results provide a rationale for the further development of modern liposomal peptide vaccines for cancer therapy.
Demyelination-derived lysophosphatidylserine promotes microglial dysfunction and neuropathology in a mouse model of Alzheimer’s disease
Authors: Yubo Zhou, Zonghui Huang, Bolong Lin, Ming Ma, Yize Hao, Juanjuan Liu, Wen Xu, Guangming Huang, Wei Mo, Xiaqiong Wang, Wei Jiang, Rongbin Zhou
Journal: Cellular and Molecular Immunology (2025)
Highly Pathogenic Avian Influenza A(H5N1) Virus Infections in Humans
Authors: Shikha Garg, Katie Reinhart, Alexia Couture, Krista Kniss, C Todd Davis, Marie K Kirby, Erin L Murray, Sophie Zhu, Vit Kraushaar, Debra A Wadford, Cara Drehoff, Allison Kohnen, Mackenzie Owen, Jennifer Morse, Seth Eckel, Jessica Goswitz, George Turabelidze, Steve Krager, Anna Unutzer, Emilio R Gonzales, Cherissa Abdul Hamid, Sascha Ellington, Alexandra M Mellis, Alicia Budd, John R Barnes, Matthew Biggerstaff, Michael A Jhung, Malia Richmond-Crum, Erin Burns, Tom T Shimabukuro, Timothy M Uyeki, Vivien G Dugan, Carrie Reed, Sonja J Olsen
Journal: New England Journal of Medicine (2024)

Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States, with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States.
Corrigendum to “Drug content on anticancer efficacy of self-assembling ketal-linked dextran-paclitaxel conjugates” [Journal of Controlled Release 359 (2023) 175–187]
Authors: Tiantian Guo, Haiping Zhong, Xingwei Li, Jingqing Mu, Tao Liu, Na Yu, Yang Zhao, Xing-Jie Liang, Shutao Guo
Journal: Journal of Controlled Release (2024)
AGEING RESEARCH REVIEWS (ARR-D-24-01334R1) Metabolic dysfunction contributes to mood disorders after traumatic brain injury
Authors: Lang Liu, Peijun Jia, Tongzhou Liu, Jiaxin Liang, Yijia Dang, Yousef Rastegar-Kashkooli, Qiang Li, Jingqi Liu, Jiang Man, Ting Zhao, Na Xing, Fushun Wang, Xuemei Chen, Jiewen Zhang, Chao Jiang, Marrietta Zille, Zhenhua Zhang, Xiaochong Fan, Junmin Wang, Jian Wang
Journal: Ageing Research Reviews (2024)
Trends and cross-country inequality in the incidence of GI cancers among the working-age population from 1990 to 2021: a Global Burden of Disease 2021 analysis
Authors: Yiming Song, Xiaoyi Wang, Yufeng Shen, Liping Chen, Liuyi Yang, Ruilan Wang, Junyu Lu, Zhifang Gao, Xiaolu Lin, Yan Song, Qingwei Zhang, Xiaobo Li
Journal: Gut (2024)

GI cancers pose an increasing global health burden, with their impact on the working-age population (WAP) aged 15-64 years remaining largely unexplored despite the crucial role of this group in societal and economic well-being.
Endocrine-targeting therapies shift the breast microbiome to reduce estrogen receptor-α breast cancer risk
Authors: Alana A Arnone, Yu-Ting Tsai, J Mark Cline, Adam S Wilson, Brian Westwood, Meghan E Seger, Akiko Chiba, Marissa Howard-McNatt, Edward A Levine, Alexandra Thomas, David R Soto-Pantoja, Katherine L Cook
Journal: Cell Reports Medicine (2024)
The phospholipid kinase PIKFYVE is essential for Th17 differentiation
Authors: Douglas S. Prado, Richard T. Cattley, Andreza B. Sonego, Parth Sutariya, Shuxian Wu, Mijoon Lee, William C. Boggess, Mark J. Shlomchik, William F. Hawse
Journal: The Journal of Experimental Medicine (2024)

T helper 17 (Th17) cells are effector cells that mediate inflammatory responses to bacterial and fungal pathogens. While the cytokine signaling inputs required to generate Th17s are established, less is known about intracellular pathways that drive Th17 differentiation. Our previously published phosphoproteomic screen identifies that PIKFYVE, a lipid kinase that generates the phosphatidylinositol PtdIns(3,5)P2, is activated during Th17 differentiation. Herein, we discovered that PIKFYVE regulates kinase and transcription factor networks to promote Th17 differentiation. As a specific example, PtdIns(3,5)P2 directly stimulates mTORC1 kinase activity to promote cell division and differentiation pathways. Furthermore, PIKFYVE promotes STAT3 phosphorylation, which is required for Th17 differentiation. Chemical inhibition or CD4-specific deletion of PIKFYVE reduces Th17 differentiation and autoimmune pathology in the experimental autoimmune encephalomyelitis murine model of multiple sclerosis. Our findings identify molecular mechanisms by which PIKFYVE promotes Th17 differentiation and suggest that PIKFYVE is a potential therapeutic target in Th17-driven autoimmune diseases.