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Proteomic Stratification of Prognosis and Treatment Options for Small Cell Lung Cancer

GENOMICS PROTEOMICS & BIOINFORMATICS 2024年第2期22卷 qzae033页

作者： Huo, Zitian Duan, Yaqi Zhan, Dongdong Xu, Xizhen Zheng, Nairen Cai, Jing Sun, Ruifang Wang, Jianping Cheng, Fang Gao, Zhan Xu, Caixia Liu, Wanlin Dong, Yuting Ma, Sailong Zhang, Qian Zheng, Yiyun Lou, Liping Kuang, Dong Chu, Qian Qin, Jun Wang, Guoping Wang, Yi Huazhong Univ Sci & Technol Tongji Hosp Inst Pathol Tongji Med Coll Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Sch Basic Med Dept Pathol Wuhan 430030 Peoples R China Huazhong Univ Sci & Technol Tongji Med Coll Tongji Hosp Natl Hlth CommissKey Lab Resp Dis Wuhan 430030 Peoples R China Beijing Pineal Diagnost Co Ltd Beijing 102206 Peoples R China Beijing Inst Life Beijing Proteome Res Ctr Natl Ctr Prot Sci Beijing State Key Lab Prote Beijing 102206 Peoples R China Huazhong Univ Sci & Technol Tongji Hosp Tongji Med Coll Dept Oncol Wuhan 430030 Peoples R China Chongqing Univ Posts & Telecommun Sch Bioinformat Chongqing Key Lab Big Data Bio Intelligence Chongqing 400065 Peoples R China Henan Univ Affiliated Hosp 1 Inst Pathol Kaifeng 475001 Peoples R China Shanxi Canc hosp Dept Tumor Biobank Taiyuan 030013 Peoples R China

Small cell lung cancer (SCLC) is a highly malignant and heterogeneous cancer with limited therapeutic options and prognosis prediction models. Here, we analyzed formalin-fixed, paraffin-embedded (FFPE) samples of surgical resections by proteomic profiling, and stratified SCLC into three proteomic subtypes (S-I, S-II, and S-III) with distinct clinical outcomes and chemotherapy responses. The proteomic subtyping was an independent prognostic factor and performed better than current tumor-node-metastasis or Veterans Administration Lung Study Group staging methods. The subtyping results could be further validated using FFPE biopsy samples from an independent cohort, extending the analysis to both surgical and biopsy samples. The signatures of the S-II subtype in particular suggested potential benefits from immunotherapy. Differentially overexpressed proteins in S-III, the worst prognostic subtype, allowed us to nominate potential therapeutic targets, indicating that patient selection may bring new hope for previously failed clinical trials. Finally, analysis of an independent cohort of SCLC patients who had received immunotherapy validated the prediction that the S-II patients had better progression-free survival and overall survival after first-line immunotherapy. Collectively, our study provides the rationale for future clinical investigations to validate the current findings for more accurate prognosis prediction and precise treatments.

关键词： Small cell lung cancer Proteomics Prognosis Chemotherapy response Immunotherapy DOMAIN-LIKE PROTEIN PROTEOGENOMIC CHARACTERIZATION PRIMARY TUMOR EXPRESSION NECROPTOSIS LINES IDENTIFICATION ESTABLISHMENT CHEMOTHERAPY BIOMARKER

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ABHD17C represses apoptosis and pyroptosis in hepatocellular carcinoma cells

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BIOCELL 2024年第9期48卷 1299-1310页

作者： Wang, Linpei Wang, Jiawei Shi, Chunfeng Wang, Wei Wu, Jian Zhejiang Univ Affiliated Hosp 1 Sch Med Dept SurgDiv Hepatobiliary & Pancreat Surg Hangzhou 310030 Peoples R China Fujian Med Univ Affiliated Hosp 2 Dept Hepatobiliary & Pancreat Surg Quanzhou 362000 Peoples R China

Background: Alpha/beta hydrolase domain-containing protein 17C (ABHD17C) is a depalmitoylation enzyme that removes the S-palmitoylation of targeted proteins. The hepatocellular carcinoma (HCC) cells SNU449 and Hep3B use ABHD17C as an oncogene; however, the exact mechanism of this action is yet unknown. Methods: The expression of ABHD17C in liver cancer tissues was analyzed by bioinformatics, and the expression of ABHD17C in clinical liver cancer tissues and adjacent normal tissues was detected. Then, the proliferative viability of HCC cells after overexpression or knockdown of ABHD17C was examined, and pyroptosis and apoptosis proteins were detected. Results: ABHD17C was overexpressed in human HCC tissues as well as numerous HCC cell lines. Depletion of ABHD17C caused reduced viability, cell cycle arrest, and defective invasion and migration in HCC cells, while overexpression of ABHD17C exhibited the opposite effect. Moreover, we discovered that the knockdown of ABHD17C resulted in enhanced apoptotic and pyroptotic phenotypes of HCC cells, whereas overexpression of ABHD17C attenuated such phenotypes. Conclusions: It suggests that ABHD17C contributes to HCC carcinogenesis, making it a promising target for medication treatment.

关键词： ABHD17C Hepatocellular carcinoma Apoptosis Pyroptosis RAS PATHWAY DISEASE

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World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis recommendation summaries

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 179-188页

作者： Du, Shi-hao Liu, Jing Chen, Sheng Wang, Shan-ze Wang, Guan-qun Du, Shuo Xie, Xiao-long Peng, Bi-hui Guo, Wei Yang, Chao Zhao, Ji-ping Beijing Univ Chinese Med Dongzhimen Hosp Dept Acupuncture & Moxibust Beijing 100700 Peoples R China China Acad Chinese Med Sci Inst Acupuncture & Moxibust Beijing 100700 Peoples R China Guangdong Prov hosp Tradit Chinese Med Dept Acupuncture & Moxibust Guangzhou 510120 Peoples R China Shanghai Jiao Tong Univ Sch Med Shanghai Peoples Hosp 9 Dept Tradit Chinese Med Shanghai 200011 Peoples R China

Clinical Practice Guideline on Acupuncture and Moxibustion: Allergic Rhinitis was revised and released by the Standards Working Committee of World Federation of Acupuncture-Moxibustion Societies (WFAS) on October 9, 2023. This is the first clinical practice guideline (CPG) on acupuncture and moxibustion for allergic rhinitis approved by an international academic organization, which provides evidence-based recommendations and the practical therapeutic protocols for acupuncture practitioners globally. This CPG was developed by following Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, and the principles of the World Health Organization Handbook for Guideline Development . The members in the guideline development group (GDG) were from different countries, with different professions, and they played a critical role in the development of clinical questions, recommendations, and therapeutic protocols. Recommendations are the core of a CPG and the direct answers to clinical questions, due to which this article focuses on the recommendations of this CPG. The recommendations were developed by using the modified Delphi method and the GRADE grid rules, based on the updated systematic reviews of clinical evidence. A total of 15 recommendations for 15 clinical questions were developed in this CPG, including one strong recommendation for intervention based on high-quality evidence, three conditional recommendations for either the intervention or the comparison based on very low quality of evidence, and 11 conditional recommendations for the intervention based on very low quality of evidence. (c) 2024 World Journal of Acupuncture - Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Allergic rhinitis Acupuncture Moxibustion Clinical practice guideline (CPG) Clinical questions COST-EFFECTIVENESS CONTROLLED-TRIAL MANAGEMENT CONSENSUS SYMPTOMS MEDICINE STRENGTH QUALITY

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Elevated levels of KLF12 impair trophoblast syncytialization via GCM1 downregulation

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REPRODUCTIVE AND DEVELOPMENTAL MEDICINE 2024年第3期8卷 131-137页

作者： Shi, Qing-Qing Wu, Xing Kang, Nan-Nan Zhou, Ji-Dong Zhen, Xin Li, Ze-Wu Yan, Gui-Jun Sun, Hai-Xiang Liu, Jing-Yu Liu, Yang Nanjing Med Univ Nanjing Drum Tower Hosp Reprod Med Ctr Clin Coll Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Ctr Reprod Med & Obstet & Gynecol Med Sch Nanjing Peoples R China Nanjing Univ Ctr Mol Reprod Med Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Med Sch Dept Obstet & Gynecol Nanjing 210000 Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Reprod Med Ctr State Key Lab Pharmaceut Biotechnol Nanjing 210000 Peoples R China Jining Med Univ Affiliated Hosp Ctr Reprod Med Jining 272000 Peoples R China

Objective: Placental dysfunction is a major contributor to miscarriages in humans. We observed elevated expression of Kruppel-like factor 12 (KLF12) in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies. This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy. Methods: To investigate the role of KLF12 in placentation, we employed a model of forskolin-induced syncytialization in BeWo cells. Results: Our findings revealed that KLF12 expression is downregulated during normal syncytialization. Conversely, we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1 (GCM1) expression. This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization. Furthermore, we observed placental deformities in KLF12-overexpressing mouse fetuses. Conclusion(s): This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression. These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.

关键词： KLF12 GCM1 Syncytialization Miscarriage PLACENTAL DEVELOPMENT MISCARRIAGE DEFECTS

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Mitochondrial metabolism blockade nanoadjuvant reversed immune-resistance microenvironment to sensitize albumin-bound paclitaxel-based chemo-immunotherapy

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 4087-4101页

作者： Zhou, Zaigang Luo, Wenjuan Zheng, Chunjuan Wang, Haoxiang Hu, Rui Deng, Hui Shen, Jianliang Wenzhou Med Univ Eye Hosp Natl Engn Res Ctr Ophthalmol & Optometry Wenzhou 325027 Peoples R China Univ Chinese Acad Sci Wenzhou Inst Zhejiang Engn Res Ctr Tissue Repair Mat Wenzhou 325001 Peoples R China Wenzhou Med Univ Sch & Hosp Stomatol Wenzhou 325027 Peoples R China Wenzhou Med Univ Dept Affiliated Hosp 2 Wenzhou 325000 Peoples R China

Currently, the efficacy of albumin-bound paclitaxel (PTX@Alb) is still limited due to the impaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution. Meanwhile, acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1 (PD-L1) expression after PTX@Alb treatment, which then leads to immune tolerance. To fill these gaps, we newly revealed that tamoxifen (TAM), a clinically widely used adjuvant therapy for breast cancer with mitochondrial metabolism blockade capacity, could also be used as a novel effective PD-L1 and TGF-beta dual-inhibitor via inducing the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) protein. Following this, to obtain a more significant effect, TPP-TAM was prepared by conjugating mitochondria-targeted triphenylphosphine (TPP) with TAM, which then further self-assembled with albumin (Alb) to form TPP-TAM@Alb nanoparticles. By doing this, TPP-TAM@Alb nanoparticles effectively decreased the expression of collagen in vitro, which then led to the enhanced accumulation of PTX@Alb in 4T1 tumors. Besides, TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-beta in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cell infiltration. All in all, we newly put forward a novel mitochondrial metabolism blockade strategy to inhibit PTX@Alb-resistant tumors, further supporting its better clinical application. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： Chemo-immunotherapy Collagen Transforming growth factor-beta Mitochondrial metabolism Programmed cell death-ligand 1 Drug accumulation Albumin-bound paclitaxel Immune-resistance microenvironment BREAST-CANCER TAMOXIFEN NANOPARTICLES PENETRATION EFFICACY

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Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification

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FRONTIERS OF MEDICINE 2024年第4期18卷 735-743页

作者： Fu, Rui Xiong, Yuanyuan Cai, Miao Li, Fang Chen, Rongrong Wu, Yilong Zhong, Wenzhao South China Univ Technol Sch Med Guangzhou 510006 Peoples R China South China Univ Technol Guangdong Acad Med Sci Guangdong Prov Peoples Hosp Guangdong Lung Canc InstGuangdong Prov Key Lab Tr Guangzhou 510080 Peoples R China Geneplus-Beijing Beijing 102206 Peoples R China

Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes.

关键词： ctDNA molecular residual disease operable NSCLC gene fusion MET exon skipping MET amplification MUTATIONS CTDNA

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Multi-rater Prism: Learning self-calibrated medical image segmentation from multiple raters

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SCIENCE BULLETIN 2024年第18期69卷 2906-2919页

作者： Wu, Junde Fang, Huihui Zhu, Jiayuan Zhang, Yu Li, Xiang Liu, Yuanpei Liu, Huiying Jin, Yueming Huang, Weimin Liu, Qi Chen, Cen Liu, Yanfei Duan, Lixin Xu, Yanwu Xiao, Li Yang, Weihua Liu, Yue South China Univ Technol Sch Future Technol Guangzhou 511442 Peoples R China Pazhou Lab Guangzhou 510320 Peoples R China Univ Oxford Oxford OX1 4AL England China Acad Chinese Med Sci Xiyuan Hosp Cardiovasc Dis Ctr Beijing 100091 Peoples R China Natl Univ Def Technol Coll Elect Engn State Key Lab Pulsed Power Laser Technol Hefei 230037 Peoples R China Univ Elect Sci & Technol China Shenzhen Inst Adv Study Shenzhen 518110 Peoples R China Univ Elect Sci & Technol China Sichuan Prov Peoples Hosp Chengdu 611731 Peoples R China Univ Hong Kong Hong Kong 999077 Peoples R China ASTAR Inst Infocomm Res Singapore 138632 Singapore Natl Univ Singapore Singapore 119276 Singapore Jinan Univ Shenzhen Eye Hosp Shenzhen 518040 Peoples R China

In medical image segmentation, it is often necessary to collect opinions from multiple experts to make the final decision. This clinical routine helps to mitigate individual bias. However, when data is annotated by multiple experts, standard deep learning models are often not applicable. In this paper, we propose a novel neural network framework called Multi-rater Prism (MrPrism) to learn medical image segmentation from multiple labels. Inspired by iterative half-quadratic optimization, MrPrism combines the task of assigning multi-rater confidences and calibrated segmentation in a recurrent manner. During this process, MrPrism learns inter-observer variability while taking into account the image's semantic properties and finally converges to a self-calibrated segmentation result reflecting inter-observer agreement. Specifically, we propose Converging Prism (ConP) and Diverging Prism (DivP) to iteratively process the two tasks. ConP learns calibrated segmentation based on multi-rater confidence maps estimated by DivP, and DivP generates multi-rater confidence maps based on segmentation masks estimated by ConP. Experimental results show that the two tasks can mutually improve each other through this recurrent process. The final converged segmentation result of MrPrism outperforms state-of-the-art (SOTA) methods for a wide range of medical image segmentation tasks. The code is available at https://***/WuJunde/MrPrism. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. This is an open access article under the CC BY license (http://***/licenses/by/4.0/).

关键词： Medical image segmentation Multiple raters Self-calibration Half-quadratic algorithm PERFORMANCE

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Flexible polydimethylsiloxane pressure sensor with micro-pyramid structures and embedded silver nanowires: A novel application in urinary flow measurement

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NANOTECHNOLOGY AND PRECISION ENGINEERING 2024年第3期7卷 1-12页

作者： Wang, Ben-Song Gao, Ang Huang, Song-Wei Ning, Qi-Hong Zhou, Cheng Song, Qi-Xiang Cui, Da-Xiang Shanghai Jiao Tong Univ Sch Elect Informat & Elect Engn Shanghai 200240 Peoples R China Shanghai Jiao Tong Univ Renji Hosp Sch Med Dept Urol Shanghai 200240 Peoples R China

Flexible pressure sensors are lightweight and highly sensitive, making them suitable for use in small portable devices to achieve precise measurements of tiny forces. This article introduces a low-cost and easy-fabrication strategy for piezoresistive flexible pressure sensors. By embedding silver nanowires into a polydimethylsiloxane layer with micro-pyramids on its surface, a flexible pressure sensor is created that can detect low pressure (17.3 Pa) with fast response (<20 ms) and high sensitivity (69.6 mA kPa(-1)). Furthermore, the pressure sensor exhibits a sensitive and stable response to a small amount of water flowing on its surface. On this basis, the flexible pressure sensor is innovatively combined with a micro-rotor to fabricate a novel urinary flow-rate meter (uroflowmeter), and results from a simulated human urination experiment show that the uroflowmeter accurately captured all the essential shape characteristics that were present in the pump-simulated urination curves. Looking ahead, this research provides a new reference for using flexible pressure sensors in urinary flow-rate monitoring.

关键词： Flexible pressure sensor Silver nanowires Portable device Uroflowmeter Healthcare HIGH-PERFORMANCE UROFLOWMETRY SYMPTOMS

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World Federation of Acupuncture-Moxibustion Societies Clinical Practice Guideline on Acupuncture-Moxibustion: Non-Specific Low Back Pain recommendation summaries

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WORLD JOURNAL OF ACUPUNCTURE-MOXIBUSTION 2024年第3期34卷 213-221页

作者： Liu, Xiao-xu Guo, Ying-ying Fei, Yu-tong Huang, Man Ye, Yong-ming Yu, Jin-na Lin, Hui-ze Yan, Wen-xi Liu, Lan-ping Zhu, Ke-xin Liang, Jun Yang, Tao China Acad Chinese Med Sci Guanganmen Hosp Dept Acupuncture & Moxibust Beijing 100053 Peoples R China Beijing Univ Chinese Med Ctr Evidence Based Med Beijing 100029 Peoples R China China Acad Chinese Med Sci Guanganmen Hosp Beijing 100053 Peoples R China

Clinical Practice Guideline on Acupuncture and Moxibustion: Nonspecific low back pain was revised and released by the Standards Working Committee of World Federation of Acupuncture-Moxibustion Societies (WFAS) on October 9, 2023. This is the first clinical practice guideline (CPG) on acupuncture and moxibustion for nonspecific low back pain approved by an international academic organization, which provides the evidence-based recommendations and practical therapeutic protocols for international acupuncture practitioners. This CPG was developed by following Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology, and the Principles of the World Health Organization Handbook for Guideline Development . The guideline development group (GDG) from different countries, with different professions, played a critical role in the formulation of clinical questions, recommendations, and therapeutic protocols. Recommendations are the key content of a CPG and the direct answers to clinical questions. Hence, this article focuses on the recommendations of this CPG. The recommendations were formulated using the modified Delphi method and the GRADE grid rules, based on the updated systematic reviews of clinical evidence. A total of seven recommendations for ten clinical questions were formulated in this CPG, including one conditional recommendation for either the intervention or the comparison based on very low quality of evidence, and six conditional recommendations for the intervention based on very low quality of evidence. (c) 2024 World Journal of Acupuncture - Moxibustion House. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license ( http://***/licenses/by-nc-nd/4.0/ )

关键词： Nonspecific low back pain Acupuncture Moxibustion Clinical practice guideline Recommendations

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Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3983-4000页

作者： Li, Ru Wei, Riqing Liu, Chenxin Zhang, Keying He, Sixiao Liu, Zhifeng Huang, Junhao Tang, Youyong An, Qiyuan Lin, Ligen Gan, Lishe Zhao, Liying Zou, Xiaoming Wang, Fudi Ping, Yuan Ma, Qiang Southern Med Univ Affiliated Hosp 7 Foshan 528244 Peoples R China Southern Med Univ Sch Lab Med & Biotechnol Dept Biopharmaceut Guangzhou 510000 Peoples R China Southern Med Univ Sch Lab Med & Biotechnol Guangdong Prov Key Lab Immune Regulat & Immunother Guangzhou 510000 Peoples R China Gen hosp Southern Theatre Command PLA Med Crit Care Med Guangzhou 510000 Peoples R China Chinese peoples Liberat Army Gen hosp Natl Clin Res Ctr Geriatr Dis Guangdong Branch Ctr Guangzhou 510000 Peoples R China University Macao Inst Chinese Med Sci State Key Lab Qual Res Chinese Med Ave Univ Macau 999078 Peoples R China Zhejiang Chinese Med Univ Sch Pharmaceut Sci Hangzhou 311402 Peoples R China Southern Med Univ Nanfang Hosp Sch Clin Med 1 Dept Gen Surg Guangzhou 510000 Peoples R China Zhejiang Univ Affiliated Hosp 4 Affiliated Hosp 1 Inst Translat MedSch MedSch Publ HlthState Key Hangzhou 310000 Peoples R China Univ South China Affiliated Hosp 1 Affiliated Hosp 2 Hengyang Med SchSch Publ HlthBasic Med Sci Hengyang 421200 Peoples R China Zhejiang Univ Coll Pharmaceut Sci Hangzhou 310000 Peoples R China Zhejiang Univ Med Ctr Liangzhu Lab Hangzhou 310000 Peoples R China

With the escalating prevalence of global heat waves, heat stroke has become a prominent health concern, leading to substantial liver damage. Unlike other forms of liver injury, heat stroke-induced damage is characterized by heat cytotoxicity and heightened inflammation, directly contributing to elevated mortality rates. While clinical assessments have identified elevated bilirubin levels as indicative of Kupffer cell dysfunction, their specific correlation with heat stroke liver injury remains unclear. Our hypothesis proposes the involvement of Kupffer cell ferroptosis during heat stroke, initiating IL-1,beta-mediated inflammation. Using single-cell RNA sequencing of murine macrophages, a distinct and highly susceptible Kupffer cell subtype, Clec4F(+)/CD206(+), emerged, with heme oxygenase 1 (HMOX-1) playing a pivotal role. Mechanistically, heat-induced HMOX-1, regulated by early growth response factor 1, mediated ferroptosis in Kupffer cells, specifically in the Clec4F(+)/CD206(+) subtype (KC2), activating phosphatidylinositol 4-kinase beta and promoting PI4P production. This cascade triggered NLRP3 inflammasome activation and maturation of IL-1,beta. These findings underscore the critical role of targeted therapy against HMOX-1 in ferroptosis within Kupffer cells, particularly in Clec4F(+)/CD206(+) KCs. Such an approach has the potential to mitigate inflammation and alleviate acute liver injury in the context of heat stroke, offering a promising avenue for future therapeutic interventions. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Chinese Pharmaceutical Association andInstitute of Materia Medica, Chinese Academy of Medical Sciences.

关键词： Heat stroke Liver injury Kupffer cells Ferroptosis Heme oxygenase 1 Phosphatidylinositol 4-kinase beta NLRP3 Early growth response factor 1 NLRP3 INFLAMMASOME PROTECTIVE ROLE MACROPHAGES EXPRESSION HO-1 ACTIVATION IL-1-BETA DEATH SUSCEPTIBILITY PYROPTOSIS

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