tbuckley/cabot-search huggingface dataset:
Genomic analysis of Brucella isolates from animals and humans, Türkiye, 2010 to 2020
Authors: Kadir Akar, Hanka Brangsch, Tariq Jamil, Gülseren Yıldız Öz, Emin Ayhan Baklan, Buket Eroğlu, Eray Atıl, Sevil Erdenlig Gürbilek, Oktay Keskin, Osman Yaşar Tel, Ayfer Güllü Yücetepe, Vassilios Sandalakis, Evridiki Boukouvala, Anna Psaroulaki, Ashraf A Abd El Tawab, Falk Melzer, Mathias W Pletz, Heinrich Neubauer, Gamal Wareth
Journal: Eurosurveillance (2024)

Background Brucellosis is a bacterial zoonosis causing severe illness in humans and animals and leading to economic losses in the livestock production in Türkiye and other endemic countries. Aim We aimed at investigating genomic differences of Brucella isolates from animals and humans in Türkiye. Methods We used whole genome sequencing (WGS) to assess the genetic diversity of Brucella isolates from 41 provinces in Türkiye and compared with isolates from other countries. We applied allele-based typing and core genome single nucleotide polymorphism (cgSNP) determination. Results Of the 106 Turkish Brucella isolates included, 57 were B. abortus and 49 were B. melitensis . One B. melitensis and two B. abortus isolates were identified as vaccine strains. Most (n = 55) B. abortus isolates clustered in three major branches, with no spatial discernible pattern. Of the B. melitensis isolates , 48 were assigned to the Eastern Mediterranean lineage with no discernible patterns between host species, location and sampling date. The Turkish isolates clustered with isolates from neighbouring countries such as Greece and Syria, but some also with isolates from human patients in European countries, like Germany, Norway and Sweden, suggesting that the source may be travel-related. Conclusion Several B. melitensis and B. abortus lineages are circulating in Türkiye. To decrease the prevalence and prevent brucellosis in animals and humans, stricter control measures are needed, particularly in areas where humans and animals have close contact. Furthermore, illegal transportation of animals across borders should be more closely controlled and regulated.
Co-circulation of monkeypox virus subclades Ia and Ib in Kinshasa Province, Democratic Republic of the Congo, July to August 2024
Authors: Tony Wawina-Bokalanga, Prince Akil-Bandali, Eddy Kinganda-Lusamaki, Emmanuel Lokilo, Daan Jansen, Adrienne Amuri-Aziza, Jean-Claude Makangara-Cigolo, Elisabeth Pukuta-Simbu, Rilia Ola-Mpumbe, Mamito Muyembe, Cris Kacita, Princesse Paku-Tshambu, Pedro HLF Dantas, Olivier Tshiani-Mbaya, Gradi Luakanda, Antoine Nkuba-Ndaye, Meris Matondo, Emmanuel Hasivirwe Vakaniaki, Sofonias Tessema, Nicaise Ndembi, Áine O’Toole, Tessa De Block, Christian Ngandu, Nicole A Hoff, Nicola Low, Lorenzo Subissi, Sydney Merritt, Jean-Jacques Muyembe-Tamfum, Laurens Liesenborghs, Martine Peeters, Eric Delaporte, Jason Kindrachuk, Anne W Rimoin, Steve Ahuka-Mundeke, Andrew Rambaut, Dieudonné Mwamba, Koen Vercauteren, Placide Mbala-Kingebeni
Journal: Eurosurveillance (2024)

Between January and August 2024, mpox cases have been reported in nearly all provinces of the Democratic Republic of the Congo (DRC). Monkeypox virus genome sequences were obtained from 11 mpox cases’ samples, collected in July–August 2024 in several health zones of Kinshasa. Characterisation of the sequences showed subclades Ia and Ib co-circulating in the Limete health zone, while phylogenetic analyses suggested multiple introductions of the two subclades in Kinshasa. This illustrates the growing complexity of Clade I mpox outbreaks in DRC.
Oral HIV pre-exposure prophylaxis use and resistance-associated mutations among men who have sex with men and transgender persons newly diagnosed with HIV in the Netherlands: results from the ATHENA cohort, 2018 to 2022
Authors: Vita W Jongen, Daniela Bezemer, Ard van Sighem, Anders Boyd, Casper Rokx, Karin Grintjes, Aafke Cents-Bosma, Eline Op de Coul, Birgit van Benthem, Annemarie Wensing, Ferdinand WNM Wit, Marc van der Valk
Journal: Eurosurveillance (2024)

Background In the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known. Aim We assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands. Methods Data on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree. Results Data on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs. Conclusion The prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.
Orthopoxvirus-specific antibodies wane to undetectable levels 1 year after MVA-BN vaccination of at-risk individuals, the Netherlands, 2022 to 2023
Authors: Leanne PM van Leeuwen, Marc C Shamier, Babs E Verstrepen, Hannelore M Götz, Katharina S Schmitz, Najlae Akhiyate, Koen Wijnans, Susanne Bogers, Martin E van Royen, Eric CM van Gorp, Marion PG Koopmans, Rory D de Vries, Corine H GeurtsvanKessel, Luca M Zaeck
Journal: Eurosurveillance (2024)

In response to the mpox outbreak in 2022 and 2023, widespread vaccination with modified vaccinia Ankara-Bavarian Nordic (MVA-BN, also known as JYNNEOS or Imvanex) was initiated. Here, we demonstrate that orthopoxvirus-specific binding and MVA-neutralising antibodies waned to undetectable levels 1 year post vaccination in at-risk individuals who received two doses of MVA-BN administered subcutaneously with an interval of 4 weeks, without prior smallpox or mpox vaccination. Continuous surveillance is essential to understand the impact of declining antibody levels.
Mechanisms of radiation‐induced tissue damage and response
Authors: Lin Zhou, Jiaojiao Zhu, Yuhao Liu, Ping‐Kun Zhou, Yongqing Gu
Journal: MedComm (2024)

Radiation-induced tissue injury (RITI) is the most common complication in clinical tumor radiotherapy. Due to the heterogeneity in the response of different tissues to radiation (IR), radiotherapy will cause different types and degrees of RITI, which greatly limits the clinical application of radiotherapy. Efforts are continuously ongoing to elucidate the molecular mechanism of RITI and develop corresponding prevention and treatment drugs for RITI. Single-cell sequencing (Sc-seq) has emerged as a powerful tool in uncovering the molecular mechanisms of RITI and for identifying potential prevention targets by enhancing our understanding of the complex intercellular relationships, facilitating the identification of novel cell phenotypes, and allowing for the assessment of cell heterogeneity and spatiotemporal developmental trajectories. Based on a comprehensive review of the molecular mechanisms of RITI, we analyzed the molecular mechanisms and regulatory networks of different types of RITI in combination with Sc-seq and summarized the targeted intervention pathways and therapeutic drugs for RITI. Deciphering the diverse mechanisms underlying RITI can shed light on its pathogenesis and unveil new therapeutic avenues to potentially facilitate the repair or regeneration of currently irreversible RITI. Furthermore, we discuss how personalized therapeutic strategies based on Sc-seq offer clinical promise in mitigating RITI.
SCR‐7952, a highly selective MAT2A inhibitor, demonstrates synergistic antitumor activities in combination with the <i>S</i>‐adenosylmethionine‐competitive or the methylthioadenosine‐cooperative protein arginine methyltransferase 5 inhibitors in methylthioadenosine phosphorylase‐deleted tumors
Authors: Zhiyong Yu, Yi Kuang, Liting Xue, Xuan Ma, Tingting Li, Linlin Yuan, Mengying Li, Grace Xue, Zhen Li, Feng Tang, Jianxing Tang, Jinwen Shan, Weijie Wang, Renhong Tang, Feng Zhou
Journal: MedComm (2024)

The metabolic enzyme methionine adenosyltransferase 2A (MAT2A) was found to elicit synthetic lethality in methylthioadenosine phosphorylase (
Applications of plant‐derived extracellular vesicles in medicine
Authors: Yawen Zhu, Junqi Zhao, Haoran Ding, Mengdi Qiu, Lingling Xue, Dongxue Ge, Gaolin Wen, Haozhen Ren, Peng Li, Jinglin Wang
Journal: MedComm (2024)

Plant-derived extracellular vesicles (EVs) are promising therapeutic agents owing to their natural abundance, accessibility, and unique biological properties. This review provides a comprehensive exploration of the therapeutic potential of plant-derived EVs and emphasizes their anti-inflammatory, antimicrobial, and tumor-inhibitory effects. Here, we discussed the advancements in isolation and purification techniques, such as ultracentrifugation and size-exclusion chromatography, which are critical for maintaining the functional integrity of these nanovesicles. Next, we investigated the diverse administration routes of EVs and carefully weighed their respective advantages and challenges related to bioavailability and patient compliance. Moreover, we elucidated the multifaceted mechanisms of action of plant-derived EVs, including their roles in anti-inflammation, antioxidation, antitumor activity, and modulation of gut microbiota. We also discussed the impact of EVs on specific diseases such as cancer and inflammatory bowel disease, highlighting the importance of addressing current challenges related to production scalability, regulatory compliance, and immunogenicity. Finally, we proposed future research directions for optimizing EV extraction and developing targeted delivery systems. Through these efforts, we envision the seamless integration of plant-derived EVs into mainstream medicine, offering safe and potent therapeutic alternatives across various medical disciplines.
p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver
Authors: Lina Zhao, Hongfeng Yuan, Yufei Wang, Chunyu Hou, Pan Lv, Huihui Zhang, Guang Yang, Xiaodong Zhang
Journal: Theranostics (2024)

Clinically, the persistence of HBV cccDNA is the major obstacle in anti-HBV therapy. However, the underlying mechanism of HBV cccDNA is poorly understood. The transcriptional factor STAT3 is able to activate HBV replication in liver.
Knocking out USP7 attenuates cardiac fibrosis and endothelial-to-mesenchymal transition by destabilizing SMAD3 in mice with heart failure with preserved ejection fraction
Authors: Shuai Yuan, Zimu Wang, Shun Yao, Yanyan Wang, Zhonglei Xie, Jingfeng Wang, Xueting Yu, Yu Song, Xiaotong Cui, Jingmin Zhou, Junbo Ge
Journal: Theranostics (2024)

: Heart failure with preserved ejection fraction (HFpEF) is a predominant type of heart failure. Exploring new pathogenesis and identifying potential novel therapeutic targets for HFpEF is of paramount importance.
Adipocytes fuel gastric cancer omental metastasis <i>via</i> PITPNC1-mediated fatty acid metabolic reprogramming: Erratum
Authors: Yujing Tan, Kelin Lin, Yang Zhao, Qijing Wu, Dongping Chen, Jin Wang, Yanxiao Liang, Jingyu Li, Jiazhu Hu, Hao Wang, Yajing Liu, Shuyi Zhang, Wanming He, Qiong Huang, Xingbin Hu, Zhiqi Yao, Bishan Liang, Wangjun Liao, Min Shi
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.28219.].
A hierarchically acidity-unlocking nanoSTING stimulant enables cascaded STING activation for potent innate and adaptive antitumor immunity
Authors: Shunyao Zhu, Tao He, Yan Wang, Yushan Ma, Wenmei Li, Songlin Gong, Yanghui Zhu, Xiangwei Wang, Xu Xu, Qinjie Wu, Changyang Gong, Yanjie You
Journal: Theranostics (2024)

Neoadjuvant chemotherapy (NAC) has been recognized as an indispensable strategy for advanced malignancies. Nevertheless, the enhancement of overall patient survival in NAC recipients has encountered challenges due to the limited sustainability of its efficacy and the inability to prevent postoperative tumor recurrence and metastasis.
Developing an enhanced chimeric permuted intron-exon system for circular RNA therapeutics
Authors: Lei Wang, Chunbo Dong, Weibing Zhang, Xu Ma, Wei Rou, Kai Yang, Tong Cui, Shaolong Qi, Lijun Yang, Jun Xie, Guocan Yu, Lianqing Wang, Xiaoyuan Chen, Zhida Liu
Journal: Theranostics (2024)

: Circular RNA (circRNA) therapeutics hold great promise as an iteration strategy in messenger RNA (mRNA) therapeutics due to their inherent stability and durable protein translation capability. Nevertheless, the efficiency of RNA circularization remains a significant constraint, particularly in establishing large-scale manufacturing processes for producing highly purified circRNAs. Hence, it is imperative to develop a universal and more efficient RNA circularization system when considering synthetic circRNAs as therapeutic agents with prospective clinical applications.
Selenoprotein S maintains intestinal homeostasis in ulcerative colitis by inhibiting necroptosis of colonic epithelial cells through modulation of macrophage polarization
Authors: Yujie Yao, Tong Xu, Xiaojing Li, Xu Shi, Hao Wu, Ziwei Zhang, Shiwen Xu
Journal: Theranostics (2024)

Macrophage polarization plays an important role in the inflammatory regulation of ulcerative colitis (UC). In this context, necroptosis is a type of cell death that regulates intestinal inflammation, and selenoprotein S (SelS) is a selenoprotein expressed in intestinal epithelial cells and macrophages that prevents intestinal inflammation. However, the underlying mechanisms of SelS in both cell types in regulating UC inflammatory responses remain unclear. Therefore, the direct effect of SelS deficiency on necroptosis in colonic epithelial cells (CECs) was investigated. In addition, whether SelS knockdown exacerbated intestinal inflammation by modulating macrophage polarization to promote necroptosis in CECs was assessed.
ROCK inhibitor enhances mitochondrial transfer via tunneling nanotubes in retinal pigment epithelium
Authors: Jing Yuan, Fangxuan Chen, Dan Jiang, Zehua Xu, Hang Zhang, Zi-Bing Jin
Journal: Theranostics (2024)

Tunnel nanotube (TNT)-mediated mitochondrial transport is crucial for the development and maintenance of multicellular organisms. Despite numerous studies highlighting the significance of this process in both physiological and pathological contexts, knowledge of the underlying mechanisms is still limited. This research focused on the role of the ROCK inhibitor Y-27632 in modulating TNT formation and mitochondrial transport in retinal pigment epithelial (RPE) cells.
Cardiomyocyte-derived small extracellular vesicle: a new mechanism driving diabetic cardiac fibrosis and cardiomyopathy
Authors: Yu Li, Yunhui Du, Yang Liu, Xiuhuan Chen, Xinxin Li, Yanru Duan, Yanwen Qin, Huirong Liu, Xinliang Ma, Shaoping Nie, Huina Zhang
Journal: Theranostics (2024)

Diabetic cardiomyopathy is one of the major diabetic cardiovascular complications in which fibrosis plays a critical pathogenetic role. However, the precise mechanisms by which diabetes triggers cardiac fibrosis in the heart remain elusive. Small extracellular vesicles (sEVs) play an important role in the cellular communication. Nevertheless, whether and how diabetes may adversely alter sEVs-mediated cardiomyocyte-fibroblast communication, promoting diabetic cardiac fibrosis and contributing to diabetic cardiomyopathy, has not been previously investigated.
Multifunctionally disordered TiO<sub>2</sub> nanoneedles prevent periprosthetic infection and enhance osteointegration by killing bacteria and modulating the osteoimmune microenvironment
Authors: Yangmengfan Chen, Liqiang Zhou, Ming Guan, Shue Jin, Peng Tan, Xiaoxue Fu, Zongke Zhou
Journal: Theranostics (2024)

Total hip arthroplasty (THA) and total knee arthroplasty (TKA) are effective interventions for end-stage osteoarthritis; however, periprosthetic infection is a devastating complication of arthroplasty. To safely prevent periprosthetic infection and enhance osteointegration, the surface modification strategy was utilized to kill bacteria, modulate the osteoimmune microenvironment, and improve new bone formation.
Nicotinamide mononucleotide enhances fracture healing by promoting skeletal stem cell proliferation
Authors: Yitian Shi, Jiayin Peng, Mengfan Liu, Xiling Qi, Siyu Li, Qiangqiang Li, Qing Jiang, Liming Zheng, Jiankun Xu, Yun Zhao, Yifeng Zhang
Journal: Theranostics (2024)

The process of skeletal regeneration initiated by stem cells following injury, especially in fractures, is significantly impaired by aging and adverse factors. Nicotinamide mononucleotide (NMN), a critical endogenous precursor of nicotinamide adenine dinucleotide (NAD), has garnered extensive attention for its multifaceted regulatory functions in living organisms and its wide-ranging therapeutic potential. However, whether NMN contributes to trauma-induced skeletal regeneration remains unclear.
A thermosensitive, reactive oxygen species-responsive, MR409-encapsulated hydrogel ameliorates disc degeneration in rats by inhibiting the secretory autophagy pathway: Erratum
Authors: Qiangqiang Zheng, Haotian Shen, Zongrui Tong, Linxiang Cheng, Yuzi Xu, Zhiyun Feng, Shiyao Liao, Xiaojian Hu, Zongyou Pan, Zhengwei Mao, Yue Wang
Journal: Theranostics (2024)

[This corrects the article DOI: 10.7150/thno.47723.].
Ferroptosis at the nexus of metabolism and metabolic diseases
Authors: Shuangwen Li, Guixiang Zhang, Jiankun Hu, Yan Tian, Xianghui Fu
Journal: Theranostics (2024)

Ferroptosis, an iron-dependent form of regulated cell death, is emerging as a crucial regulator of human physiology and pathology. Increasing evidence showcases a reciprocal relationship between ferroptosis and dysregulated metabolism, propagating a pathogenic vicious cycle that exacerbates pathology and human diseases, particularly metabolic disorders. Consequently, there is a rapidly growing interest in developing ferroptosis-based therapeutics. Therefore, a comprehensive understanding of the intricate interplay between ferroptosis and metabolism could provide an invaluable resource for mechanistic insight and therapeutic development. In this review, we summarize the important metabolic substances and associated pathways in ferroptosis initiation and progression, outline the cascade responses of ferroptosis in disease development, overview the roles and mechanisms of ferroptosis in metabolic diseases, introduce the methods for ferroptosis detection, and discuss the therapeutic perspectives of ferroptosis, which collectively aim to illustrate a comprehensive view of ferroptosis in basic, translational, and clinical science.
Hypoxanthine is a metabolic biomarker for inducing GSDME-dependent pyroptosis of endothelial cells during ischemic stroke
Authors: Jing Ye, Xinyuan Bi, Shiyu Deng, Xianghui Wang, Ze Liu, Qian Suo, Jiao Wu, Haoran Chen, Yong Wang, Kun Qian, Rubing Shi, Jing Zhao, Guo-Yuan Yang, Jian Ye, Yaohui Tang
Journal: Theranostics (2024)

Stroke induces metabolic changes in the body, and metabolites have become potential biomarkers for stroke. However, the specific metabolites involved in stroke and the mechanisms underlying brain injury during stroke remain unclear.
Collagen type I PET/MRI enables evaluation of treatment response in pancreatic cancer in pre-clinical and first-in-human translational studies
Authors: Shadi A Esfahani, Hua Ma, Shriya Krishna, Sergey Shuvaev, Mark Sabbagh, Caitlin Deffler, Nicholas Rotile, Jonah Weigand-Whittier, Iris Y Zhou, Ciprian Catana, Onofrio A Catalano, David T Ting, Pedram Heidari, Eric Abston, Michael Lanuti, Genevieve M Boland, Priyanka Pathak, Hannah Roberts, Kenneth K Tanabe, Motaz Qadan, Carlos Fernandez-Del Castillo, Angela Shih, Aparna R Parikh, Colin D Weekes, Theodore S Hong, Peter Caravan
Journal: Theranostics (2024)

Pancreatic ductal adenocarcinoma (PDAC) is an invasive and rapidly progressive malignancy. A major challenge in patient management is the lack of a reliable imaging tool to monitor tumor response to treatment. Tumor-associated fibrosis characterized by high type I collagen is a hallmark of PDAC, and fibrosis further increases in response to neoadjuvant chemoradiotherapy (CRT). We hypothesized that molecular positron emission tomography (PET) using a type I collagen-specific imaging probe,
Enhancing photothermal therapy of tumors with image-guided thermal control of gene-expressing bacteria
Authors: Fengyi Zeng, Meng Du, Yaozhang Yang, Jinghui Fang, Yuanyuan Wang, MeeiChyn Goh, Yan Lin, Huaiyu Wang, Fei Yan, Zhiyi Chen
Journal: Theranostics (2024)

Bacteria-mediated tumor therapy has showed promising potential for cancer therapy. However, the efficacy of bacterial monotherapy treatment which can express and release therapeutic proteins in tumors has been found to be unsatisfactory. To date, synergistic therapy has emerged as a promising approach to achieve stronger therapeutic outcomes compared to bacterial monotherapy. It is a challenge to visualize these tumor-homing bacteria
Noninvasive closed-loop acoustic brain-computer interface for seizure control
Authors: Junjie Zou, Houminji Chen, Xiaoyan Chen, Zhengrong Lin, Qihang Yang, Changjun Tie, Hong Wang, Lili Niu, Yanwu Guo, Hairong Zheng
Journal: Theranostics (2024)

The brain-computer interface (BCI) is core tasks in comprehensively understanding the brain, and is one of the most significant challenges in neuroscience. The development of novel non-invasive neuromodulation technique will drive major innovations and breakthroughs in the field of BCI.
Subarachnoid hemorrhage distinctively disrupts the glymphatic and meningeal lymphatic system in beagles
Authors: Jiaqi Wang, Tao Lv, Feng Jia, Yang Li, Weiwei Ma, Zhi-Peng Xiao, Weifeng Yu, Heng Zhao, Xiaohua Zhang, Qin Hu
Journal: Theranostics (2024)

Subarachnoid hemorrhage (SAH) induced acute impairment of the glymphatic system, but few have investigated the dysfunction of the meningeal lymphatic system and their contribution to the pathophysiology of SAH. In addition, most studies were conducted in rodent animals. We aimed to investigate the impact of SAH on glymphatic and meningeal lymphatic function in a large animal model using beagles and to evaluate the effects of intermittent cistern magna CSF drainage on these systems.
Air bag-embedded MIL-101(Fe) metal-organic frameworks for an amplified tumor microenvironment activation loop through strategic delivery of iron ions and lentinan
Authors: Tao Han, Yan Sun, Xi Jiang, Chengming Gong, Fei Kong, Yi Luo, Chang Ge, Congyan Liu, Yuping Liu, Yanfei Mou, Huangqin Zhang, Jianming Ju, Yan Chen, Ding Qu
Journal: Theranostics (2024)

Iron-based nanocarriers have demonstrated potential in redirecting tumor associated macrophages (TAMs) polarization towards the M1 phenotype, critical for activating the tumor microenvironment (TME) in triple negative breast cancer (TNBC). However, their real-world effectiveness is curtailed by insufficient Fe
Hepatocyte-specific Smad4 deficiency inhibits hepatocarcinogenesis by promoting CXCL10/CXCR3-dependent CD8<sup>+</sup>- T cell-mediated anti-tumor immunity
Authors: Xin Xin, Zhao Li, Xuanxuan Yan, Ting Liu, Zuyin Li, Zhuomiaoyu Chen, Xinlong Yan, Fanxin Zeng, Lingling Hou, Jinhua Zhang
Journal: Theranostics (2024)

Sma mothers against decapentaplegic homologue 4 (Smad4) is a key mediator of the transforming growth factor β (TGF-β) pathway and plays complex and contradictory roles in hepatocellular carcinoma (HCC). However, the specific role of Smad4 in hepatocytes in regulating hepatocarcinogenesis remains poorly elucidated.