1.TGF-β1-engineered Biomimetic Platelet Nanoparticles for Targeted Therapy of Ischemic Stroke
Li-Qi CHEN ; Tian-Fang KANG ; Guo-Jun HUANG ; Ting YIN ; Ai-Qing MA ; Lin-Tao CAI ; Hong PAN
Progress in Biochemistry and Biophysics 2026;53(3):697-710
ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.
2.Guidelines for standardized implementation of pharmacist-managed clinics (2026 edition)
Pengxiang ZHOU ; Maobai LIU ; Xiaoli DU ; Xiaoyang LU ; Mei DONG ; Rong DUAN ; Ruigang HOU ; Xiaoyu LI ; Qi CHEN ; Yanxiao XIANG ; Weiyi FENG ; Rong CHEN ; Deshi DONG ; Yong YANG ; Li LI ; Xiaocong ZUO ; Jinfang HU ; Hongliang ZHANG ; Qingchun ZHAO ; Qi LIN ; Yang HU ; Jiaying WU ; Rongsheng ZHAO
China Pharmacy 2026;37(9):1105-1112
OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics ( 2026 edition ) in response to the challenges faced by such clinics in China, including uneven development, large discrepancies in service specifications, insufficient patient awareness, and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association, the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association, and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association, a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research, current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections: definition and connotation of pharmacist-managed clinics, establishment requirements, implementation and management, post competency, and practical research. Firstly, the definition and connotation included three operational forms of pharmacist-managed clinics (independent mode, physician-pharmacist joint mode, and online pharmacist-managed clinic mode) and classified service modes (specialty-specific, drug-specific, and disease-specific pharmacist-managed clinics). The establishment requirements were further refined, covering system construction (pharmaceutical service management system, quality control and assessment mechanism), personnel qualifications (professional credentials, continuing education and professional training, etc), service recipients, as well as service venues and facilities. Subsequently, the implementation and management of pharmacist-managed clinics were proposed, involving service procedures, intervention measures, documentation and records, patient education and follow-up, humanistic care, as well as risk management and quality control. Finally, post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics, as well as the suggestions on teaching methods; practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment, management, teaching, and research, fill the guideline gap in this field, and can promote the high-quality development of pharmacist-managed clinics.
3.Research on the High-Quality Development Path of Laboratory Animal Management in Jiangsu Province Empowered by Digital Transformation
Lin CHEN ; Housen ZHANG ; Man AI ; Chongyang QI
Laboratory Animal and Comparative Medicine 2026;46(3):426-436
Digital government refers to the wide application of digital technology in government management and services, promoting the optimization of government governance processes, model innovation, and performance enhancement, and building a new form of digital and intelligent government operation. Laboratory animal management is an important national foundational and strategic support work. It is closely related to digital government construction, and is not only an important part of digital government construction but also a typical application of government digital transformation in the field of science and technology. Digital transformation empowering laboratory animal management is a new proposition of government governance in the digital age, and research on its systematic and holistic reform is crucial. Through digital technologies such as artificial intelligence, big data, and cloud computing, the government can optimize approval process, strengthen in-process and post-event supervision, and promote regional coordination, thereby improving laboratory animal management capacity and service levels. In addition, laboratory animal data sharing contributes to government scientific decision-making and industry supervision. This article summarizes the experience and practices of domestic leading regions in recent years, reviews the background and development process of digital transformation of laboratory animal management in Jiangsu Province, describes the current status of such digital transformation in Jiangsu Province across areas including digital infrastructure, data sharing, and government services, analyzes existing challenges in top-level design, data governance, and data sharing, and, focusing on institutional mechanisms, government functions, data governance, and support systems, puts forward corresponding transformation ideas, frameworks, and pathways and provides an outlook. Thereby it provides a reference for the high-quality development of laboratory animal management in Jiangsu Province and other regions.
4.Efficacy and safety of Chinese herbal compounds for pulmonary nodules: A systematic review and meta-analysis
Yanlong LI ; Xinze ZHENG ; Lingyan LAN ; Ying WANG ; Wei SU ; Jiahui CHEN ; Xiangjun QI ; Xuewei LI ; Bo AN ; Ling YU ; Lingling SUN ; Lizhu LIN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(07):1119-1128
Objective To systematically evaluate the efficacy and safety of traditional Chinese medicine (TCM) compound in treating pulmonary nodules, providing evidence-based medical evidence for TCM intervention in pulmonary nodules. Methods Computer search of PubMed, CNKI, Wanfang, VIP, and SinoMed was conducted to select randomized controlled trials (RCTs) of TCM compound intervention in pulmonary nodules, with the retrieval time from the inception to November 29, 2023. The Cochrane bias risk assessment tool was used to evaluate the quality of the included studies, and Review Manager 5.4 was used for Meta-analysis. Results A total of 18 RCTs were included, covering 8 provinces across the country, with a total sample size of 1301 patients. The TCM compounds used in the included studies all incorporated the method of dissolving phlegm and dissipating nodules. There was a high risk of bias uncertainty in the included studies. Meta-analysis results suggested that TCM compound could significantly reduce the diameter of pulmonary nodules [MD=−1.41, 95%CI (−1.70, −1.13), P<0.001], decrease the number of nodules [MD=−0.37, 95%CI (−0.73, −0.01), P=0.05], alleviate clinical symptoms [MD=−4.84, 95%CI (−6.04, −3.64), P<0.001], and improve lung function [forced expiratory volume in one second (FEV1), MD=0.55, 95%CI (0.09, 1.01), P=0.02; FEV1/forced vital capacity, MD=6.12, 95%CI (4.47, 7.78), P<0.001]. However, there was no statistically significant difference in the probability of malignancy between the experimental group and the control group [MD=−0.01, 95%CI (−0.01, 0.00), P=0.09]. Conclusion TCM compound can significantly reduce the diameter of pulmonary nodules, decrease the number of nodules, alleviate clinical symptoms, and improve lung function, but future multicenter, large-sample, high-quality RCTs are still needed to further explore and verify this conclusion.
5.Efficacy and Mechanism of Shenling Qushi Prescription in Treatment of Hyperuricaemia Mice
Xuan LIU ; Jialu QUE ; Caixia PANG ; Shuhui TAN ; Luyu CHEN ; Yihuan LI ; Xiaofeng LIN ; Qi LIANG ; Cuiling LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(19):197-206
ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups (n=9): Control, model, low-dose (6 g·kg-1) Shenling Qushi prescription, medium-dose (12 g·kg-1) Shenling Qushi prescription, high-dose (24 g·kg-1) Shenling Qushi prescription, medium-dose Shenling Qushi prescription plus febuxostat (12+0.003 g·kg-1), and febuxostat (3 mg·kg-1). A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide (250 mg·kg-1) combined with oral administration of allopurinol (300 mg·kg-1) over a 28-day period. Concurrently, the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment, mouse body weight, food intake, water consumption, and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid (SUA) and urinary uric acid (UUA) levels, along with xanthine oxidase (XOD) and adenosine deaminase (ADA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the renal tissue, alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group, model mice exhibited reduced food intake and body weight (P<0.01), decreased water consumption yet increased urine output, no significant change in the liver index but increased kidney index (P<0.01). Pathological findings revealed renal tissue damage including glomerular atrophy, epithelial cell detachment, and inflammatory cell infiltration. Furthermore, the model group exhibited elevated UUA and SUA levels (P<0.01), enhanced activities of ALT, AST, XOD, and ADA in the liver tissue (P<0.05, P<0.01), upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue (P<0.05), alongside markedly elevated mRNA levels of XOD and ADA in the liver (P<0.01). Compared with the model group, the Shenling Qushi prescription groups showed no significant changes in body weight or food intake, with water consumption and urine output remaining within normal ranges, alleviated glomerular atrophy, with reduced pathological damage such as inflammatory infiltration, declined UUA and SUA levels (P<0.01), and increased activities of ALT, AST, XOD, and ADA in the serum (P<0.01). Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue (P<0.05, P<0.01) and XOD and ADA in the hepatic tissue (P<0.05, P<0.01). Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 (P<0.05, P<0.01). ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels, thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.
6.Effect of Draxin on the migration characteristics of trunk neural crest cells in the embryonic mouse spinal cord
Zu-Qi CUI ; Xiao-Jin MIAO ; Ze-Lin GU ; Meng-Fei GONG ; Huan CHEN ; Shu-Han YANG ; Tong-Yu LIU ; San-Bing ZHANG ; Yu-Hong SU
Acta Anatomica Sinica 2025;56(2):150-157
Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.
7.Risk factors for postoperative hypoxemia after whole lung lavage in patients with pneumoconiosis and the predictive value of ultrasound indicators
Lingwei LI ; Lin CHEN ; Qinghua ZHONG ; Yucheng DENG ; Qi LIU
China Occupational Medicine 2025;52(5):564-569
Objective To analyze the influencing factors of postoperative hypoxemia after whole lung lavage (WLL) in patients with pneumoconiosis and to evaluate the predictive value of lung ultrasound scores. Methods A total of 757 patients with pneumoconiosis who underwent unilateral large-volume WLL were selected as the research subjects by continuous sampling method. The patients with hypoxemia after large-volume WLL were assigned to the observation group (82 cases), and those without hypoxemia were assigned to the control group (675 cases). Patients′ basic information and clinical data of the two groups were collected using a retrospective investigation method. The binary logistic regression analysis was used to analyze the influencing factors of hypoxemia after large-volume WLL in patients with pneumoconiosis, and receiver operating characteristic (ROC) curve analysis was conducted to assess the predictive value of ultrasound indicators. Results The combined rate of postoperative hypoxemia in the patients was 10.8% (82/757). The multivariate logistic regression analysis showed that the risk of hypoxemia in patients aged ≥65 years was higher than that in patients aged <65 years (P<0.05). The risk of hypoxemia was higher in patients with increased pre-extubation lung ultrasound score than those with lower pre-extubation lung ultrasound score (P<0.01). Patients with a higher partial pressure of carbon dioxide in arterial blood (PaCO2) had a higher risk of concurrent hypoxemia than those with a lower pressure (P<0.01), while patients with lower arterial partial pressure of oxygen (PaO2) had a higher risk of concurrent hypoxemia than those with higher PaO2 (P<0.01). Pearson correlation analysis showed that lung ultrasound scores were negatively correlated with PaO2 and positively correlated with PaCO2 (both P<0.01). The ROC curve analysis showed that the area under the curve was 0.855, the 95% confidence interval was 0.828 to 0.879, the diagnostic sensitivity was 84.2%, and the specificity was 75.1%. Conclusion Age, pre-extubation lung ultrasound score, and PaCO₂ are risk factors for hypoxemia after WLL in patients with pneumoconiosis, while PaO₂ is a protective factor. Pre-extubation lung ultrasound scoring demonstrates good accuracy in predicting postoperative hypoxemia among pneumoconiosis patients after WLL.
8.Wendan Decoction ameliorates metabolic phenotypes in rats with metabolic syndrome and phlegm syndrome by modulating the gut microbiota-bile acid axis
Kaiyue HUANG ; Jingxin QI ; Wenqian LUO ; Yixuan LIN ; Meimei CHEN ; Huijuan GAN
Journal of Southern Medical University 2025;45(6):1174-1184
Objective To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome(MS).Methods Forty Wistar rats were randomly divided into normal control group(n=8)and 3 phlegm syndrome model groups(induced by high-fat,high-sugar,and high-salt feeding and a single-dose intraperitoneal STZ injection;n=24)treated with daily gavage of saline,Wendan Decoction(3.6 g/kg),or metformin(0.1 g/kg)for 4 weeks.General conditions and glucose and lipid metabolism parameters of the rats were monitored,and serum LPS,liver histopathology,hepatic expressions of FXR,CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined.Gut microbiota structure was analyzed using 16S rDNA sequencing,and serum bile acids were quantified with UHPLC-MS/MS.Results The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis,increased body weight,abdominal circumference,Lee's index,FBG,FINS,HOMA-IR,TG,TC,LDL and LPS,and decreased HDL level.The abundance of Bacteroidetes,Megamonas,and Bacteroides in gut microbiota increased while Firmicutes,Lachnospiraceae_NK4A136_group,isohyodeoxycholic acid,and glycohyodeoxycholic acid decreased significantly;hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models.Treatment with Wendan Decoction effectively alleviated hepatic pathology,reduced body weight and abdominal circumference,improved glucose and lipid metabolic profiles and gut microbiota structure,and reversed the changes in hepatic and ileal protein expressions.Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes,Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid.Conclusion Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.
9.Coral calcium hydride promotes peripheral mitochondrial division and reduces AT-Ⅱ cells damage in ARDS via activation of the Trx2/Myo19/Drp1 pathway
Qian LI ; Yang ANG ; Qing-Qing ZHOU ; Min SHI ; Wei CHEN ; Yujie WANG ; Pan YU ; Bing WAN ; Wanyou YU ; Liping JIANG ; Yadan SHI ; Zhao LIN ; Shaozheng SONG ; Manlin DUAN ; Yun LONG ; Qi WANG ; Wentao LIU ; Hongguang BAO
Journal of Pharmaceutical Analysis 2025;15(3):610-624
Acute respiratory distress syndrome(ARDS)is a common respiratory emergency,but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures.Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS,but the application of hydrogen has flammable and explosive safety concerns.Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance,thus improving ARDS in patients and animal models.Coral calcium hydrogenation(CCH)is a new solid molecular hydrogen carrier prepared from coral calcium(CC).Whether and how CCH affects acute lung injury in ARDS re-mains unstudied.In this study,we observed the therapeutic effect of CCH on lipopolysaccharide(LPS)induced acute lung injury in ARDS mice.The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable,demonstrating a significant improvement compared to the untreated ARDS model group.CCH treatment significantly reduced pulmonary hemorrhage and edema,and improved pulmonary function and local microcirculation in ARDS mice.CCH promoted mitochon-drial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2(Trx2),improved lung mitochondrial dysfunction induced by LPS,and reduced oxidative stress damage.The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation.
10.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

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