1.Primary Cilium-mediated Mechano-metabolic Coupling: Cross-system Homeostatic Regulation of The Nervous, Bone, Vascular, and Renal Systems
Liang-Chen DUAN ; Hao-Liang HU ; Shu-Zhi WANG ; Jia-Long YAN ; Lin-Xi CHEN
Progress in Biochemistry and Biophysics 2026;53(3):577-592
Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.
2.Analysis of the effect of bladder artery embolization combined with sequential TURBt in the treatment of bladder cancer
Hao ZHENG ; Chengtao GU ; Hao XU ; Shaochen WANG ; Zilong ZHANG ; Long CHENG
Journal of Interventional Radiology 2025;34(12):1338-1342
Objective To evaluate the efficacy and safety of preoperative bladder artery embolization followed by transurethral resection of bladder tumor(TURBt)in treating bladder cancer.Methods A retrospective analysis was conducted on the clinical data of 129 bladder cancer patients treated at the Fourth Affiliated Hospital of Soochow University from January 2021 to June 2024.Exclusions included 2 cases of acute bleeding with shock,3 cases requiring staged surgery due to poor intraoperative visualization,7 cases with other malignancies,12 cases without TURBt performed within 24 hours after embolization,and 1 case where selective bladder artery embolization failed.Patients were divided into two groups based on whether they underwent pre-TURBt embolization.Group A(n=61)underwent TURBt alone,while Group B(n=43)underwent TURBt within 24 hours after bladder artery embolization.There were no statistically significant differences in gender composition,tumor size,or other clinical characteristics between the two groups(P>0.05).Statistical comparisons were made between the two groups regarding operation time,intraoperative blood loss,postoperative hospital stay,duration of postoperative catheterization,and incidence of adverse reactions.Results In Group A,the mean operation time was(67.9±14.2)min,intraoperative blood loss was(80.7±24.7)mL,postoperative hospital stay was(8.5±1.6)days,and catheterization duration was(6.9±1.1)days.In Group B,the mean operation time was(54.0±12.6)min,intraoperative blood loss was(58.6±27.3)mL,postoperative hospital stay was(7.3±1.4)days,and catheterization duration was(6.4±0.9)days.Operation time,intraoperative blood loss,postoperative hospital stay,and catheterization duration were significantly lower in Group B compared to Group A(P<0.05).There was no statistically significant difference in the incidence of postoperative adverse reactions between the two groups(P>0.05).Conclusion Preoperative bladder artery embolization followed by TURBt for bladder cancer reduces tumor blood supply,thereby decreasing intraoperative bleeding.This approach effectively minimizes surgical bleeding,shortens operation time and postoperative hospital stay,with minimal side effects.It represents a safe and effective combined treatment method worthy of clinical promotion and application.
3.Non-invasive Modulation of Deep Brain Nuclei by Temporal Interference Stimulation.
Long LI ; Hao BAI ; Linyan WU ; Liang ZHENG ; Liang HUANG ; Yang LI ; Wenlong ZHANG ; Jue WANG ; Shunnan GE ; Yan QU ; Tian LIU
Neuroscience Bulletin 2025;41(5):853-865
Temporal interference (TI) is a form of stimulation that epitomizes an innovative and non-invasive approach for profound neuromodulation of the brain, a technique that has been validated in mice. Yet, the thin cranial bone structure of mice has a marginal influence on the effect of the TI technique and may not effectively showcase its effectiveness in larger animals. Based on this, we carried out TI stimulation experiments on rats. Following the TI intervention, analysis of electrophysiological data and immunofluorescence staining indicated the generation of a stimulation focus within the nucleus accumbens (depth, 8.5 mm) in rats. Our findings affirm the viability of the TI methodology in the presence of thick cranial bones, furnishing efficacious parameters for profound stimulation with TI administered under such conditions. This experiment not only sheds light on the intervention effects of TI deep in the brain but also furnishes robust evidence in support of its prospective clinical utility.
Animals
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Deep Brain Stimulation/methods*
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Nucleus Accumbens/physiology*
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Male
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Rats
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Rats, Sprague-Dawley
;
Time Factors
4.The Near-infrared II Emission of Gold Clusters and Their Applications in Biomedicine
Zhen-Hua LI ; Hui-Zhen MA ; Hao WANG ; Chang-Long LIU ; Xiao-Dong ZHANG
Progress in Biochemistry and Biophysics 2025;52(8):2068-2086
Optical imaging is highly valued for its superior temporal and spatial resolution. This is particularly important in near-infrared II (NIR-II, 1 000-3 000 nm) imaging, which offers advantages such as reduced tissue absorption, minimal scattering, and low autofluorescence. These characteristics make NIR-II imaging especially suitable for deep tissue visualization, where high contrast and minimal background interference are critical for accurate diagnosis and monitoring. Currently, inorganic fluorescent probes—such as carbon nanotubes, rare earth nanoparticles, and quantum dots—offer high brightness and stability. However, they are hindered by ambiguous structures, larger sizes, and potential accumulation toxicity in vivo. In contrast, organic fluorescent probes, including small molecules and polymers, demonstrate higher biocompatibility but are limited by shorter emission wavelengths, lower quantum yields, and reduced stability. Recently, gold clusters have emerged as a promising class of nanomaterials with potential applications in biocatalysis, fluorescence sensing, biological imaging, and more. Water-soluble gold clusters are particularly attractive as fluorescent probes due to their remarkable optical properties, including strong photoluminescence, large Stokes shifts, and excellent photostability. Furthermore, their outstanding biocompatibility—attributed to good aqueous stability, ultra-small hydrodynamic size, and high renal clearance efficiency—makes them especially suitable for biomedical applications. Gold clusters hold significant potential for NIR-II fluorescence imaging. Atomic-precision gold clusters, typically composed of tens to hundreds of gold atoms and measuring only a few nanometers in diameter, possess well-defined three-dimensional structures and clear spatial coordination. This atomic-level precision enables fine-tuned structural regulation, further enhancing their fluorescence properties. Variations in cluster size, surface ligands, and alloying elements can result in distinct physicochemical characteristics. The incorporation of different atoms can modulate the atomic and electronic structures of gold clusters, while diverse ligands can influence surface polarity and steric hindrance. As such, strategies like alloying and ligand engineering are effective in enhancing both fluorescence and catalytic performance, thereby meeting a broader range of clinical needs. In recent years, gold clusters have attracted growing attention in the biomedical field. Their application in NIR-II imaging has led to significant progress in vascular, organ, and tumor imaging. The resulting high-resolution, high signal-to-noise imaging provides powerful tools for clinical diagnostics. Moreover, biologically active gold clusters can aid in drug delivery and disease diagnosis and treatment, offering new opportunities for clinical therapeutics. Despite the notable achievements in fundamental research and clinical translation, further studies are required to address challenges related to the standardized synthesis and complex metabolic behavior of gold clusters. Resolving these issues will help accelerate their clinical adoption and broaden their biomedical applications.
5.Value of DCE-MRI quantitative parameters in differential diagnosis of brain metastases from non-small cell lung cancer
Rui-peng LIANG ; Yong-long LI ; Hao-tian WANG ; Dan SU ; Xiu-fu ZHANG ; Jun ZHOU
Chinese Medical Equipment Journal 2025;46(5):54-59
Objective To evaluate the value of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)in differentiating histopathological types of brain metastases from non-small cell lung cancer(NSCLC).Methods Sixty-eight patients with brain metastases confirmed by pathology were collected,including 47 lung adenocarcinoma patients divided into a lung adenocarcinoma group and 21 lung squamous cell carcinoma patients into a lung squamous cell carcinoma group.The two groups were compared in terms of the DCE-MRI derived parameters including volume transfer constant(Ktrans),extra vascular extracellular volume fraction(Ve)and plasma volume fraction(Vp);ROC curves were used to assess the diagnostic efficacy of different quantitative parameters for the pathologic types of brain metastases from lung adenocarcinoma group or lung squamous cell carcinoma.SPSS 22.0 software was used for statistical analysis.Results The lung adenocarcinoma group had the values of Ktrans,Ve,Vp and Ve+Vp higher than those of the lung squamous cell carcinoma group,with the differences being statistically significant(all P<0.05).ROC curve analysis results showed that Ktrans,Vp and Ve had high differential diagnosis values for the pathologic types of brain metastases from lung adenocarcinoma group or lung squamous cell carcinoma,with the AUC being 1.000,0.998 and 0.875,the optimal Youden index being 0.183 min-1,0.039 and 0.270,the sensitivity being 100.00%,100.00%and 80.56%and the specificity being 100.00%,97.06%and 80.88%,respectively.Conclusion The quantitative parameters of DCE-MRI gain advantages in the differential diagnosis of NSCLC brain metastases,and provide references for the diagnosis and treatment of brain metastases of lung cancer.[Chinese Medical Equipment Journal,2025,46(5):54-59]
6.Engineering CHO Cell Lines to Stably Express B4GALT1,ST6GAL1,and GnTⅢ with Site-directed Integration
Xian-Hong LI ; Run-Qing JIA ; You-Liang WANG ; Wei-Ling MAN ; Tian-Hao ZHU ; Xin-Long YAN ; Yan-Li LIN
Chinese Journal of Biochemistry and Molecular Biology 2025;41(4):576-585
Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P<0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.
7.Habitat radiomics model in predicting the early therapeutic efficacy of hepatic arterial infusion chemotherapy combined with targeted therapy or immunotherapy for advanced hepatocellular carcinoma: a multi-center retrospective study
Mingsong WU ; Zenglong QUE ; Guanhui LI ; Jie LONG ; Yuxin TANG ; Hao ZHONG ; Shujie LAI ; Qixian YAN ; Jun WANG ; Xiang LAN ; Liangzhi WEN
Chinese Journal of Digestion 2025;45(2):89-99
Objective:To develop habitat radiomics models to predict early treatment responses to the hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy or immunotherapy in advanced hepatocellular carcinoma (HCC) patients, and to guide clinical diagnosis and treatment.Methods:From October 2021 to Decemeber 2023, at Army Characteristic Medical Center of PLA (Chongqing Daping Hospital) and the First Affiliated Hospital of Chongqing Medical University, 94 patients with advanced HCC who received HAIC combined with targeted therapy or immunotherapy were retrospectively enrolled. According to the treatment results, the patients were divided into response group and non-response group. Univariate and multivariate logistic regression were performed to analyze the clinical data of the patients. Based on contrast-enhanced CT images, tumor habitats were delineated and habitat features were extracted with k-means clustering, and the imaging features of arterial and venous phases were also extracted. The least absolute shrinkage and selection operator (LASSO) was used for dimensionality reduction. Feature selection was performed using LASSO to reduce dimensions, and then the selected features were further refined through stepwise logistic regression analysis.Binary logistic regression models were conducted to develop the habitat radiomics model, arterial phase radiomics model (APRM), venous phase radiomics model (VPRM), clinical data model, as well as the combination of radiomics model and clinical data model to predict early treatment (after 2 treatment cycles) response. Receiver operating characteristic curves (ROC) were plotted, and model performance was evaluated by the area under the curve (AUC), calibration curves, and decision curve. The models were validated through Bootstrap methods (1 000 times). DeLong test was used to compare AUC values.Results:The results of cluster analysis identified 3 characteristic habitats in HCC imaging: low-, medium-, and high-enhancement tumor habitats. The proportion of high-enhancement habitats was higher than that in the non-response group. A predictive model was established based on the proportions of these 3 habitats. Based on the proportion of low-, medium-, and high-enhancement habitats within the tumor, a habitat radiomics model was constructed. After LASSO selection and logistic regression analysis, 3 arterial phase and 3 venous phase radiomic features were selected to build the APRM and VPRM, respectively. Logistic regression analysis identified the following factors for the clinical data model: comorbidities ( OR=0.275, P=0.031), maximum tumor diameter ( OR=1.149, P=0.019), red blood cell count ( OR=0.463, P=0.022), alpha fetoprotein >400 μg/L ( OR=3.452, P=0.017), and tyrosine kinase inhibitor therapy ( OR=3.072, P=0.048). Among the single predictive model′s comparison, the AUC of habitat radiomics model was 0.860 (95% confidence interval(95% CI): 0.789 to 0.932), while those of the APRM、VPRM and clinical data model were 0.850 (95% CI: 0.773 to 0.926), 0.855 (95% CI: 0.782 to 0.928), and 0.774 (95% CI: 0.681 to 0.867), respectively, and there were no statistically significant among these models (all P>0.05). Among the combination models, the AUC of the habitat rediomic-clinical data combination model was 0.881 (95% CI: 0.814 to 0.947); the AUC of arterial phase rediomic-clinical data combination model was 0.897 (95% CI: 0.833 to 0.961); and the AUC of venous phase rediomic-clinical data combination model was 0.888 (95% CI: 0.826 to 0.951), but there were no statistically significant among the 3 models (all P>0.05). The calibration curve showed that the habitat rediomic-clinical data combination model had the most accurate predictive probability. Internal validation showed that the AUC of habitat rediomic-clinical data combination model was 0.848 (95% CI: 0.772 to 0.922), and the predictive performance was better than that of the clinical-data model (0.733 (95% CI: 0.670 to 0.863)). Conclusion:The habitat radiomics model based on enhanced CT can effectively predict early treatment responses to the HAIC combined with targeted therapy or immunotherapy in advanced HCC patients, which provides theoretical basis for individualized treatment in advanced HCC.
8.Effects of honey-processed Astragalus on energy metabolism and polarization of RAW264.7 cells
Hong-chang LI ; Ke PEI ; Wang-yang XIE ; Xiang-long MENG ; Zi-han YU ; Wen-ling LI ; Hao CAI
Acta Pharmaceutica Sinica 2025;60(2):459-470
In this study, RAW264.7 cells were employed to investigate the effects of honey-processed
9.Urban-rural disparities in mortality due to stroke subtypes in China and its provinces, 2015-2020.
Yi REN ; Jia YANG ; Peng YIN ; Wei LIU ; Zheng LONG ; Chen ZHANG ; Zixin WANG ; Haijie LIU ; Maigeng ZHOU ; Qingfeng MA ; Junwei HAO
Chinese Medical Journal 2025;138(11):1345-1354
BACKGROUND:
Death burden of stroke is severe with over one-third rural residents in China, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths.
METHODS:
This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate.
RESULTS:
From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of ischemic stroke ASMR make rural males the focus of stroke management.
CONCLUSIONS
The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.
Humans
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China/epidemiology*
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Stroke/mortality*
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Rural Population/statistics & numerical data*
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Male
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Female
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Urban Population/statistics & numerical data*
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Middle Aged
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Aged
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Aged, 80 and over
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Adult
10.Anti-tumor effect of metal ion-mediated natural small molecules carrier-free hydrogel combined with CDT/PDT.
Wen-Min PI ; Gen LI ; Xin-Ru TAN ; Zhi-Xia WANG ; Xiao-Yu LIN ; Hai-Ling QIU ; Fu-Hao CHU ; Bo WANG ; Peng-Long WANG
China Journal of Chinese Materia Medica 2025;50(7):1770-1780
Metal ion-promoted chemodynamic therapy(CDT) combined with photodynamic therapy(PDT) offers broad application prospects for enhancing anti-tumor effects. In this study, glycyrrhizic acid(GA), copper ions(Cu~(2+)), and norcantharidin(NCTD) were co-assembled to successfully prepare a natural small-molecule, carrier-free hydrogel(NCTD Gel) with excellent material properties. Under 808 nm laser irradiation, NCTD Gel responded to the tumor microenvironment(TME) and acted as an efficient Fenton reagent and photosensitizer, catalyzing the conversion of endogenous hydrogen peroxide(H_2O_2) within the tumor into oxygen(O_2), and hydroxyl radicals(·OH, type Ⅰ reactive oxygen species) and singlet oxygen(~1O_2, type Ⅱ reactive oxygen species), while depleting glutathione(GSH) to stabilize reactive oxygen species and alleviate tumor hypoxia. In vitro and in vivo experiments demonstrated that NCTD Gel exhibited significant CDT/PDT synergistic therapeutic effects. Further safety evaluation and metabolic testing confirmed its good biocompatibility and safety. This novel hydrogel is not only simple to prepare, safe, and cost-effective but also holds great potential for clinical transformation, providing insights and references for the research and development of metal ion-mediated hydrogel-based anti-tumor therapies.
Hydrogels/chemistry*
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Animals
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Photochemotherapy
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Humans
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Mice
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Antineoplastic Agents/administration & dosage*
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Photosensitizing Agents/chemistry*
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Neoplasms/metabolism*
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Female
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Copper/chemistry*
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Reactive Oxygen Species/metabolism*
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Tumor Microenvironment/drug effects*
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Cell Line, Tumor
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Male

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