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Construction of complex three-dimensional vascularized liver tissue model in vitro based on a biphasic cell-laden embedding medium

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INTERnational JOURNAL OF EXTREME MANUFACTURING 2025年第3期7卷 035002-035002页

作者： Lv, Weikang Yu, Haoran Aazmi, Abdellah Naren, Tuya Cheng, Wanli Yu, Mengfei Wang, Zhen Xu, Xiaobin Yang, Huayong Ma, Liang Zhejiang Univ State Key Lab Fluid Power & Mechatron Syst Hangzhou 310058 Peoples R China Zhejiang Univ Sch Mech Engn Hangzhou 310058 Peoples R China Zhejiang Univ Affiliated Stomatol Hosp Sch Med Hangzhou 310003 Peoples R China Zhejiang Prov Peoples Hosp Affiliated Peoples Hosp Hangzhou Med Coll Ctr Lab MedAllergy CtrDept Transfus Med Hangzhou 310014 Zhejiang Peoples R China Tongji Univ Sch Mat Sci & Engn Shanghai 201804 Peoples R China

Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation, mimicking physiological heterogeneous structures, and recreating the cellular microenvironment. However, the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink, making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials. To overcome this limitation, we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel. This medium possesses yield stress and self-healing properties, facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it. By adjusting the printing speed, we controlled the filament diameter, achieving a range from 250 mu m to 1000 mu m, and ensuring precise control over ink deposition locations and filament shapes. Using the in situ endothelialization method, we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells. In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue. We also investigated the impact of varying vascular densities on liver tissue function. Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways. In summary, this method is adaptable to various materials, allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels, thus enabling precise regulation of the liver tissue microenvironment. Additionally, it facilitates the rapid construction of three-dimensional vascular structures within liver tissue. The resulting vascularized liver tissue model exhibits enhanced biological functionality, openi

关键词： 3D bioprinting biphasic cell-laden medium sacrificial embedded printing vascularized liver tissue model

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Metabolic profiling of Perilla leaves of different colors: insights into metabolite variation and bioactive compound distribution

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BMC PLANT BIOLOGY 2025年第1期25卷 1-11页

作者： Dossou, Senouwa Segla Koffi Deng, Qianchun Li, Feng Wang, Lei Jiang, Nanjun Kefale, Habtamu Zhou, Rong Li, Donghua Tan, Meilian Wang, Linhai Chinese Acad Agr Sci Oil Crops Res Inst Minist Agr Key Lab Biol Genet Improvement Oil Crops Wuhan 430062 Peoples R China Univ Lome Lab Plant Biotechnol & Physiol 01 BP 1515 Lome Togo Amway China Bot R&D Ctr Wuxi 214115 Peoples R China

BackgroundPerilla frutescens (L.) Britt. (Lamiaceae) leaves are essential culinary and medicinal herbs, native to East Asian countries. Three types of Perilla leaves, including green, green/purple and purple, are mainly found, and the leaf color is a critical attribute for consumer preferences. However, the extent of diversity and variability of metabolites in Perilla leaves of different colors remain elusive. Thus, in this study, we applied LC-QqQ-MS (liquid chromatography triple quadrupole tandem mass spectrometry)-based widely targeted metabolic profiling to investigate variation in the metabolite profiles of green (PF1), green/purple (PF2) and purple (PF3) Perilla *** qualitatively and quantitatively identified a total of 1239 metabolites in Perilla leaves of different colors. Amino acids and derivatives (15.50%), flavonoids (14.77%), phenolic acids (12.19%), lipids (9.60%), carbohydrates and derivatives (8.47%), organic acids and derivatives (7.99%), nucleotides and derivatives (7.99%), and terpenoids (5.25%) were the major classes of metabolites in perilla leaves. In contrast to green leaves, the principal component analysis and correlation analysis revealed a considerable influence of genotypes for the variation in purple leaves' metabolite profiles. Differentially accumulated metabolites (DAMs) analysis revealed that flavonoids, phenolic acids, and amino acids and derivatives were the major DAMs, and the phenylpropanoid pathway was the most differentially regulated. All DAMs, including four potential metabolic discriminative biomarkers, were screened out. In addition, we revealed the accumulation patterns of bioactive compounds in the leaves of different colors. It was noteworthy that most of the differentially accumulated flavonoids showed a higher relative content in PF3, followed by PF2 and PF1. Glycosylated cyanidins and delphinidins were identified as the key compounds responsible for the purple coloration of leaves. Finally, we found that

关键词： Perilla Metabolite profiling Leaf color Differentially accumulated metabolites LC-MS/MS

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Virological and Immunological Characteristics of HBeAg-Positive Chronic Hepatitis B Patients With Low HBsAg Levels

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS 2025年第5期61卷 814-823页

作者： Chen, Yuxin Wang, Guiyang Li, Ming Wang, Jian Gu, Jiaqi Huang, Rui Wu, Chao Zhang, Quan Liu, Yong Nanjing Univ Nanjing Drum Tower Hosp Med Sch Dept Lab MedAffiliated Hosp Nanjing Peoples R China Nanjing Univ Inst Viruses & Infect Dis Nanjing Peoples R China Nanjing Univ Nanjing Drum Tower Hosp Affiliated Hosp Dept Infect DisMed Sch Nanjing Peoples R China Nanjing Univ Chinese Med Nanjing Drum Tower Hosp Clin Coll Dept Infect Dis Nanjing Peoples R China

BackgroundHBeAg-positive chronic hepatitis B (CHB) with low HBsAg levels represents a relatively rare serological pattern and is closely associated with the severity of liver disease. However, the underlying mechanisms in such cases remain largely ***-na & iuml;ve HBeAg-positive CHB patients with low HBsAg levels in china were enrolled and analysed. In vitro cell experiments and immunoassays were conducted to investigate the effects of the preS2 deletion mutation on virus reproduction and host immune ***-na & iuml;ve HBeAg-positive CHB patients with low HBsAg levels (low HBsAg group) exhibited higher fibrosis scores and a greater prevalence of quasispecies mutations introduced by preS2 deletion compared to patients with positive HBeAg and high HBsAg levels (high HBsAg group). Further analysis revealed that fibrosis scores in CHB patients with the preS2 deletion mutations were significantly higher compared to both in wild-type patients and the high HBsAg group. In vitro assays indicated that while this mutation may not impact HBV replication, it significantly reduced viral infectivity. The number of viral-specific IFN-gamma-secreting cells induced by the mutant was significantly lower than that induced by the wild-type strain. Additionally, the levels of HBs-specific B cells and cytokine secretion from lymphocytes triggered by the mutant strain were significantly ***-positive CHB patients with low HBsAg and genotype C exhibited higher noninvasive fibrosis indexes compared with typical patients, accompanied by a significant increase in quasispecies variants associated with preS2 deletion. The emergence of the preS2 deletion mutants in patients could be due to its enhanced ability to evade the host immunity.

关键词： HBeAg HBsAg host immunity liver fibrosis preS2 deletion mutation

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Tegaserod maleate exerts anti-tumor effects on prostate cancer via repressing sonic hedgehog signaling pathway

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MOLECULAR MEDICINE 2025年第1期31卷 1-12页

作者： Cai, Maoping Ge, Shengdong Hong, Yaying Chen, Yao Ren, Yang-Zi Zhong, Dacai Chen, Mingkun Liu, Yuan Chen, Zhe-Sheng Feng, Ninghan Chen, Zhanghui Zhao, Shan-Chao Southern Med Univ Affiliated Hosp 5 Dept Urol Guangzhou 510920 Guangdong Peoples R China Southern Med Univ Clin Coll 3 Guangzhou 510630 Guangdong Peoples R China Cent Peoples Hosp Zhanjiang Zhanjiang Inst Clin Med Zhanjiang 524045 Guangdong Peoples R China Southern Med Univ Nanfang Hosp Dept Urol Guangzhou 510515 Guangdong Peoples R China 8th Med Ctr Chinese PLA Gen Hosp Coll Pulm & Crit Care Med Beijing Peoples R China Guangzhou Univ Chinese Med Affiliated Hosp 1 Dept Oncol Guangzhou 510405 Guangdong Peoples R China Southern Med Univ Dept Urol Affiliated Hosp 3 Guangzhou 510630 Guangdong Peoples R China St Johns Univ Coll Pharm & Hlth Sci Dept Pharmaceut Sci Queens NY 11439 USA Jiangnan Univ Med Ctr Dept Urol Wuxi 214002 Peoples R China Jiangnan Univ Wuxi Sch Med Wuxi 214002 Peoples R China Nanjing Med Univ Affiliated Wuxi 2 Hosp Dept Pathol Wuxi 214002 Peoples R China

Prostate cancer (PCa) is a highly common type of malignancy and affects millions of men in the world since it is easy to recur or emerge therapy resistance. Therefore, it is urgent to find novel treatments for PCa patients. In the current study, we found that tegaserod maleate (TM), an FDA-approved agent, inhibited proliferation, colony formation, migration as well as invasion, caused the arrest of the cell cycle, and promoted apoptosis of PCa cells in vitro. In addition, TM suppressed the tumor growth in the cell-derived xenograft (CDX) mouse model in vivo. Mechanistically, TM exerted anti-tumor effects via downregulating GLI2, and its downtream targets, thus inhibiting the sonic hedgehog (SHH) signaling pathway. In brief, our findings demonstrated that TM effectively inhibited the activities of PCa cells by suppressing the SHH signaling pathway and provided a potential new agent for the treatment of PCa.

关键词： Prostate cancer (PCa) Tegaserod maleate (TM) Sonic hedgehog (SHH) signaling GLI2 Treatment

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Pupillometry Analysis of Rapid Serial Visual Presentation at Five Presentation Rates

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Tsinghua Science and Technology 2024年第2期29卷 543-552页

作者： Xi Luo Yanfei Lin Rongxiao Guo Xirui Zhao Shangen Zhang Xiaorong Gao School of Integrated Circuits and Electronics Beijing Institute of TechnologyBeijing 100081China School of Computer and Communication Engineering University of Science and Technology BeijingBeijing 100083China School of Medicine Tsinghua UniversityBeijing 100084China

In this study,the effect of presentation rates on pupil dilation is investigated for target recognition in the Rapid Serial Visual Presentation(RSVP)*** this experiment,the RSVP paradigm with five different presentation rates,including 50,80,100,150,and 200 ms,is *** pupillometry data of 15 subjects are collected and *** pupillometry results reveal that the peak and average amplitudes for pupil size and velocity at the 80-ms presentation rate are considerably higher than those at other presentation *** average amplitude of pupil acceleration at the 80-ms presentation rate is significantly higher than those at the other presentation *** latencies under 50-and 80-ms presentation rates are considerably lower than those of 100-,150-,and 200-ms presentation ***,no considerable differences are observed in the peak,average amplitude,and latency of pupil size,pupil velocity,and acceleration under 100-,150-,and 200-ms presentation *** results reveal that with the increase in the presentation rate,pupil dilation first increases,then decreases,and later reaches *** 80-ms presentation rate results in the largest point of pupil *** correlation is observed between pupil dilation and recognition accuracy under the five presentation rates.

关键词： pupil dilation presentation rate Rapid Serial Visual Presentation(RSVP)

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Exosomes derived from ccRCC cells confers fibroblasts activation to foster tumor progression through Warburg effect by downregulating PANK3

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CELL DEATH DISCOVERY 2025年第1期11卷 1-11页

作者： Yang, Yang Cheng, Qiang Zhu, Jie Han, Ce Huang, Yan Li, Xiu-bin Fan, Wen-mei Zhang, Xu Gao, Yu Chinese Peoples Liberat Army Gen Hosp Med Ctr 3 Dept Urol Beijing Peoples R China Chinese PLA Med Sch Beijing Peoples R China

The interaction between tumor-derived exosomes and stroma plays a crucial role in tumor progression. However, the mechanisms through which tumor cells influence stromal changes are not yet fully understood. In our study, through single-cell sequencing analysis of clear cell renal cell carcinoma tissues at varying stages of progression, we determined that the proportion of cancer-associated fibroblasts (CAFs) in advanced renal cell carcinoma tissues was notably higher compared to localized renal cell carcinoma tissues. Comparison of transcriptome sequencing and energy metabolism tests between CAFs primarily isolated from advanced renal cell carcinoma tissues and normal fibroblasts (NFs) revealed the occurrence of the Warburg effect during the fibroblast activation process. Additionally, we observed an increase in glucose transporter GLUT1 expression, total reactive oxygen species (ROS) levels, lactic acid production, and subsequent excretion of excess lactic acid through monocarboxylate transporter-4 (MCT4) in CAFs. Interestingly, renal cancer cells were found to uptake lactic acid via MCT1 upon interaction with CAFs, thereby enhancing their malignant phenotypes. Furthermore, the down-regulation of PANK3 induced by exosomes derived from renal cancer cells was identified as a crucial step in fibroblast activation. These findings indicate that exosomes play a role in facilitating intercellular communication between renal cancer cells and fibroblasts. Targeting this communication pathway could potentially offer new strategies for the prevention and treatment of advanced renal cell carcinoma.

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Advances in Prenatal Cell-Free DNA Screening for Dominant Monogenic Conditions: A Review of Current Progress and Future Directions in Clinical Implementation

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PRENATAL DIAGNOSIS 2025年第4期45卷 445-452页

作者： Liao, Jun Xu, Naixin Gao, Harry Hardy, Tristan Levy, Brynn Mehta, Lakshmi Choy, Kwong Wai Huang, Hefeng Zhang, Jinglan Columbia Univ Irving Med Ctr Dept Pathol & Cell Biol New York NY USA Fudan Univ Obstet & Gynecol Hosp Shanghai Peoples R China Fulgent Genet Inc El Monte CA USA Monash IVF Genet Dulwich Australia Columbia Univ Irving Med Ctr Dept Pediat Div Clin Genet New York NY USA Chinese Univ Hong Kong Dept Obstet & Gynaecol Hong Kong Peoples R China Zhejiang Univ Womens Hosp Sch Med Key Lab Reprod GenetMinist Educ Hangzhou Peoples R China Zhejiang Univ Womens Hosp Sch Med Dept Reprod Endocrinol Hangzhou Peoples R China Zhejiang Univ Inst Med Genet & Dev Hangzhou Peoples R China

Prenatal cell-free DNA (cfDNA) screening has advanced significantly, extending beyond detecting aneuploidies to sub-chromosomal copy number variations. However, its application for screening dominant single-gene conditions, often caused by de novo variants, remains underutilized in the general obstetric population. This study reviews recent data and experience on prenatal cfDNA screening for dominant monogenic conditions using multiple-gene panels, highlighting its potential to enhance early detection and management of genetic disorders. Integrating comprehensive cfDNA screening into routine prenatal care could complement current imaging techniques and standard prenatal cfDNA screening, which may overlook pre-symptomatic fetuses with dominant monogenic conditions in early gestation. Despite promising initial results, further research is needed to confirm the clinical validity and utility of cfDNA screening for these conditions. Larger and more diverse studies are necessary to assess the broader applicability of this technology. In addition, key challenges such as access, genetic counseling, ethical considerations, and policy development need to be addressed. A comprehensive approach, including rigorous test design, informed consent, and robust counseling, is essential for the successful adoption of expanded cfDNA screening, ultimately improving clinical outcomes.

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Identification of the Hub Gene LDB3 in Stanford Type A Aortic Dissection Based on Comprehensive Bioinformatics Analysis

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JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 2025年第6期29卷 e70471页

作者： Liu, Xinyi Liu, Xing Wan, Bin Ge, Yipeng Hu, Haiou Yu, Hong Zhao, Meng Li, Huadong Zhu, Junming Capital Med Univ Beijing Aort Dis Ctr Dept Cardiovasc Surg Beijing Anzhen Hosp Beijing Peoples R China Army Med Univ Dept Cardiovasc Surg Xinqiao Hosp Chongqing Peoples R China Max Planck Insititute Human Cognit & Brain Sci Leipzig Germany Inst Neurosci & Med INM 7 Brain & Behav Res Ctr Julich Julich Germany Huazhong Univ Sci & Technol Union Hosp Tongji Med Coll Dept Otorhinolaryngol Wuhan Peoples R China Fudan Univ Sch Basic Med Sci Dept Physiol & Pathophysiol Shanghai Peoples R China Huazhong Univ Sci & Technol Dept Cardiovasc Surg Union Hosp Tongji Med Coll Dept Cardiovasc Surg Wuhan Peoples R China

Stanford type A aortic dissection (TAAD) is a life-threatening disease. This study explored the role of LIM domain binding 3 (LDB3) in TAAD progression. Four datasets from the Gene Expression Omnibus were analyzed to identify TAAD-related hub genes. LDB3 single nucleotide polymorphisms (SNPs) were assessed in the UK Biobank. Western blotting and immunofluorescence detected LDB3 expression in angiotensin II (Ang II) stimulated human aortic vascular smooth muscle cells (HA-VSMC), human samples, and a murine model. Bioinformatics identified tissue inhibitor of metalloproteinase-1 (TIMP1) and LDB3 as TAAD hub genes. TIMP1 was expressed in macrophages, mesenchymal cells, and smooth muscle cells, while LDB3 was mostly expressed in smooth muscle cells. Validation showed TIMP1 was upregulated and LDB3 downregulated in TAAD. Six LDB3 SNPs were associated with aortic aneurysm and dissection in the UK Biobank. In human and murine samples, LDB3 expression was reduced in diseased tissues and co-localized with smooth muscle. Ang II-stimulated HA-VSMC exhibited LDB3 reduction and altered intercellular connections. The aforementioned findings suggest that the newly identified gene LDB3 is crucial in the progression of TAAD.

关键词： bioinformatics differentially expressed genes LDB3 single-cell sequencing Stanford type a aortic dissection weighted gene coexpression network analysis

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Individualized Data Generation in Personalized Federated Learning

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IEEE Transactions on Mobile Computing 2025年第7期24卷 6628-6642页

作者： Cai, Yunyun Xi, Wei Shen, Yuhao Sun, Cerui Wang, Shuai Gong, Wei Zhao, Jizhong Xi'an Jiaotong University Faculty of Electronic and Information Engineering Xi'an China Southeast University School of Computer Science and Engineering Nanjing China University of Science and Technology of China School of Computer science and Technology Hefei China

Most Personalized Federated Learning (PFL) algorithms merge the model parameters of each client with other (similar or generic) model parameters to optimize the personalized model (PM). However, the merged model parameters in these algorithms may fit low relevance data, thereby limiting the performance of PM. In this paper, we generate similar data for each client through the collaboration of a generic model (GM) on the server, rather than merging model parameters. To train a generator capable of generating data for all classes on the server without real data, we employ the GM as the discriminator in adversarial training with the generator. Additionally, we introduce a similarity assessment metric, which allows for the assessment of the similarity between local data and data from other classes. Nevertheless, the presence of non-IID data among clients can weaken the performance of the GM, consequently impacting the training of the generator and similarity assessment. To address this issue, we design a directive mechanism so that GM can be optimized during adversarial training without the need for additional training. The experimental results validate the superiority of our algorithm over state-of-the-art algorithms in terms of accuracy, loss, and convergence speed. © 2002-2012 IEEE.

关键词： Federated learning

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Azimuthal Phase-Shifting Demodulation Method for Orbital-Angular-Momentum Interferometer

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IEEE PHOTONICS TECHNOLOGY LETTERS 2024年第5期36卷 321-324页

作者： Zhao, Hua Xu, Jiayang Huang, Xunhua Xu, Jiannan Hao, Hui Lu, Huali Nanjing Normal Univ Sch Comp & Elect Informat Nanjing 210023 Peoples R China

The orbital-angular-momentum (OAM) beams- based interferometer (OAMI) has shown its potential in high-precision metrology. However, most phase-demodulation methods for OAMIs require the analysis of interferograms captured by charge-coupled device (CCD) cameras, resulting in limited performance in terms of demodulation rate and resolution. In this study, an azimuthal phase-shifting demodulation method has been proposed for extracting the phase from interferograms produced by a Michelson structure-based OAMI (MOAMI). In contrast to other phase-demodulation methods for OAMIs, the proposed method requires only four-spot light intensity located in four specific azimuthal directions of the interferograms, which can be sampled by four photodetectors (PDs) instead of CCD cameras. To our knowledge, this is the first demonstration of four-spot light intensity-based demodulation method for OAMIs, which may greatly improve the measurement speed. Using the proposed MOAMI and demodulation method, the displacements ranging from 0 to 3100 nm were precisely measured with a relative error less than 1%, demonstrating the validity of the proposed method.

关键词： Demodulation Interference Measurement by laser beam Charge coupled devices Extraterrestrial measurements Cameras Phase shifting interferometry OAM beams-based interferometer (OAMI) Michelson structure-based OAMI (MOAMI) azimuthal phase-shifting demodulation method high-speed measurement

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