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Lymphoma cell-driven IL-16 is expressed in activated B-cell-like diffuse large B-cell lymphomas and regulates the pro-tumor microenvironment

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HAEMATOLOGICA 2025年第2期110卷 425-438页

作者： Guan, xuwen Wang, Yi fang, Teng Wang, Jingya Li, Ru Hao, Mu Qiu, Lugui Chinese Acad Med Sci & Peking Union Med Coll Inst Hematol & Blood Dis Hosp Natl Clin Res Ctr Blood Dis State Key Lab Expt HematolHaihe Lab Cell Ecosyst Tianjin Peoples R China Tianjin Inst Hlth Sci Tianjin Peoples R China Tianjin First Cent Hosp Dept Hematol Tianjin Peoples R China Nankai Univ Affiliated Cent Hosp 1 Dept Hematol Tianjin Peoples R China Tianjin Med Univ Tianjin Med Univ Canc Inst & Hosp Natl Clin Res Ctr Canc Tianjin Peoples R China Tianjin Med Univ Tianjin Canc Inst & Hosp Key Lab Canc Prevent & Therapy Tianjin Peoples R China Tianjin Med Univ Tianjin Canc Inst & Hosp Tianjins Clin Res Ctr Canc Tianjin Peoples R China Tianjin Med Univ Tianjin Canc Inst & Hosp Tianjin Lung Canc Ctr Dept Thorac Oncol Tianjin Peoples R China

The activated B-cell-like subtype of diffuse large B-cell lymphoma (ABC-DLBCL) displays a worse outcome than the germinal center B-cell-like subtype (GCB-DLBCL). Currently, targeting the tumor microenvironment (TME) is the most promising approach to cure DLBCL with profound molecular heterogeneity;however, the factors affecting the tumor-promoting TME of ABC-DLBCL remain elusive. Here, cytokine interleukin-16 (IL-16) is expressed in tumor cells of ABC-DLBCL and secreted by the cleavage of active caspase-3. The serum IL-16 levels are not only a sensitive marker of treatment response, but also positively correlated with unfavorable prognosis in DLBCL patients. While IL-16 shows few direct promotional effects on tumor cell growth in vitro, its bioactive form significantly promotes tumor progression in vivo. Mechanically, IL-16 increases the infiltration of macrophages by the chemotaxis of CD4+ monocytes in the TME, enhancing angiogenesis and the expression of cytokine IL-6 and IL-10, as well as decreasing T-cell infiltration to accelerate tumor progression. This study demonstrates that IL-16 exerts a novel role in co-ordinating the bidirectional interactions between tumor progression and the TME. IMM0306, a fusion protein of CD20 mAb with the CD47 binding domain of SIRP alpha, reverses the tumor-promoting effects of IL-16, providing new insights into treatment strategy in ABC-DLBCL.

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Transcriptomic and physiological changes in western mosquitofish (Gambusia affinis) after exposure to norgestrel

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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2019年 171卷 579-586页

作者： Hou, Liping Chen, Shanduo Liu, Juan Guo, Jingwen Chen, Zhong Zhu, Qiaoling Zhang, Wei Xu, GuoLiang Liang, Ye Wu, Rongrong fang, xuwen Zhang, Cuiping Xing, Ke Guangzhou Univ Sch Life Sci Guangzhou 510655 Guangdong Peoples R China Shantou Univ Guangdong Prov Key Lab Marine Biotechnol Shantou 515063 Peoples R China Guangzhou Univ Key Lab Water Qual & Conservat Pearl River Delta Guangdong Prov Key Lab Radionuclides Pollut Contr Minist EducInst Environm Res Greater Bay Guangzhou 510006 Guangdong Peoples R China Guangzhou Univ Coll Environm Sci & Engn Guangzhou 510655 Guangdong Peoples R China NanWu Middle Sch Guangzhou 510655 Guangdong Peoples R China Guangzhou Tieyi Middle Sch Guangzhou 510655 Guangdong Peoples R China Rural Nonpoint Source Pollut Comprehens Managemen Guangzhou 510655 Guangdong Peoples R China

Norgestrel (NGT) is a synthetic progestin used in human and veterinary medicine. Adult female mosquitofish were exposed to NGT for 42 d at 377 ng L-1. The fin morphology and the liver transcriptome were assessed. NGT exposure increased ray 4:6 length ratio. As compared to the control, NGT treatment affected the expression of 11,772 annotated transcripts in female mosquitofish. Specifically, we found 5780 were repressed while 5992 were significantly induced. Gene ontology (GO) analysis showed that 53 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways and 158 GO terms were significantly over expressed. Genes showing the largest magnitude of expression changes were related to fin development, androgen biosynthesis, and lipid and fatty acid metabolisms, suggesting the involvement of these biological processes in response to NGT exposure in G. affinis. This first comprehensive study on the transcriptomic alterations by NGT in G. affinis not only provides valuable information on the development of molecular markers but also opens new avenues for studies on the molecular mechanisms of effects of NGT in particular and possibly other progestins in G. affinis.

关键词： Endocrine disruption Norgestrel Secondary sexual characteristics transcriptomics Gambusia affinis

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Pharmaco-toxicological effects of the synthetic cannabinoids 4F-ABUTINACA, SDB-005, and JWH-018 in mice. In vitro and in vivo studies

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EUROPEAN JOURNAL OF PHARMACOLOGY 2025年 996卷 177586页

作者： Luo, xuwen Kuai, Lixin Shi, Xuesong Qiao, Yanling Li, Kaixi Xu, Deli Di, Bin Yan, fang Xu, Peng China Pharmaceut Univ Sch Pharm Nanjing 210009 Peoples R China China Pharmaceut Univ Joint Lab Key Technol Narcot Control Off China Natl Narcot Control Commiss Beijing 100193 Peoples R China Minist Publ Secur Drug Intelligence & Forens Ctr Key Lab Drug Monitoring & Control Beijing 100193 Peoples R China

Background: Synthetic cannabinoids (SCs) are currently one of the most severely abused new psychoactive substances in the world. However, there remains a notable lack of pharmacological data on the newly emerged synthetic cannabinoids. In the present study, the in vitro and in vivo pharmacological effects of the fourth-generation synthetic cannabinoids 4F-ABUTINACA and SDB-005 are determined and compared to those of the first-generation synthetic cannabinoid JWH-018. Methods: In this study, the affinities of three SCs for CB1 receptors were evaluated using surface plasmon resonance (SPR) experiments. The acute toxicity of these three SCs was assessed through the up-and-down procedure, while their cannabinoid-specific pharmacological effects were determined through tetrad assays, which examined parameters such as temperature regulation, analgesia, locomotor activity, and catalepsy. Additionally, conditioned place preference (CPP) experiments and a precipitated withdrawal tests were conducted to assess the psychoactive effects and physical dependence of the SCs. Results: SPR experiments and acute toxicity tests demonstrated that in vitro KD values were positively correlated with in vivo ED50 potency estimates. All SCs were found to induce the classical "tetrad effects" in a dose-dependent manner. Notably, all SCs displayed significant biphasic effects in CPP experiments. Following the administration of the CB1 receptor antagonist rimonabant, a significant increase in head twitches and paw tremors was observed, indicating that the physical dependence manifested after the ingestion of SCs is mediated by the CB1 receptor. Conclusions: These findings suggest that these SCs have cannabinoid-specific pharmacological effects and abuse potential, providing robust experimental data to support future regulatory efforts.

关键词： 4F-ABUTINACA SDB-005 JWH-018 Tetrad CPP Precipitated withdrawal

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Synergistic optimization strategies for the development of multienzymatic cascade system-based electrochemical biosensors with enhanced performance

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BIOSENSORS & BIOELECTRONICS 2025年 274卷 117222页

作者： Zhu, Yuzhuo Cheng, Zhaoming Wang, Xueqi Zhang, Chuanjun Li, xuwen Wei, Yanxue Wang, Jiajia fang, Yuxin Wang, Yi Zhang, Di Tianjin Univ Tradit Chinese Med Coll Pharmaceut Engn Tradit Chinese Med Tianjin 301617 Peoples R China Tianjin Univ Tradit Chinese Med Inst Tradit Chinese Med Tianjin 301617 Peoples R China Tianjin Key Lab Intelligent & Green Pharmaceut Tra Tianjin 301617 Peoples R China State Key Lab Chinese Med Modernizat Tianjin 301617 Peoples R China Tianjin Univ Tradit Chinese Med Coll Acumox & Tuina Res Ctr Expt Acupuncture Sci Tianjin 301617 Peoples R China Natl Clin Res Ctr Chinese Med Acupuncture & Moxibu Tianjin 301617 Peoples R China

Multienzymatic cascade system (MCS) strategies have been a topic of growing interest in the electrochemical biosensor research field owing to their many advantages. By combining two or more enzymes in an appropriate manner, MCS approaches can extend the range of detection for particular analytes while improving the overall efficiency of biocatalytic cascade reactions. Compared with mono-enzyme biosensors, the integration of MCS and electrochemical biosensor platforms is inherently more challenging owing to the increased complexity of the resultant system. In recent years, substantial progress in the development of MCS-based electrochemical biosensors with enhanced analytical performance has been made. This review provides an overview of the types of MCS strategies and their biosensor applications, together with a summary of synergistic optimization approaches that can help improve key parameters including sensitivity, selectivity, and stability when designing MCS-based electrochemical biosensors. These discussions include examples of published biosensor platforms (2016-2024) while also surveying key advances in associated research areas including redox mediators/enzyme coimmobilization, enzyme engineering, multienzyme spatial regulation, enzyme-nanozyme integration and others. Lastly, a brief overview of current challenges and future perspectives pertaining to MCS-based electrochemical biosensor design is provided.

关键词： Multienzymatic system Electrochemical biosensor Cascade reaction Synergistic strategy Enzymatic biosensor

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Development and Validation of a Screening Tool for Generalized Anxiety and Major Depressive Disorder in Patients with Chronic Obstructive Pulmonary Disease

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LUNG 2025年第1期203卷 1-12页

作者： Liu, Meishan Yang, xuwen Wang, Dong fang, Jiexin Li, Boyu An, Li Chang, Yuhan Liu, Haiman Hu, Yongdong Huang, Kewu Capital Med Univ Beijing Inst Resp Med Dept Resp & Crit Care Med 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp Dept Clin Psychol 8Gongti South Rd Beijing 100020 Peoples R China Capital Med Univ Beijing Chao Yang Hosp Dept Pharm Beijing Peoples R China

PurposeAnxiety and depression are often underdiagnosed in patients with chronic obstructive pulmonary disease (COPD). This study aimed to develop and validate a screening tool for anxiety and depression in COPD *** COPD patients were consecutively recruited from November 2021 to October 2023 and underwent a psychiatric interview to diagnose generalized anxiety disorder (GAD) and/or major depressive disorder (MDD) based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Patients were split into training and validation sets according to their recruitment time. We assessed known risk factors and used core items from the Patient Health Questionnaire Anxiety and Depression Scale (PHQ-ADS) to develop a prediction nomogram. Multivariable logistic regression with least absolute shrinkage and selection operator (LASSO) were used to construct the *** the enrolled COPD patients (n = 329), 58 (25.6%) in the training cohort and 33 (32.4%) in the validation cohort were diagnosed with GAD and/or MDD. Three variables were identified in the prediction nomogram: COPD Assessment Test score and two core items from PHQ-ADS. The under the curve (AUC) value for the nomogram was 0.826 (95% CI: 0.755-0.897) and 0.855 (95% CI: 0.767-0.942) in the training and validation cohorts, respectively. The calibration curve was close to the diagonal. The discriminatory power of the screening nomogram was comparable to that of PHQ-ADS (AUC: 0.826 vs. 0.831, P = 0.832).ConclusionThe new screening tool for GAD and MDD in COPD patients is concise and valid, with discriminatory power comparable to existing anxiety/depression screening questionnaires.

关键词： Chronic obstructive pulmonary disease Anxiety Depression Screening Nomogram

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Aquaponics model can provide better productivity: Microorganisms affect the growth and health of tilapia

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AQUACULTURE REPORTS 2025年 40卷

作者： Fan, Dingyue Xu, Huimin Meng, Shunlong Fan, Limin Song, Chao Qiu, Liping Li, Dandan fang, Longxiang Liu, Zhuping Bing, xuwen Shanghai Ocean Univ Coll Fisheries & Life Sci Shanghai Peoples R China Chinese Acad Fishery Sci Freshwater Fisheries Res Ctr Sci Observing & Expt Stn Fishery Resources & Envir Wuxi 214081 Peoples R China

Aquaponics is a novel ecological agricultural strategy that combines aquaculture and hydroponic cultivation. The relationships between fish immunological and digestive functions, water quality, and bacterial populations were not well understood. This study aims to investigate the effects of aquaponics on aquaculture water quality, fish growth performance, and fish health, as well as exploring the roles of microbial taxa in these processes. In the present study, three aquaponics systems were established, and three same sized recirculating aquaculture systems (RAS) were constructed to act as controls. To evaluate bacterial community diversity and compositions across different microhabitats in the two systems, we used amplicon-based high-throughput sequencing technique targeting the 16S rRNA gene. In aquaponics, fish had a much greater nitrogen utilization rate, weight gain rate (WGR), feed conversion ratio (FCR), and specific growth rate (SGR) than in controls. The activities of alkaline phosphatase (AKP), acid phosphatase (ACP), lysozyme (LYS), lipase (LPS), and trypsin (TRP) in tissues, all of which are indicators of fish health, were significantly greater in aquaponics than in controls. Aquaponics effectively lowered chlorophyll-a levels while having little effect on other water quality metrics, indicating their potential for better algae control. Water quality measures such as dissolved organic carbon, chlorophyll-a, dissolved oxygen, and ammonia nitrogen had a substantial impact on the fish's immunological and digestive capabilities. In terms of microbial influence, particular gut bacteria-such as the bacterial orders Pseudomonadales, Caulobacterales, Defluviicoccales, Exiguobacterales, and Gemmatales-have been identified as influencing various functions in fish. Among these bacterial orders, we found that Pseudomonadales and Exiguobacterales were more abundant in aquaponics than control systems. This study demonstrated that aquaponics can increase fish health an

关键词： Aquaponics Tilapia growth and health Water quality Microbial community

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Modeling Hydro-Dynamics in a Harbor Area in the Daishan Island, China

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WATER 2019年第2期11卷 192页

作者： Li, Yuting Song, Zhiyao Peng, Guoqiang fang, xuwen Li, Ruijie Chen, Peng Hong, Haoyuan Nanjing Normal Univ Key Lab Virtual Geog Environm Nanjing 210023 Jiangsu Peoples R China State Key Lab Cultivat Base Geog Environm Evolut Nanjing 210023 Jiangsu Peoples R China Jiangsu Ctr Collaborat Innovat Geog Informat Reso Nanjing 210023 Jiangsu Peoples R China Anhui Transport Survey & Design Inst Co Ltd Hefei 230000 Anhui Peoples R China Hohai Univ Key Lab Coastal Disaster & Def Minist Educ Nanjing 210098 Jiangsu Peoples R China Hohai Univ Coll Oceanog Nanjing 210098 Jiangsu Peoples R China

This study presents an incorporation and application of a two-dimensional, unstructured-grid hydrodynamic model with a suspended sediment transport module in Daishan, China. The model is verified with field measurement data from 2017: water level, flow velocities and suspended sediment concentration (SSC). In the application on the Daishan, the performance of the hydrodynamic model has been satisfactorily validated against observed variations of available measurement stations. Coupled with the hydrodynamic model, a sediment transport model has been developed and tested. The simulations agreed quantitatively with the observations. The validated model was applied to the construction of breakwaters and docks under a different plan. The model can calculate the flow field and siltation situation under different breakwater settings. After we have analyzed the impact of existing breakwater layout schemes and sediment transport, a reasonable plan will be selected. The results show that the sea area near the north of Yanwo Shan and Dongken Shan has a large flow velocity exceeding 2.0 m/s and the flow velocity within the isobath of 5 m is small, within 0.6 m/s. According to the sediment calculation, the dock project is feasible. However, the designed width of the fairway should be increased to ensure the navigation safety of the ship according to variation characteristics of cross flow velocity in channel.

关键词： suspended sediment concentration numerical simulation breakwater the dock project

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Impact analysis of different axis layouts of detached breakwater on flow and sediment transport

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ARABIAN JOURNAL OF GEOSCIENCES 2021年第8期14卷 705-705页

作者： Yu, Haitao Luo, Feng Li, Ruijie Liu, Yanran fang, xuwen Li, Yuting Hohai Univ Minist Educ Key Lab Coastal Disaster & Def Nanjing 210098 Peoples R China Hohai Univ Coll Harbour Coastal & Offshore Engn Nanjing 210098 Peoples R China Hohai Univ Coll Oceanog Nanjing 210098 Peoples R China Nanjing Environm Monitoring Ctr Nanjing 210098 Peoples R China Xiamen Univ Marine Monitoring & Informat Serv Ctr Xiamen 361005 Peoples R China Nanjing Normal Univ Key Lab Virtual Geog Environm Nanjing 210023 Peoples R China

An incorporation and application of a two-dimensional, unstructured grid hydrodynamic model with a suspended sediment transport module is presented in the study. The model has a satisfactory verification with available measured data. After the verification, the variation of tidal current field and the seabed evolution are simulated. Based on the simulation results, the paper compares and analyzes the effects of different axis layouts of detached breakwater on flow field and seabed evolution. The results show that after the construction of the breakwater, the flow velocity of the both sides of the breakwater decreases, the flow velocity of the east entrance increases, and the erosion and siltation of sediment are consistent with the change of the flow field. In addition, the smaller the angle between the breakwater axis and the depth contour is, the smaller the impact on the change of the tidal current field and sediment erosion and siltation is.

关键词： Detached breakwater Axis layout Flow and sediment transport Hydrodynamic model

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微加工悬臂梁在横向冲击下的响应分析

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Journal of Semiconductors 2005年第2期26卷 379-384页

作者：方绪文唐洁影黄庆安东南大学MEMS教育部重点实验室南京210096

分析了微加工悬臂梁在横向冲击下的响应 .将悬臂梁看作一个质量分布参数系统 ,利用模态叠加法计算悬臂梁在冲击下的位移和应力分布 ,并根据位移和应力的最大值判断悬臂梁可能的失效模式 ,从而为MEMS器件的可靠性设计提供依据 .

关键词： MEMS 悬臂梁冲击分布参数

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A Methionine Allocation Nanoregulator for the Suppression of Cancer Stem Cells and Support to the Immune Cells by Epigenetic Regulation

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ADVANCED SCIENCE 2025年第15期12卷 e2415207页

作者： Su, Boyu Chen, Qinjun Li, xuwen fang, Mingzhu Wang, Yu Song, Haolin You, Haoyu Zhou, Zheng Wu, Yuxing Zhao, Zhenhao Chen, Yun Fan, Hongrui Li, Chufeng Jiang, Chen Sun, Tao Fudan Univ State Key Lab Med Neurobiol Sch Pharm Dept PharmaceutKey Lab Smart Drug DeliveryMinist Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Digest Dis Binhai Campus Fuzhou 350212 Peoples R China Quzhou Fudan Inst Quzhou 324003 Peoples R China

Epigenetic dysregulation is prevalent in human cancers, affecting gene expression and metabolic patterns to meet the demands of malignant evolution and abnormal epigenetic processes, and resulting in a protumor immune microenvironment. Tumors require a steady supply of methionine for maintaining epigenetic flexibility, which is the only exogenous precursor of methyl donor S-adenosylmethionine for methylation, crucial for their resistance to therapies and survival in a nutrient-deficient microenvironment. Thus, tumor cells upregulate the Lat4 transporter to compete and deprive methionine in the microenvironment, sustaining their malignant phenotypes and also impairing immune cell functions. Addressing this methionine addiction is the key to overcoming drug resistance and improving immune response. Despite the challenge of lacking specific Lat4 inhibitors, an oxaliplatin prodrug crosslinked fluorinated polycation/anti-Lat4 small interfering RNA complex nanoregulator (AS-F-NP) has been designed and developed here. This nanoregulator restricted the greedy methionine uptake of tumor cells by knocking down Lat4, which in turn inhibited the malignant evolution of the tumor while restoring the viability and function of tumor-infiltrating immune cells.

关键词： cancer therapy epigenetic immune methionine oxaliplatin siRNA

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