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Strength through unity: Alkaline phosphatase-responsive AIEgen nanoprobe for aggregation-enhanced multi-mode imaging and photothermal therapy of metastatic prostate cancer

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Chinese Chemical Letters 2025年第2期36卷 289-296页

作者： Ze Wang Hao Liang Annan Liu Xingchen Li Lin Guan Lei Li Liang He Andrew K.Whittaker Bai Yang Quan Lin State Key Laboratory of Supramolecular Structure and Materials College of Chemistry Jilin University Department of Endocrinology Lequn Branch the First Hospital of Jilin University Department of Urology the First Hospital of Jilin University Australian Institute for Bioengineering and Nanotechnology the University of Queensland

Prostate cancer(PCa) is characterized by high incidence and propensity for easy metastasis, presenting significant challenges in clinical diagnosis and treatment. Tumor microenvironment(TME)-responsive nanomaterials provide a promising prospect for imaging-guided precision therapy. Considering that tumor-derived alkaline phosphatase(ALP) is over-expressed in metastatic PCa, it makes a great chance to develop a theranostics system with ALP responsive in the TME. Herein, an ALP-responsive aggregationinduced emission luminogens(AIEgens) nanoprobe AMNF self-assembly was designed for enhancing the diagnosis and treatment of metastatic PCa. The nanoprobe exhibited self-aggregation in the presence of ALP resulted in aggregation-induced fluorescence, and enhanced accumulation and prolonged retention period at the tumor site. In terms of detection, the fluorescence(FL)/computed tomography(CT)/magnetic resonance(MR) multi-mode imaging effect of nanoprobe was significantly improved post-aggregation, enabling precise diagnosis through the amalgamation of multiple imaging modes. Enhanced CT/MR imaging can achieve assist preoperative tumor diagnosis, and enhanced FL imaging technology can achieve “intraoperative visual navigation”, showing its potential application value in clinical tumor detection and surgical guidance. In terms of treatment, AMNF showed strong absorption in the near infrared region after aggregation, which improved the photothermal treatment effect. Overall, our work developed an effective aggregation-enhanced theranostic strategy for ALP-related cancers.

关键词： AIE ALP responsive Enhanced multi-mode imaging Enhanced photothermal therapy Prostate cancer

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C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway as a therapeutic target and regulatory mechanism for spinal cord injury

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Neural Regeneration Research 2025年第8期20卷 2231-2244页

作者： Xiangzi Wang Xiaofei Niu Yingkai Wang Yang Liu Cheng Yang Xuyi Chen Zhongquan Qi School of Medicine Guangxi UniversityNanningGuangxi Zhuang Autonomous RegionChina Graduate School of Tianjin university of Traditional Chinese Medicine TianjinChina Characteristic medical Center of People’s Armed Police Forces TianjinChina fujian Maternity and Child Health Hospital FuzhouFujian ProvinceChina

Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory *** expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after *** studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for *** review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord ***,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted ***,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 *** review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.

关键词： apoptosis C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 pathway C-C motif chemokine receptor 2 antagonists chemokine ligand 2 chemokine receptor 2 inflammation macrophage microglia spinal cord injury therapeutic method

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The Impact of PCSK9 on Risk Factors for Ischemic Stroke and Potential Mechanisms

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American Journal of Molecular Biology 2025年第1期15卷 110-122页

作者： Zehua He Mingtian Lu Zhejing Ding Zhengwei Chen Tianyang Guan Zhongliang Li Cheng Zhou Haiquan Tao Guangsen Cheng Yu Liu Cerebrovascular Diseases Department Zhuhai Clinical Medical College of Jinan University (Zhuhai Peoples Hospital) The First Affiliated Hospital of Faculty of Medicine Macao University of Science and Technology Zhuhai China

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the proprotein convertase (PCs) family, which facilitates the degradation of low-density lipoprotein receptors (LDL-R) via intracellular and cell surface pathways, consequently elevating serum LDL-C levels. PCSK9 is implicated in various processes such as lipid metabolism, atherosclerosis, oxidative stress, inflammatory responses, thrombosis, and apoptosis. It is closely linked to ischemic stroke through its role in inducing and advancing atherosclerosis. PCSK9 inhibitors play a useful role in both acute and secondary prevention of ischemic stroke and can reduce the risk of ischemic stroke. This review examines the influence of PCSK9 on the risk factors associated with ischemic stroke and explores its potential mechanisms, and briefly describes the application of PCSK9 inhibitors in ischemic stroke.

关键词： Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Ischemic Stroke Atherosclerosis Inflammation

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Protective Effect of Selenium Supplementation on Cerebral Ischemia-Reperfusion Injury after Ischemic Stroke

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Journal of Biosciences and Medicines 2025年第1期13卷 184-195页

作者： Mingtian Lu Zehua He Zhejing Ding Zhengwei Chen Tianyang Guan Zhongliang Li Guomin Huang Guangsen Cheng Shaoqin Liao Yu Liu Cerebrovascular Diseases Department Zhuhai Clinical Medical College of Jinan University (Zhuhai Peoples Hospital) The First Affiliated Hospital of Faculty of Medicine Macao University of Science and Technology Zhuhai China

With the wide application of thrombolytic drugs and the advancement of endovascular therapeutic techniques, the recanalization treatment of acute artery occlusion in ischemic stroke (IS) has made a leap forward, but ischemic brain tissues still face ischemia-reperfusion injury after recanalization. Nowadays, effective neurological protective agents still cannot completely resist the multiple damages of ischemia-reperfusion injury. As an iron-dependent mode of programmed cell death, ferroptosis occupies an important position in ischemia-reperfusion injury. Selenium plays a unique protective role in ischemia-reperfusion injury as an active site element in the center of glutathione peroxidase. Therefore, the study mainly aims to review the protective role of selenium in IS and the related mechanisms, as well as the effect of selenium on the risk factors of IS.

关键词： Selenium Ischemic Stroke Cerebral Ischemia-Reperfusion Injury GPx4

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Evaluation of the therapeutic significance of Glehniae Radix polysaccharides on the ulcerative colitis through DSS-induced rat model

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Food Science and Human Wellness 2025年

作者： Jie Liu Xufang Geng Yuxin Yang Jiao Xu Haoran Feng Tianshuo Zhang Guangzhao Zhou Man Wang Changshun Wang Dongsheng Jia Yuting Chen Bin Cong Ding Zhao The Postdoctoral Mobile Station of Basic Medicine， Hebei medical university The Department of Pharmacognosy， School of Pharmacy， Hebei medical university Hebei Key Laboratory of Forensic Medicine， college of Forensic Medicine， Hebei medical university

Glehniae Radix has a wide range of pharmaceutical applications， and research on its main components has mainly focused on coumarins， alkaloids， lignans， and flavonoids， while neglecting the research on polysaccharides. Literature reports and our previous studies have shown that polysaccharides have certain therapeutic significance in immune regulation， antioxidant， anti-inflammatory and other aspects. Herein， the rat model of ulcerative colitis (UC) was established to evaluate the anti-inflammatory efficacy of the prepared Glehniae Radix polysaccharide (GLP) from the perspectives of inflammatory factors， intestinal tissue morphology， and microflora changes. The polysaccharides are mainly composed of galacturonic acid， rhamnose， glucose， galactose， and arabinose in molar ratios of 1.4:9.2:33.3:2.5:2.9， and GLP could downregulate the expression pro-inflammatory factors (interleukin-6， tumor necrosis factor-α， and interferon-γ) and significantly upregulate the expression of anti-inflammatory factor (interleukin-10). In addition， Glehniae Radix aqueous extract (GLA)， GLP with low dosage (GLPL) and GLP with high dosage (GLPH) could increase the number of goblet cells， enhance the integrity of crypt structure， and reverse the status of inflammatory infiltrating cells. Moreover， GLA and GLPH could upregulate Lactobacillus and Lachnoclostridium in UC rats， and appropriately downregulate Lachnospiraceae＿NK4A136＿group， thereby optimizing the proportion of bacterial flora and improving the intestinal microbial environment. Our findings not only be valuable as theoretical materials for the further clinical applications of GLP， but the identified biomarkers and metabolic pathways also provide new clues for the diagnosis of UC.

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Tianxiangdan(TXD) alleviates myocardial ischemia reperfusion-induced ferroptosis through the activation of estrogen receptor alpha(ERα)

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Chinese Journal of Natural Medicines 2025年第1期23卷 102-110页

作者： Yuanjia Yue Yu Li Xing Rong Zhao Ji Huimin Wang Liang Chen Lin Jiang Department of Pharmacy The Fourth College of Clinical Medicine Xinjiang Medical University Department of Pharmacy Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central Asia Xinjiang Medical University Department of Neurosurgery ICU Xinjiang Uygur Autonomous Region People's Hospital

Tianxiangdan（TXD）, a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion（I/R）-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. Highperformance liquid chromatography-mass spectrometry（HPLC-MS） identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase（LDH）,malondialdehyde（MDA）, superoxide dismutase（SOD） activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha（ERα）protein expression and estradiol（E2） levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group(300 nmol·L-1AZD9496 and 15% TXD serum) was compared to a TXD group（15% TXD serum）. The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0 μmol·L-1Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERαproteins. A DCFH-DA probe detected reactive oxygen species（ROS） and Fe2+, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers（LDH, MDA, and SOD）, alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe2+levels, while the AZ group（treated with AZD9496） exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4（GPX4）, with reduced levels of P53

关键词： Estrogen receptor alpha Ferroptosis Myocardial ischemia-reperfusion injury Network pharmacology Tianxiangdan

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Activatable chemiluminescence probe based on four-arm PEGconjugated-pyropheophorbide-a for in vivo autofluorescence-free imaging of peroxynitrite

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Science China Chemistry 2025年

作者： Jianmei Ke Lei Ding Ronggui Lian Cheng Zheng Wenjun Li Aixian Zheng Yupeng Sun Ming Wu Yongyi Zeng Xiaolong Liu Maochun Hong Xiaolong Zhang The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Ganjiang Innovation Academy Chinese Academy of Sciences School of Rare Earths University of Science and Technology of China college of Chemistry Fuzhou University State Key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences

Peroxynitrite（ONOO-） is a highly reactive nitrogen species that plays pivotal roles in cell signal transduction and physiological or pathological progresses. However, commonly used ONOO-optical imaging probes are still hampered by high background/autofluorescence（fluorescence probe）, short emission wavelength, or poor selectivity in the case of chemiluminescence. Herein,we report a facile method to prepare an activatable chemiluminescence probe（PPA-PEG） with good biocompatibility and functionality for in vivo autofluorescence-free imaging of ONOO-. The PPA-PEG consists of pyropheophorbide-a（PPA）, a typical deep red photosensitizer that acts as both the recognition and signaling element, and 4-arm poly（ethylene glycol）(4-arm PEG), which improves the biosafety and water solubility of probe. These components can self-assemble into nanoparticles（namely PPA-PEG nanoprobe） in aqueous solution. The PPA-PEG nanoprobe showed an ultra-low chemiluminescence signal before interacting with ONOO-, but exhibited good selectivity, high sensitivity and a fast response toward ONOO-. The PPAPEG was successfully applied to image cellular ONOO-changes, as well as the endogenous ONOO-changes in inflammation models and subcutaneous or orthotopic hepatocellular carcinoma（HCC） tumors models in living mice. In vitro and in vivo studies verified the good detection and imaging capabilities of PPA-PEG for peroxynitrite, demonstrating suitable tissue penetration and a high signal-to-background ratio（SBR）. Thus, our nanoprobe can serve as a valuable activatable chemiluminescence imaging tool for studying important peroxynitrite-related chemical and biological applications.

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Chimeric antigen receptor T cells targeting CD312 as a therapy for acute myeloid leukemia

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中华医学杂志(英文版) 2025年第1期138卷 2024 Nov 5页

作者： Xie Danni Wang Bing Bai Xue Jin Xin Lu Wenyi Zhang Meng Zhang Yi Cao Xinping Zhao Mingfeng first Central clinical college Tianjin Medical University Tianjin China Department of Hematology Tianjin First Central Hospital Tianjin China Liangzhu Laboratory Zhejiang University Medical Center Hangzhou Zhejiang China

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Association between echocardiography utilization and prognosis in patients with cardiac arrest

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World Journal of Emergency Medicine 2025年第1期16卷 63-66页

作者： Nan Zhang Qingting Lin Huadong Zhu Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Radiology the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

Despite efforts to develop treatment technology for cardiac arrest (CA),CA incidence and mortality rates are still high.^([1,2])A recent study of CA patients in emergency departments revealed that the incidence of CA is increasing annually,and the in-hospital survival rate of CA patients is only approximately 28.7%.^([3])Echocardiography has been widely used as an important monitoring tool in critical care and helps to identify the cause of shock,monitor hemodynamics,and guide fluid therapy utilization.^([4])One study reported that approximately one-third of patients underwent formal echocardiography during hospitalization in the intensive care unit (ICU).

关键词： patients echocardiography cardiac

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Bacteria and host: what does this mean for sepsis bottleneck?

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World Journal of Emergency Medicine 2025年第1期16卷 10-17页

作者： Azzah S Alharbi Raghad Hassan Sanyi Esam I Azhar Department of clinical Microbiology and Immunology Faculty of MedicineKing Abdulaziz UniversityJeddah 21362Saudi Arabia Special Infectious Agent Unit King Fahad Medical Research CenterKing Abdulaziz UniversityJeddah 21362Saudi Arabia college of Health and medical Technology Middle Technical UniversityBaghdad 10047Iraq Department of medical Laboratory Sciences Faculty of Applied Medical SciencesKing Abdulaziz UniversityJeddah 21362Saudi Arabia

BACKGROUND: Sepsis is a life-threatening inflammatory condition in which the invading pathogen avoids the host's defense mechanisms and continuously stimulates and damages host cells. Consequently, many immune responses initially triggered for protection become harmful because of the failure to restore homeostasis, resulting in ongoing hyperinflammation and immunosuppression. METHODS: A literature review was conducted to address bacterial sepsis, describe advances in understanding complex immunological reactions, critically assess diagnostic approaches, and emphasize the importance of studying bacterial bottlenecks in the detection and treatment of ***: Diagnosing sepsis via a single laboratory test is not feasible;therefore, multiple key biomarkers are typically monitored, with a focus on trends rather than absolute values. The immediate interpretation of sepsis-associated clinical signs and symptoms, along with the use of specific and sensitive laboratory tests, is crucial for the survival of patients in the early stages. However, long-term mortality associated with sepsis is now recognized, and alongside the progression of this condition, there is an in vivo selection of adapted ***: Bacterial sepsis remains a significant cause of mortality across all ages and societies. While substantial progress has been made in understanding the immunological mechanisms underlying the inflammatory response, there is growing recognition that the ongoing host-pathogen interactions, including the emergence of adapted virulent strains, shape both the acute and long-term outcomes in sepsis. This underscores the urgent need for novel high-throughput diagnostic methods and a shift toward more pre-emptive, rather than reactive, treatment strategies in sepsis care.

关键词： Sepsis Bacteria Bottleneck Inflammation

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