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PIG3 downregulation enhances the radiosensitivity of NSCLC cells by promoting G2/M cell cycle arrest and apoptosis PIG3下调通过促进G2/M细胞周期阻滞和凋亡增强NSCLC细胞的放射敏感性
Q1 Health Professions Pub Date : 2023-03-01 DOI: 10.1016/j.radmp.2022.10.003
Hao Zhou , Linfeng Tang , Zeng-Fu Shang , Ping-Kun Zhou , Ming Li

Objective

To investigate the mechanism of p53-induced gene 3 (PIG3)-regulation of radioresistance in human non-small cell lung cancer (NSCLC) cells, in order to explore new biomarkers and therapeutic targets to combat radioresistance and improve the 5-year survival rate.

Methods

The PIG3 gene was knocked down in A549 ​cells using siRNA, and was overexpressed in H1299 ​cells using a PIG3 expression plasmid. After confirming PIG3 knockdown and overexpression through the Western blot analysis, the radiosensitivity, DNA damage, cell cycle distribution, and apoptosis in these cells were analyzed using colony formation assay, immunofluorescence staining for γH2AX, and flow cytometry, respectively.

Results

PIG3 silencing markedly increased the radiosensitivity of NSCLC cells, with radiosensitization ratios of 1.12 and 1.25. Compared with the corresponding negative control, PIG3 knockdown significantly enhanced G2/M phase arrest (siNC: 26.12 ​± ​2.50, siPIG3#1: 34.98 ​± ​4.19, siPIG3#2: 37.79 ​± ​3.53, P ​< ​0.05), promoted radiation-induced apoptosis (siNC: 14.61 ​± ​1.85, siPIG3#1: 17.26 ​± ​1.14, siPIG3#2: 20.70 ​± ​2.04, P ​< ​0.05), and reduced the number of γ-H2AX foci 0.5, 1, and 2 ​h after radiation (P ​< ​0.05). Conversely, PIG3 overexpression markedly decreased the radiosensitivity of NSCLC cells, as evidenced by the reduction of G2/M phase arrest (NC: 33.18 ​± ​2.11 vs. PIG3: 24.21 ​± ​3.09, P ​< ​0.05) and apoptosis (NC: 15.49 ​± ​0.56 vs. PIG3: 12.79 ​± ​0.29, P ​< ​0.05), and increased DNA damage (P ​< ​0.05).

Conclusions

PIG3 downregulation increases the radiosensitivity of NSCLC cells, and PIG3-upregulation leads to the progression in radioresistance. Therefore, PIG3 is a potential target for radiotherapy for NSCLC.

目的探讨p53诱导的基因3 (PIG3)调控人非小细胞肺癌(NSCLC)细胞放射耐药的机制,探索新的生物标志物和治疗靶点,以对抗放射耐药,提高5年生存率。方法利用siRNA在A549细胞中敲低PIG3基因,利用PIG3表达质粒在H1299细胞中过表达。Western blot分析证实PIG3敲低和过表达后,分别用集落形成法、γ - h2ax免疫荧光染色法和流式细胞术分析细胞的放射敏感性、DNA损伤、细胞周期分布和凋亡情况。结果spig3沉默可显著提高NSCLC细胞的放射敏感性,其放射敏感性比值分别为1.12和1.25。与相应的阴性对照组相比,PIG3敲低显著增强G2/M相阻滞(siNC: 26.12±2.50,siPIG3#1: 34.98±4.19,siPIG3#2: 37.79±3.53,P <0.05),提升辐射诱导细胞凋亡(siNC: 14.61±1.85,siPIG3 # 1: 17.26±1.14,siPIG3 # 2: 20.70±2.04,P & lt;0.05),辐照后0.5、1、2 h γ-H2AX焦点数量减少(P <0.05)。相反,PIG3过表达显著降低NSCLC细胞的放射敏感性,G2/M期阻滞降低(NC: 33.18±2.11 vs PIG3: 24.21±3.09,P <0.05)和细胞凋亡(NC: 15.49±0.56 vs PIG3: 12.79±0.29,P & lt;0.05), DNA损伤增加(P <0.05)。结论spig3下调可增加NSCLC细胞的放射敏感性,而pig3上调可导致NSCLC细胞放射耐药的进展。因此,PIG3是NSCLC放疗的潜在靶点。
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引用次数: 0
Risk of cataract of different morphological types in Urals population chronically exposed at low doses 长期低剂量接触乌拉尔人群不同形态白内障的风险
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.09.001
L.D. Mikryukova , A.V. Akleyev

Objective

To assess the risk of lens opacity depending on the dose in the population exposed to external and internal radiation for a long time, based on a long-term clinical follow-up of the cohorts of people exposed to radiation as a result of two radiation accidents in the South Urals.

Methods

A layer-by-layer morphological study of the lens of 1,377 exposed individuals was conducted according to a special program in the Clinical Department of the Urals Research Center for Radiation Medicine (URCRM) 68 years after the onset of exposure. Lens changes were classified in accordance with the lens opacities classification (LOCS) III and included images of lens. To calculate the doses to lens, the data were taken into account, including the person's residence history in the radioactively contaminated territory, age and sex that affected their lifestyle and diet, radionuclide distribution in organs and tissues. Individualized lens doses were calculated using Techa River Dosimetry System (TRDS)-2016. Case-control method was used for statistical analysis.

Results

Individual values of absorbed dose to lens ranged from 0 to 600 ​mGy. A dose-dependent increased risk of posterior subcapsular cataract (PSC) (OR ​1.54, 95%CI: 1.04–2.27) and nuclear cataract (OR ​1.84, 95%CI: 1.14–2.95) was found among chronically exposed individuals by a case-control method. No evidence of dose effect was found for cortical cataracts.

Conclusions

The results showed that population exposed to long-term chronic low-dose radiation was subjected to an increased risk of PSC and nuclear cataract development.

目的通过对南乌拉尔地区两起辐射事故中受辐射人群的长期临床随访,评估长期受内外照射人群晶状体混浊风险与剂量的关系。方法根据乌拉尔辐射医学研究中心(URCRM)临床部的特殊计划,对1377名受照者的晶状体进行了照射68年后的逐层形态学研究。根据Lens opacity classification (LOCS) III对晶状体变化进行分类,纳入晶状体图像。为了计算对透镜的剂量,数据被考虑在内,包括该人在放射性污染地区的居住历史,影响其生活方式和饮食的年龄和性别,器官和组织中的放射性核素分布。使用Techa River剂量测定系统(TRDS)-2016计算个体化晶状体剂量。采用病例对照法进行统计分析。结果晶状体吸收剂量在0 ~ 600 mGy之间。通过病例对照法发现,慢性暴露人群发生后囊膜下白内障(PSC) (OR 1.54, 95%CI: 1.04-2.27)和核性白内障(OR 1.84, 95%CI: 1.14-2.95)的风险呈剂量依赖性增加。皮质性白内障没有剂量效应的证据。结论长期慢性低剂量辐射暴露人群PSC和核性白内障发生风险增加。
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引用次数: 0
Overall results and prospects of the cancer risk assessment in the Urals population affected by chronic low dose-rate exposure 在受慢性低剂量率暴露影响的乌拉尔人群中进行癌症风险评估的总体结果和前景
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.08.002
Alexander Vasilyevich Akleyev , Marina Olegovna Degteva , Ludmila Yurievna Krestinina

The paper presents the key milestones and outcomes of 65-year studies of the carcinogenic consequences of accidental radiation exposure of the population of the Ural region. The radioactive contamination of the Techa River and the 1957 accident at the Mayak Production Association were the reasons of the long-term population exposure at a wide dose-range. The most important tasks of the study were the reconstruction of individual doses, follow-up of the solid cancer and leukemia incidence and mortality among cohort members. The research results have shown that chronic human exposure, in comparison to acute exposure, does not reduce the risk of developing malignant tumors and leukemias. The value of the dose-rate factor does not exceed "one".

Thus, according to our data, the Publication 103 of the International Commission on Radiological Protection seemed to underestimate the radiation risk of malignant tumors and leukemias in case of low dose-rate exposure of the population by a factor of two. Prospects for further radio-epidemiological studies in the Urals are associated with the analysis of the cohort of Southern Urals Populations Exposed to Radiation, which includes about 63 thousand exposed people and makes it possible to assess the radiation risk of solid cancers of certain localizations, certain types of leukemia, and non-cancer effects.

本文介绍了乌拉尔地区人口意外辐射暴露致癌性后果65年研究的关键里程碑和结果。特查河的放射性污染和1957年马亚克生产协会的事故是人口长期受到大剂量范围辐射的原因。本研究最重要的任务是重建个体剂量,随访队列成员的实体癌和白血病发病率和死亡率。研究结果表明,与急性接触相比,人类慢性接触并不能降低患恶性肿瘤和白血病的风险。剂量率因子的值不超过“1”。因此,根据我们的数据,国际放射防护委员会第103号出版物似乎低估了人口在低剂量率照射下患恶性肿瘤和白血病的辐射风险,低估了两倍。乌拉尔地区进一步放射流行病学研究的前景与对乌拉尔南部受辐射人群队列的分析有关,该队列包括约63000名受辐射者,从而有可能评估某些地区实体癌的辐射风险、某些类型的白血病和非癌症影响。
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引用次数: 0
Review of methodological workflow, interpretation and limitations of nomogram application in cancer study 综述了nomogram在癌症研究中的应用的方法学流程、解释和局限性
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.08.004
Wingyi Lee , Sai-Kit Lam , Yuanpeng Zhang , Ruijie Yang , Jing Cai

Nomograms have been increasingly adopted in cancer studies for predicting a variety of clinical outcomes. Compared to conventional prediction approaches, nomograms present an excellent graphical easy-to-interpret visualization and by combining patients’ characteristics and statistical models constructed based on diagnostic tests, higher accuracy could be achieved, facilitating the clinical decision-making process. However, with the increasing number of nomograms being proposed, misinterpretations may often occur, introducing a large degree of uncertainties in clinical situations. This review article aims to provide a methodological summary for nomogram applications, construction, and interpretation, with a demonstrative example of nasopharyngeal carcinoma patient data in the field of radiation medicine. Common misunderstandings and limitations are also discussed to underscore the applicability of nomograms in different scenarios. The overarching goal of this review article is to provide general audiences with fundamental and essential knowledge toward comprehending and implementing nomograms in cancer studies.

在癌症研究中越来越多地采用图来预测各种临床结果。与传统的预测方法相比,nomograph具有良好的图形化,易于解释的可视化效果,并且将患者特征与基于诊断试验构建的统计模型相结合,可以达到更高的准确性,便于临床决策。然而,随着越来越多的线图被提出,误解可能经常发生,在临床情况下引入了很大程度的不确定性。本文以鼻咽癌患者资料为例,对放射医学中nomogram应用、构建和解释的方法学进行综述。还讨论了常见的误解和限制,以强调图在不同情况下的适用性。这篇综述文章的总体目标是为普通读者提供基本的和必要的知识,以便在癌症研究中理解和实施范式图。
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引用次数: 1
Combining radiation with immune checkpoint inhibitors therapy for HCC: From the alteration of the immune microenvironment by radiotherapy 放疗联合免疫检查点抑制剂治疗肝癌:从放疗对免疫微环境的改变看
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.07.005
Kaixiao Zhou , Yabo Jiang , Shuang Feng , Tingya Wang , Lili Wang , Jianping Cao , Yang Jiao

Hepatocellular carcinoma (HCC), one of the deadliest cancers all over the world, had a limited prognosis in the past. Recently, the remarkable efficacy of immune checkpoint inhibitors (ICIs) therapy has been shown in various solid tumors. What's more, the occurrence of HCC is associated with immune escape and therefore various ICIs have been applied to clinical trials for HCC. However, the special immune environment of the liver creates the complex tumor microenvironment (TME) of HCC, which impairs the overall survival (OS) and overall response rate (OCR) of ICIs as a monotherapy. Lately, various therapies have been used in combination with ICIs therapy to improve its clinical efficacy. Among which, radiotherapy is widely concerned because of its unique immunoreaction. A large number of basic and clinical studies have demonstrated that the combined radiotherapy and ICIs therapy has advantages in improving the OCR and efficacy, as compared with ICIs therapy alone. Herein, this article reviews the studies on the advantages and possible mechanisms of the combination of radiotherapy and ICIs therapy for HCC.

肝细胞癌(HCC)是世界上最致命的癌症之一,过去预后有限。近年来,免疫检查点抑制剂(ICIs)治疗多种实体瘤的疗效显著。更重要的是,HCC的发生与免疫逃逸有关,因此各种ICIs已被应用于HCC的临床试验。然而,肝脏特殊的免疫环境造成HCC复杂的肿瘤微环境(TME),损害了ICIs作为单药治疗的总生存期(OS)和总缓解率(OCR)。近年来,各种治疗方法与ICIs治疗相结合,以提高其临床疗效。其中,放射治疗因其独特的免疫反应而受到广泛关注。大量的基础和临床研究表明,与单独使用ICIs治疗相比,放疗联合ICIs治疗在提高OCR和疗效方面具有优势。本文就肝细胞癌放疗与ICIs联合治疗的优势及可能机制的研究进展进行综述。
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引用次数: 1
A review of the impact of FLASH radiotherapy on the central nervous system and glioma FLASH放射治疗对中枢神经系统和胶质瘤的影响
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.10.002
Lin Li, Yayi Yuan, Yahui Zuo

Glioma has received considerable attention because of its potential of inducing high rates of morbidity, disability, and mortality. FLASH radiotherapy (FLASH-RT) has emerged as a popular topic in current research because of its ability to protect normal tissues. The present review summarized the current development of FLASH-RT in both the central nervous system and glioblastomas, explored the potential mechanisms underlying FLASH-RT-mediated protective effects on the central nervous system, and revealed the advantages of this new technique for glioma therapy. This study highlights the benefits and challenges of the present research and provides a reference for future research.

神经胶质瘤因其潜在的高发病率、致残率和死亡率而受到广泛关注。FLASH放射治疗(FLASH- rt)因其保护正常组织的能力而成为当前研究的热门课题。本文综述了FLASH-RT在中枢神经系统和胶质母细胞瘤中的研究进展,探讨了FLASH-RT介导的中枢神经系统保护作用的潜在机制,并揭示了这项新技术在胶质瘤治疗中的优势。本研究突出了当前研究的优势和挑战,并为未来的研究提供了参考。
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引用次数: 0
Analysis of gamma-emitting radionuclides in soils around high energy accelerators 高能加速器周围土壤中放射放射性核素的分析
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.10.004
Jiaying Wang , Yu Chen , Zhongjian Ma , Lu Zhang , Zhen Zhang

Objective

To investigate the specific activities of gamma radionuclides in the soils around high energy accelerators, and to analyze the influence of rays emitted by nuclides with characteristic peaks at similar energy points on nuclide measurement results, in order to provide reference for the accurate identification of radionuclides.

Methods

GR5021 high-purity germanium gamma spectroscopy system was used to measure the specific activities of gamma-emitting radionuclides 226Ra, 232Th, 238U, 40K and artificial radionuclides 54Mn, 52Mn, 7Be, 22Na, 59Fe, 95Zr in six soil samples around three kinds of high energy accelerators, and the theoretical counts of the characteristic peak of 835.7 ​keV were compared with the measured counts of the characteristic peak of 54Mn.

Results

The specific activity ranges of gamma-emitting radionuclides 226Ra, 232Th, 238U and 40K in the soils around three kinds of high energy accelerators were 55.5–171, 34.9–99.9, 21.9–79.3 and 247–680 Bq/kg, respectively. The specific activities of artificial radionuclides 52Mn, 7Be, 22Na, 59Fe and 95Zr were basically lower than the minimum detection limit. A characteristic peak was found at the energy point of 835.7 ​keV in six soil samples, and the corresponding total absorption peak counts were from 228Ac of 232Th ​decay daughter.

Conclusions

The specific activities of gamma-emitting radionuclides were at the normal natural background levels. The specific activities of artificial radionuclides were basically lower than the minimum detection limits. For 232Th, when its specific activity is above 40 Bq/kg, characteristic peak of its decay daughter 228Ac could be misjudged as characteristic peak of 54Mn.

目的研究高能加速器周围土壤中γ放射性核素的比活度,分析具有相似能量点特征峰的核素放射的射线对核素测量结果的影响,为放射性核素的准确鉴定提供参考。方法采用gr5021高纯锗伽马能谱仪测定三种高能加速器周围6种土壤样品中γ发射核素226Ra、232Th、238U、40K和人工放射性核素54Mn、52Mn、7Be、22Na、59Fe、95Zr的比活度,并将835.7 keV特征峰的理论计数与54Mn特征峰的实测计数进行比较。结果三种高能加速器周围土壤中γ -发射核素226Ra、232Th、238U和40K的比活度范围分别为55.5 ~ 171、34.9 ~ 99.9、21.9 ~ 79.3和247 ~ 680 Bq/kg。52Mn、7Be、22Na、59Fe、95Zr等人工放射性核素比活度基本低于最低检出限。6个土壤样品在835.7 keV的能量点处发现了一个特征峰,对应的总吸收峰计数来自228Ac的232Th衰变子。结论放射性核素比活度处于正常的自然本底水平。人工放射性核素比活度基本低于最低检出限。对于232Th,当其比活度大于40 Bq/kg时,其衰变子228Ac的特征峰可能被误判为54Mn的特征峰。
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引用次数: 0
Review of the 5·7 Nanjing 192Ir source radiological accident 南京5·7 192Ir源放射性事故回顾
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.10.001
Yuanyuan Zhou , Ningle Yu , Jin Wang , Wei Chen , Pengfei Cai

This paper gives a detailed description of a radiological accident of 192Ir source occurring on May 7, 2014 in Nanjing, China (the 5⋅7 accident), encompassing a combination of accident overview, emergency response, investigation process and results, dose estimation, medical treatment, experience and lessons learnt. The investigation showed that the accident was mainly caused by insufficient attention to the radiation safety, non-compliance with licensing conditions and employment of untrained temporary radiographer without equipped with alarm dosimeters. Additionally, no area radiation survey meter was used to verify whether the source would have retracted to radiography camera after every exposure. It therefore is the important means to strengthen the management of radioactive source safety and put the strict management measures in place, implement the requirements for personnel qualification management, strengthen regulatory inspection and actively poster safety culture, which are necessary to avoid accidents. This paper aims to provide experience and reference for the emergency response and countermeasure of radiological accidents involving industrial radioactive sources.

本文详细介绍了2014年5月7日发生在中国南京的一起192Ir源放射性事故(5⋅7事故),包括事故概述、应急响应、调查过程和结果、剂量估计、医疗救治、经验教训等内容。调查显示,事故的主要原因是对辐射安全的重视不足、不遵守发牌条件,以及聘用未经训练的临时放射技师而没有配备警报剂量计。此外,没有使用区域辐射测量仪来验证每次曝光后光源是否会缩回到射线照相相机中。因此,加强放射源安全管理,落实严格的管理措施,落实人员资质管理要求,加强监管检查,积极宣传安全文化,是避免事故发生的重要手段。本文旨在为工业放射源辐射事故的应急响应与对策提供经验和借鉴。
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引用次数: 1
Low melting point MCP-69, MCP-96, MCP-137, and MCP-200 alloys for radiation protection in radiological and therapeutic processes 低熔点MCP-69, MCP-96, MCP-137和MCP-200合金用于放射和治疗过程中的辐射防护
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.08.003
Michael W. Perrigin , Kendall A. Williams , Brandon K. Wright , Malaika Maqbool , Emily Caffrey , Remo George , Ghafar Ali , Muhammad Maqbool

Objective

To evaluate the low melting-point MCP-69, MCP-96, MCP-137, and MCP-200 alloys, and characterize them for their potential to protect from the harms associated with radiation and eliminate radiation hazards during radiological procedures and treatment of cancer.

Methods

The Klein-Nishina formula was used to calculate the electronic and atomic cross-sections of these alloys using photon beams with energies 4, 6, 9, 12, and 18 ​MeV. Energy transfer coefficients, Compton mass attenuation coefficient, mass-energy transfer coefficient, and recoil energy of electrons in the specific photon energies of 4–18 ​MeV were calculated. The alloys' effective charge number and the photon energy were key factors in determining the properties found by utilizing the Klein-Nishina formula and Compton effects.

Results

The cross sections and energy transfer coefficients increased with the increasing effective charge number Z of the alloys and decreased as the photon energy increased. The Compton recoil of the ejected electrons was observed to have a direct relationship with photon energy, but mass-energy transfer decreased with increasing photon energy. These alloys can replace the toxic lead for environmentally cleaned radiation applications.

Conclusions

These calculations and characteristics of the MCP alloys can help further determine their viability as materials for radiation shielding, their use in safe cancer diagnosis, treatment, and environmental hazards protection.

目的评价低熔点MCP-69、MCP-96、MCP-137和MCP-200合金,并对其在放射治疗和癌症治疗过程中防止辐射危害和消除辐射危害的潜力进行表征。方法采用Klein-Nishina公式计算能量分别为4、6、9、12和18 MeV的光子束流下合金的电子和原子截面。计算了在4-18 MeV特定光子能量范围内电子的能量传递系数、康普顿质量衰减系数、质能传递系数和反冲能。利用Klein-Nishina公式和Compton效应发现,合金的有效电荷数和光子能量是决定合金性质的关键因素。结果合金的横截面和能量传递系数随有效电荷数Z的增加而增大,随光子能量的增加而减小。发射电子的康普顿反冲与光子能量有直接关系,但质能传递随光子能量的增加而减小。这些合金可以代替有毒的铅用于环境清洁辐射应用。结论这些计算和MCP合金的特性有助于进一步确定其作为辐射屏蔽材料的可行性,以及在癌症安全诊断、治疗和环境危害防护中的应用。
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引用次数: 1
Reflections on nuclear safety culture from the perspective of traditional Chinese culture 从中国传统文化的角度对核安全文化的思考
Q1 Health Professions Pub Date : 2022-12-01 DOI: 10.1016/j.radmp.2022.09.002
Haiyan Chen , Yiyao Cao , Yi Cao

Nuclear safety is a major concern given the rapid development of nuclear power in the modern era. Fostering a nuclear safety culture is an important means of ensuring nuclear safety. In China, a country with a rich historical and cultural heritage, traditional culture will influence the development of a nuclear safety culture. This study explored the origin and levels of nuclear safety culture and reflected on nuclear safety culture from the perspective of traditional Chinese culture. The purpose of this study is to integrate the essence of traditional culture into the nuclear safety culture and foster a nuclear safety culture with Chinese characteristics.

随着现代核电的快速发展,核安全成为人们关注的焦点。建设核安全文化是确保核安全的重要手段。在中国这样一个有着丰富历史文化底蕴的国家,传统文化会影响核安全文化的发展。本研究探讨了核安全文化的起源和层次,并从中国传统文化的角度对核安全文化进行了反思。本研究的目的是将传统文化的精髓融入核安全文化,培育具有中国特色的核安全文化。
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引用次数: 1
期刊
Radiation Medicine and Protection
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