首页 > 最新文献

ACS Applied Energy Materials最新文献

英文 中文
Cost-effectiveness analysis of vaccination strategies against meningococcal disease for children under nine years of age in China. 中国九岁以下儿童脑膜炎球菌病疫苗接种策略的成本效益分析。
IF 4.1 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-13 DOI: 10.1080/21645515.2024.2313872
Haonan Zhang, Haijun Zhang, Hai Fang

Meningococcal vaccination strategies in China are intricate, including multiple vaccines targeting different serogroups. The current National Immunization Program (NIP) includes two polysaccharide vaccines for serogroups A and C (MPV-A and MPV-AC), covering limited serogroups and requiring adaptation. This study aims to evaluate the cost-effectiveness of replacing the current strategy with alternative strategies utilizing non-NIP vaccines to inform policy decisions. From a societal perspective, a decision tree-Markov model was constructed to simulate the economic and health consequences of meningococcal disease in a 2019 birth cohort with four vaccination strategies. Epidemiology, vaccine efficacy, cost, and other parameters were derived from previous studies. We conducted sensitivity analyses to assess the robustness of the findings and explored prices for non-NIP vaccines that enable cost-effective strategies. Compared to the current strategy, alternative strategies using quadrivalent polysaccharide vaccine (MPV-4), bivalent conjugate vaccine (MCV-AC), and quadrivalent conjugate vaccine (MCV-4) could avoid 91, 286, and 455 more meningococcal cases. The ICERs were estimated at approximately $250 thousand/QALY, $450 thousand/QALY, and $1.5 million/QALY, all exceeding the threshold of three times GDP per capita. The alternative strategies were not cost-effective. However, if vaccine prices were reduced to $3.9 for MPV-4, $9.9 for MCV-AC, and $12 for MCV-4, the corresponding strategy would be cost-effective. The current meningococcal vaccination strategy in China could effectively prevent the disease at a low cost, but with limited serogroup coverage. Strategies using MPV-4, MCV-AC, or MCV-4 could increase health benefits at a substantial cost, and might become cost-effective if vaccine prices decrease.

中国的脑膜炎球菌疫苗接种策略错综复杂,包括针对不同血清群的多种疫苗。目前的国家免疫规划(NIP)包括针对 A 和 C 血清群的两种多糖疫苗(MPV-A 和 MPV-AC),覆盖的血清群有限,需要进行调整。本研究旨在评估利用非 NIP 疫苗替代现行战略的成本效益,为政策决策提供依据。从社会角度出发,我们构建了一个决策树-马尔科夫模型,模拟在 2019 年出生队列中使用四种疫苗接种策略对脑膜炎球菌疾病造成的经济和健康后果。流行病学、疫苗疗效、成本和其他参数均来自先前的研究。我们进行了敏感性分析,以评估研究结果的稳健性,并探讨了非国家免疫规划疫苗的价格,以实现具有成本效益的策略。与目前的策略相比,使用四价多糖疫苗 (MPV-4)、二价结合疫苗 (MCV-AC) 和四价结合疫苗 (MCV-4) 的替代策略可分别避免 91 例、286 例和 455 例脑膜炎球菌病例。ICER 估计约为 25 万美元/QALY、45 万美元/QALY 和 150 万美元/QALY,均超过人均 GDP 三倍的临界值。替代战略不具有成本效益。然而,如果疫苗价格降至 MPV-4 3.9 美元、MCV-AC 9.9 美元和 MCV-4 12 美元,相应的策略将具有成本效益。中国目前的脑膜炎球菌疫苗接种策略可以低成本有效预防疾病,但血清群覆盖率有限。使用 MPV-4、MCV-AC 或 MCV-4 的接种策略可增加健康效益,但成本较高,如果疫苗价格下降,这种策略可能具有成本效益。
{"title":"Cost-effectiveness analysis of vaccination strategies against meningococcal disease for children under nine years of age in China.","authors":"Haonan Zhang, Haijun Zhang, Hai Fang","doi":"10.1080/21645515.2024.2313872","DOIUrl":"10.1080/21645515.2024.2313872","url":null,"abstract":"<p><p>Meningococcal vaccination strategies in China are intricate, including multiple vaccines targeting different serogroups. The current National Immunization Program (NIP) includes two polysaccharide vaccines for serogroups A and C (MPV-A and MPV-AC), covering limited serogroups and requiring adaptation. This study aims to evaluate the cost-effectiveness of replacing the current strategy with alternative strategies utilizing non-NIP vaccines to inform policy decisions. From a societal perspective, a decision tree-Markov model was constructed to simulate the economic and health consequences of meningococcal disease in a 2019 birth cohort with four vaccination strategies. Epidemiology, vaccine efficacy, cost, and other parameters were derived from previous studies. We conducted sensitivity analyses to assess the robustness of the findings and explored prices for non-NIP vaccines that enable cost-effective strategies. Compared to the current strategy, alternative strategies using quadrivalent polysaccharide vaccine (MPV-4), bivalent conjugate vaccine (MCV-AC), and quadrivalent conjugate vaccine (MCV-4) could avoid 91, 286, and 455 more meningococcal cases. The ICERs were estimated at approximately $250 thousand/QALY, $450 thousand/QALY, and $1.5 million/QALY, all exceeding the threshold of three times GDP per capita. The alternative strategies were not cost-effective. However, if vaccine prices were reduced to $3.9 for MPV-4, $9.9 for MCV-AC, and $12 for MCV-4, the corresponding strategy would be cost-effective. The current meningococcal vaccination strategy in China could effectively prevent the disease at a low cost, but with limited serogroup coverage. Strategies using MPV-4, MCV-AC, or MCV-4 could increase health benefits at a substantial cost, and might become cost-effective if vaccine prices decrease.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2313872"},"PeriodicalIF":4.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10865926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139724675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reconsidering the inclusion of Ladapo's work in the meta-analysis: Validity concerns and implications. 重新考虑将拉达波的工作纳入荟萃分析:有效性问题及影响
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-15 DOI: 10.1080/21645515.2024.2315711
Borja Somovilla Del Saz

This is a response to Marchand & Masoud's response letter regarding my criticism "Response to Dr. Somovilla del Saz's letter to the editor regarding "Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies."" The response is a defense of the initial criticism to the paper regarding the validity of the inclusion of Ladapo´s paper.

这是对 Marchand 和 Masoud 就我的批评所写的回信的回应,"回应 Somovilla del Saz 博士写给编辑的关于 "接种 COVID-19 疫苗后的全因和心脏相关死亡风险:自我对照病例系列研究的荟萃分析""。该回复是对最初对该论文提出的关于纳入拉达波论文的有效性的批评的辩护。
{"title":"Reconsidering the inclusion of Ladapo's work in the meta-analysis: Validity concerns and implications.","authors":"Borja Somovilla Del Saz","doi":"10.1080/21645515.2024.2315711","DOIUrl":"10.1080/21645515.2024.2315711","url":null,"abstract":"<p><p>This is a response to Marchand & Masoud's response letter regarding my criticism \"Response to Dr. Somovilla del Saz's letter to the editor regarding \"Risk of all-cause and cardiac-related mortality after vaccination against COVID-19: A meta-analysis of self-controlled case series studies.\"\" The response is a defense of the initial criticism to the paper regarding the validity of the inclusion of Ladapo´s paper.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2315711"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A phase 3, single-arm, open-label study to evaluate the safety, tolerability, and immunogenicity of a 15-valent pneumococcal conjugate vaccine, V114, in a 3+1 regimen in healthy infants in South Korea (PNEU-PED-KOR). 一项 3 期、单臂、开放标签研究,旨在评估 15 价肺炎球菌结合疫苗 V114 在韩国健康婴儿中采用 3+1 方案的安全性、耐受性和免疫原性 (PNEU-PED-KOR)。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-03-18 DOI: 10.1080/21645515.2024.2321035
Alvino Maestri, Su Eun Park, Fiona Fernandes, Zhongyi Lucy Li, Yae-Jean Kim, Yun-Kyung Kim, Jin Lee, Ji Young Park, Dong Hyun Kim, GyongSeon Yang, Hyunjung Lim, Jin Oh Kim, Robert Lupinacci, Tina M Sterling, Marissa Wilck, Alejandra Esteves-Jaramillo, Natalie Banniettis

There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 μg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (N = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.

尽管使用了肺炎球菌结合疫苗 (PCV),但儿童肺炎球菌疾病的负担仍在持续。这项 3 期、开放标签、单臂、多站点、描述性研究旨在评估 15 价 PCV V114 (VAXNEUVANCE™) 3 + 1 方案在韩国婴幼儿中的安全性和免疫原性。在接种任何疫苗后的 14 天内报告不良事件 (AE),在整个研究期间报告严重不良事件。血清型特异性免疫球蛋白 G (IgG) 反应率(达到 IgG 阈值≥0.35 μg/mL 的参与者比例)和 15 种血清型的几何平均浓度 (GMC) 作为终点进行评估,评估时间为接种后 30 天(PD3)和接种后 30 天(PD4)。出生后 42-90 天的健康婴儿接种了 V114 疫苗(57 人)。最常报告的AE是试验中征集的AE。大多数报告的不良反应是一过性的,属于轻度或中度。报告的严重不良反应很少;没有一起不良反应与疫苗有关。没有参与者死亡,也没有参与者因不良反应而停止接种疫苗。根据30 d PD3的IgG应答率以及30 d PD3和30 d PD4的IgG GMCs评估,V114对疫苗所含的全部15种血清型均具有免疫原性。在健康的韩国婴幼儿中以 3+1 方案接种 V114 疫苗,其耐受性和免疫原性良好。
{"title":"A phase 3, single-arm, open-label study to evaluate the safety, tolerability, and immunogenicity of a 15-valent pneumococcal conjugate vaccine, V114, in a 3+1 regimen in healthy infants in South Korea (PNEU-PED-KOR).","authors":"Alvino Maestri, Su Eun Park, Fiona Fernandes, Zhongyi Lucy Li, Yae-Jean Kim, Yun-Kyung Kim, Jin Lee, Ji Young Park, Dong Hyun Kim, GyongSeon Yang, Hyunjung Lim, Jin Oh Kim, Robert Lupinacci, Tina M Sterling, Marissa Wilck, Alejandra Esteves-Jaramillo, Natalie Banniettis","doi":"10.1080/21645515.2024.2321035","DOIUrl":"10.1080/21645515.2024.2321035","url":null,"abstract":"<p><p>There is an ongoing burden of pneumococcal disease in children despite the use of pneumococcal conjugate vaccines (PCVs). This phase 3, open-label, single-arm, multisite, descriptive study was designed to evaluate the safety and immunogenicity of a 3 + 1 regimen of V114 (VAXNEUVANCE™), a 15-valent PCV, in South Korean infants and toddlers. Adverse events (AEs) were reported for 14 d following any vaccination, and throughout the study period for serious AEs. Serotype-specific immunoglobulin G (IgG) response rates (proportion of participants meeting an IgG threshold value of ≥0.35 μg/mL) and geometric mean concentrations (GMCs) for the 15 serotypes at 30 d postdose 3 (PD3) and at 30 d postdose 4 (PD4) were evaluated as endpoints. Healthy infants enrolled at 42-90 d after birth were vaccinated with V114 (<i>N</i> = 57). The most commonly reported AEs were those solicited in the trial. The majority of reported AEs were transient and of mild or moderate intensity. Few serious AEs were reported; none were vaccine related. No participants died nor discontinued the study vaccine because of an AE. V114 was immunogenic for all 15 serotypes contained in the vaccine, as assessed by IgG response rates at 30 d PD3 and IgG GMCs at 30 d PD3 and at 30 d PD4. V114 was well tolerated and immunogenic when administered as a 3 + 1 regimen in healthy South Korean infants and toddlers.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2321035"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Community based participatory research as a promising practice for addressing vaccine hesitancy, rebuilding trust and addressing health disparities among racial and ethnic minority communities. 以社区为基础的参与式研究是解决疫苗接种犹豫、重建信任和解决少数种族和少数族裔社区健康差距问题的一种可行做法。
IF 4.1 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-03-18 DOI: 10.1080/21645515.2024.2326781
Sophie E O'Bryan, Fatima Muñoz, David Smith, Adriana Bearse, Blanca Melendrez, Biren Kamdar, Cynthia James-Price, Daniel Ramirez, Argentina E Servin

The COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), Project 2VIDA! was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were - whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.

COVID-19 大流行对全美少数种族和族裔社区的影响尤为严重。尽管有色人种社区面临的 COVID-19 负担过重,但黑人和西班牙裔社区完全接种疫苗的可能性却低于非西班牙裔白人。健康不平等和疫苗接种犹豫是一种复杂的现象,需要针对每个社区的独特需求采取多层次的应对措施,而这一过程本身就需要社区的高度参与,以制定最有效的健康干预措施。根据社区参与式研究(CBPR)的原则,在美国国立卫生研究院(NIH)的支持下,2VIDA!项目应运而生。是一个由学术研究人员、社区成员和临床医生组成的多学科合作组织,旨在促进可持续的合作关系,减轻南加州西班牙裔和黑人社区的 COVID-19 负担。我们的模式旨在满足社区成员的需求--无论是午休时间还是接孩子放学的时间。这种社区公共政策研究模式深受社区成员的欢迎。未来以减少健康差异为重点的健康干预措施应优先考虑社区的作用,充分利用主要社区合作伙伴的声音,并以公平分享权力为基础。
{"title":"Community based participatory research as a promising practice for addressing vaccine hesitancy, rebuilding trust and addressing health disparities among racial and ethnic minority communities.","authors":"Sophie E O'Bryan, Fatima Muñoz, David Smith, Adriana Bearse, Blanca Melendrez, Biren Kamdar, Cynthia James-Price, Daniel Ramirez, Argentina E Servin","doi":"10.1080/21645515.2024.2326781","DOIUrl":"10.1080/21645515.2024.2326781","url":null,"abstract":"<p><p>The COVID-19 pandemic disproportionately affected racial and ethnic minority communities across the United States (U.S.). Despite the disproportionate burden of COVID-19 faced by communities of color, Black and Hispanic communities are less likely to be fully vaccinated than White non-Hispanic Persons. Health inequity and vaccine hesitancy are complex phenomena that require multilevel responses tailored to the unique needs of each community, a process that inherently necessitates a high level of community engagement in order to develop the most effective health interventions. Building on the principles of community based participatory research (CBPR) and with the support of the National Institutes of Health (NIH), <i>Project 2VIDA!</i> was born. A multidisciplinary collaborative of academic researchers, community members, and clinicians whose aim is to foster sustainable partnerships to reduce the burden of COVID-19 in Hispanic and Black communities across Southern California. Our model was designed to meet our community members where they were - whether on their lunch break or picking their children from school. This CBPR model has been well received by community members. Future health interventions focused on reducing health disparities should prioritize the role of the community, leverage the voices of key community partners, and be grounded in equitable power sharing.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2326781"},"PeriodicalIF":4.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formulation development of a stable influenza recombinant neuraminidase vaccine candidate. 稳定型流感重组神经氨酸酶候选疫苗的配方开发。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-03-18 DOI: 10.1080/21645515.2024.2304393
Bing Li, Irina V Ustyugova, Lisa Szymkowicz, Shaolong Zhu, Marin Ming, Karen Y Y Fung, Guadalupe Cortés, D Andrew James, Michael Hrynyk, Nausheen Rahman, Roger H Brookes, Salvador F Ausar

Current influenza vaccines could be augmented by including recombinant neuraminidase (rNA) protein antigen to broaden protective immunity and improve efficacy. Toward this goal, we investigated formulation conditions to optimize rNA physicochemical stability. When rNA in sodium phosphate saline buffer (NaPBS) was frozen and thawed (F/T), the tetrameric structure transitioned from a "closed" to an "open" conformation, negatively impacting functional activity. Hydrogen deuterium exchange experiments identified differences in anchorage binding sites at the base of the open tetramer, offering a structural mechanistic explanation for the change in conformation and decreased functional activity. Change to the open configuration was triggered by the combined stresses of acidic pH and F/T. The desired closed conformation was preserved in a potassium phosphate buffer (KP), minimizing pH drop upon freezing and including 10% sucrose to control F/T stress. Stability was further evaluated in thermal stress studies where changes in conformation were readily detected by ELISA and size exclusion chromatography (SEC). Both tests were suitable indicators of stability and antigenicity and considered potential critical quality attributes (pCQAs). To understand longer-term stability, the pCQA profiles from thermally stressed rNA at 6 months were modeled to predict stability of at least 24-months at 5°C storage. In summary, a desired rNA closed tetramer was maintained by formulation selection and monitoring of pCQAs to produce a stable rNA vaccine candidate. The study highlights the importance of understanding and controlling vaccine protein structural and functional integrity.

可以通过加入重组神经氨酸酶(rNA)蛋白抗原来增强目前的流感疫苗,从而扩大保护性免疫并提高疗效。为此,我们研究了优化 rNA 理化稳定性的配制条件。当磷酸钠生理盐水缓冲液(NaPBS)中的 rNA 被冷冻和解冻(F/T)时,四聚体结构会从 "封闭 "构象转变为 "开放 "构象,从而对功能活性产生负面影响。氢氘交换实验确定了开放四聚体底部锚定结合位点的差异,为构象改变和功能活性降低提供了结构机理解释。酸性 pH 值和 F/T 值的双重压力引发了开放构型的变化。所需的封闭构象在磷酸二氢钾缓冲液(KP)中得以保留,最大限度地降低了冷冻时的 pH 值下降,并加入了 10%的蔗糖以控制 F/T 应力。在热应力研究中进一步评估了稳定性,通过酶联免疫吸附试验(ELISA)和尺寸排阻色谱法(SEC)很容易检测到构象的变化。这两项测试都是稳定性和抗原性的合适指标,被认为是潜在的关键质量属性(pCQA)。为了解更长期的稳定性,对 6 个月热应激 rNA 的 pCQA 曲线进行了建模,以预测在 5°C 储存条件下至少 24 个月的稳定性。总之,通过配方选择和 pCQA 监测,可保持理想的 rNA 封闭四聚体,从而生产出稳定的 rNA 候选疫苗。这项研究强调了了解和控制疫苗蛋白质结构和功能完整性的重要性。
{"title":"Formulation development of a stable influenza recombinant neuraminidase vaccine candidate.","authors":"Bing Li, Irina V Ustyugova, Lisa Szymkowicz, Shaolong Zhu, Marin Ming, Karen Y Y Fung, Guadalupe Cortés, D Andrew James, Michael Hrynyk, Nausheen Rahman, Roger H Brookes, Salvador F Ausar","doi":"10.1080/21645515.2024.2304393","DOIUrl":"10.1080/21645515.2024.2304393","url":null,"abstract":"<p><p>Current influenza vaccines could be augmented by including recombinant neuraminidase (rNA) protein antigen to broaden protective immunity and improve efficacy. Toward this goal, we investigated formulation conditions to optimize rNA physicochemical stability. When rNA in sodium phosphate saline buffer (NaPBS) was frozen and thawed (F/T), the tetrameric structure transitioned from a \"closed\" to an \"open\" conformation, negatively impacting functional activity. Hydrogen deuterium exchange experiments identified differences in anchorage binding sites at the base of the open tetramer, offering a structural mechanistic explanation for the change in conformation and decreased functional activity. Change to the open configuration was triggered by the combined stresses of acidic pH and F/T. The desired closed conformation was preserved in a potassium phosphate buffer (KP), minimizing pH drop upon freezing and including 10% sucrose to control F/T stress. Stability was further evaluated in thermal stress studies where changes in conformation were readily detected by ELISA and size exclusion chromatography (SEC). Both tests were suitable indicators of stability and antigenicity and considered potential critical quality attributes (pCQAs). To understand longer-term stability, the pCQA profiles from thermally stressed rNA at 6 months were modeled to predict stability of at least 24-months at 5°C storage. In summary, a desired rNA closed tetramer was maintained by formulation selection and monitoring of pCQAs to produce a stable rNA vaccine candidate. The study highlights the importance of understanding and controlling vaccine protein structural and functional integrity.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2304393"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10950269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts. 在不同 CD4+ T 淋巴细胞数量的 HIV 感染者中接种异源疫苗 CoronaVac(希诺威)和 Vaxzevria(阿斯利康)后的免疫原性和中和抗体反应比较。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-01-31 DOI: 10.1080/21645515.2024.2309734
Sorawit Chittrakarn, Pisud Siripaitoon, Sarunyou Chusri, Siripen Kanchanasuwan, Boonsri Charoenmak, Thanaporn Hortiwakul, Phaiwon Kantikit, Narongdet Kositpantawong

The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies (nAbs) were analyzed at 2 and 12 weeks after immunization. Participants in the low and high CD4+ groups had mean CD4+ counts of 139 and 575 cell/µL, respectively. Two and 12 weeks after immunization, in the low CD4 group, the median anti-RBD-IgG levels were 159 IU/mL and 143 IU/mL, respectively, whereas the nAb level was 71% and decreased to 47.2%, respectively. Contrarily, the median anti-RBD-IgG levels in the high CD4+ group were 273 IU/mL and 294 IU/mL, respectively, whereas the nAb levels were 89.3% and relatively stable at 81.6%. However, although immune responses between the two study groups were not significantly different, a decline in nAb levels was observed at 12 weeks in the low CD4+ group. Therefore, a COVID-19 booster vaccine dose is suggested for immunoprotection.

艾滋病病毒感染者(PLWH)对异源冠状病毒病(COVID-19)疫苗接种的免疫反应尚不清楚。在此,我们的前瞻性队列研究旨在比较 CD4 细胞数≤ 200 cells/µL(低 CD4+)和大于 200 cells/µL(高 CD4+)的艾滋病病毒感染者接种冠状病毒(COVID-19)异源疫苗后的免疫反应。免疫2周和12周后,对抗受体结合域(RBD)免疫球蛋白G(IgG)水平和中和抗体(nAbs)抑制百分比进行分析。低 CD4+ 组和高 CD4+ 组参与者的平均 CD4+ 细胞数分别为 139 和 575 cells/µL。免疫2周和12周后,低CD4组的抗RBD-IgG水平中位数分别为159 IU/mL和143 IU/mL,而nAb水平分别为71%和47.2%。相反,高 CD4+ 组的抗 RBD-IgG 水平中位数分别为 273 IU/mL 和 294 IU/mL,而 nAb 水平为 89.3%,相对稳定在 81.6%。不过,虽然两个研究组之间的免疫反应没有显著差异,但在 12 周时,低 CD4+ 组的 nAb 水平出现了下降。因此,建议接种 COVID-19 加强剂量疫苗以获得免疫保护。
{"title":"Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts.","authors":"Sorawit Chittrakarn, Pisud Siripaitoon, Sarunyou Chusri, Siripen Kanchanasuwan, Boonsri Charoenmak, Thanaporn Hortiwakul, Phaiwon Kantikit, Narongdet Kositpantawong","doi":"10.1080/21645515.2024.2309734","DOIUrl":"10.1080/21645515.2024.2309734","url":null,"abstract":"<p><p>The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies (nAbs) were analyzed at 2 and 12 weeks after immunization. Participants in the low and high CD4+ groups had mean CD4+ counts of 139 and 575 cell/µL, respectively. Two and 12 weeks after immunization, in the low CD4 group, the median anti-RBD-IgG levels were 159 IU/mL and 143 IU/mL, respectively, whereas the nAb level was 71% and decreased to 47.2%, respectively. Contrarily, the median anti-RBD-IgG levels in the high CD4+ group were 273 IU/mL and 294 IU/mL, respectively, whereas the nAb levels were 89.3% and relatively stable at 81.6%. However, although immune responses between the two study groups were not significantly different, a decline in nAb levels was observed at 12 weeks in the low CD4+ group. Therefore, a COVID-19 booster vaccine dose is suggested for immunoprotection.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2309734"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139651994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Agricultural chemical use and the rural-urban divide in Canada. 加拿大农业化学品的使用和城乡差别。
IF 3.9 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-20 DOI: 10.1080/21645698.2024.2318876
Stuart J Smyth, Sylvain Charlebois

Innovation is of fundamental importance for improving food production, as well as sustainability food production. Since 1960, food production has benefited from innovations in plant breeding technologies, fertilizer, chemicals and equipment. These innovations have dramatically increased food production, while the amount of land used has minimally increased. However, future food production increases are jeopardized from widening knowledge gaps between rural food producers and large urban food consuming populations. Over time, that gap has fueled disinformation. The development of disinformation business models contributes to urban consumers receiving inaccurate information about the importance of inputs essential to food production, resulting in political pressures being applied that are targeted at reductions in the use of many food production inputs. The use of chemicals are a frequent target of disinformation campaigns. This article examines how the lack of government clarity about the safe use of chemicals contributes to a lack of public information.

创新对于提高粮食产量和粮食生产的可持续性至关重要。自 1960 年以来,粮食生产得益于植物育种技术、化肥、化学品和设备方面的创新。这些创新极大地提高了粮食产量,而土地使用量的增加却微乎其微。然而,由于农村粮食生产者与庞大的城市粮食消费人口之间的知识差距不断扩大,未来的粮食增产受到威胁。随着时间的推移,这种差距助长了虚假信息。虚假信息商业模式的发展导致城市消费者对粮食生产所必需的投入品的重要性获得不准确的信息,从而施加政治压力,要求减少许多粮食生产投入品的使用。化学品的使用经常成为虚假宣传的目标。本文探讨了政府对化学品的安全使用缺乏明确规定是如何造成公众信息匮乏的。
{"title":"Agricultural chemical use and the rural-urban divide in Canada.","authors":"Stuart J Smyth, Sylvain Charlebois","doi":"10.1080/21645698.2024.2318876","DOIUrl":"10.1080/21645698.2024.2318876","url":null,"abstract":"<p><p>Innovation is of fundamental importance for improving food production, as well as sustainability food production. Since 1960, food production has benefited from innovations in plant breeding technologies, fertilizer, chemicals and equipment. These innovations have dramatically increased food production, while the amount of land used has minimally increased. However, future food production increases are jeopardized from widening knowledge gaps between rural food producers and large urban food consuming populations. Over time, that gap has fueled disinformation. The development of disinformation business models contributes to urban consumers receiving inaccurate information about the importance of inputs essential to food production, resulting in political pressures being applied that are targeted at reductions in the use of many food production inputs. The use of chemicals are a frequent target of disinformation campaigns. This article examines how the lack of government clarity about the safe use of chemicals contributes to a lack of public information.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"15 1","pages":"32-39"},"PeriodicalIF":3.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the GMO narrative through labeling: strategies, products, and politics. 通过标签探索转基因叙述:战略、产品和政治。
IF 3.9 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-25 DOI: 10.1080/21645698.2024.2318027
Camille D Ryan, Elizabeth Henggeler, Samantha Gilbert, Andrew J Schaul, John T Swarthout

Labels are influential signals in the marketplace intended to inform and to eliminate buyer confusion. Despite this, food labels continue to be the subject of debate. None more so than non-GMO (genetically modified organisms) labels. This manuscript provides a timeline of the evolution of GMO labels beginning with the early history of the anti-GMO movement to the current National Bioengineered Food Disclosure Standard in the United States. Using media and market intelligence data collected through Buzzsumo™ and Mintel™, public discourse of GMOs is analyzed in relation to sociopolitical events and the number of new food products with anti-GMO labels, respectively. Policy document and publication data is collected with Overton™ to illustrate the policy landscape for the GMO topic and how it has changed over time. Analysis of the collective data illustrates that while social media and policy engagement around the topic of GMOs has diminished over time, the number of new products with a GMO-free designation continues to grow. While discourse peaked at one point, and has since declined, our results suggest that the legacy of an anti-GMO narrative remains firmly embedded in the social psyche, evidenced by the continuing rise of products with GMO-free designation. Campaigns for GMO food labels to satisfy consumers' right to know were successful and the perceived need for this information now appears to be self-sustaining.

标签是市场上有影响力的信号,旨在提供信息并消除购买者的困惑。尽管如此,食品标签仍然是争论的焦点。非转基因(转基因生物)标签更是如此。本手稿提供了转基因生物标签演变的时间轴,从早期的反转基因运动历史开始,到美国现行的《国家生物工程食品披露标准》。通过 Buzzsumo™ 和 Mintel™ 收集的媒体和市场情报数据,分别结合社会政治事件和带有反转基因生物标签的新食品数量,分析了公众对转基因生物的讨论。我们还利用 Overton™ 收集了政策文件和出版物数据,以说明转基因生物主题的政策状况及其随着时间的推移而发生的变化。对集体数据的分析表明,虽然随着时间的推移,围绕转基因生物话题的社交媒体和政策参与有所减少,但带有无转基因生物标识的新产品数量却在持续增长。虽然讨论一度达到顶峰,但后来有所下降,我们的研究结果表明,反转基因论调在社会心理中仍然根深蒂固,这一点可以从不含转基因产品的持续增加中得到证明。为满足消费者的知情权而开展的转基因食品标签运动取得了成功,现在看来,对这一信息的认知需求正在自我维持。
{"title":"Exploring the GMO narrative through labeling: strategies, products, and politics.","authors":"Camille D Ryan, Elizabeth Henggeler, Samantha Gilbert, Andrew J Schaul, John T Swarthout","doi":"10.1080/21645698.2024.2318027","DOIUrl":"10.1080/21645698.2024.2318027","url":null,"abstract":"<p><p>Labels are influential signals in the marketplace intended to inform and to eliminate buyer confusion. Despite this, food labels continue to be the subject of debate. None more so than non-GMO (genetically modified organisms) labels. This manuscript provides a timeline of the evolution of GMO labels beginning with the early history of the anti-GMO movement to the current National Bioengineered Food Disclosure Standard in the United States. Using media and market intelligence data collected through Buzzsumo™ and Mintel™, public discourse of GMOs is analyzed in relation to sociopolitical events and the number of new food products with anti-GMO labels, respectively. Policy document and publication data is collected with Overton™ to illustrate the policy landscape for the GMO topic and how it has changed over time. Analysis of the collective data illustrates that while social media and policy engagement around the topic of GMOs has diminished over time, the number of new products with a GMO-free designation continues to grow. While discourse peaked at one point, and has since declined, our results suggest that the legacy of an anti-GMO narrative remains firmly embedded in the social psyche, evidenced by the continuing rise of products with GMO-free designation. Campaigns for GMO food labels to satisfy consumers' right to know were successful and the perceived need for this information now appears to be self-sustaining.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"15 1","pages":"51-66"},"PeriodicalIF":3.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139974590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis. 抗PD-1/PDL-1和抗CTLA-4疗法中的免疫调节和肿瘤微环境对癌症免疫逃避的影响:文献计量分析。
IF 4.8 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-02-28 DOI: 10.1080/21645515.2024.2318815
Yi Huang, Zhijian Chen, Gang Shen, Shuogui Fang, Junjiong Zheng, Zepai Chi, Yuanfeng Zhang, Yitong Zou, Qinghua Gan, Chengxiao Liao, Yuhui Yao, Jianqiu Kong, Xinxiang Fan

This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.

本研究旨在采用可视化工具,对1999年至2022年与抗CTLA-4和抗PD-1/PD-L1疗法相关的肿瘤免疫逃避文献进行文献计量分析。文章特别强调了肿瘤微环境、信号通路、免疫细胞和免疫逃避之间的相互作用,数据来源于科学网核心数据库(WoSCC)。研究人员利用 VOSviewer、Citespace 和 Scimago Graphica 等先进工具分析了各种参数,如合著/合引模式、区域贡献、期刊偏好、关键词共现和重要引文突发。在审查的 4778 篇论文中,以免疫逃避为重点的研究明显增加,其中以膀胱癌最为突出。从地域上看,中国、美国和日本是主要的贡献者。MD 安德森癌症中心、哈佛大学医学院、复旦大学和中山大学等著名机构成为主要参与者。该领域的知名期刊包括《免疫学前沿》、《癌症》和《肿瘤学前沿》。Ehen LP 和 Wang W 被认为是这一主题的多产作者,而 Topalian SL 则是被引用次数最多的作者之一。当前的研究形势正显著转向免疫疗法耐药性和驱动耐药性的复杂信号通路等挑战。这项文献计量学研究旨在全面概述过去和当前的研究趋势,强调肿瘤微环境、信号通路和免疫细胞在免疫检查点抑制剂(ICIs)和肿瘤免疫逃避中的潜在作用。
{"title":"Immune regulation and the tumor microenvironment in anti-PD-1/PDL-1 and anti-CTLA-4 therapies for cancer immune evasion: A bibliometric analysis.","authors":"Yi Huang, Zhijian Chen, Gang Shen, Shuogui Fang, Junjiong Zheng, Zepai Chi, Yuanfeng Zhang, Yitong Zou, Qinghua Gan, Chengxiao Liao, Yuhui Yao, Jianqiu Kong, Xinxiang Fan","doi":"10.1080/21645515.2024.2318815","DOIUrl":"10.1080/21645515.2024.2318815","url":null,"abstract":"<p><p>This study aims to conduct a bibliometric analysis, employing visualization tools to examine literature pertaining to tumor immune evasion related to anti-CTLA-4 and anti-PD-1/PD-L1 therapy from 1999 to 2022. A special emphasis is placed on the interplay between tumor microenvironment, signaling pathways, immune cells and immune evasion, with data sourced from the Web of Science core collection (WoSCC). Advanced tools, including VOSviewer, Citespace, and Scimago Graphica, were utilized to analyze various parameters, such as co-authorship/co-citation patterns, regional contributions, journal preferences, keyword co-occurrences, and significant citation bursts. Out of 4778 publications reviewed, there was a marked increase in research focusing on immune evasion, with bladder cancer being notably prominent. Geographically, China, the USA, and Japan were the leading contributors. Prestigious institutions like MD Anderson Cancer Center, Harvard Medical School, Fudan University, and Sun Yat Sen University emerged as major players. Renowned journals in this domain included Frontiers in Immunology, Cancers, and Frontiers in Oncology. Ehen LP and Wang W were identified as prolific authors on this topic, while Topalian SL stood out as one of the most cited. Research current situation is notably pivoting toward challenges like immunotherapy resistance and the intricate signaling pathways driving drug resistance. This bibliometric study seeks to provide a comprehensive overview of past and current research trends, emphasizing the potential role of tumor microenvironment, signaling pathways and immune cells in the context of immune checkpoint inhibitors (ICIs) and tumor immune evasion.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"20 1","pages":"2318815"},"PeriodicalIF":4.8,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139991578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation. TOP2A 通过 AKT/mTOR 通路调节信号,促进卵巢癌细胞增殖。
IF 3.6 3区 材料科学 Q2 CHEMISTRY, PHYSICAL Pub Date : 2024-12-31 Epub Date: 2024-03-06 DOI: 10.1080/15384047.2024.2325126
Kaiwen Zhang, Xingyu Zheng, Yiqing Sun, Xinyu Feng, Xirong Wu, Wenlu Liu, Chao Gao, Ye Yan, Wenyan Tian, Yingmei Wang

Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

卵巢癌(OC)是一种妇科恶性肿瘤,与女性生殖道的其他癌症相比,卵巢癌患者的预后更差。拓扑异构酶 II α(TOP2A)通常被认为是一种与多种癌症的恶性疾病进展相关的致癌基因,但它在卵巢癌中的机理功能尚未得到确定。我们通过在线数据库、临床样本、体外和体内实验探索了TOP2A在OC中的作用。对公共数据库的初步分析显示,患者样本中与 OC 相关的 TOP2A 高表达与较差的预后有关。这一点在临床样本中得到了证实,与健康组织相比,OC 中的 TOP2A 表达更高。Kaplan-Meier分析进一步表明,TOP2A表达水平越高,OC患者的预后越差。在体外,TOP2A 基因敲除可抑制 OC 细胞的增殖,使细胞进入 G1 期停滞并随之凋亡。在挽救实验中,TOP2A被证实通过AKT/mTOR通路的活性调节细胞增殖和细胞周期。小鼠模型实验进一步证实了 TOP2A 在 OC 细胞增殖中的关键驱动作用。这些数据提供了强有力的证据,支持 TOP2A 成为与 OC 进展和不良预后相关的致癌介质和预后生物标志物。在机理层面,TOP2A 可通过 AKT/mTOR 通路调节控制肿瘤细胞的生长。这些初步结果为今后的研究奠定了基础,有助于探索基于TOP2A抑制剂的联合治疗方案在铂耐药复发性OC患者中的应用。
{"title":"TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation.","authors":"Kaiwen Zhang, Xingyu Zheng, Yiqing Sun, Xinyu Feng, Xirong Wu, Wenlu Liu, Chao Gao, Ye Yan, Wenyan Tian, Yingmei Wang","doi":"10.1080/15384047.2024.2325126","DOIUrl":"10.1080/15384047.2024.2325126","url":null,"abstract":"<p><p>Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.</p>","PeriodicalId":4,"journal":{"name":"ACS Applied Energy Materials","volume":"25 1","pages":"2325126"},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936659/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
ACS Applied Energy Materials
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1