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Optimizing the delivery of combination therapy for tumors： A mathematical model

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International Journal of Biomathematics 2017年第3期10卷 179-194页

作者： Clara Rojas Rodriguez juan belmonte-beitia Departamento de Matematicas E. T. S. de Ingenieros Industriales Universidad de CastiUa-La Mancha 13071 Ciudad Real Spain Instituto de Matemdtica Aplicada a la Ciencia y la Ingenierla (IMA CI) Universidad de Castilla-La Mancha 13071 Ciudad Real Spain

We present in this paper a new mathematical model for the scheduling of angiogenic inhibitors in combination with a chemotherapeutic agent for a tumor. Our model takes into account the process of angiogenesis and the quality of the vasculature discriminating between stable blood vessels and unstable blood vessels. We characterize theoretically the optimal controls on drug distribution to minimize the number of cancer cells at the end of the treatment in a free horizon time problem with restrictions on the total amount of drug doses. Finally, we solve the optimal control problem by using numerical simulations, obtaining as a result that, despite the number of the tumor cells decrease with anti-angiogenic treatment, the best results are reached at the end of the chemotherapy treatment.

关键词： Mathematical modeling of tumor growth anti-angiogenic treatment chemotherapy singular control bang bang control.

The labyrinth of nuclear reprogramming

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Journal of Molecular Cell Biology 2011年第6期3卷 327-329页

作者： Ignacio Sancho-Martinez Emmanuel Nivet juan Carlos Izpisua belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Center for Regenerative Medicine in Barcelona Dr Aiguader 88Barcelona 08003Spain

Human embryonic stem cells(ESCs)have the capability to differentiate into all somatic cell types,a process that recapitu-lates the early stages of human ***,the use of ESCs raises several controversies,particularly concern-ing the ethical dilemma regarding the use of human embryonic material and the need for embryo *** discov-ery of induced pluripotent stem cell(iPSC)technology in 2006(Takahashi and Yamanaka,2006)opened the door for possible application of pluripotent stem-cell-related therapies in the clinic as well as for the generation of patient-derived pluripotent stem cells suitable for disease modeling in vitro.

关键词： programming destruction opened

Human induced pluripotent stem cells derived hepatocytes:rising promise for disease modeling,drug development and cell therapy

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Protein & Cell 2012年第4期3卷 246-250页

作者： Fei Yi Guang-Hui Liu juan Carlos Izpisua belmonte Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCA 92037USA Center for Regenerative Medicine in Barcelona 08003 BarcelonaSpain National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China

Recent advances in the study of human hepatocytes derived from induced pluripotent stem cells(iPSC)represent new promises for liver disease study and drug *** hepatocytes or hepatocyte-like cells differentiated from iPSC recapitulate many func-tional properties of primary human hepatocytes and have been demonstrated as a powerful and efficient tool to model human liver metabolic diseases and fa-cilitate drug development *** this review,we summarize the recent progress in this field and discuss the future perspective of the application of human iPSC derived hepatocytes.

关键词： induced pluripotent stem cells hepatocytes disease modeling drug development cell therapy

Adenine base editing disease mutations in to mimic or correcl rodents

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Protein & Cell 2018年第9期9卷 752-753页

作者： Ruotong Ren juan Carlos Izpisua belmonte Guang-Hui Liu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital of Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla California 92037 USA Institute of Stem cell and Regeneration Chinese Academy of Sciences Beijing 100101 China

Cytidine base editors （CBEs, rAPOBECI-nCas9-UGI） and adenine base editors （ABEs, TadA-TadA＊-nCas9） are newly developed genome-editing tools that have enabled highly efficient base conversions （CoG to T·A or A·T to G·C） at designated target sites （Komor et al., 2016; Gaudelli et al., 2017）. Both types of base editors enzymatically catalyze deamination of target bases and respectively replace C with U or A with I.

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Sora文生视频大模型对学术期刊出版的机遇、挑战及应对

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新疆师范大学学报（哲学社会科学版） 2025年第2期46卷 79-88页

作者：刘娟新疆师范大学期刊社新疆乌鲁木齐830017

随着Sora文生视频大模型的迅猛发展,学术期刊出版正在经历深刻的变革与重塑。Sora技术的多模态特征与智能化能力,一方面促进学术信息的动态整合与开放获取,推动传统出版模式向协同创新与知识共享的新范式转型;另一方面,赋予著作权归属... 详细信息

随着Sora文生视频大模型的迅猛发展,学术期刊出版正在经历深刻的变革与重塑。Sora技术的多模态特征与智能化能力,一方面促进学术信息的动态整合与开放获取,推动传统出版模式向协同创新与知识共享的新范式转型;另一方面,赋予著作权归属和著作权风险治理等新的价值意蕴。面对Sora文生视频大模型对学术期刊出版带来的机遇和挑战,学术期刊应构建跨学科协作网络、重塑基于价值的学术评价标准、创新人才培养机制,强化全球学术出版治理。文本通过系统分析大语言模型、文生视频大模型驱动下的新兴学术生态,旨在为学术界提供理论视角和实践样态,实现知识生产的原创性与伦理性,推动学术出版在新技术环境中的学术治理现代化及可持续高质量发展。

关键词： Sora 学术期刊出版技术伦理学术伦理学术生态系统

Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao Pan juan Xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

Navigating medial patellotibial ligament reconstruction:Clinical perspectives and surgical strategies

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World Journal of Clinical Cases 2025年第1期13卷 6-10页

作者： juan Pablo Zicaro Ignacio Garcia-Mansilla Division of Knee Hospital Italiano de Buenos AiresBuenos Aires 1109Argentina

The surgical approach for patellar instability usually refers to reconstruction of the medial patellofemoral ligament associated with an osteotomy of the tibial tuberosity or a trochleoplasty when *** medial patellotibial ligament and the medial patellomeniscal ligament are secondary stabilizers of the *** this,both the medial patellotibial and patellofemoral ligaments aid in patellar rotation and tilt when the knee is flexed beyond 45°.The medial patellotibial ligament plays a particularly important role in the final stages of stretching in extension and between 40 degrees to 90 degrees of *** clinical relevance and surgical indications for medial patellotibial ligament reconstruction associated with medial patellofemoral ligament reconstruction are still *** editorial explores the surgical indications and clinical results for medial patellotibial ligament reconstruction to improve readers’understanding of this technique,especially because reported clinical outcomes have remained sparse.

关键词： Medial patellotibial ligament Patellar instability Reconstruction Surgical

Anti-amyloid antibodies in Alzheimer’s disease: what did clinical trials teach us?

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Neural Regeneration Research 2025年第4期20卷 1092-1093页

作者： Danko Jeremic Lydia Jiménez-Díaz juan D.Navarro-López NeuroPhysiology&Behavior Lab University of Castilla-La ManchaBiomedical Research Center(CRIB)School of Medicine of Ciudad RealCiudad RealSpain

Although many causes of Alzheimer’s disease(AD)may exist,both the original amyloid cascade and tau hypotheses posit that abnormal misfolding and accumulation of amyloid-β(Aβ)and tau protein is the central event causing the ***,that conclusion could be only partly true,and there is conflicting evidence about the role of both proteins in AD,being able to precede and influence one *** researchers argue that these proteins are mere executors rather than primary causes of ***,there have been continuing refinements of both hypotheses,with alternative explanations proposed.Aβand tau proteins may be independently involved in specific neurotoxic pathways;yet there may be other crucial processes going on in early ***,accumulating evidence suggests that Aβand tau act synergistically,rather than additively in disease onset(Jeremic et al.,2021,2023a).

关键词： amyloid Alzheimer additive

Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

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Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation Base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina Department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2