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Fine-tuning cell organelle dynamics during mitosis by small GTPases

《医学前沿（英文）》 2022年 第16卷 第3期   页码 339-357 doi: 10.1007/s11684-022-0926-1

摘要： During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer’s disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

关键词： small GTPase     cell organelle     mitosis    

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A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

《医学前沿（英文）》 2015年 第9卷 第1期   页码 108-111 doi: 10.1007/s11684-014-0344-0

摘要：

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54-year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour (GIST) of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient’s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

关键词： gastrointestinal stromal tumour     hemoperitoneum     small bowel GIST     small bowel neoplasm     imatinib    

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Simulation and experimental improvement on a small-scale Stirling thermo-acoustic engine

Mao CHEN,Yonglin JU

《能源前沿（英文）》 2016年 第10卷 第1期   页码 37-45 doi: 10.1007/s11708-015-0390-6

摘要： Compared with the traditional engines, the thermo-acoustic engines are relatively new and can act as the linear compressors for refrigerators. Many institutes have shown great interest in this kind of machine for its absence of moving mechanical part. In this paper, the influence of the dimensions of the main parts of the small-scale Stirling thermo-acoustic engine was numerically simulated using a computer code called DeltaEC. The resonator and the resonator cavity were found to be the most convenient and effective in improving the performance of the engine. Based on the numerical simulation, a small-scale Stirling thermo-acoustic engine were constructed and experimentally investigated. Currently, with a resonator length of only 1 m, the working frequency of the engine was decreased to 90 Hz and the onset temperature difference was decreased to 198.2 K.

关键词： thermo-acoustic Stirling engine     small-scale     simulation     experiment    

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Discovery of small molecule degraders for modulating cell cycle

《医学前沿（英文）》   页码 823-854 doi: 10.1007/s11684-023-1027-5

摘要： The cell cycle is a complex process that involves DNA replication, protein expression, and cell division. Dysregulation of the cell cycle is associated with various diseases. Cyclin-dependent kinases (CDKs) and their corresponding cyclins are major proteins that regulate the cell cycle. In contrast to inhibition, a new approach called proteolysis-targeting chimeras (PROTACs) and molecular glues can eliminate both enzymatic and scaffold functions of CDKs and cyclins, achieving targeted degradation. The field of PROTACs and molecular glues has developed rapidly in recent years. In this article, we aim to summarize the latest developments of CDKs and cyclin protein degraders. The selectivity, application, validation and the current state of each CDK degrader will be overviewed. Additionally, possible methods are discussed for the development of degraders for CDK members that still lack them. Overall, this article provides a comprehensive summary of the latest advancements in CDK and cyclin protein degraders, which will be helpful for researchers working on this topic.

关键词： PROTAC     molecular glue     degrader     cell cycle     CDK     cyclin    

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Gut microbiota and its implications in small bowel transplantation

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 239-248 doi: 10.1007/s11684-018-0617-0

摘要：

The gut microbiota is mainly composed of a diverse population of commensal bacterial species and plays a pivotal role in the maintenance of intestinal homeostasis, immune modulation and metabolism. The influence of the gut microbiota on solid organ transplantation has recently been recognized. In fact, several studies indicated that acute and chronic allograft rejection in small bowel transplantation (SBT) is closely associated with the alterations in microbial patterns in the gut. In this review, we focused on the recent findings regarding alterations in the microbiota following SBT and the potential roles of these alterations in the development of acute and chronic allograft rejection. We also reviewed important advances with respect to the interplays between the microbiota and host immune systems in SBT. Furthermore, we explored the potential of the gut microbiota as a microbial marker and/or therapeutic target for the predication and intervention of allograft rejection and chronic dysfunction. Given that current research on the gut microbiota has become increasingly sophisticated and comprehensive, large cohort studies employing metagenomic analysis and multivariate linkage should be designed for the characterization of host–microbe interaction and causality between microbiota alterations and clinical outcomes in SBT. The findings are expected to provide valuable insights into the role of gut microbiota in the development of allograft rejection and other transplant-related complications and introduce novel therapeutic targets and treatment approaches in clinical practice.

关键词： gut microbiota     small bowel transplantation     acute rejection     chronic rejection     mucosal immunity     biomarker     microbiota-targeted therapy    

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Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

《医学前沿（英文）》 2013年 第7卷 第2期   页码 157-171 doi: 10.1007/s11684-013-0272-4

摘要：

Non-small-cell lung cancer (NSCLC) is the most common cause of premature death among the malignant diseases worldwide. The current staging criteria do not fully capture the complexity of this disease. Molecular biology techniques, particularly gene expression microarrays, proteomics, and next-generation sequencing, have recently been developed to facilitate effectively its molecular classification. The underlying etiology, pathogenesis, therapeutics, and prognosis of NSCLC based on an improved molecular classification scheme may promote individualized treatment and improve clinical outcomes. This review focuses on the molecular classification of NSCLC based on gene expression microarray technology reported during the past decade, as well as their applications for improving the diagnosis, staging and treatment of NSCLC, including the discovery of prognostic markers or potential therapeutic targets. We highlight some of the recent studies that may refine the identification of NSCLC subtypes using novel techniques such as epigenetics, proteomics, or deep sequencing.

关键词： non-small-cell lung cancer     molecular typing     individualized medicine     molecular-targeted therapy     gene expression profiling    

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Performance prediction of switched reluctance generator with time average and small signal models

Jyoti KOUJALAGI, B. UMAMAHESWARI, R. ARUMUGAM

《能源前沿（英文）》 2013年 第7卷 第1期   页码 56-68 doi: 10.1007/s11708-012-0216-8

摘要： This paper presents the complete mathematical model and predicts the performance of switched reluctance generator with time average and small signal models. The complete mathematical model is developed in three stages. First, a switching model is developed based on quasi-linear inductance profile. Next, based on the switching behaviour, a time average model is obtained to measure the difference between the excitation and generation time in each switching cycle. Finally, to track control voltage and current wave shapes, a small signal model is designed. The effectiveness of the complete multilevel model combining electrical machine, power converter, load and control with programming language is demonstrated through simulations. A PI controller is used for controlling the voltage of the generator. The results presented show that the controller exhibits accurate tracking control of load voltage under different operating conditions. This demonstrates that the proposed model is able to perform an accurate control of the generated output voltage even in transient situations. The simulation is performed to choose the control parameters and study the performance of switched reluctance generator prior to its actual implementation. Initial experimental results are presented using NI-Data acquisition card to control the output power according to load requirements.

关键词： generator     reluctance     switching model     small signal model     time average model    

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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿（英文）》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要： With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词： non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

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Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

《医学前沿（英文）》 2022年 第16卷 第2期   页码 176-184 doi: 10.1007/s11684-021-0885-y

摘要： Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring. However, studies that explore the mechanisms that meditate this transmission are rare. Recently, small noncoding RNAs (sncRNAs) in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure, and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line. Hence, by reviewing relevant literature, this study intends to answer the following research concepts: (1) paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs, (2) potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process, and (3) the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance. In summary, increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance. Therefore, in the future, more studies should focus on the origin of RNA alteration, the target of RNA regulation, and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

关键词： small noncoding RNAs     epigenetic inheritance     paternal intergenerational inherence     extracellular vesicles    

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Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell

《医学前沿（英文）》 2022年 第16卷 第4期   页码 610-617 doi: 10.1007/s11684-021-0827-8

摘要： Bevacizumab, an anti-VEGF monoclonal antibody, has significantly improved the clinical outcomes of patients with advanced non-squamous NSCLC (ns-NSCLC). However, the safety and efficacy of bevacizumab for elderly patients with advanced NSCLC require further investigation. Thus, 59 patients were included in the present retrospective study, 22 patients in the bevacizumab plus pemetrexed and platinum (B+PP) group, and 37 patients in the pemetrexed and platinum (PP) group. For the entire cohort of patients, the median OS was 33.3 months, and the 1-year and 2-year overall survival rates were 88.5% and 67.8%, respectively. The median OS and 1-year and 2-year OS rates were 20.5 months, 70.3% and 0%, respectively, in the B+PP group and 33.4 months, 97.0% and 89.4%, respectively, in the PP group (P <0.001). The incidence of grade≥3 adverse events was higher in the B+PP group than in the PP group (27.3% vs. 10.8%, respectively; P=0.204). Univariate and multivariate analyses suggested that the receipt of≥5 cycles of first-line chemotherapy was an independent favorable prognostic factor for OS, whereas the addition of bevacizumab was an unfavorable prognostic factor. With increased toxicities, the addition of bevacizumab to PP does not improve the overall survival of elderly patients with advanced ns-NSCLC.

关键词： bevacizumab     elderly patient     advanced non-small-cell lung cancer     overall survival     toxicity    

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Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

《化学科学与工程前沿（英文）》 2017年 第11卷 第1期   页码 15-26 doi: 10.1007/s11705-017-1629-z

摘要： Overproduction of small-molecule chemicals using engineered microbial cells has greatly reduced the production cost and promoted environmental protection. Notably, the rapid and sensitive evaluation of the concentrations of the desired products greatly facilitates the optimization process of cell factories. For this purpose, many genetic components have been adapted into biosensors of small molecules, which couple the intracellular concentrations of small molecules to easily detectable readouts such as fluorescence, absorbance, and cell growth. Such biosensors allow a high-throughput screening of the small-molecule products, and can be roughly classified as protein-based and RNA-based biosensors. This review summarizes the recent developments in the design and applications of biosensors for small-molecule products.

关键词： biosensor     small molecule product     transcription factor     riboswitch     high-throughput screening    

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Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 53-60 doi: 10.1007/s11684-011-0121-2

摘要：

Video-assisted thoracoscopic surgery (VATS) provides a new approach for treating early-stage lung cancer. Lobectomy by VATS has many advantages over conventional thoracotomy, such as shorter recovery time, less postoperative pain, and faster resumption of a normal lifestyle. However, there is still much debate on the role of VATS in lobectomy for the treatment of lung cancer. Concerns regarding safety, the extent of mediastinal lymph node dissection, and long-term survival have made some surgeons apprehensive of its validity for lung cancer. In this paper, we review the development of thoracoscopy, the present status of VATS for early stage of non-small cell lung cancer (NSCLC), and comparison between VATS and open thoracotomy in the management of NSCLC.

关键词： non-small cell lung cancer     video-assisted thoracoscopic surgery     lobectomy    

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Accurate quantification of 3′-terminal 2′-O-methylated small RNAs by utilizing oxidative deep sequencing

《医学前沿（英文）》 2022年 第16卷 第2期   页码 240-250 doi: 10.1007/s11684-021-0909-7

摘要： The continuing discoveries of novel classes of RNA modifications in various organisms have raised the need for improving sensitive, convenient, and reliable methods for quantifying RNA modifications. In particular, a subset of small RNAs, including microRNAs (miRNAs) and Piwi-interacting RNAs (piRNAs), are modified at their 3′-terminal nucleotides via 2′-O-methylation. However, quantifying the levels of these small RNAs is difficult because 2′-O-methylation at the RNA 3′-terminus inhibits the activity of polyadenylate polymerase and T4 RNA ligase. These two enzymes are indispensable for RNA labeling or ligation in conventional miRNA quantification assays. In this study, we profiled 3′-terminal 2′-O-methyl plant miRNAs in the livers of rice-fed mice by oxidative deep sequencing and detected increasing amounts of plant miRNAs with prolonged oxidation treatment. We further compared the efficiency of stem-loop and poly(A)-tailed RT-qPCR in quantifying plant miRNAs in animal tissues and identified stem-loop RT-qPCR as the only suitable approach. Likewise, stem-loop RT-qPCR was superior to poly(A)-tailed RT-qPCR in quantifying 3′-terminal 2′-O-methyl piRNAs in human seminal plasma. In summary, this study established a standard procedure for quantifying the levels of 3′-terminal 2′-O-methyl miRNAs in plants and piRNAs. Accurate measurement of the 3′-terminal 2′-O-methylation of small RNAs has profound implications for understanding their pathophysiologic roles in biological systems.

关键词： small RNAs     2′-O-methylation     sequencing     RT-qPCR    

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Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

null

《医学前沿（英文）》 2017年 第11卷 第4期   页码 449-461 doi: 10.1007/s11684-017-0589-5

摘要：

In recent years, unexpected outbreaks of infectious diseases caused by emerging and re-emerging viruses have become more frequent, which is possibly due to environmental changes. These outbreaks result in the loss of life and economic hardship. Vaccines and therapeutics should be developed for the prevention and treatment of infectious diseases. In this review, we summarize and discuss the latest progress in the development of small-molecule viral inhibitors against highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, Ebola virus, and Zika virus. These viruses can interfere with the specific steps of viral life cycle by blocking the binding between virus and host cells, disrupting viral endocytosis, disturbing membrane fusion, and interrupting viral RNA replication and translation, thereby demonstrating potent therapeutic effect against various emerging and re-emerging viruses. We also discuss some general strategies for developing small-molecule viral inhibitors.

关键词： emerging and re-emerging viruses     small-molecule inhibitor     coronavirus     Ebola virus     Zika virus     life cycle    

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A better way to do small-for-size liver transplantation in rats

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 106-110 doi: 10.1007/s11684-011-0113-2

摘要：

Establishing a model for small-for-size liver transplantation is the basis for this study of partial and living donor graft liver transplantation. This study aims to explore a simpler and more effective way of establishing a 30% small-for-size liver transplantation in rats. Sprague-Dawley rats were selected as the donors and recipients. Small-for-size orthotopic liver transplantation was performed using Kamada’s two-cuff method. The donor’s liver was flushed via the abdominal aorta and hepatectomy was performed in situ. The animals were divided into three groups depending on the graft selected, with 40 pairs of rats in each group. In group I, the median lobe of the liver was used as graft; in group II, the right half of the median lobe and the right lobe were used as graft; and in group III, the median and right lobes were used as graft. In groups I and II, the bodyweights of donors were the same as those of recipients; however, in group III the bodyweights of donors were 100–120 g less than those of the recipients. The duration needed for transplantation, the 7-day survival rates, and the technical complication rates were compared among these three groups. The time required for hepatectomy was shorter in group III compared with groups I and II (8.8?±?0.7 min vs. 11.5?±?1.1 min and 10.1?±?1.0 min, P = 0.001). The cold ischemia time for the grafts, the anhepatic times, and the transplantation times for the recipients were not significantly different among the three groups. Compared with groups I and II, the incidence of bleeding, bile leakage, and inferior vena caval strictures were significantly decreased in group III (P<0.05). No significant differences between the three groups were found based on other complications after the operation (P>0.05). Group III had better 7-day survival rates and longer median survival times but the differences were not statistically significant. The method of small for donor bodyweight using the median and right lobes for grafting may be a more effective and simpler way of establishing a 30% small-for-size liver transplantation in rats, as shown by the shorter hepatectomy time and the occurrence of fewer complications after the operation.

关键词： liver transplantation     small-for-size     rats    

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标题 作者 时间 类型 操作

Fine-tuning cell organelle dynamics during mitosis by small GTPases

期刊论文

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

null

期刊论文

Simulation and experimental improvement on a small-scale Stirling thermo-acoustic engine

Mao CHEN,Yonglin JU

期刊论文

Discovery of small molecule degraders for modulating cell cycle

期刊论文

Gut microbiota and its implications in small bowel transplantation

null

期刊论文

Molecular classification of non-small-cell lung cancer: diagnosis, individualized treatment, and prognosis

null

期刊论文

Performance prediction of switched reluctance generator with time average and small signal models

Jyoti KOUJALAGI, B. UMAMAHESWARI, R. ARUMUGAM

期刊论文

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational

期刊论文

Bevacizumab in combination with pemetrexed and platinum for elderly patients with advanced non-squamous non-small-cell

期刊论文

Genetic biosensors for small-molecule products: Design and applications in high-throughput screening

Qingzhuo Wang,Shuang-Yan Tang,Sheng Yang

期刊论文

Lobectomy by video-assisted thoracoscopic surgery (VATS) for early stage of non-small cell lung cancer

null

期刊论文

Accurate quantification of 3′-terminal 2′-O-methylated small RNAs by utilizing oxidative deep sequencing

期刊论文

Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging

null

期刊论文

A better way to do small-for-size liver transplantation in rats

null

期刊论文