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A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

《医学前沿（英文）》 2023年第17卷第2期页码 330-338 doi: 10.1007/s11684-022-0933-2

摘要： Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’ hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

关键词： Clouston syndrome whole exome sequencing GJB6 gene novel variant unique phenotype

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A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodesthe candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

《医学前沿（英文）》 2023年第17卷第3期页码 458-475 doi: 10.1007/s11684-022-0968-4

摘要： The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

关键词： LU domain-containing protein family novel human gene LY6A pituitary tumor biomarker nonsynonymous SNP GPI-anchored protein

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Construction of 6HRE-GFAP-Baxα system specific for glioma gene therapy

TIAN Yongji, LI Guilin, GAO Jun, WANG Renzhi, KONG Yanguo, ZHANG Zhenxing, LI Shifang, TIAN Shiqiang, DOU Wanchen, ZHANG Bo

《医学前沿（英文）》 2007年第1卷第1期页码 49-53 doi: 10.1007/s11684-007-0010-x

摘要： The aim of this paper is to construct a specific and high-performance gene therapy system for glioma. We constructed a combined promoter 6HRE-GFAP (Hypoxia Responsive Element, Glial Fibrillary Acidic Protein) by gene recombination techniques according to the hypoxia microenvironment in glioma and tested its efficacy and specificity in cultured cells, and then constructed GFAP-Baxα gene expressing system and determined its promoting of apoptosis in glioma cells. Our primary results showed that in U251 and BT325 cell lines, the activity of GFAP promoter was 16.40 and 4.73-fold of the promoter of hTERT (Human Telomerase Reverse Transcriptase), respectively. The activities of 6HRE-GFAP-promoter increased by 3.08 and 1.30-fold under 2% O condition compared with those under 18% O condition, while under 0.2% O condition increased by 8.90 and 2.69-fold, respectively. The glioma cells showed typical apoptotic signs 90 hours after the transient transfection of GFAP-Baxα. In these primary experiments, it showed that 6HRE-GFAPBaxα system could promote glioma cell apoptosis. It was specific and effective for glioma gene therapy.

关键词： GFAP-Baxα BT325 Fibrillary apoptotic specificity

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微波辐射下离子液体［RMIm］PF6（R=P, B, C6）的合成及其电导率研究

何永福

《中国工程科学》 2008年第10卷第9期页码 92-95

摘要： 1－溴己烷)在80 ℃回流加热10 min，可制得咪唑类离子液体的中间体溴代1－丁基－3－甲基咪唑（［BMIm］Br）、溴代1－丙基－3－甲基咪唑（［PMIm］Br）、溴代1－己基－3－甲基咪唑（［C6MIm］Br），进一步与HPF6在室温搅拌反应4 h，制得憎水性的咪唑类离子液体［BMIm］PF6，［PMIm］PF6和［C6MIm］PF6。

关键词：离子液体微波辐射电导率 [BMIm]PF6 [PMIm]PF6 [C6MIm]PF6

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Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

《医学前沿（英文）》 doi: 10.1007/s11684-023-1044-4

摘要： As of May 3, 2023, the coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 760 million confirmed cases and over 6.9 million deaths. Several patients have developed pneumonia, which can deteriorate into acute respiratory distress syndrome. The primary etiology may be attributed to cytokine storm, which is triggered by the excessive release of proinflammatory cytokines and subsequently leads to immune dysregulation. Considering that high levels of interleukin-6 (IL-6) have been detected in several highly pathogenic coronavirus-infected diseases, such as severe acute respiratory syndrome in 2002, the Middle East respiratory syndrome in 2012, and COVID-19, the IL-6 pathway has emerged as a key in the pathogenesis of this hyperinflammatory state. Thus, we review the history of cytokine storm and the process of targeting IL-6 signaling to elucidate the pivotal role played by tocilizumab in combating COVID-19.

关键词： SARS-CoV-2 COVID-19 cytokine storm interleukin-6 tocilizumab

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FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

《医学前沿（英文）》 2023年第17卷第4期页码 714-728 doi: 10.1007/s11684-022-0959-5

摘要： FRMD6, a member of the 4.1 ezrin–radixin–moesin domain-containing protein family, has been reported to inhibit tumor progression in multiple cancers. Here, we demonstrate the involvement of FRMD6 in lung cancer progression. We find that FRMD6 is overexpressed in lung cancer tissues relative to in normal lung tissues. In addition, the enhanced expression of FRMD6 is associated with poor outcomes in patients with lung squamous cell carcinoma (n = 75, P = 0.0054) and lung adenocarcinoma (n = 94, P = 0.0330). Cell migration and proliferation in vitro and tumor formation in vivo are promoted by FRMD6 but are suppressed by the depletion of FRMD6. Mechanistically, FRMD6 interacts and colocalizes with mTOR and S6K, which are the key molecules of the mTOR signaling pathway. FRMD6 markedly enhances the interaction between mTOR and S6K, subsequently increasing the levels of endogenous pS6K and downstream pS6 in lung cancer cells. Furthermore, knocking out FRMD6 inhibits the activation of the mTOR signaling pathway in Frmd6^−/− gene KO MEFs and mice. Altogether, our results show that FRMD6 contributes to lung cancer progression by activating the mTOR signaling pathway.

关键词： FRMD6 lung cancer mTOR pathway

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人类遗传病的家系收集疾病基因定位克隆与疾病基因功能的研究

夏家辉

《中国工程科学》 2000年第2卷第11期页码 1-11

摘要：定位于Yp11.32带；1991年以来收集遗传病家系345种共590个；1996年用显微切割、PCR、微克隆技术克隆了EXT2基因；1998年用基因家族-候选疾病基因克隆方法克隆了遗传性神经性耳聋基因GJB3

关键词：遗传病家系基因定位和克隆基因家族-候选疾病基因克隆基因组扫描基因功能研究

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Molecular engineering of dendrimer nanovectors for siRNA delivery and gene silencing

Yu Cao, Xiaoxuan Liu, Ling Peng

《化学科学与工程前沿（英文）》 2017年第11卷第4期页码 663-675 doi: 10.1007/s11705-017-1623-5

摘要： Small interfering RNA (siRNA) therapeutics hold great promise to treat a variety of diseases, as long as they can be delivered safely and effectively into cells. Dendrimers are appealing vectors for siRNA delivery by virtue of their well-defined molecular architecture and multivalent cooperativity. However, the clinical translation of RNA therapeutics mediated by dendrimer delivery is hampered by the lack of dendrimers that are of high quality to meet good manufacturing practice standard. In this context, we have developed small amphiphilic dendrimers that self-assemble into supramolecular structures, which mimic high-generation dendrimers synthesized with covalent construction, yet are easy to produce in large amount and superior quality. Indeed, the concept of supramolecular dendrimers has proved to be very promising, and has opened up a new avenue for dendrimer-mediated siRNA delivery. A series of self-assembling supramolecular dendrimers have consequently been established, some of them out-performing the currently available nonviral vectors in delivering siRNA to various cell types and , including human primary cells and stem cells. This short review presents a brief introduction to RNAi therapeutics, the obstacles to their delivery and the advantages of dendrimer delivery vectors as well as our bio-inspired structurally flexible dendrimers for siRNA delivery. We then highlight our efforts in creating self-assembling amphiphilic dendrimers to construct supramolecular dendrimer nanosystems for effective siRNA delivery as well as the related structural alterations to enhance delivery efficiency. The advent of self-assembling supramolecular dendrimer nanovectors holds great promise and heralds a new era of dendrimer-mediated delivery of RNA therapeutics in biomedical applications.

关键词： gene therapy RNAi therapeutics dendrimer nanovectors gene silencing

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RNA m⁶A modification and its function in diseases

null

《医学前沿（英文）》 2018年第12卷第4期页码 481-489 doi: 10.1007/s11684-018-0654-8

摘要：

N⁶-methyladenosine (m⁶A) is the most common post-transcriptional RNA modification throughout the transcriptome, affecting fundamental aspects of RNA metabolism. m⁶A modification could be installed by m⁶A “writers” composed of core catalytic components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m⁶A “erasers” (FTO and ALKBH5). The function of m⁶A is executed by m⁶A “readers” that bind to m⁶A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or indirectly (HNRNPA2B1). In the past few years, advances in m⁶A modulators (“writers,” “erasers,” and “readers”) have remarkably renewed our understanding of the function and regulation of m⁶A in different cells under normal or disease conditions. However, the mechanism and the regulatory network of m⁶A are still largely unknown. Moreover, investigations of the m⁶A physiological roles in human diseases are limited. In this review, we summarize the recent advances in m⁶A research and highlight the functional relevance and importance of m⁶A modification in in vitro cell lines, in physiological contexts, and in cancers.

关键词： RNA modification m⁶A immunity cancer epigenetics

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The antibiotic resistome: gene flow in environments, animals and human beings

null

《医学前沿（英文）》 2017年第11卷第2期页码 161-168 doi: 10.1007/s11684-017-0531-x

摘要：

The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs (antibiotic resistome) in bacterial communities of natural environments, human and animals, i.e., in the one health settings. We propose that the resistance gene flow in nature is “from the natural environments” and “to the natural environments”; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene “circulation.”

关键词： antibiotic resistance resistome microbiome gene flow

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Reflections on the system of evaluation of gene-edited livestock

Ziyao FAN, Tianwen WU, Kui WU, Yulian MU, Kui LI

《农业科学与工程前沿（英文）》 2020年第7卷第2期页码 211-217 doi: 10.15302/J-FASE-2019303

摘要：

The rapid development of biotechnology has provided a greater understanding of the biological functions of major candidate genes that have important functions regarding economic traits, and new materials for livestock breeding have been obtained through gene editing (GE) and embryo manipulation with the purpose of improving quality and output and reducing the costs and risk of disease. Public concerns, particularly over safety risks and production performance, must be addressed. Evaluation is the most important component of the regulation of gene-edited livestock and is a crucial guarantee of public safety before the marketing of gene-edited animal products. Here, the system of evaluation of gene-edited livestock is discussed in terms of public safety and production performance. The search for safe and ethical applications in the GE of livestock, a case-by-case evaluation strategy, and classification and simplification are used in order to promote a more efficient, objective, comprehensive and operable evaluation system.

关键词： evaluation gene editing livestock performance safety

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Antibacterial and anti-flaming PA6 composite with metathetically prepared nano AgCl@BaSO

Wei Zhang, Boren Xu, Caihong Gong, Chunwang Yi, Shen Zhang

《化学科学与工程前沿（英文）》 2021年第15卷第2期页码 340-350 doi: 10.1007/s11705-020-1942-9

摘要： In this study, a facile and environmentally friendly method with low energy consumption for preparing nanoscale AgCl and BaSO co-precipitates (AgCl@BaSO co-precipitates) was developed based on the metathetical reaction. Then, the dried co-precipitates were melt-compounded with polyamide 6 (PA6) resins at a specified mass ratio in a twin-screw extruder. The results demonstrated that in the absence of any coating agent or carrier, the nanoparticles of AgCl@BaSO co-precipitates were homogeneously dispersed in the PA6 matrix. Further analysis showed that after the addition of AgCl@BaSO co-precipitates, the antibacterial performance, along with the flame-retardance and anti-dripping characteristics of PA6, was enhanced significantly. In addition, the PA6 composites possessed high spinnability in producing pre-oriented yarn.

关键词： nano AgCl@BaSO₄ co-precipitates antibacterial flame resistance PA6 composite PA6 yarn

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Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

《医学前沿（英文）》 2022年第16卷第4期页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1 gene mutation acute myeloid leukemia transcriptional repression DNA methylation

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Construction of lentiviral vector carrying Rab9 gene and its expression in mouse brain

Youguo HAO, Min ZHANG, Jinzhi XU, Bitao BU, Jiajun WEI

《医学前沿（英文）》 2009年第3卷第2期页码 141-147 doi: 10.1007/s11684-009-0041-6

摘要： Rab proteins and their effectors facilitate vesicular transport by tethering donor vesicles to their respective target membranes. Rab9 mediates late endosome-to- -Golgi-network trafficking. To explore the possibility of Rab9-related gene therapy for neurodegenerative diseases, we packed Lentivirus encoding Rab9. The expressing plasmid pCDH1-MCF1-Rab9-EF1-copGFP was constructed by using molecular biological techniques. The Lentivirus encoding Rab9 cDNA was packed by Lifectamine-2000 mediated co-transfection of the plasmid pPACKH1- , pPACKH1- and pVSV- into 293T cells. DNA sequencing proved the successful construction of pCDH1-MCF1-Rab9-EF1-copGFP. After 72 hours, the expression of GFP could be detected in BV-2 cells. Western blotting revealed that the Rab9 gene expression in BALB/c mice brain was up-regulated significantly 4 weeks after injection with Lentivirus encoding Rab9, which evidenced a satisfactory increasing effect of this virus. Administration of Lenti-Rab9 to postnatal day 3 Niemann-Pick disease type C (NPC) mice reduced motor defects and prevented the weight loss associated with female NPC mice, as well as modulating the death rate of Purkinje neurons. It is concluded that the packaging of Lentivirus encoding Rab9 was successful. Lentivirus encoding Rab9 can increase the expression of Rab9 gene effectively, which might offer a novel means for the treatment of neurodegenerative diseases.

关键词： Rab9 lentivirus gene therapy gene transfer

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A rolling 6U parallel mechanism

Zhihuai MIAO, Yanan YAO

《机械工程前沿（英文）》 2011年第6卷第1期页码 96-98 doi: 10.1007/s11465-011-0214-2

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标题作者时间类型操作

A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

期刊论文

A systematic survey of LU domain-containing proteins reveals a novel human gene, LY6A, which encodesthe candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

期刊论文

Construction of 6HRE-GFAP-Baxα system specific for glioma gene therapy

TIAN Yongji, LI Guilin, GAO Jun, WANG Renzhi, KONG Yanguo, ZHANG Zhenxing, LI Shifang, TIAN Shiqiang, DOU Wanchen, ZHANG Bo

期刊论文

微波辐射下离子液体［RMIm］PF6（R=P, B, C6）的合成及其电导率研究

何永福

期刊论文

Cytokine storm and translating IL-6 biology into effective treatments for COVID-19

期刊论文

FERM domain-containing protein FRMD6 activates the mTOR signaling pathway and promotes lung cancer progression

期刊论文

人类遗传病的家系收集疾病基因定位克隆与疾病基因功能的研究