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Association of gene variants with juvenile amyotrophic lateral sclerosis

《医学前沿（英文）》 doi: 10.1007/s11684-023-1005-y

摘要： Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons, and it demonstrates high clinical heterogeneity and complex genetic architecture. A variation within TRMT2B (c.1356G>T; p.K452N) was identified to be associated with ALS in a family comprising two patients with juvenile ALS (JALS). Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS, and three more variants were identified in a public ALS database including 3317 patients with ALS. A decreased number of mitochondria, swollen mitochondria, lower expression of ND1, decreased mitochondrial complex I activities, lower mitochondrial aerobic respiration, and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 cells. Further, TRMT2B variations overexpression cells also displayed decreased ND1. In conclusion, a novel JALS-associated gene called TRMT2B was identified, thus broadening the clinical and genetic spectrum of ALS.

关键词： TRMT2B     amyotrophic lateral sclerosis     mitochondrial complex I     tRNA methylation     reactive oxygen species    

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<i>Ni>-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probesfor <i>in vivoi> cell H2S imaging

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 64-71 doi: 10.1007/s11705-021-2048-8

摘要： Heterocyclic compound quinoline and its derivatives exist in natural compounds and have a broad spectrum of biological activity. They play an important role in the design of new structural entities for medical applications. Similarly, indoles and their derivatives are found widely in nature. Amino acids, alkaloids and auxin are all derivatives of indoles, as are dyes, and their condensation with aldehydes makes it easy to construct reaction sites for nucleophilic addition agents. In this work, we combine these two groups organically to construct a rapid response site (within 30 s) for H S, and at the same time, a ratiometric fluorescence response is presented throughout the process of H S detection. As such, the lower detection limit can reach 55.7 nmol/L for H S. In addition, cell imaging shows that this probe can be used for the mitochondrial targeted detection of endogenous and exogenous H S. Finally, this probe application was verified by imaging H S in nude mice.

关键词： heterocyclic compound     hydrogen sulfide     ratiometric     mitochondrial targeted    

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hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

《化学科学与工程前沿（英文）》 2022年 第16卷 第1期   页码 92-102 doi: 10.1007/s11705-021-2063-9

摘要： Mitochondrial DNA has a special structure that is prone to damage resulting in many serious diseases, such as genetic diseases and cancers. Therefore, the rapid and specific monitoring of mitochondrial DNA damage is urgently needed for biological recognition. Herein, we constructed an in situ hydrophobic environment-triggering reactive fluorescence probe named MBI-CN. The fluorophore was 2-styrene-1H-benzo[d]imidazole, and malononitrile was introduced as a core into a molecule to initiate the hydrolysis reaction in the specific environment containing damaged mitochondrial DNA. In this design, MBI-CN conjugates to mitochondrial DNA without causing additional damages. Thus, MBI-CN can be hydrolyzed to generate MBI-CHO in an in situ hydrophobic environment with mitochondrial DNA damage. Meanwhile, MBI-CHO immediately emitted a significative fluorescence signal changes at 437 and 553 nm within 25 s for the damaged mitochondria DNA. Give that the specific and rapid response of MBI-CN does not cause additional damages to mitochondrial DNA, it is a potentially effective detection tool for the real-time monitoring of mitochondrial DNA damage during cell apoptosis and initial assessment of cell apoptosis.

关键词： hydrolysis reaction     mitochondrial DNA damage     in situ hydrophobic environment trigger     fluorescence probe     apoptosis    

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Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via tworeceptors: apolipoprotein E receptor 2' and glycoprotein I bα

null

《医学前沿（英文）》 2016年 第10卷 第1期   页码 76-84 doi: 10.1007/s11684-015-0426-7

摘要：

Anti-β2 glycoprotein I (anti-β2GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β2GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β2GP I antibodies in complexes with β2GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β2GP I /β2GP I complex. The interaction between the anti-β2GP I /β2GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B2 production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β2GP I /β2GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β2GP I /β2GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

关键词： anti-β2GP I /β2GP I complex     platelet     GP I bα     apoER2'     thrombosis    

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Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

《医学前沿（英文）》 2022年 第16卷 第2期   页码 216-226 doi: 10.1007/s11684-022-0920-7

摘要： Hepatocellular carcinoma (HCC), which makes up the majority of liver cancer, is induced by the infection of hepatitis B/C virus. Biomarkers are needed to facilitate the early detection of HCC, which is often diagnosed too late for effective therapy. The tRNA-derived small RNAs (tsRNAs) play vital roles in tumorigenesis and are stable in circulation. However, the diagnostic values and biological functions of circulating tsRNAs, especially for HCC, are still unknown. In this study, we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum. We identified tRF-Gln-TTG-006, which was remarkably upregulated in HCC serum (training cohort: 24 HCC patients vs. 24 healthy controls). In the validation stage, we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity (80.4%) and specificity (79.4%) even in the early stage (Stage I: sensitivity, 79.0%; specificity, 74.8%; 155 healthy controls vs. 153 HCC patients from two cohorts). Moreover, in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells, and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays. In summary, our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

关键词： tsRNA     biomarker     hepatocarcinoma    

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Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

《农业科学与工程前沿（英文）》 2017年 第4卷 第3期   页码 358-365 doi: 10.15302/J-FASE-2017158

摘要： Substantial variation in gene organization and arrangement has been reported for sequenced mitochondrial (mt) genomes from the suborders of the insect order Psocoptera. In this study we sequenced the complete mt genome of , the first representative of the family Stenopsocidae from the suborder Psocomorpha. Relative to the ancestral pattern, rearrangements of a protein-coding gene ( ) and five tRNA genes ( , , , , ) were found. This pattern was similar to that of two barklice from the family Psocidae, with the exception of the translocation of , and Based on comparisons of pairwise breakpoint distances of gene rearrangements, gene number and chromosome number, it was concluded that mt genomes of Stenopsocidae and Psocidae share a relatively conserved pattern of gene rearrangements; mt genomes within the Psocomorpha have been generally stable over long evolutionary history; and mt gene rearrangement has been substantially faster in the booklice (suborder Troctomorpha) than in the barklice (suborders Trogiomorpha and Psocomorpha). It is speculated that the change of life history and persistence of unusual reproductive systems with maternal inheritance contributed to the contrasting rates in mt genome evolution between the barklice and booklice.

关键词： gene rearrangement     mitochondrial genome     Psocoptera     Stenopsocidae     TDRL model    

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Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

《医学前沿（英文）》 doi: 10.1007/s11684-023-0983-0

摘要： Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission and Ca homeostasis in a murine model of HFpEF

关键词： mitochondrial fission Ca     Berberine alleviates myocardial     murine model HFpEF    

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初生多肽相关复合物调控小麦禾谷镰刀菌生长发育和致病性 Article

王旭丽, 谢鑫, 刘敬, 王国梁, 邱德文

《工程（英文）》 2020年 第6卷 第5期   页码 546-552 doi: 10.1016/j.eng.2019.07.025

摘要：

对植物病原菌而言，维持蛋白质内稳态对其生存和繁殖至关重要。然而，当前对参与维持蛋白质内稳态的因子在真菌致病过程中的作用仍缺乏科学的认识。在本研究中，我们鉴定了十大病原真菌之一—禾谷镰刀菌（Fusarium graminearum）的初生多肽相关复合物（FgNAC）的功能。研究发现，FgNAC中的α亚基（FgNACα）与其在酵母和其他物种中的同源基因在结构和功能方面表现出高度相似性。禾谷镰刀菌NACα缺失突变体虽可存活但其菌丝生长、分生孢子产生和致病性受到严重削弱。此外，通过酵母双杂交实验发现FgNACα可以和FgNACβ亚基发生互作。亚细胞定位结果表明FgNACα和FgNACβ主要发生在细胞质中。未来的研究应致力于解析初生多肽相关复合物调节蛋白质代谢从而调控真菌发育和致病性的作用机制。

关键词： 小麦赤霉病     初生多肽相关复合物     基因敲除     致病性     亚细胞定位    

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用二极管统一构建两个n阶电路网络 Research Article

林小燕,谭志中

《信息与电子工程前沿（英文）》 2023年 第24卷 第2期   页码 289-298 doi: 10.1631/FITEE.2200360

摘要： 本文通过二极管将两个不同的n阶拓扑电路网络连接起来，建立起一个统一的网络模型，这是一个以前没有研究解决的新问题。该网络模型不仅包含五个电阻元件，还包含二极管器件，因此该网络包含多种不同的网络类型。该问题可以通过三个主要步骤来解决：首先，将网络简化为两个不同的等效电路模型；其次，应用基尔霍夫定律建立非线性差分方程模型；最后，对结构相似的两个方程进行统一处理，并利用等效变换技术得到非线性差分方程的通解。作为应用，文章推导出几个有趣的特殊结果。网络模型的研究非常重要，可以应用于跨学科研究。

关键词： 复杂网络；等效变换；非线性差分方程；等效电阻    

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NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

《医学前沿（英文）》 2010年 第4卷 第2期   页码 177-184 doi: 10.1007/s11684-010-0038-1

摘要： Potent combination antiretroviral therapy (cART) has significantly improved the life expectancy of people living with human immunodeficiency virus (HIV), but it has many side effects such as lipodystrophy (LD), hepatic steatosis, and lactic acidosis. Nucleoside reverse transcriptase inhibitors (NRTIs) could damage the mitochondria by inhibiting the human DNA polymerase gamma, leading to mtDNA deletion. However, it remains uncertain whether NRTIs could induce the hypervariable region (HV) mutations of the D loop of mitochondria in Chinese HIV/AIDS patients, and whether that effect is different between individuals with and without LD. Hereby, 30 Chinese AIDS patients who were receiving antiretroviral drugs were recruited, among which 16 had symptomatic LD and 14 did not. Blood samples were collected prior to and after 96 weeks of treatment. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs). Fragments of 728 bp in length containing HV 2 were amplified by standard polymerase chain reaction (PCR). Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants between paired longitudinal samples. Alterations were compared with the revised Cambridge Reference Sequence (rCRS) to determine mutation or polymorphism. Results showed that two years after ART, totally seven cases exhibited sequence variations, five individuals showed 73€A→G revised variation (two with and three without LD), while two cases of LD were found to have other nucleotide alterations. There was no new alteration in individuals without LD. In conclusion, NRTIs could induce mutation of mtDNA HV 2, which might contribute to the development of LD.

关键词： nucleoside reverse transcriptase inhibitors     human immunodeficiency virus     mitochondrial DNA     D loop     mutation    

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GID complex regulates the differentiation of neural stem cells by destabilizing TET2

《医学前沿（英文）》 doi: 10.1007/s11684-023-1007-9

摘要： Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/− mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.

关键词： TET2     GID complex     neural stem cells     differentiation of neurons    

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Non-genetic mechanisms of diabetic nephropathy

null

《医学前沿（英文）》 2017年 第11卷 第3期   页码 319-332 doi: 10.1007/s11684-017-0569-9

摘要：

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.

关键词： diabetic nephropathy     immune inflammatory response     epithelial–mesenchymal transition     apoptosis     mitochondrial damage     epigenetics     podocyte–endothelial communication    

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Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1

《医学前沿（英文）》 doi: 10.1007/s11684-023-1003-0

摘要： Lipin proteins including Lipin 1–3 act as transcriptional co-activators and phosphatidic acid phosphohydrolase enzymes, which play crucial roles in lipid metabolism. However, little is known about the function of Lipin3 in triglyceride (TG) metabolism. Here, we identified a novel mutation (NM_001301860: p.1835A>T/p.D612V) of Lipin3 in a large family with hypertriglyceridemia (HTG) and obesity through whole-exome sequencing and Sanger sequencing. Functional studies revealed that the novel variant altered the half-life and stability of the Lipin3 protein. Hence, we generated Lipin3 heterozygous knockout (Lipin3-heKO) mice and cultured primary hepatocytes to explore the pathophysiological roles of Lipin3 in TG metabolism. We found that Lipin3-heKO mice exhibited obvious obesity, HTG, and non-alcoholic fatty liver disorder. Mechanistic study demonstrated that the haploinsufficiency of Lipin3 in primary hepatocytes may induce the overexpression and abnormal distribution of Lipin1 in cytosol and nucleoplasm. The increased expression of Lipin1 in cytosol may contribute to TG anabolism, and the decreased Lipin1 in nucleoplasm can reduce PGC1α, further leading to mitochondrial dysfunction and reduced TG catabolism. Our study suggested that Lipin3 was a novel disease-causing gene inducing obesity and HTG. We also established a relationship between Lipin3 and mitochondrial dysfunction.

关键词： Lipin3     Lipin1     hypertriglyceridemia     obesity     mitochondrial dysfunction    

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Footholds optimization for legged robots walking on complex terrain

《机械工程前沿（英文）》 2023年 第18卷 第2期 doi: 10.1007/s11465-022-0742-y

摘要： This paper proposes a novel continuous footholds optimization method for legged robots to expand their walking ability on complex terrains. The algorithm can efficiently run onboard and online by using terrain perception information to protect the robot against slipping or tripping on the edge of obstacles, and to improve its stability and safety when walking on complex terrain. By relying on the depth camera installed on the robot and obtaining the terrain heightmap, the algorithm converts the discrete grid heightmap into a continuous costmap. Then, it constructs an optimization function combined with the robot’s state information to select the next footholds and generate the motion trajectory to control the robot’s locomotion. Compared with most existing footholds selection algorithms that rely on discrete enumeration search, as far as we know, the proposed algorithm is the first to use a continuous optimization method. We successfully implemented the algorithm on a hexapod robot, and verified its feasibility in a walking experiment on a complex terrain.

关键词： footholds optimization     legged robot     complex terrain adapting     hexapod robot     locomotion control    

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Special issue: Reliability management of complex system

《工程管理前沿（英文）》 2021年 第8卷 第4期   页码 477-479 doi: 10.1007/s42524-021-0175-z

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标题 作者 时间 类型 操作

Association of gene variants with juvenile amyotrophic lateral sclerosis

期刊论文

<i>Ni>-Positive ion activated rapid addition and mitochondrial targeting ratiometric fluorescent probesfor <i>in vivoi> cell H2S imaging

Yan Shi, Fangjun Huo, Yongkang Yue, Caixia Yin

期刊论文

hydrophobic environment triggering reactive fluorescence probe to real-time monitor mitochondrial DNA

期刊论文

Anti-β glycoprotein I antibodies in complex with β2 glycoprotein I induce platelet activation via tworeceptors: apolipoprotein E receptor 2' and glycoprotein I bα

null

期刊论文

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

期刊论文

Conserved gene arrangement in the mitochondrial genomes of barklouse families Stenopsocidae and Psocidae

Xiaochen LIU, Hu LI, Yao CAI, Fan SONG, John-James WILSON, Wanzhi CAI

期刊论文

Berberine alleviates myocardial diastolic dysfunction by modulating Drp1-mediated mitochondrial fission

期刊论文

初生多肽相关复合物调控小麦禾谷镰刀菌生长发育和致病性

王旭丽, 谢鑫, 刘敬, 王国梁, 邱德文

期刊论文

用二极管统一构建两个n阶电路网络

林小燕,谭志中

期刊论文

NRTIs’ effect on the sequence of mitochondrial DNA HV 2 in HIV infected patients

Ya-Song WU MD, PhD, Xin-Yue CHEN MD, Ying SHI PhD, Hao WU MD, De-Xi CHEN MD, PhD, Yu SUN MD, Fu-Jie ZHANG MD,

期刊论文

GID complex regulates the differentiation of neural stem cells by destabilizing TET2

期刊论文

Non-genetic mechanisms of diabetic nephropathy

null

期刊论文

Haploinsufficiency of Lipin3 leads to hypertriglyceridemia and obesity by disrupting the expression and nucleocytoplasmic localization of Lipin1

期刊论文

Footholds optimization for legged robots walking on complex terrain

期刊论文

Special issue: Reliability management of complex system

期刊论文