المؤلفون: Xiu Kui Gao, Zu Kang Sheng, Ye Hong Lu, Yu Ting Sun, Xi Sheng Rao, Lin Jing Shi, Xiao Xia Cong, Xiao Chen, Hao Bo Wu, Man Huang, Qiang Zheng, Jian-sheng Guo, Liang Jun Jiang, Li Ling Zheng, Yi Ting Zhou

المصدر: Cell Discovery, Vol 9, Iss 1, Pp 1-18 (2023)

مصطلحات موضوعية: Cytology, QH573-671

الوصف: Abstract The scaffold protein IRS-1 is an essential node in insulin/IGF signaling. It has long been recognized that the stability of IRS-1 is dependent on its endomembrane targeting. However, how IRS-1 targets the intracellular membrane, and what type of intracellular membrane is actually targeted, remains poorly understood. Here, we found that the phase separation-mediated IRS-1 puncta attached to endoplasmic reticulum (ER). VAPB, an ER-anchored protein that mediates tethers between ER and membranes of other organelles, was identified as a direct interacting partner of IRS-1. VAPB mainly binds active IRS-1 because IGF-1 enhanced the VAPB-IRS-1 association and replacing of the nine tyrosine residues of YXXM motifs disrupted the VAPB-IRS-1 association. We further delineated that the Y745 and Y746 residues in the FFAT-like motif of IRS-1 mediated the association with VAPB. Notably, VAPB targeted IRS-1 to the ER and subsequently maintained its stability. Consistently, ablation of VAPB in mice led to downregulation of IRS-1, suppression of insulin signaling, and glucose intolerance. The amyotrophic lateral sclerosis (ALS)-derived VAPB P56S mutant also impaired IRS-1 stability by interfering with the ER-tethering of IRS-1. Our findings thus revealed a previously unappreciated condensate-membrane contact (CMC), by which VAPB stabilizes the membraneless IRS-1 signalosome through targeting it to ER membrane.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2056-5968Test

الوصول الحر: https://doaj.org/article/750a3b7e14b6488496e3dbd0be4e9768Test

المؤلفون: Xiu Kui Gao, Xi Sheng Rao, Xiao Xia Cong, Zu Kang Sheng, Yu Ting Sun, Shui Bo Xu, Jian Feng Wang, Yong Heng Liang, Lin Rong Lu, Hongwei Ouyang, Huiqing Ge, Jian-sheng Guo, Hang-jun Wu, Qi Ming Sun, Hao-bo Wu, Zhang Bao, Li Ling Zheng, Yi Ting Zhou

المصدر: Cell Discovery, Vol 8, Iss 1, Pp 1-19 (2022)

مصطلحات موضوعية: Cytology, QH573-671

الوصف: Abstract As a critical node for insulin/IGF signaling, insulin receptor substrate 1 (IRS-1) is essential for metabolic regulation. A long and unstructured C-terminal region of IRS-1 recruits downstream effectors for promoting insulin/IGF signals. However, the underlying molecular basis for this remains elusive. Here, we found that the C-terminus of IRS-1 undergoes liquid-liquid phase separation (LLPS). Both electrostatic and hydrophobic interactions were seen to drive IRS-1 LLPS. Self-association of IRS-1, which was mainly mediated by the 301–600 region, drives IRS-1 LLPS to form insulin/IGF-1 signalosomes. Moreover, tyrosine residues of YXXM motifs, which recruit downstream effectors, also contributed to IRS-1 self-association and LLPS. Impairment of IRS-1 LLPS attenuated its positive effects on insulin/IGF-1 signaling. The metabolic disease-associated G972R mutation impaired the self-association and LLPS of IRS-1. Our findings delineate a mechanism in which LLPS of IRS-1-mediated signalosomes serves as an organizing center for insulin/IGF-1 signaling and implicate the role of aberrant IRS-1 LLPS in metabolic diseases.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2056-5968Test

الوصول الحر: https://doaj.org/article/61e3a10be1d3437791635da611d63910Test

المؤلفون: Anjali Bansal Gupta, Liang En Wee, Yi Ting Zhou, Michael Hortsch, Boon Chuan Low

المصدر: PLoS ONE, Vol 7, Iss 3, p e33863 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: The CRAL_TRIO protein domain, which is unique to the Sec14 protein superfamily, binds to a diverse set of small lipophilic ligands. Similar domains are found in a range of different proteins including neurofibromatosis type-1, a Ras GTPase-activating Protein (RasGAP) and Rho guanine nucleotide exchange factors (RhoGEFs). Proteins containing this structural protein domain exhibit a low sequence similarity and ligand specificity while maintaining an overall characteristic three-dimensional structure. We have previously demonstrated that the BNIP-2 and Cdc42GAP Homology (BCH) protein domain, which shares a low sequence homology with the CRAL_TRIO domain, can serve as a regulatory scaffold that binds to Rho, RhoGEFs and RhoGAPs to control various cell signalling processes. In this work, we investigate 175 BCH domain-containing proteins from a wide range of different organisms. A phylogenetic analysis with ~100 CRAL_TRIO and similar domains from eight representative species indicates a clear distinction of BCH-containing proteins as a novel subclass within the CRAL_TRIO/Sec14 superfamily. BCH-containing proteins contain a hallmark sequence motif R(R/K)h(R/K)(R/K)NL(R/K)xhhhhHPs ('h' is large and hydrophobic residue and 's' is small and weekly polar residue) and can be further subdivided into three unique subtypes associated with BNIP-2-N, macro- and RhoGAP-type protein domains. A previously unknown group of genes encoding 'BCH-only' domains is also identified in plants and arthropod species. Based on an analysis of their gene-structure and their protein domain context we hypothesize that BCH domain-containing genes evolved through gene duplication, intron insertions and domain swapping events. Furthermore, we explore the point of divergence between BCH and CRAL-TRIO proteins in relation to their ability to bind small GTPases, GAPs and GEFs and lipid ligands. Our study suggests a need for a more extensive analysis of previously uncharacterized BCH, 'BCH-like' and CRAL_TRIO-containing proteins and their significance in regulating signaling events involving small GTPases.

وصف الملف: electronic resource

العلاقة: https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479462/?tool=EBITest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/4ca4bbea28124c5bb271f56e107c3fbdTest

المؤلفون: Yi-Ting Zhou, Da-Dao An, Yi-Xin Xu, Ying Zhou, Qing-Qing Li, Hai-Bin Dai, Xiang-Nan Zhang, Yi Wang, Min Lou, Zhong Chen, Wei-Wei Hu

المصدر: Fundamental Research, Vol 4, Iss 1, Pp 188-198 (2024)

مصطلحات موضوعية: Chronic cerebral hypoperfusion, Optogenetic stimulation, Oligodendrocyte progenitor cell, Ischemic vascular dementia, Glutamatergic neuron, Remyelination, Science (General), Q1-390

الوصف: Chronic cerebral hypoperfusion can cause progressive demyelination as well as ischemic vascular dementia, however no effective treatments are available. Here, based on magnetic resonance imaging studies of patients with white matter damage, we found that this damage is associated with disorganized cortical structure. In a mouse model, optogenetic activation of glutamatergic neurons in the somatosensory cortex significantly promoted oligodendrocyte progenitor cell (OPC) proliferation, remyelination in the corpus callosum, and recovery of cognitive ability after cerebral hypoperfusion. The therapeutic effect of such stimulation was restricted to the upper layers of the cortex, but also spanned a wide time window after ischemia. Mechanistically, enhancement of glutamatergic neuron-OPC functional synaptic connections is required to achieve the protection effect of activating cortical glutamatergic neurons. Additionally, skin stroking, an easier method to translate into clinical practice, activated the somatosensory cortex, thereby promoting OPC proliferation, remyelination and cognitive recovery following cerebral hypoperfusion. In summary, we demonstrated that activating glutamatergic neurons in the somatosensory cortex promotes the proliferation of OPCs and remyelination to recover cognitive function after chronic cerebral hypoperfusion. It should be noted that this activation may provide new approaches for treating ischemic vascular dementia via the precise regulation of glutamatergic neuron-OPC circuits.

العلاقة: http://www.sciencedirect.com/science/article/pii/S266732582200348XTest; https://doaj.org/toc/2667-3258Test; https://doaj.org/article/0cb94d8c49024a2c83dd7da977138830Test

الإتاحة: https://doi.org/10.1016/j.fmre.2022.08.007Test
https://doaj.org/article/0cb94d8c49024a2c83dd7da977138830Test

المؤلفون: Yu-Dan Ding, Xiao Chen, Zuo-Bing Chen, Le Li, Xue-Ying Li, Francisco Xavier Castellanos, Tong-Jian Bai, Qi-Jing Bo, Jun Cao, Zhi-Kai Chang, Guan-Mao Chen, Ning-Xuan Chen, Wei Chen, Chang Cheng, Yu-Qi Cheng, Xi-Long Cui, Jia Duan, Yi-Ru Fang, Qi-Yong Gong, Zheng-Hua Hou, Lan Hu, Li Kuang, Feng Li, Hui-Xian Li, Kai-Ming Li, Tao Li, Yan-Song Liu, Zhe-Ning Liu, Yi-Cheng Long, Bin Lu, Qing-Hua Luo, Hua-Qing Meng, Dai-Hui Peng, Hai-Tang Qiu, Jiang Qiu, Yue-Di Shen, Yu-Shu Shi, Tian-Mei Si, Yan-Qing Tang, Chuan-Yue Wang, Fei Wang, Kai Wang, Li Wang, Xiang Wang, Ying Wang, Yu-Wei Wang, Xiao-Ping Wu, Xin-Ran Wu, Chun-Ming Xie, Guang-Rong Xie, Hai-Yan Xie, Peng Xie, Xiu-Feng Xu, Hong Yang, Jian Yang, Jia-Shu Yao, Shu-Qiao Yao, Ying-Ying Yin, Yong-Gui Yuan, Yu-Feng Zang, Ai-Xia Zhang, Hong Zhang, Ke-Rang Zhang, Lei Zhang, Zhi-Jun Zhang, Jing-Ping Zhao, Ru-Bai Zhou, Yi-Ting Zhou, Jun-Juan Zhu, Zhi-Chen Zhu, Chao-Jie Zou, Xi-Nian Zuo, Chao-Gan Yan, Wen-Bin Guo

المصدر: Translational Psychiatry, Vol 12, Iss 1, Pp 1-9 (2022)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Abstract The nucleus accumbens (NAc) is considered a hub of reward processing and a growing body of evidence has suggested its crucial role in the pathophysiology of major depressive disorder (MDD). However, inconsistent results have been reported by studies on reward network-focused resting-state functional MRI (rs-fMRI). In this study, we examined functional alterations of the NAc-based reward circuits in patients with MDD via meta- and mega-analysis. First, we performed a coordinated-based meta-analysis with a new SDM-PSI method for all up-to-date rs-fMRI studies that focused on the reward circuits of patients with MDD. Then, we tested the meta-analysis results in the REST-meta-MDD database which provided anonymous rs-fMRI data from 186 recurrent MDDs and 465 healthy controls. Decreased functional connectivity (FC) within the reward system in patients with recurrent MDD was the most robust finding in this study. We also found disrupted NAc FCs in the DMN in patients with recurrent MDD compared with healthy controls. Specifically, the combination of disrupted NAc FCs within the reward network could discriminate patients with recurrent MDD from healthy controls with an optimal accuracy of 74.7%. This study confirmed the critical role of decreased FC in the reward network in the neuropathology of MDD. Disrupted inter-network connectivity between the reward network and DMN may also have contributed to the neural mechanisms of MDD. These abnormalities have potential to serve as brain-based biomarkers for individual diagnosis to differentiate patients with recurrent MDD from healthy controls.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2158-3188Test

الوصول الحر: https://doaj.org/article/9d20cf1f719342a0b44bb2e78b8508ffTest

المؤلفون: Zhi-Yuan Zhang, Feng Li, Jie Zhang, Lei Zhang, Huan-Huan Liu, Ning Zhao, Fan Yang, Qi Kong, Yi-Ting Zhou, Ling-Ling Qian, Ru-Xing Wang

المصدر: Frontiers in Cardiovascular Medicine, Vol 10 (2023)

مصطلحات موضوعية: atrial fibrillation, intracardiac echocardiography, transesophageal echocardiography, left atrial appendage closure, implantable devices, cardiac mapping, Diseases of the circulatory (Cardiovascular) system, RC666-701

الوصف: BackgroundAccumulated clinical studies utilized intracardiac echocardiography (ICE) to guide percutaneous left atrial appendage occlusion (LAAO). However, its procedural success and safety compared to traditional transesophageal echocardiography (TEE) remained elusive. Therefore, we performed a meta-analysis to compare efficacy and safety of ICE and TEE for LAAO.MethodsWe screened studies from four online databases (including the Cochrane Library, Embase, PubMed, and Web of Science) from their inception to 1 December 2022. We used a random or fixed-effect model to synthesize the clinical outcomes and conducted a subgroup analysis to identify the potential confounding factors.ResultsA total of twenty eligible studies with 3,610 atrial fibrillation (AF) patients (1,564 patients for ICE and 2,046 patients for TEE) were enrolled. Compared with TEE group, there was no significant difference in procedural success rate [risk ratio (RR) = 1.01; P = 0.171], total procedural time [weighted mean difference (WMD) = −5.58; P = 0.292], contrast volume (WMD = −2.61; P = 0.595), fluoroscopic time (WMD = −0.34; P = 0.705; I2 = 82.80%), procedural complications (RR = 0.82; P = 0.261), and long-term adverse events (RR = 0.86; P = 0.329) in the ICE group. Subgroup analysis revealed that ICE group might be associated with the reduction of contrast use and fluoroscopic time in the hypertension proportion <90 subgroup, with lower total procedure time, contrast volume, and the fluoroscopic time in device type subgroup with multi-seal mechanism, and with the lower contrast use in paroxysmal AF (PAF) proportion ≤50 subgroup. Whereas, ICE group might increase the total procedure time in PAF proportion >50 subgroup and contrast use in multi-center subgroup, respectively.ConclusionOur study suggests that ICE may have comparable efficacy and safety compared to TEE for LAAO.

العلاقة: https://www.frontiersin.org/articles/10.3389/fcvm.2023.1194771/fullTest; https://doaj.org/toc/2297-055XTest; https://doaj.org/article/f6c86d5ed49d455eb047f5059d55ef6aTest

الإتاحة: https://doi.org/10.3389/fcvm.2023.1194771Test
https://doaj.org/article/f6c86d5ed49d455eb047f5059d55ef6aTest

المؤلفون: Chen Zhu, Chun-Xiao Long, Yi-Ting Zhou, Peng-Fei Wei, Bo Ren, Wan-Li Wang

المصدر: Results in Physics, Vol 34, Iss , Pp 105248- (2022)

مصطلحات موضوعية: (2+1)-dimensional Korteweg–de Vries–Sawada–Kotera–Ramani equation, Hirota bilinear method, Long wave limit, Lump, Physics, QC1-999

الوصف: The (2+1)-dimensional Korteweg–de Vries–Sawada–Kotera–Ramani (KdVSKR) equation is proposed by extending one dimension of the (1+1)-dimensional KdVSKR equation. The bilinear form of the (2+1)-dimensional KdVSKR equation is obtained by the independent transformation. The multi-solitons are obtained by solving the Hirota bilinear form of the (2+1)-dimensional KdVSKR equation. By using the long wave limit method, the multi-order lumps, interaction between lump and solitons are derived. The paths of lump wave can be given by calculating the critical points of the lump wave. The dynamics of these solutions are shown both in numerical simulations and graphs ways.

العلاقة: http://www.sciencedirect.com/science/article/pii/S2211379722000535Test; https://doaj.org/toc/2211-3797Test; https://doaj.org/article/8b87a1c1ef49418787984411671f4606Test

الإتاحة: https://doi.org/10.1016/j.rinp.2022.105248Test
https://doaj.org/article/8b87a1c1ef49418787984411671f4606Test

المؤلفون: Juan Chen, Xin Yi Chen, Xiao Xia Cong, Shen Wang, Shui Bo Xu, Yu Ting Sun, Yi Ting Zhou, Li Ling Zheng, Man Huang

المصدر: Shock. 59:646-656

مصطلحات موضوعية: Emergency Medicine, Critical Care and Intensive Care Medicine

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::10a2454f80648b8e38f1389612d6092cTest
https://doi.org/10.1097/shk.0000000000002086Test

المؤلفون: Yi-Ting Zhou, Lin Zhu, Yunyun Yuan, Shuang Ling, Jin-Wen Xu

المصدر: Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)

مصطلحات موضوعية: Cytology, QH573-671

الوصف: During the aging process, senescent cells gradually accumulate in the organs; they secrete proinflammatory cytokines and other factors, collectively known as the senescence-associated secretory phenotype (SASP). SASP secretions contribute to “inflammaging,” which is a state of chronic, systemic, sterility, low-grade inflammatory microenvironment and a key risk factor in the development of aging-related diseases. Fructus psoraleae is a traditional Chinese medical herb best known for delaying aging and treating osteoporosis. Prenylflavonoids from fructus psoraleae are the main bioactive compounds responsible for its pharmacological applications, such as beaching, bavachinin, bavachalcone, isobavachalcone, and neobavaisoflavone. In previous decades, there have been some promising studies on the pharmacology of fructus psoraleae. Here, we focus on the anti-inflammatory and antiaging diseases of five psoralea prenylflavonoids, such as cardiovascular protection, diabetes and obesity intervention, neuroprotection, and osteoporosis, and discuss the mechanism of these active ingredients for better understanding the material basis and drug application of fructus psoraleae in Chinese medicine.

العلاقة: http://dx.doi.org/10.1155/2020/2128513Test; https://doaj.org/toc/1942-0900Test; https://doaj.org/toc/1942-0994Test; https://doaj.org/article/44518d194ba04c62be5ebe52c7282c53Test

الإتاحة: https://doi.org/10.1155/2020/2128513Test
https://doaj.org/article/44518d194ba04c62be5ebe52c7282c53Test

المؤلفون: Sugai Liang, Wei Deng, Xiaojing Li, Andrew J. Greenshaw, Qiang Wang, Mingli Li, Xiaohong Ma, Tong-Jian Bai, Qi-Jing Bo, Jun Cao, Guan-Mao Chen, Wei Chen, Chang Cheng, Yu-Qi Cheng, Xi-Long Cui, Jia Duan, Yi-Ru Fang, Qi-Yong Gong, Wen-Bin Guo, Zheng-Hua Hou, Lan Hu, Li Kuang, Feng Li, Kai-Ming Li, Yan-Song Liu, Zhe-Ning Liu, Yi-Cheng Long, Qing-Hua Luo, Hua-Qing Meng, Dai-Hui Peng, Hai-Tang Qiu, Jiang Qiu, Yue-Di Shen, Yu-Shu Shi, Tian-Mei Si, Chuan-Yue Wang, Fei Wang, Kai Wang, Li Wang, Xiang Wang, Ying Wang, Xiao-Ping Wu, Xin-Ran Wu, Chun-Ming Xie, Guang-Rong Xie, Hai-Yan Xie, Peng Xie, Xiu-Feng Xu, Hong Yang, Jian Yang, Hua Yu, Jia-Shu Yao, Shu-Qiao Yao, Ying-Ying Yin, Yong-Gui Yuan, Yu-Feng Zang, Ai-Xia Zhang, Hong Zhang, Ke-Rang Zhang, Zhi-Jun Zhang, Jing-Ping Zhao, Ru-Bai Zhou, Yi-Ting Zhou, Chao-Jie Zou, Xi-Nian Zuo, Chao-Gan Yan, Tao Li

المصدر: NeuroImage: Clinical, Vol 28, Iss , Pp 102514- (2020)

مصطلحات موضوعية: Biotypes, Default mode network, Major depressive disorder, Resting-state fMRI, Machine learning, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429

الوصف: Background: Major depressive disorder (MDD) is heterogeneous disorder associated with aberrant functional connectivity within the default mode network (DMN). This study focused on data-driven identification and validation of potential DMN-pattern-based MDD subtypes to parse heterogeneity of the disorder. Methods: The sample comprised 1397 participants including 690 patients with MDD and 707 healthy controls (HC) registered from multiple sites based on the REST-meta-MDD Project in China. Baseline resting-state functional magnetic resonance imaging (rs-fMRI) data was recorded for each participant. Discriminative features were selected from DMN between patients and HC. Patient subgroups were defined by K-means and principle component analysis in the multi-site datasets and validated in an independent single-site dataset. Statistical significance of resultant clustering were confirmed. Demographic and clinical variables were compared between identified patient subgroups. Results: Two MDD subgroups with differing functional connectivity profiles of DMN were identified in the multi-site datasets, and relatively stable in different validation samples. The predominant dysfunctional connectivity profiles were detected among superior frontal cortex, ventral medial prefrontal cortex, posterior cingulate cortex and precuneus, whereas one subgroup exhibited increases of connectivity (hyperDMN MDD) and another subgroup showed decreases of connectivity (hypoDMN MDD). The hyperDMN subgroup in the discovery dataset had age-related severity of depressive symptoms. Patient subgroups had comparable demographic and clinical symptom variables. Conclusions: Findings suggest the existence of two neural subtypes of MDD associated with different dysfunctional DMN connectivity patterns, which may provide useful evidence for parsing heterogeneity of depression and be valuable to inform the search for personalized treatment strategies.

العلاقة: http://www.sciencedirect.com/science/article/pii/S221315822030351XTest; https://doaj.org/toc/2213-1582Test; https://doaj.org/article/47f100d9b2f24a0cbed8e8038a8d31f5Test

الإتاحة: https://doi.org/10.1016/j.nicl.2020.102514Test
https://doaj.org/article/47f100d9b2f24a0cbed8e8038a8d31f5Test