The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability

人类与其他动物相比的重要区别在于人类拥有高等认知能力，这种能力集中体现在学习记忆和语言表达方面。厦门大学医学院神经科学研究所王鑫教授团队发现人科动物特异性基因USP6作为一个新的NMDA受体调控因子，可通过去泛素化途径调节NMDA型谷氨酸受体的降解和稳定性，进而调控突触可塑性和学习记忆能力。 本研究工作由王鑫教授指导完成，博士生曾凡伟、马学海与硕士生朱琳为共同第一作者，王鑫教授为通讯作者。Ubiquitin-specific protease (USP) 6 is a hominoid deubiquitinating enzyme previously implicated in intellectual disability and autism spectrum disorder. Although these findings link USP6 to higher brain function, potential roles for USP6 in cognition have not been investigated. Here, we report that USP6 is highly expressed in induced human neurons and that neuron-specific expression of USP6 enhances learning and memory in a transgenic mouse model. Similarly, USP6 expression regulates N-methyl-D-aspartate-type glutamate receptor (NMDAR)-dependent long-term potentiation and long-term depression in USP6 transgenic mouse hippocampi. Proteomic characterization of transgenic USP6 mouse cortex reveals attenuated NMDAR ubiquitination, with concomitant elevation in NMDAR expression, stability, and cell surface distribution with USP6 overexpression. USP6 positively modulates GluN1 expression in transfected cells, and USP6 down-regulation impedes focal GluN1 distribution at postsynaptic densities and impairs synaptic function in neurons derived from human embryonic stem cells. Together, these results indicate that USP6 enhances NMDAR stability to promote synaptic function and cognition.This work was partially supported by the National Natural Science Foundation of China (31871077, 81822014, 81571176 to XW; 81701349 to Hongfeng Z.; 81701130 to QZ; and 81471160 to HS), the National Key R&D Program of China (2016YFC1305900 to XW and HS), the Natural Science Foundation of Fujian Province of China (2017J06021 to XW), the Fundamental Research Funds for the Chinese Central Universities (20720150061 to XW and 20720180040 to ZS), Open Research Fund of State Key Laboratory of Cellular Stress Biology, Xiamen University (SKLCSB2019KF012 to QZ), and China Postdoctoral Science Foundation (2017M612130 to QZ).该研究得到了国家自然科学基金面上项目和优秀青年基金项目的支持

Tumor-Targeted Fluorescence Imaging and Mechanisms of Tumor Cell-Derived Carbon Nanodots

An ideal cancer diagnostic probe should possess precise tumor-targeted accumulation with negligible sojourn in normal tissues. Herein, tumor cell-derived carbon nanodots (C-CNDU87 and C-CNDHepG2) about 3~7 nm were prepared by a solvothermal method with stable fluorescence and negligible cytotoxicity. More interestingly, due to the differences in gene expression of cancers, C-CND structurally mimicked the corresponding precursors during carbonization in which carbon nanodots were functionalized with α-amino and carboxyl groups with different densities on their edges. With inherent homology and homing effect, C-CND were highly enriched in precursor tumor tissues. Mechanistic studies showed that under the mediation of the original configuration of α-amino and carboxyl groups, C-CND specifically bound to the large neutral amino acid transporter 1 (LAT1, overexpressed in cancer cells), achieving specific tumor fluorescence imaging. This work provided a new vision about tumor cell architecture-mimicked carbon nanodots for tumor-targeted fluorescence imaging

Anions-responsive supramolecular gels: A review

Recently, supramolecular low-molecular-weight gels have attracted more and more attentions and have potential applications in many areas due to the dynamic nature of noncovalent interactions that form the gel networks. The adaptability, adjustability and stimulus responsibility were the desired properties of supramolecular gel beyond traditional nanoscale materials. Of the external stimulus sources, anions are of particular interest because of their essential role in environment and many biological processes. Generally, the design of anions-responsive supramolecular gelators contained three parts: the binding site (or reaction site), the linker and the assistant self-assembly moieties (usually hydrophobic or hydrophilic groups). In this review, we discuss three types of anions-responsive supramolecular gels by giving the latest summaries (from 2015 to 2020), including the responsive properties of various structures, design strategy, mechanisms and drawbacks. We also believe that although current researches of those gels are mainly focused on the visual detection of anions in vitro, with the deep understanding of the properties and mechanism of the anions -responsive supramolecular gels, the applications should be paid more and more attention in vivo like anionic related drug targeted delivery and rapid detection of diseases

Recent Developments in CaCO₃ Nano-Drug Delivery Systems: Advancing Biomedicine in Tumor Diagnosis and Treatment

Calcium carbonate (CaCO3), a natural common inorganic material with good biocompatibility, low toxicity, pH sensitivity, and low cost, has a widespread use in the pharmaceutical and chemical industries. In recent years, an increasing number of CaCO3-based nano-drug delivery systems have been developed. CaCO3 as a drug carrier and the utilization of CaCO3 as an efficient Ca2+ and CO2 donor have played a critical role in tumor diagnosis and treatment and have been explored in increasing depth and breadth. Starting from the CaCO3-based nano-drug delivery system, this paper systematically reviews the preparation of CaCO3 nanoparticles and the mechanisms of CaCO3-based therapeutic effects in the internal and external tumor environments and summarizes the latest advances in the application of CaCO3-based nano-drug delivery systems in tumor therapy. In view of the good biocompatibility and in vivo therapeutic mechanisms, they are expected to become an advancing biomedicine in the field of tumor diagnosis and treatment

China’s construction industry-linked economy-resources-environment flow in international trade

During construction, a large number of resources are consumed; concurrently, a large amount of greenhouse gas is emitted, which contributes to air pollution. There exist close interactions among construction regions. This study examined the main economy-resources-environment indexes associated with China’s construction industry, embodied in international trade based on the Eora database, by using the input-output model. It investigated the linkages of the economy-resources-environment nexus and suggests recommendations accordingly. We found that the total amount of input consumption and output emissions in China’s construction activities increased rapidly, both locally and abroad. China pulled much more emissions from construction-related activities abroad than the latter pulled from China. The overseas regions’ dependence on China’s construction industry gradually increased. Overall, China’s construction activities accelerated the rate of foreign countries’ resource utilization and air pollution more than it did economic profits for some of these countries. The effects on countries differed. China’s construction industry was closely related to the Asian, African, and Latin American undeveloped regions. In regard to the developed regions, cooperation with Australia, the UK, Sweden and Russia was more frequent. There existed a close relationship between all the economy-resources-environment indexes. Based on the findings, protective measures were suggested, including avoiding unnecessary construction activities, optimizing China’s economic and energy use structure, improving the efficient use of resources, strengthening environmental protection both abroad and locally, as well as reducing the export of products with high energy or resources consumption

Transcriptome Data Revealed the circRNA–miRNA–mRNA Regulatory Network during the Proliferation and Differentiation of Myoblasts in Shitou Goose

CircRNA, a recently characterized non-coding RNA (ncRNA) variant, functions as a molecular sponge, exerting regulatory control by binding to microRNA (miRNA) and modulating the expression of downstream proteins, either promoting or inhibiting their expression. Among poultry species, geese hold significant importance, prized by consumers for their delectable taste and rich nutritional content. Despite the prominence of geese, research on the growth and development of goose muscle, particularly the regulatory role of circRNAs in goose muscle formation, remains insufficiently explored. In this study, we constructed comprehensive expression profiles of circRNAs and messenger RNAs (mRNAs) within the myoblasts and myotubes of Shitou geese. We identified a total of 96 differentially expressed circRNAs (DEcircRNAs) and 880 differentially expressed mRNAs (DEmRNAs). Notably, the parental genes of DEcircRNAs and DEmRNAs exhibited enrichment in the Wnt signaling pathway, highlighting its potential impact on the proliferation and differentiation of goose myoblasts. Employing RNAhybrid and miRDB, we identified circRNA-miRNA pairs and mRNA-miRNA pairs that may play a role in regulating myogenic differentiation or muscle growth. Subsequently, utilizing Cytoscape, we constructed a circRNA–miRNA–mRNA interaction network aimed at unraveling the intricate regulatory mechanisms involved in goose muscle growth and development, which comprises 93 circRNAs, 351 miRNAs, and 305 mRNAs. Moreover, the identification of 10 hub genes (ACTB, ACTN1, BDNF, PDGFRA, MYL1, EFNA5, MYSM1, THBS1, ITGA8, and ELN) potentially linked to myogenesis, along with the exploration of their circRNA–miRNA–hub gene regulatory axis, was also conducted. These competitive endogenous RNA (ceRNA) regulatory networks elucidate the molecular regulatory mechanisms associated with muscle growth in Shitou geese, providing deeper insights into the reciprocal regulation of circRNA, miRNA, and mRNA in the context of goose muscle formation

The embodied flow of built-up land in China?s interregional trade and its implications for regional carbon balance

Built-up land intensively concentrates human activities, and its area or the changes in its intensity dramatically affect the regional carbon balance. This study proposed a new framework to assess how in China, the interregional trade?s use of built-up land affects regional carbon balance with regard to the initial maintained land and the expanded built-up land. Then, a multiregional input-output model was used to simultaneously analyse China?s built-up land flow in interregional trade and the effect on carbon balance. Finally, hidden regional inequality was analysed. The results show that the domestic trade pulled indirect external built-up land use reached to 100286 km2 in 2012 and caused 28084 ? 104 t external province pulled carbon emissions for whole China, including 286 ? 104 t from vegetation carbon storage loss. Regionally, more developed regions were always net receivers of built-up land use, in contrast, less developed regions more frequently acted as net suppliers, but most regions experienced economic and environmental deficits. The majority of other provinces experienced a contradictory status of loss of economic profit or environmental profit. For sustainable development and regional equality, more developed regions should provide more economic and technological support for effective built-up land use and emissions reduction to less developed regions

Receptor-Mediated Drug Delivery Systems Targeting to Glioma

Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications

Close-packed assemblies of discrete tiny silver nanoparticles on triangular gold nanoplates as a high performance SERS probe

Bimetallic nanocatalysts often display enhanced physical and chemical properties compared to those of their monometallic counterparts. Herein, we introduce a simple method to fabricate an island like array of tiny Ag nanoparticles bounded on triangular Au nanoplates as the surface-enhanced Raman scattering (SERS) substrate. The surface morphology of the synthesized nanoparticles was characterized via field emission scanning electron microscopy (FE-SEM), and atomic force microscopy (AFM). Rhodamine 6G (R6G) is used as a model analyte to evaluate the performance of the tiny Ag nanoparticle bounded triangular Au nanoplates as a SERS-active substrate and validate the SERS effect. The fabricated SERS substrate showed drastically enhanced intensity with a SERS enhancement factor as high as 107, which is enough to detect a single molecule, and excellent reproducibility (less than +/- 5%) of the signal intensity. This is because of the island-like tiny Ag nanoparticle bounded triangular Au nanoplates and their large number of "hot spots". This substrate could also be used for label-free immunoassays, biosensing, and nanoscale optical antennas and light sources