Abstract:中国共产党优秀党员，中国科学院院士，著名生物化学家杨福愉先生，因病医治无效，于2023年1月5日20时46分在北京逝世，享年96岁。
　　杨福愉先生原籍浙江宁波镇海，1927年10月30日出生于上海市，1946年毕业于上海南洋模范中学，1950年毕业于浙江大学化学系，1960年在前苏联莫斯科大学生物系获哲学副博士学位，回国后一直在中国科学院生物物理研究所工作，历任生物物理研究所副研究员、研究员，1991年当选为中国科学院学部委员(院士)；曾任生物物理研究所副所长、学术委员会主任、生物大分子国家重点实验室主任等职，是中国生物膜领域的主要奠基人之一。
　　杨福愉先生1950年毕业于浙江大学后，进入中国科学院（上海）实验生物学研究所，在贝时璋先生等老一辈科学家的言行垂范下获得科学启蒙；1956~1960年留苏期间，获得了系统的科研训练；回国后在生物物理研究所带领线粒体结构与功能研究小组，研究电离辐射对线粒体氧化磷 酸化功能的影响，从此确立了为之奋斗一生的“生物膜结构与功能”这一重要研究方向。
　　杨福愉先生长期围绕膜脂-膜蛋白相互作用及其调控机理开展系统、深入的原创性研究。提出镁离子通过改变膜脂流动性影响ATP酶的结构与活性模型，为膜脂物理状态影响膜蛋白的结构与功能提供清晰的实例；在此基础上开展跨膜钙离子浓度梯度调节膜蛋白的构象与活性的研究，揭示膜脂物理状态调控钙ATP酶及G蛋白偶联跨膜信号转导通路的新机制；发现胰凝乳蛋白酶不只是消化酶，还介导溶酶体-线粒体细胞凋亡新途径。同时，杨福愉先生非常重视基础理论研究与实际应用的结合。曾在核爆炸现场承担放射生物学科研任务，总结出的慢性放射病早期诊断生化指标为核安全打下基础；用“匀浆互补法”预测农作物杂交优势，为促进农业增产提供科学依据；开展克山病病因的研究，提出“克山病是一种心肌线粒体病”的观点等。在研究中，杨福愉先生善于以多学科交叉融合的研究方法从不同层次开展研究，研究成果彰显开拓性、富于原创性。杨福愉先生在国内外学术期刊发表科研论文200余篇，出版《生物膜》等专著2部，在国际上产生深远影响，获得广泛承认，先后获得国家自然科学奖、中国科学院自然科学奖、何梁何利奖等重要奖项。
　　杨福愉先生重视学术团体、学术会议、学术期刊在科学研究中的重要作用，曾任中国生物物理学会理事、中国生物化学与分子生物学学会副理事长、北京市生物化学与分子生物学学会理事长、《生物物理学报》主编等职，积极推动1981年首届全国膜生物学讨论会举办，并担任首届会议大会主席。
　　杨福愉先生重视青年人才培养。作为2013年中国生物物理学会贝时璋杰出贡献奖得主，杨福愉先生于2018年向贝时璋奖捐款30万元，用于表彰后续贝时璋青年奖获奖者，表达了老一辈科学家对生物物理学领域青年科技工作者的殷切期望。
　　先贤虽去，风范永存。杨福愉先生的家国情怀与学术精神将永远指引我们奋斗！
　　杨福愉先生千古！
（感谢黄有国研究员为此文撰写提供历史线索和整理、凝练素材。）

Abstract:ERI-1 is a 3"→5" exoribonuclease with one ERI-1_3"hExo_like domain and a SAP domain. It is conserved in Schizosaccharomyces pombe, Mus musculus, Homo sapiens, Drosophila melanogaster and Arabidopsis thaliana. Although it is conserved in lower fungi, basidiomycetes and Schizosaccharomyces, ERI-1 is lost in filamentous ascomycetes and most budding yeasts. As an important regulator of RNAi, ERI-1 was first identified in a screen for mutants with enhanced sensitivity to dsRNA in Caenorhabditis elegans. It negatively regulates RNAi through degrading siRNA and miRNA. However, the C. elegans ERI-1 can completely bind to the core endogenous RNAi component DCR-1 to inhibit exogenous RNAi and promote specific endogenous siRNA production. The Schizosaccharomyces pombe ERI-1 degrades heterochromatin siRNA and influences the formation of heterochromatin. In addition, ERI-1 plays conservative roles in the 3" terminal modification of 5.8S rRNA. Moreover, the mammalian ERI-1 binds to the ACCCA sequence and excises two unpaired nucleotides, thus participating in the processing and degradation of histone mRNA at the end of S phase. The influenza A virus interacts with ERI-1 to promote viral transcription and proliferation, suggesting that ERI-1 has the potential to be a target of anti-virus drugs. This review summarizes the recent advances of ERI-1 functions in multiple RNA processing pathways, and further discusses the evolutionary loss and medical potentials of ERI-1. Suggestions about future research topics are also provided.

Abstract:Osteoarthritis is a degenerative disease of the joints, which involves all components of joints including articular cartilage, subchondral bone, synovium, ligaments, joint capsule, and muscles around the joints. It can lead to severe disability, the most common of which is knee osteoarthritis (KOA). Exosomes are extracellular vesicles with a diameter of 40-100 nm secreted by different cells, which can transmit DNA, microRNA, mRNA, protein and other substances, and carry out intercellular information transmission and function regulation in a variety of ways. Mesenchymal stem cells (MSCs) can be isolated from bone marrow, fat, synovium, peripheral blood and other tissues, and are a kind of progenitor cells with multi-direction differentiation potential. Stem-based therapies can repair cartilage damage and combat the development of KOA. Mesenchymal stem cells can secrete a variety of nutritional factors to regulate the damaged microenvironment, among which exosomes derived from mesenchymal stem cells are believed to play an important role in the inflammatory response and chondrocyte metabolism of KOA. It can regulate the metabolism of B cells, T cells, synovial cells, chondrocytes and the decomposition and synthesis balance of extracellular matrix in the knee joint microenvironment, and maintain cartilage homeostasis. A number of recent studies have shown that exosomes derived from mesenchymal stem cells from different tissues have definite therapeutic effects on osteoarthritis. This paper reviews the specific mechanism of exosomes derived from MSCs in the treatment of KOA, in order to provide theoretical basis for stem cell treatment of KOA.

Abstract:Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. The commonly used treatments for PD include drug therapy and neurosurgery. At present, there is no definite method to prevent the development of the disease and new treatment schemes need to be explored. Ultrasound has been widely concerned and used as one of the treatment methods for PD due to its non-invasive, high spatial resolution and high penetrability characteristics. In recent years, MRI-guided focused ultrasound(MRgFUS) ablation technology, MRgFUS open blood brain barrier drug delivery technology, low-intensity focused ultrasound stimulation technology and sonogenetics have all achieved promising results in clinical research or preclinical animal models. MRgFUS ablation surgery is generally used to ablate unilateral nuclei to treat PD motor symptoms. This surgery has the advantages of non-invasiveness, small damage and quick effect, which shows a good application prospect in the treatment of PD. The blood brain barrier is a major obstacle for the effective delivery of macromolecule drugs to the brain. MRgFUS coupled with microbubbles can temporarily open the blood brain barrier, allowing drugs to enter the target area. The MRgFUS open blood brain barrier drug delivery technology has shown good therapeutic effect in PD animal models, its safety and reversibility have been preliminarily proved in human experiments. However, several key problems, such as effective ultrasound parameters, optimal microbubble size and administration dose, need to be resolved before clinical application. Low-intensity focused ultrasound stimulation technology is an emerging treatment method in recent years. It has demonstrated neuromodulation and neuroprotection functions in PD animal model studies, which can reverse animal movement disorders. low-intensity focused ultrasound stimulation is a potential treatment option for PD, but it also faces the problem of unstandardized treatment parameters. Sonogenetics is a new technology developed based on focused ultrasound, which is controllable in terms of spatiotemporal resolution and cell type. Several ultrasound-sensitive ion channels have been discovered, but whether these ion channels can be expressed in the human body and the related safety issues remain to be verified. This technology is currently in the early research stage and has great potential for development. The main progress of transcranial ultrasound in the treatment of PD in recent five years from the above four aspects are reviewed and some scientific problems are discussed in this paper, hoping to provide certain reference and help for the study of the pathogenesis and treatment of PD.

Abstract:The brain-like tissue phantom is the equivalent material tissue or digital model that can effectively simulate the shape and properties of human brain tissue. It can represent certain physiological properties of human brain tissue in the experiment to achieve specific research objectives. Based on its physical form, the brain-like tissue phantom can usually be classified into 3 categories: solid, liquid, and digital. Among them, the gelatin and agar phantom is the most common solid phantom, which has advantages of being easy to shape and simulate the brain tissue well; the most common liquid phantom is saline, which has advantages of simple configuration and good acoustic characteristics; the digital phantom is generated by computer, and its advantage is that it can not only develop and test the algorithm, but also carry out complex multi-physical field finite element simulation experiments. The brain-like tissue phantom is safe, economical, easy to configure and reusable thus is widely used in fields of brain disease diagnosis and system security evaluation, for instance, motor and neurological disorders, Alzheimer’s disease and craniocerebral injury. Configuring different types of phantoms to simulate the relevant brain physical characteristics can not only find and avoid the problems and risks that may exist in the real experiment, but also accelerate the experimental process and have irreplaceable advantages. However, at the current stage, brain-like tissue phantom still has a lot of room for development, such as reducing the gap between physical morphology and physical characteristics between brain tissue and real brain tissue, and configuring phantom which is more suitable for use in complex environment. This article discusses the classification, physical properties and applications of brain-like tissue phantoms for brain science research. By comparing the differences between the brain tissue phantom and real brain tissue, this article elaborates the promising application of the former in replacing real brain tissue in experiments.

Abstract:The hybrid systems of semiconductor materials and oxidation-reduction enzymes have become a research hotpot in recent years, providing new ideas and directions for industrial production, environmental management and other fields. In this paper, we systematically introduce the hybrid system of semiconductors and oxidation-reduction enzymes in three aspects: the selection of semiconductors, the application of enzymes in the system and the types of sacrificial agents. Moreover, the characteristics and the uses of each component are also summarized and analyzed in this paper. We also introduce the compositions and reaction characteristics of different hybrid systems, by taking “semiconductor-nitrogenase” hybrid system, “semiconductor-hydrogenase” hybrid system and “semiconductor-CO₂ reductase /CO dehydrogenase” hybrid system as examples. Besides, we briefly describe the working process and two different electron transfer pathways of the hybrid system, the direct pathway of “sacrificial agent-semiconductor-enzyme” and indirect pathway of “sacrificial agent-semiconductor-intermedia-enzyme” Finally, we summarize some limitations in the past research, such as the toxicity of semiconductor materials and the low electronic utilization efficiency, we propose new prospects and research directions in bionic organelle and optimization of the reaction chain.

Abstract:Asprosin (ASP) is a newly discovered glucogenic protein hormone in 2016, it is mainly produced and secreted by adipocytes and can act on a variety of tissues and organs. Current studies have found that ASP targets the liver by binding to the Olfr734 receptor, promoting hepatic glucose release and maintaining blood sugar balance; affects the activity of feeding neurons and increases appetite after crossing the blood-brain barrier; acts on fat, inhibits the browning of white fat and promotes adipogenesis; acts on the pancreas, inhibits β-cell autophagy and promotes β-cell inflammation; acts on skeletal muscle, reduces insulin sensitivity. Therefore, ASP is involved in regulating the occurrence and development of diseases such as obesity, diabetes, insulin resistance and polycystic ovarian syndrome, and is expected to become a new molecular target for the treatment of metabolic diseases. The changes of ASP levels in pathological states may be quite different in people of different ages, genders and obesity levels. It is not clear whether the elevated ASP levels are a consequence of disease or a protective feedback mechanism under disease states. The research on ASP and metabolic syndrome mostly focuses on the causal relationship, and more molecular mechanisms are needed to reveal the function and role of ASP. ASP stimulates the release of sex hormones through the hypothalamus-pituitary-gonadal axis, improves sperm parameters, and affects reproductive function. The increase in ASP in pathological conditions inhibits reproductive potential, but this decline in reproductive potential needs to be further confirmed by knocking out the FBN gene, the knockout of Olfr734 receptor cannot fully explain the effect of ASP gene on reproduction. In addition, whether the effect of ASP on testosterone is only centrally and not peripherally, further studies are needed to confirm. Revealing the effect of ASP gene on reproductive function will help to explain the molecular mechanism of adipokines involved in regulating male reproductive function. Exercise is an effective means to improve metabolic syndrome and enhance reproductive function. Exercise can regulate the level of adipokines. At present, there are few studies on exercise and ASP, and there is controversy. Only by increasing the experimental research on the effect of exercise on ASP can better explain the exact effect of exercise on ASP; exercise can also reverse the reproductive effect caused by metabolic imbalance. Functional decline, the relationship between exercise and ASP and reproduction in metabolic syndrome can be explored in the future.

Abstract:Interleukin-27 (IL-27) is a heterodimeric cytokine composed of p28 and Epstein-Barr virus-induced 3 (EBI3), which belongs to the IL-6/ IL-12 family group. IL-27 exerts its biological functions mainly by activating downstream signals such as Janus kinase signal transduction/transcriptional activator (JAK/STAT) and mitogen activated protein kinases (MAPK). Initially, IL-27 was considered to be an inflammatory factor with pro-inflammatory and anti-inflammatory effects. However, with the development of research in recent years, it has been confirmed that IL-27 plays a role in the body’s immunity and participates in osteogenesis and osteoclast differentiation, phagocytosis and improve insulin sensitivity. IL-27 mainly exerts immunosuppressive effects on CD4+ T cells, CD8+ T cells, and B cells. In CD4+ T cells, IL-27 has dual roles due to different stages of cell differentiation, local microenvironment changes, or activated downstream signals, e.g., IL-27 promotes Th1 cell differentiation in CD4+ T cells and can inhibit differentiation in a highly polarized state of Th1 cells. In CD8+ T cells, IL-27 promotes their proliferative activation and thus plays a role in the immune response and the efficacy of subunit vaccination. In B cells, due to different activation patterns and differentiation stages, IL-27 also has a dual role. It enhances the phosphorylation levels of STAT1 and STAT3 in naive B cells and promotes B cell proliferation; but in memory B cells, its effect is weakened and cannot promote B cell proliferation. In osteoblasts (OB) and osteoclasts (OC), IL-27 promotes OB differentiation mainly through Smad2/3 and STAT1, and inhibits OB differentiation through M-CSF/sRANKL in bone marrow-derived macrophage-like cells OC generation, thereby participating in the regulation of bone growth and remodeling. In addition, the latest research has confirmed that IL-27 can directly target adipocytes, promote adipocyte (AD) thermogenesis, and improve insulin sensitivity through the p38MAPK-PGC-1α signaling pathway, which also suggests that IL-27 plays an important role in metabolic great potential in disease. This article reviews the structure and biological function of IL-27, aiming to provide a reference for the research and application of IL-27.

Abstract:Stroke is an acute cerebrovascular disease caused by cerebrovascular occlusion or hemorrhage, and approximately 84% of clinical stroke patients is suffered from cerebral ischemia (Ischemic stroke). Studies indicated that autophagy is extensively involved and prominently affects the pathophysiological development of stroke. Autophagy is a metabolic process by which delivers old proteins, damaged organelles and superfluous cytoplasmic components to lysosomes for degradation. It comprises a series of processes including activation of autophagy, formation and maturation of autophagosomes, fusion of autophagosomes with lysosomes, and digestion and degradation of autophagic substrates in autolysosomes. Autophagic flux is usually defined as autophagic/lysosomal signaling machinery. Recent studies reveal that dysfunction of autophagic flux is a critical pathogenesis of neuronal injury after ischemic stroke. However, disruption in any step in the autophagic/lysosomal pathway can lead to impairment of autophagic flux. This article is to be reviewed from the following four items. Firstly, excessive activation of autophagy, deficiency of autophagosome formation, fusion blockage of autophagosomes with lysosomes, as well as lysosomal inefficiency can drive dysfunction of autophagic flux and thereby aggravating neuronal injury. Secondly, fusion disruption between autophagosomes and lysosomes is an important cause of autophagic/lysosomal dysfunction in neurons. Consequently, a massive of autophagic substrates is accumulated within cells to worsen post-stroke damage. Thirdly, the fusion of autophagosomes with lysosomes is mainly mediated by the membrane-to-membrane fusion machinery via the three core elements: NSF (N-ethyl-maleimide sensitive factor ATPase), SNAP (soluble NSF attachment protein), and SNAREs (soluble NSF attachment protein receptors). SNAP is an adaptor attaching NSF to SNAREs, which are the proteins directly mediate the membrane fusion. After membrane-membrane fusion, SNAREs must be reactivated by NSF for the next round of fusion. It is vital that NSF is the sole ATPase to regenerate active SNAREs. SNF inactivation represses the reactivation of SNAREs and thereby disrupting the fusion between autophagosomes and lysosomes after ischemic stroke. Subsequently, the autophagic/lysosomal dysfunction in neurons is created to aggravate the neurological injury. Additionally, the insufficiency of the tethering proteins and inefficiency of the GTPases are also the pathologies to interrupt the fusion between autophagosomes and lysosomes. Accordingly, the impaired autophagic flux in neurons may be restored by facilitating fusion of autophagosomes with lysosomes, via pharmacological intervene, gene modulation, microenvironment amelioration, or mTOR signaling regulation. Finally, based on the mechanism of autolysosome formation, more therapeutic clues may be sought to alleviate neurological injury after ischemic stroke.

Abstract:Emotional pictures are generally better remembered than neutral ones. However, in recent years, researchers have proposed that this emotional memory enhancement is not a unitary phenomenon but a compound process involving two opposite effects, especially when the memorized picture is a complex scene. On the one hand, emotional information may selectively enhance the memory of the emotionally arousing central item within the scene while impairing the memory of the peripheral background, leading to the “emotion-induced memory trade-offs”. On the other hand, emotion can enhance memory in a non-selective manner across central and background information, resulting in the “emotion-induced memory broadening”. Studies show that the occurrences of these two effects hinge on various factors related to stimulus properties and memory processes. As to the stimulus-relevant factors, memorized stimuli with negative and positive valences are more likely to drive the trade-offs and the broadening effects, respectively. Moreover, the intensity of the center-background association within the affective scene can also influence the selectivity of memory enhancement. Concerning the memory processes, task manipulations at the encoding (e.g., passive viewing vs. strategical processing), consolidation (e.g., sleep vs. no sleep), and retrieval (e.g., recognition vs. cued-recall) phases may differently affect the selectivity of emotion-induced memory enhancement. Hitherto, the cognitive and neural mechanisms underlying the emotional memory trade-offs and broadening effects remain unclear. There is a debate on whether the memory trade-offs effect is an automatic process independent of attention narrowing and post-stimulus elaboration. Besides, a few studies reveal that a core neural network involving the amygdala, hippocampus, fusiform, temporal pole, and inferior frontal gyrus is associated with the trade-offs effect, with the activation of some other brain regions dependent on valence and arousal levels of the stimuli. Further research needs to compare the mechanisms of the emotion-induced memory broadening with those of the trade-offs at both behavioral and neural levels, particularly taking a closer look at the automaticity of and the forms of memory representations involved in these effects. In addition, extending these effects from spatial to other (e.g., temporal) dimensions may help elucidate how emotional signals selectively enhance the memory of complex scenes from different perspectives.

Abstract:The human brain receives a lot of visual information all the time, due to the limited ability of the human brain to process information, it is crucial to allocate attention to relevant information in a larger visual field and suppress irrelevant information that causes attention distraction in order to perform goal-oriented behavior. This process of selective and active processing of visual information to adapt to the current target is called visual attention, visual attention can be divided into two different functions: top-down attention and bottom-up attention. Since neural oscillations from brain electrical signals play an important role in cognitive processing, the close relationship between visual attention and neural oscillations has been reviewed, but the relationship between different attentional functions and neural oscillations has not been discussed. In this paper, we investigated the relationship between different attentional functions and neural oscillations. We found that the theta oscillations in the fronto-parietal region reflected top-down cognitive control, while the theta oscillations in the posterior brain region correlated with bottom-up attention. Lateralization of alpha oscillations in the parietal-occipital region contributes to attention allocation, while large-scale synchronization of alpha oscillations contributes to top-down effects of attention on the visual cortex. Beta oscillations mediate the interaction between top-down information and bottom-up information, and as information carriers promote visual information processing. Gamma oscillations may be related to top-down and bottom-up inter-attention integration. This paper reviews the research status of the relationship between visual attention function and neural oscillations in order to reveal the role of different neural oscillations in specific visual attention function.

Abstract:Mass spectrometry-based proteomics aims to identify peptides and proteins to give direct proofs of gene expressions, analyze structures and functions of proteins, study the relationship between proteins and diseases, and provide targeted treatment options. All these studies are based on the credibility of identified peptides and proteins. However, it is impossible to manually check all identified peptides because a large number of identifications can be collected from one mass spectrometry experiment. Thus, target-decoy approach (TDA) is proposed and always used to control the quality of identified peptides and proteins, and has been expanded to subclasses of peptides (including ordinary subclasses of peptides, variant peptides, and modified peptides) and cross-linking peptides. However, TDA still has two limitations: (1) the estimation of false discovery rate (FDR) is inaccurate and (2) validation of single identification cannot be supported. Thus, the identification results that passed the TDA-based FDR control need to be further validated and other validation methods which are used after TDA-FDR filtration (referred to as Beyond-TDA methods) have been developed to enhance peptide validation. This paper reviews TDA and its extensions as well as Beyond-TDA methods and discusses the advantages and disadvantages of each method. In the first part of this paper, we introduce the goal of proteomics, the process of mass spectrometry acquisition and analysis, the validation problem, and the early statistical methods to evaluate the identification credibility. Then, in the second part of this paper, we describe in detail the ordinary TDA-FDR method, including the assumption that random matches are equally likely to appear in target and decoy databases, the construction methods to generate the decoy database, and the computational formula of TDA-FDR. We also introduce the extensions of TDA-FDR on ordinary subclasses of peptides, variant peptides, modified peptides, proteogenomics peptides, cross-linking peptides, and glycopeptides. However, TDA cannot model the homologous incorrect peptides, thus TDA-FDR underestimates the actual false rate. So, after TDA-FDR filtration, it is necessary to use more strict validation methods, i.e., Beyond-TDA methods, which are reviewed in detail in the third part of this paper, to control validation credibility. In this part, four kinds of methods are introduced, including validation methods based on search space (trap database validation and open search validation), spectra similarity (synthetic peptide validation and theoretical spectra prediction), chemical information (retention time prediction and stable isotopic labeling validation) and machine learning technology (Percolator, pValid, and DeepRescore). Lastly, we summarize the content of this paper and discuss the future improvement directions of validation methods.

Abstract:Objective Repetitive transcranial magnetic stimulation (rTMS) has been widely used in clinics to realize the treatment of neurological and psychiatric diseases, especially in depression and pain. In recent years, many studies have applied it as an adjuvant approach to treatment of Parkinson’s disease (PD) in order to relieve the patient’s motor symptoms and improve motor function. At present, the unified Parkinson’s disease scale and motor task are used to evaluate the adjuvant treatment effect of rTMS on motor symptoms, but there are few studies exploring the regulatory mechanism of high-frequency rTMS stimulation.Methods In this study, 10 Hz rTMS over the primary motor cortex (M1) on the contralateral side of the limb symptom onset side in 16 PD patients. By comparing the changes of brain neuron activity and the interactions between brain function before and after stimulation, we investigated the regulatory effect of repeated sessions of M1 high-frequency rTMS on brain neuron activity in PD patients.Results The results showed that after 10 d of M1 stimulation, beta oscillations increased and gamma oscillation significantly decreased (P<0.05) in motor cortex, and the connectivity between the frontal and parietal cortex was reduced (P<0.05).Conclusion It shows that 10 Hz rTMS mainly changes the beta and gamma rhythm in PD patients. The changes of beta and gamma oscillations in motor cortex may be related to the improvement of motor function, and the changes in prefrontal gamma oscillations may be due to inhibits abnormal neuron firing activities and modulates the patient’s motor control function.

Abstract:Objective Beta-secretase 1 (BACE1) is the key enzyme for amyloid β (Aβ) production in the Alzheimer’s disease (AD) brain. The dystroglycan (DG) protein anchors astroglial endfeet onto cerebral blood vessels forming glia limitans, a supportive element in the blood-brain barrier. An untargeted proteomics study predicted that BACE1 downregulates DG expression. Here, this study investigated whether BACE1 modulates the protein levels of DG and its hypothetic mechanism.Methods Transient transfection technique was used to express target protein in HEK-293T cells and in primary mouse astrocytes. And the protein levels of targets were analyzed by Western blot. Quantitative polymerase chain reaction and co-immunoprecipitation were used to explore the potential mechanisms of BACE1-dependent regulation of DG.Results This study found that addition of BACE1 resulted in significantly lower levels of β subunit DG (β-DG) protein, both in HEK-293T cells and in primary mouse astrocytes. And in HEK-293T cells, this down-regulation of β-DG protein dependent on the enzyme activity of BACE1.Conclusion BACE1 lowers β-DG protein levels in HEK-293T cells and in mouse astrocytes.

Abstract:Objective The aim of this study is to investigate the effect of matrix stiffness changes on the differentiation of neural stem cells (NSCs) and the underlying mechanism.Methods A rat model of spinal cord injury was constructed. Polyacrylamide gel substrates with different stiffness (0.7 kPa, 40 kPa) were prepared, and were cultured with primary rat NSCs. NSCs cells were transfected with piezo type mechanosensitive ion channel component 1 (Piezo1) shRNA plasmid. Immunofluorescence staining was used to detect the percentage of positive cells for the neuron marker doublecortion(DCX) and the astrocyte marker GFAP. Immunohistochemistry experiment and Western blot were used to detect the protein expression of Piezo1.Results The results showed that compared with the 0.7 kPa group, the number of DCX-positive cells in the 40 kPa group increased, while the number of GFAP-positive cells decreased, as well as the protein expression of Piezo1 increased. The expression of Piezo1 was significantly up-regulated in the injured tissue of rats with spinal cord injury compared with the sham group. Silencing of Piezo1 reverse the effect of 40 kPa matrix stiffness on NSCs proliferation, as indicated by decreased number of DCX-positive cells, and increased number of GFAP-positive cells increased. Further studies found that knockdown of Piezo1 leads to decreased expression of collagen IV and fibronectin. Recombinant fibronectin reversed the effect of sh-Piezo1 on the differentiation of NSCs.Conclusion Rigid base stiffness regulates the differentiation of NSCs by promoting the expression of Piezo1 protein and up-regulating the expression of type IV collagen and fibronectin. This study provides a new perspective for the treatment of spinal cord injury based on biomaterials.

Abstract:Objective The exosome, a type of extracellular vesicle, is considered a kind of information carrier and biomarker and has a significant role in extracellular physiologic activities and disease progression. Research into the characteristics of exosomes is key to addressing numerous fundamental issues in pathologic processes. Exosomes are secreted by tumor cells into the tumor microenvironment through exocytosis. Exosome vesicles carry a large amount of genetic information related to the tumor cells from which they are derived. So exosome plays an important role in the tumor microenvironment, such as information transmission, immune regulation, promotion of tumor invasion and metastasis, and regulation of tumor response to drugs. At present,most exosomes research focuses on the bioinformatics exploration of protein expression, mRNA, lncRNA and other aspects of exosomes, and there is still a lot of space to explore the microscopic morphology and physical characteristics of exosomes. This study investigated the physical characteristics of plasma exosomes from patients with lymphoma through atomic force microscopy (AFM).Methods The exosome has been extracted from clinical cancer patients’ peripheral blood samples. The samples contain diffuse large B cell lymphoma and follicular lymphoma. At first, the electrostatic adsorption method has been utilized to fix the isolated exosomes onto the mica substrates, the discrete living exosomes have been scanned with AFM method. The multi-parameter exosome images at nano/micro scale can be obtained in situ.Results The multi-parameter mechanical properties of isolated living exosomes have been visualized and quantitatively measured. The significant fringe effect at the edge of the exosome has been revealed in the AFM adhesion image, which means more energy dissipation can be produced there. The Young’s modulus of plasma exosomes was different in patients with lymphoma from different pathological subtypes.Conclusion Plasma exosomes from patients with hematological tumors can be successfully extracted. Due to the convenient and less invasive characteristics of peripheral blood, plasma exosomes can be used as biomarkers for dynamic monitoring and analysis of tumor diagnosis and treatment, and the extracted exosomes can be captured by AFM probes through treatment and fixation. In this study, the morphological details and mechanical properties of exosomes at nano and micro scales were revealed. The physical properties of exosomes may be related to their biological properties.The multi-dimensional understanding of exosome performance opens up a new perspective for the future application and in-depth study of exosomes.

Abstract:Objective Implantable brain computer interface has been widely used in the treatment of neurological diseases, where the effectiveness of the treatment depends on the electrodes in contact with the neural tissue. Compared with the electrodes made of rigid materials, the carbon based microfiber electrodes have small scale, good biocompatibility and small tissue inflammatory reaction. It can reduce the foreign body reaction after implantation, improve the signal-to-noise ratio of nerve recording signals, and maintain stable electrode characteristics for a long time.Methods A modification method of flexible carbon nanotubes (CNTs) fiber electrode was designed in this paper. Poly(3,4-ethylenedioxythiophene) (PEDOT) films can be deposited on CNTs fiber electrode as microelectrode coating by electrochemical polymerization. In order to prove that the modified coating has good mechanical stability on the electrode surface, we treated the modified electrode with ultrasonic treatment. In addition, PEDOT films were deposited on ITO glass to evaluate the biocompatibility of PEDOT films.Results PEDOT coating deposited on the surface of CNTs fiber electrode in constant current mode reduced the electrochemical impedance of the electrode and improved the electrochemical performance of the electrode. The longer PEDOT deposition time, the more obvious the reduction of impedance. After ultrasonic treatment, the electrochemical impedance of the electrode did not change significantly, indicating that there was less peeling of PEDOT coating after ultrasonic treatment, which proved that the modified coating had good mechanical stability on the electrode surface. Finally, cell experiments show that PEDOT film has the same cell compatibility as ITO conductive glass.Conclusion PEDOT film can improve the stability of CNTs fiber electrode, and is expected to improve the service life and reliability of brain computer interface system. It has the prospect of application in long-term recording of neuroelectrical signals.