Spatial and temporal expression of germ cell nuclear factorin murine epididymis

Aim: To investigate the spatial and temporal expression of germ cell nuclear factor (GCNF) in mouse and rat epididymis during postnatal period. Methods: The epididymal sections from different postnatal days were stained for GCNF by the indirect immunofluorescence technique and digital photographs were taken by a Carl Zeiss confocal microscope. Results: GCNF was first detected on day 12 in mouse epididymis and day 14 in rat epididymis. The highest expression of GCNF was observed on day 35 in both mouse and rat epididymis. In adults, GCNF exhibited a region-specific expression pattern, i.e., it was expressed predominantly in the initial segment, caput and proximal corpus of rat epididymis and was abundant in the proximal corpus of mouse epididymis. GCNF could be found in the nuclei of the principal, apical, narrow, clear and halo cells. Conclusion: GCNF may play an important role in epididymal differentiation and development and in sperm maturation.

Effects of butternut squash extract on dentate gyrus cell proliferation and spatial learning in male adult rats

Previous studies reported that some plants, including butternut squash, exert positive effects on the brain. However, few studies have examined the effects of butternut squash on learning, memory, and neurogenesis. This study studied the effects of butternut squash extract on spatial learning and cell proliferation in the dentate gyrus of healthy male rats. Thirty-five male Wistar rats were intraperitoneally injected with 0, 50, 100, 200 and 400 mg/kg butternut squash extract once daily for 2 months. After the last administration, rat＇s spatial memory was studied using the Morris water maze. Finally, rats were sacrificed and hippocampal sections were prepared for light microscopy and bromodeoxyuridine immunohistochemistry studies. The results revealed that escape latency and swim distance decreased in all treatment groups compared with the control rats, and that the number of bromodeoxyuridine-positive cells in the dentate gyrus was significantly increased in the treatment groups compared with the controls. These findings suggest that butternut squash extract improves the learning and memory abilities of male rats, and increases the proliferation of dentate gyrus cells.

Sciatic nerve injury alters the spatial arrangement of neurons and glial cells in the anterior horn of the spinal cord

The spatial arrangement of the cell is important and considered as underlying mechanism for mathematical modeling of cell to cell interaction.The ability of cells to take on the characteristics of other cells in an organism,it is important to understand the dynamical behavior of the cells.This method implements experimental parameters of the cell-cell interaction into the mathematical simulation of cell arrangement.The purpose of this research was to explore the three-dimensional spatial distribution of anterior horn cells in the rat spinal cord to examine differences after sciatic nerve injury.Sixteen Sprague-Dawley male rats were assigned to control and axotomy groups.Twelve weeks after surgery,the anterior horn was removed for first-and second-order stereological studies.Second-order stereological techniques were applied to estimate the pair correlation and cross-correlation functions using a dipole probe superimposed onto the spinal cord sections.The findings revealed 7% and 36% reductions in the mean volume and total number of motoneurons,respectively,and a25% increase in the neuroglial cell number in the axotomized rats compared to the control rats.In contrast,the anterior horn volume remained unchanged.The results also indicated a broader gap in the pair correlation curve for the motoneurons and neuroglial cells in the axotomized rats compared to the control rats.This finding shows a negative correlation for the distribution of motoneurons and neuroglial cells in the axotomized rats.The cross-correlation curve shows a negative correlation between the motoneurons and neuroglial cells in the axotomized rats.These findings suggest that cellular structural and functional changes after sciatic nerve injury lead to the alterations in the spatial arrangement of motoneurons and neuroglial cells,finally affecting the normal function of the central nervous system.The experimental protocol was reviewed and approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences(approval No.IR.SBMU.MSP.REC1395.375) on October 17,2016.

The Dendritic Cells’ Immunological Behaviors Modulated by the Spatial Confinements of Deposited Fibrin Matrix

Implant materials,as foreign objects to host,can cause various degrees of inflammation in most cases.The inflammation is triggered by a series of immune responses and directly impacts the tissue regeneration process,which determines the outcome of tissue repair.The immune responses are complex process involving numerous immune cells and can be divide into innate immune and adaptive immune responses.Once materials are implanted,innate immune responses are activated under the mediation of several immune cells(e.g.neutrophils and macrophages),meanwhile immature dendritic cells(imDCs)are recruited to the implant sites to recognize,internalize and process antigens.Upon antigen uptake,imDCs gradually differentiate into mature dendritic cells(mDCs)and migrate to secondary lymph nodes.In the lymph nodes,mDCs present processed antigen peptides to naive T lymphocytes and activate their antigen specific proliferation,resulting in initiation of adaptive immune responses.Due to their key position in the immune system,serving to bridge innate and adaptive immunity,DCs are crucial to guiding and modulating the immune responses caused by implanted materials.Therefore,figuring out the response of DCs to implanted materials and the exact role of DCs in tissue healing processes will provide deeper insight for the rational design of biomaterials.Previous studies on the effects of implants on immune functions of DCs are mainly focused on physical and chemical properties of the materials(e.g.released chemical composition,surface chemistry,substrate stiffness and surface topography).All these factors will change the microenvironment of the tissue around implant materials,which affect the immune functions of DCs.However,the change of microenvironment not only directly derives from the physical and chemical properties of the material(intrinsic),but also indirectly results from the remodeled extracellular matrix(ECM)caused by implanted materials.When blood or tissue fluid contact with materials after implantation,proteins(e.g.fibrin and collagen)will absorb and deposit on the surface of implants,leading to a provisionally stable matrix with microporous fibrous-liked network structure.It means that the remodeled ECM can provide adhesion sites for recruited DCs and form spatial confinement.DCs,as a kind of cells that are extremely sensitive to mechanical stimuli,theoretically,can response to the mechanical stimuli coming from spatial confinement of remodeled ECM,which may lead to a series of modulations in their cell morphologies and immune functions.Then,the remodeled ECM is a non-negligible mechanical cue.However,to the best of our knowledge,there is a lack of a simple and effective model to establish the relationship between the immune functions of DCs and remodeled ECM.Most studies on the responses of DCs to implanted materials are still based on suspension culture model,which is the normal status of DCs in vitro culture systems.In addition,the processes by which DC exerts immune functions(both endocytosis and antigen presentation)are dynamically physical interaction.It means that the changes of DCs’immune functions are highly correlated with the changes of their biomechanical characteristics caused by remodeled ECM.In this work,we have found that the ECM was remodeled by a large amount of fibrin matrix deposited on the surface of implants in the early stage of the inflammations following implantation.Thus,we used non-toxic salmon fibrin hydrogels with microporous fibrous-liked network structure to mimic the deposited fibrin matrix.Then,human monocyte-derived DCs were cultured on the surface and inside of the fibrin hydrogels to mimic the different spatial confinement states of fibrin matrix.Our results indicated that cell morphologies and cytoskeleton structures of DCs were regulated by the spatial confinement of fibrin hydrogels,resulting in generating mechanical stimuli for DCs.Furthermore,we have found that the biomechanical characteristics and the immune functions of both imDCs and mDC were also modulated.Considering the changes in surface markers,secreted cytokines and biomechanical characteristics of DCs,it indicates that the tendency and magnitude of modulations were highly associated with the spatial confinement of fibrin hydrogels.This model demonstrated that mechanical stimuli deriving from spatial confinement of deposited fibrin matrix is an important factor for regulating the biomechanical characteristics and immune functions of DCs.

整合组织学图像信息增强空间转录组细胞聚类的分辨率

【目的】增加空间转录组基因表达的空间分辨率以提升遗传发育与疾病研究中的细胞谱系和类型变化的精度,提供更精细的分子表型信息。【方法】通过图像分割实现空间转录组点阵的细胞空间分布模拟,使用线性插值方法重构超分辨率基因空间表达,并利用图聚类方法揭示组织中细胞分布的空间偏好性。【结果】将新方法SpaGMM在小鼠后脑10X Visium数据集上进行检验,可以精确识别小鼠脑神经空间结构域。通过与几种空间转录组聚类的常用方法进行比较,结果显示SpaGMM的聚类结果更加符合组织学区域的注释,这些区域具有大量标记基因的空间表达支持。SpaGMM还可以从小鼠小脑区域中区分出浦肯野细胞(Purkinje cell)和伯格曼胶质细胞(Bergmann glial cell)所对应的组织区域,发现不同细胞层中存在互补的基因表达模式。【结论】SpaGMM可以通过提高点阵的空间分辨率揭示组织结构域的精细结构。

单细胞测序和空间转录组技术在口腔医学的应用进展

单细胞测序和空间转录组技术在生命科学领域的应用是近年的研究热点,通过联合单细胞测序及空间转录组技术,能够在单细胞水平揭示细胞特定空间位置上的信息,以进一步探究疾病发生发展的机制及疾病的防治。在口腔医学领域,这一技术已被应用于口腔组织干细胞、口腔组织发生发育、口腔微生物及各类口腔疾病的研究中。该文阐述了单细胞测序和空间转录组技术在口腔领域的应用进展并展望两者联合应用的前景,以期为口腔疾病的诊疗提供新思路。

空间转录组技术的进展及其在骨研究中的应用

骨组织中细胞的结构和功能异质性与其空间位置密切相关。空间转录组(spatial transcriptomics)技术能够同时获得组织内空间单元的位置信息和转录组变化。近年来,空间转录组技术的迅速发展使组织器官的高分辨率和高通量转录组分析得以实现,并不断应用于骨骼系统的研究中。本文就空间转录组技术的进展及其在骨研究中的应用作一综述。

Expression of germ cell nuclear factor in mouse germ cells and sperm during postnatal period

Aim: To assess the spatial and temporal expression of germ cell nuclear factor (GCNF) in male mouse germ cells during postnatal development and in sperm before and after capacitation. Methods: The indirect immun-ofluorescence method with anti-GCNF antiserum was used to investigate the GCNF expression in mice at day 8, 10, 14, 17, 20, 28, 35, 70, and 420 after birth and in sperm before and after capacitation. Results: With the proceeding of spermatogenesis, GCNF was first detected in the nuclei of spermatogonia and a few early stage primary sperma-tocytes at day 8, which was increased gradually at day 10 to 14 inclusive. From day 17 to day 20, the GCNF was concentrated in round spermatids, while both spermatogonia and early stage primary spermatocytes became GCNF negative. From day 28 until day 420, strong GCNF expression was shown in round spermatids and pachytene spermatocytes, while spermatogonia, early primary spermatocytes and elongating spermatids were all GCNF negative. In addition, it was also found that GCNF was localized on the acrosomal cap region of spermatozoa and there was a big change in GCNF expression during capacitation, from 98 % GCNF positive before capacitation to about 20 % positive following capacitation. The localization of GCNF in caput and cauda spermatozoa was similar. Conclusion: GCNF may play important roles in spermatogenesis, capacitation and fertilization.

Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions

Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells （1 ×10^5 cells/μL） were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-la- beled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

基于3σ-CEEMDAN-LSTM的空间负荷预测方法

为有效利用从配电网采集的海量数据以及改善空间负荷预测效果,提出一种基于3σ准则、自适应噪声完备集合经验模态分解(CEEMDAN)和长短期记忆神经网络(LSTM)的空间负荷预测方法。基于3σ准则对每个Ⅰ类元胞的实测负荷数据进行奇异值检测和处理;运用CEEMDAN技术将处理后的Ⅰ类元胞负荷数据分解为若干个频率和幅值均不同的本征模态函数(IMF);分别对每个IMF分量构建LSTM模型进行预测;将所有IMF分量预测结果进行线性叠加,得到目标年基于Ⅰ类元胞的空间负荷预测结果,在此基础上使用空间电力负荷网格化技术求得基于Ⅱ类元胞的空间负荷预测结果。算例分析结果验证了所提方法的正确性和有效性。

高通量单细胞及空间转录组技术在肝脏疾病中的应用

肝脏是人体重要的免疫器官,在检测、捕获、清除病原体和外来抗原中发挥着重大作用。本文主要简述高通量单细胞及空间组学技术解析肝脏在感染性疾病中的应用。随着高通量单细胞技术的发展,现在可以在单细胞水平上破译复杂器官和疑难疾病的异质性、分化、细胞间通信等,从而认识到过去未知的致病途径和疾病机制,有利于开发新的治疗靶点。并且随着技术不断成熟,单细胞转录组可以和空间转录组学、表观遗传组、蛋白组、代谢组、微生物组以及临床数据进行整合分析,有益于将患者分层并进行精准治疗。

中药作用靶点及分子机制的转录组学研究思路与方法

中医药是我国的传统和特色医学,一直以来为人们的健康保驾护航,但随着现代医学的发展,它逐渐面临着如何实现客观化、精确化和靶向化的难题。转录组学是连接基因与表型的桥梁,决定遗传物质表达与否,受外源和内源因素的共同调控,能反映内部基因组与外部物理特征的整体网络动态联系,该特点与中医整体观理论相合,符合中药多靶点、多层次整体网络治疗的特性。因此,越来越多的学者从转录组学层面研究中药作用靶点和分子机制,以探索中医药的精准医疗。相关研究已如雨后春笋,相应检测技术也从传统的基因芯片、RNA测序,向单分子测序、单细胞测序及空间转录组发展,但转录组学作为一个相对年轻的领域,在中医药的应用仍需不断探索和完善,才能成为挖掘中医药宝藏的有力武器。有鉴于此,本文系统梳理了当前转录组学在中药研究中的现状、转录组学研究常用的检测技术,以及基于基因芯片、RNA测序、单细胞测序、空间转录组和RNA干扰技术等的转录组学研究思路与方法,并指出现有研究可能存在的问题,以期为中药在转录组层面的靶点和机制研究提供方法学基础。

基于时空双细胞状态的轴承剩余使用寿命预测方法

轴承作为众多生产设备中重要的部件之一,对其剩余使用寿命的研究有较大的价值。文中针对传统轴承剩余使用寿命预测中未充分考虑不同环境下的衰减状态变化和时序相关性而导致的预测误差大的问题,提出了一种基于时空双细胞状态自适应网络(ST-DCSN)的轴承剩余使用寿命预测方法。采用一种时间状态和空间状态并存的内嵌卷积操作双状态循环网络,并引入时空双细胞状态和子细胞状态差分机制,实现对轴承衰减状态的自适应感知。该方法在时间和空间维度上对轴承监测数据进行特征状态有效捕捉,从而解决轴承剩余使用寿命预测中环境和时序问题对预测性能的影响。为了探究文中所提方法的有效性以及对比其他近年优秀方法的优越性,采用两个真实的轴承寿命加速衰减实验数据集FEMTO-ST和XJTU-SY对文中所提方法进行了验证,分别进行了消融实验和对比实验,并以4种指标对预测性能进行评价。消融实验结果表明,相比去除空间状态细胞和去除动静态子细胞的组别,完全版本的ST-DCSN能够得到更平稳以及性能指标更好的预测结果。对比其他方法,文中所提方法能够得到更优秀的预测性能,体现在拟合性更高以及轴承寿命末期预测结果的平稳性更好,证明了ST-DCSN方法能有效提高轴承剩余使用寿命预测的准确性。

Low dose of corticosterone treatment with exercise increases hippocampal cell proliferation, and improves cognition

Intermediate level of stress is beneficial for brain functions, whereas extreme low level or high level of stress is deleterious. We have previously shown that chronic exposure to high doses of corticosterone （CORT） suppressed hippocampal plasticity and physical exercise in terms of running counteracted the detrimental effects of CORT treatment. We aimed to study whether a mild stress, that mimicked by a treatment with low CORT dose, improved hippocampal plasticity in terms of hippocampal cell proliferation and dendritic remodeling, and to examine whether running with CORT treatment showed an additive effect on improving hippocampal plasticity. The rats were treated with 20 mg/kg CORT for 14 days with or without running, followed by Morris water maze test or forced swim test. The hippocampal proliferating cells was labeled by intraperitoneal injection of 5-bromo-2＇-deoxyuridine. The dendritic morphology was analyzed using Golgi staining method. Treatment with 20 mg/kg CORT alone yielded a higher number of hippocampal cell proliferation and significantly increased dendritic branching compared to vehicle-treated non-runners, but had no behavioral effects. In contrast, CORT treatment with running showed an additive increase in hippocampal cell proliferation and dendritic remodeling that was associated with improved spatial learning and decreased depression-like behavior; however, there was no additive improvement in behavior compared to vehicle-treated runners. These findings suggest that mild stress does not always cause detrimental effect on the brain, and combining mild stress with running could promote hippocampal plasticity via inducing cell proliferation and dendritic remodeling.

基于运行数据时空特征和Stacking集成学习的质子交换膜燃料电池故障诊断

为实现质子交换膜燃料电池(proton exchange membrane fuel cell,PEMFC)故障诊断的快速性和准确性,提出基于运行数据时空特征和Stacking集成学习的故障诊断方法。首先,采用客观赋权法为反映PEMFC运行状态的电压、电流、温度和压力等变量进行赋权,基于核主成分分析和长短时记忆神经网络提取其空间、时间特征,基于add思想融合空间、时间特征,构建时空特征集。然后,建立以卷积神经网络(convolutional neural network,CNN)、随机森林、K最近邻算法、极端梯度提升树(extreme gradient boosting,XGBoost)为基分类器,XGBoost为元分类器的Stacking集成学习框架,实现了对PEMFC系统正常、水淹、膜干和氢气泄漏四种运行状态的诊断。最后,算例结果表明,所构建的时空特征集在5种单一分类模型的平均诊断准确率为99.23%,相比空间特征集提升2.83%,在Stacking模型的诊断准确率为99.99%。同时,在满足相同损失函数的前提下,使CNN的运算时间减少28s。因此,所提方法能够实现对PEMFC系统故障的快速准确诊断。

单细胞转录组和空间转录组技术及其在畜禽中的应用

转录组是研究细胞表型和功能的重要手段。单细胞转录组测序(Single-cell RNA-Sequencing,scRNA-seq)技术构建了每个细胞的表达谱,充分反映细胞的异质性;空间转录组(Spatial Transcriptomics,ST)技术能解析三维空间上的细胞表达信息,进一步推进对组织原位细胞真实基因表达的研究;2项技术结合可构建起具有高分辨率和多维度的细胞表达图谱。目前,这2项技术已在众多生物学研究领域得到应用,但在畜禽上仍处于起步阶段。本文介绍了scRNA-seq技术和ST技术的基本原理、检测和分析方法,并综述了2项技术在牛、猪、羊和鸡等畜禽上的研究应用,为今后更多地在畜禽上应用单细胞转录组和空间转录组测序技术提供参考。

单细胞多模态组学测序及其在针灸研究中的运用展望

单细胞多模态测序技术是近年来检测细胞类型特异性和探索基因调控细胞过程的前沿生物技术方法,根据单细胞不同组学的联合运用,可形成13种组合模式,从而形成了“多维度”、“多尺度”测序的特点。本文从针灸单细胞多模态数据库的建立、数据的预处理、预测模型的建立进行了分析,提出了具体的路径和策略。采用单细胞多模态测序技术结合传统针灸,是中医药交叉学科现代化发展的有益探索。以针灸单细胞多模态数据为驱动,建立针灸单细胞融合组学预测模型,可以推断针灸单细胞调控异质景观,将有望深度解码针灸治疗疾病的多维细胞调控机制。

疫情前后北京中心城区早餐点分布对比研究

本文基于2019年和2020年对北京中心城区的实地调研,结合职住通勤密度数据,应用空间句法的拓扑空间可达性分析早餐点分布规律。统计发现疫情后早餐点总量减少且分布不平衡状况进一步加剧,但其聚集中心的位置稳定。高拓扑可达性街道上的早餐点在疫情冲击下更易存续且恢复力更强。回归分析显示居住密度的影响普遍大于工作密度;拓扑可达性高、临近地铁站的街道对早餐点聚集具有稳定的支持作用。

细胞间通信预测方法研究进展

基于配体-受体(L-R)互作的细胞间通信是细胞相互协同完成复杂生命活动的重要方式。随着单细胞测序技术的快速发展,在单细胞水平上系统地解析细胞间通信网络及功能迅速成为细胞生物学研究的热点。生物信息学家已开发了大量细胞间信号通信预测的方法及平台,为细胞间信号通信研究提供了重要技术支撑。该文简要阐述了细胞间通信的基本生物学过程;并系统比较了目前较具代表性的细胞间通信预测相关数据库、算法以及评测分析研究;最后系统总结了细胞间通信预测方法的发展趋势,并展望了其未来的研究方向。