Suppression of current-induced membrane discharge of bipolar membranes by regulating ion crossover transport

Bipolar membranes(BPMs)exhibit the unique capability to regulate the operating environment of electrochemical system through the water dissociation-combination processes.However,the industrial utilization of BPMs is limited by instability and serious energy consumption.The current-induced membrane discharge(CIMD)at high-current conditions has a negative influence on the performance of anion-exchange membranes,but the underlying ion transport mechanisms in the BPMs remain unclear.Here,the CIMD-coupled Poisson-Nernst-Planck(PNP)equations are used to explore the ion transport mechanisms in the BPMs for both reverse bias and forward bias at neutral and acid-base conditions.It is demonstrated that the CIMD effect in the reverse-bias mode can be suppressed by enhancing the diffusive transport of salt counter-ions(Na^(+)and Cl^(−))into the BPMs,and that in the forward-bias mode with acid-base electrolytes can be suppressed by matching the transport rate of water counter-ions(H_(3)O^(+)and OH^(−)).Suppressing the CIMD can promote the water dissociation in the reverse-bias mode,as well as overcome the plateau of limiting current density and reduce the interfacial blockage of salt co-ions(Cl^(−))in the anion-exchange layer in the forward-bias mode with acid-base electrolytes.Our work highlights the importance of regulating ion crossover transport on improving the performance of BPMs.

MACS-W:A modified optical clearing agent for imaging 3D cell cultures

Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.

Preface–Introduction to the Special Issue for Chinese-Russian Workshop on Biophotonics and Biomedical Optics

The Chinese-Russian Workshop on Biophotonics and Biomedical Optics 2023 was held online twice on 18–21 September and 25–26 September 2023.The bilateral workshop brought together both Russian and Chinese scientists,engineers,and clinical researchers from a variety of disciplines engaged in applying optical science,photonics,and imaging technologies to problems in biology and medicine.During the workshops,two plenary lectures and twenty invited presentations were presented.This special issue selects some papers from both Russian and Chinese sides,consisting of one review and seven original research articles.

Tissue optical clearing for neural regeneration research

Nerve injury,whether traumatic or degenerative,disrupts the transmission of information in the nervous syste m,leading to dysfunction.It is widely known that neural regeneration is vital to the restoration of function after nerve injury.Still,outcomes are often limited by the misguidance of axonal regeneration and complex pathological changes in neurons and glia,as well as the longterm denervation of target organs.

基于生物信息学探索DKK1在肺腺癌发生中的作用

背景与目的肺癌是我国最常见的恶性肿瘤,肺腺癌(lung adenocarcinoma,LUAD)是肺癌的主要类型,严重威胁着人民的生命健康,目前关于血清分泌型蛋白1(Dikkopf 1,DKK1)在LUAD中的作用研究较少,本研究旨在通过生物信息学方法探究DKK1在LUAD发生发展中的作用及潜在的预后价值。方法应用基因型组织表达(genotype-tissue expression,GTEx)、癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库和肿瘤与免疫系统交互网站(tumor-immune system interactions database,TISIDB)等多个数据库,对DKK1在LUAD中的表达、临床病理特征、免疫细胞浸润、预后和甲基化等进行分析,同时应用LinkedOmics数据库分析DKK1的共表达基因及其功能富集。收集2016年至2017年于新疆医科大学附属肿瘤医院行手术治疗的59例石蜡包埋的LUAD患者病理样本,通过免疫组织化学试验(immunohistochemistry,IHC)进行表达预后验证。结果生信分析结果显示DKK1在LUAD组织的表达水平高于正常组织,晚期癌症中的表达高于早期阶段,实验验证后发现59例LUAD中阴性表达15例(25.4%),弱阳性表达18例(30.5%),强阳性表达26例(44.1%)。DKK1的不同表达情况与甲基化、预后以及多种免疫细胞的活动相关。功能富集显示DKK1可能参与表皮发育、细胞-基质连接等过程,京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析表明DKK1与ABC转运蛋白相关。生物信息学分析及临床病例标本显示DKK1高表达与LUAD患者较差的预后有关。结论DKK1在LUAD中高表达,与患者预后不良有关,并且DKK1与肿瘤免疫细胞浸润和通路密切相关。DKK1可能是LUAD潜在的预后标志物和免疫治疗新靶点。

A systematic identification of cold tolerance genes in peanut using yeast functional screening system

Peanut(Arachis hypogaea L.)is a thermophilic crop,and low temperature leads to a significant reduction in annual yields.Despite a few cold tolerant germplasms or cultivars have been discovered and developed,molecular mechanisms governing peanut cold tolerance is poorly understood.Identification of keys genes involved in cold tolerance is the first step to address the underlying mechanism.In this study,we isolated and characterized 157 genes with potentials to confer cold tolerance in peanut by using a yeast functional screening system.GO(Gene ontology)and KEGG(Kyoto encyclopedia of genes and genomes)enrichment analysis of these genes revealed that ribosome and photosynthesis proteins might play essential roles in peanut cold response.Transcriptome results indicated that 60 cold tolerance candidate genes were significantly induced or depressed by low temperature.qRT-PCR analysis demonstrated that several candidate genes could be also regulated by salt or drought stress.Individual overexpression of two UDP-glycosyltransferases(AhUGT2 and AhUGT268)in transgenic yeast cells could enhance their tolerance to multiple abiotic stress.In conclusion,this study advances our understanding of the mechanisms associated with the cold stress responses in peanut,and offers valuable gene resources for genetic improvement of abiotic stress tolerance in crops.

Exploration of the Inner Laws of Urbanization Economic Operation and Application Analysis

Exploring the inner law of the economic operation of urbanization can understand the regulation mechanism of the optimal distribution of urban resource allocation. In this regard, we propose to explore and analyze the inner law of urbanization economic operation and its application. The study found that the urbanization economy originated from the urban agglomeration effect, which includes the agglomeration economic operation mechanism and spillover effect operation mechanism, based on which three kinds of inner laws of urbanization economic operation are explored, combined with the economic operation law, the non-equilibrium state of the declining cities are regulated and applied, and the results show that the analysis of the inner laws of urbanization economic operation has a direct significance in guiding the real economic process.

解偶联蛋白-1(UCP1)的研究进展及其应用前景

UCP1是唯一在褐色脂肪组织(BAT)中表达的解偶联蛋白质。有别于解偶联蛋白家族其他成员的功能,UCP1的主要功能是参与BAT的产热调节和能量代谢来维持机体的能量代谢平衡。陆续有研究阐明调控UCP1参与BAT产热调节和能量代谢的分子机制,逐渐揭示了UCP1在BAT能量代谢过程中涉及的信号通路与转录调控。这不仅让我们更好地理解UCP1在BAT能量代谢调控中的重要作用,而且为基于褐色脂肪组织的肥胖治疗提供了理论依据。本文阐述了近年来研究发现的UCP1在BAT能量代谢过程中发挥重要作用的信号通路与转录调控,并讨论了多种基于针对褐色脂肪组织的肥胖治疗手段的有效性与可行性。

High-Speed Rail Station Interconnectivity and Ridership

The objective of this study was to quantify multimodal connectivity of HSR stations and its impact on ridership in four countries: France, Spain, Japan and China. In this study, multimodal connectivity is measured by the number of different modes of transportation connected to HSR stations, the number of installed arrival and departure facilities for each mode, the transfer time from connecting modes to boarding platforms at HSR stations, and the arrival time intervals of public transportation modes. Data were collected from HSR systems of these four countries. The relationship between ridership and the characteristics of multimodal connectivity was identified using regression models developed in this study. All the connectivity variables considered in this study influence ridership in these four countries in different ways. On the whole, bus, subway, and regional railroad services influence ridership significantly. For instance, the more bus services connected to the station, the higher the ridership. This trend is apparent in three of the four countries, France being the exception. Also, subway, light rail, and traditional rail are modes of high-capacity transportation. Their connection to HSR stations always implies high ridership for high-speed rail. The number of facilities also shows significant impacts on HSR ridership. For instance, the more bus and subway stops, and the more bicycle parking and taxi stands, the higher the ridership. Transfer time also has a significant influence.

鞘内合成的肿瘤标志物与血脑屏障完整性在肺癌软脑膜转移诊断中的价值

背景与目的脑脊液(cerebrospinal fluid,CSF)中肿瘤标志物(tumor markers,TM)对软脑膜转移(leptomeningeal metastasis,LM)具有诊断意义,但因TM在CSF中浓度很大程度上取决于血清水平以及血脑屏障(blood brain barrier,BBB)的状态,因此,CSF中TM诊断LM的价值常常被忽视。明确鞘内TM合成、BBB的完整性可为LM临床诊断提供帮助。因此,本研究从BBB完整性和鞘内TM合成角度出发,进一步探讨CSF中TM对肺癌LM诊断的临床价值。方法收集2016年12月-2020年3月于南京鼓楼医院治疗的肺癌伴LM的患者25例,另选本院同期治疗的57例非恶性神经系统疾病(nonmalignant neurological diseases,NMNDs)患者为对照组,分析比较BBB完整性和鞘内TM合成的差异,评估LM组CSF中TM检出阳性率与鞘内TM合成的相关性,并动态监测1例LM患者脑室内化疗过程中CSF细胞学、BBB完整性以及鞘内TM合成的变化。结果LM患者中94%存在BBB破坏。所有LM患者CSF中至少存在一项TM的鞘内合成,其中1例患者,首次CSF细胞学阴性,但是存在鞘内TM合成,重复腰穿CSF细胞学阳性确诊为LM。LM组CSF中TM检出阳性率与TM鞘内合成不一致。对照组中仅3.5%(2/57)NMNDs患者有BBB破坏,且未在鞘内合成TM,差异有统计学意义(P<0.05)。另外,动态监测CSF细胞学、BBB完整性和CSF鞘内合成的TM与疗效评价一致,且鞘内TM合成的变化早于细胞学。结论BBB的评估及鞘内TM合成的分析可为LM患者提供一个早期辅助诊断的工具,动态监测TM可能有助于疗效评估,值得临床推广应用。

肺腺癌软脑膜转移患者的脑脊液和血液中不同的基因突变谱:基于循环肿瘤DNA的液体活检

背景与目的软脑膜转移(leptomeningeal metastasis,LM)是晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一种严重并发症,通常预后较差。对于驱动基因阳性的NSCLC患者,表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)是治疗的首选,但常伴随着无法解决的耐药问题。本研究旨在探讨NSCLC-LM患者的脑脊液(cerebrospinal fluid,CSF)和血液中不同的基因突变谱及突变丰度,筛查相关耐药基因,以期能精确指导个体化的治疗。方法采用二代基因测序(next generation sequencing,NGS)的液体活检技术,检测、对比分析TKI耐药后NSCLC患者同期的外周血及脑脊液中的循环肿瘤DNA(circulating tumor DNA,ct DNA)。结果共纳入18例NSCLC伴有LM的患者,基础突变中11例(61.11%)为EGFR,6例(33.33%)为间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK),1例(5.56%)为原癌基因酪氨酸蛋白激酶ROS(ROS protooncogene 1,receptor tyrosine kinase,ROS1),伴随突变中肿瘤蛋白P53(tumor protein p53 gene,TP53)、间质-上皮细胞转化因子(mesenchymal-epithelial transition factor,MET)检出率相对较高。CSF样本的靶向基因突变检出率明显高于外周血(100.00%vs 66.67%,P=0.006),且基础突变基因的CSF丰度均明显高于血浆样本(P<0.001)。CSF样本检测出丰富的单核苷酸变异(single-nucleotide variations,SNV)和拷贝数变异(copy number variants,CNV),数量均多于血液样本;且相较于只接受过单一TKI治疗的患者,使用多种TKI后脑脊液和血液中会产生更多的SNV突变。结论NSCLC-LM患者CSF中的ct DNA,相较于外周血,能更加准确、全面地反映出LM的真实基因突变状态,在指导用药、耐药监测、预后评估等方面具有广泛的应用前景,可作为液体活检的优选。

Current applications and future prospects of nanotechnology in cancer immunotherapy

Cancer immunotherapy is an artificial stimulation of the immune system to recognize cancer cells and activate specific immune cells to target and attack cancer cells.In clinical trials, immunotherapy has recently shown impressive results in the treatment of multiple cancers.Thus, cancer immunotherapy has gained a lot of attention for its unique advantages and promising future.With extensive research on cancer immunotherapy, its safety and effectiveness has gradually been revealed.However, it is still a huge challenge to expand and drive this therapy while maintaining low toxicity, high specificity, and long-lasting efficacy.As a unique technology, nanotechnology has been applied in many fields, the advantages of which will promote the development of cancer immunotherapies.Researchers have tried to apply nanomaterials to cancer immunotherapy due to their advantageous properties,such as large specific surface areas, effective drug delivery, and controlled surface chemistry, to improve treatment efficacy.Here,we briefly introduce the current applications of nanomaterials in cancer immunotherapy, including adoptive cell therapy(ACT),therapeutic cancer vaccines, and monoclonal antibodies, and throw light on future directions of nanotechnology-based cancer immunotherapy.

Characterization of the imprinting and expression patterns of ZAG2 in maize endosperm and embryo

ZAG2 has been identified as a maternally expressed imprinted gene in maize endosperm.Our study revealed that paternally inherited ZAG2 alleles were imprinted in maize endosperm and embryo at 14 days after pollination(DAP), and consistently imprinted in endosperm at 10, 12, 16, 18, 20, 22, 24, 26, and 28 DAP in reciprocal crosses between B73 and Mo17. ZAG2 alleles were also imprinted in reciprocal crosses between Zheng 58 and Chang7-2 and between Huang C and 178. ZAG2 alleles exhibited differential imprinting in hybrids of 178 × Huang C and B73 × Mo17, while in other hybrids ZAG2 alleles exhibited binary imprinting. The tissue-specific expression pattern of ZAG2 showed that ZAG2 was expressed at a high level in immature ears, suggesting that ZAG2 plays important roles in not only kernel but ear development.

Optical angiography for diabetes-induced pathological changes in microvascular structure and function:An overview

Diabetes mellitus(DM)is a kind of metabolic disorder characterized by chronic hyperglycemia and glucose intolerance due to absolute or relative lack of insulin,leading to chronic damage of vasculature within various organ systems.These detrimental e®ects on the vascular networks will result in the development of various diseases associated with microvascular injury.Modern optical imaging techniques provide essential tools for accurate evaluation of the structural and functional changes of blood vessels down to capillaries level,which can o®er valuable insight on understanding the development of DM-associated complications and design of targeted therapy.This review will brie°y introduce the DM-induced structural and functional alterations of vasculature within di®erent organs such as skin,cerebrum and kidneys,as well as how novel optical imaging techniques facilitate the studies focusing on exploration of these pathological changes of vasculature caused by DM both in-vivo and ex-vivo.

Mechanical force-driven TNFαendocytosis governs stem cell homeostasis

Mesenchymal stem cells(MSCs)closely interact with the immune system,and they are known to secrete inflammatory cytokines in response to stress stimuli.The biological function of MSC-derived inflammatory cytokines remains elusive.Here,we reveal that even under physiological conditions,MSCs produce and release a low level of tumor necrosis factor alpha(TNFα),which is unexpectedly required for preserving the self-renewal and differentiation of MSCs via autocrine/paracrine signaling.Furthermore,TNFαcritically maintains MSC function in vivo during bone homeostasis.Mechanistically,we unexpectedly discovered that physiological levels of TNFαsafeguard MSC homeostasis in a receptor-independent manner through mechanical force-driven endocytosis and that endocytosed TNFαbinds to mammalian target of rapamycin(mTOR)complex 2 and restricts mTOR signaling.Importantly,inhibition of mTOR signaling by rapamycin serves as an effective osteoanabolic therapeutic strategy to protect against TNFαdeficiency and mechanical unloading.Collectively,these findings unravel the physiological framework of the dynamic TNFαshuttlebased mTOR equilibrium that governs MSC and bone homeostasis.

Three-dimensional,isotropic imaging of mouse brain using multi-view deconvolution light sheet microscopy

We present a threedimensional(3D)isotropic imaging of mouse brain using light-sheet fuo-rescent microscopy(LSFM)in conjumction with a multi-view imaging computation.Unlike common single view LSFM is used for mouse brain imaging,the brain tissue is 3D imaged under eight views in our study,by a home-built selective plane ilumination microscopy(SPIM).An output image containing complete structural infornation as well as significantly improved res olution(~4 times)are then computed based on these eight views of data,using a bead-guided multi-view registration and deconvolution.With superior imaging quality,the astrocyte and pyrarmidal neurons together with their subcellular nerve fbers can be clearly visualized and segmented.With further incuding other computational methods,this study can be potentially scaled up to map the conectome of whole mouse brain with a simple light.sheet microscope.

Long non-coding RNAs in cancer

Long non-coding RNAs （IncRNAs）, gradually being paid attention to, have been found playing a critical role in regulation of cellular processes such as cell growth and apoptosis, what is more, accumulating evidence indicates that IncRNAs also play a critical role in regulation of carcinogenesis and cancer progression. Here, we will summarize the recent researches about some IncRNAs in the development of cancers, hoping to give a new view about the study in the mechanisms involved in carcinogenesis and tumor progression.

Cytokine-induced killer cell combination with TACE in the treatment of hepatocellular cancers:a meta-analysis

Objective：The aim of the study was to evaluate the ef icacy and safety of cytokine-induced kil er （CIK） cellcombined with transcatheter arterial chemoembolization （TACE） therapy in the treatment of hepatocellular carcinoma （HCC）. Methods：Randomized control ed trials （RCTs） on CIK cells combination with TACE based-therapy were identified by elec-tronic searches in the Cochrane Library, MEDLINE, Pubmed, Wanfang, VIP, CNKI and other electronic databases. We in-cluded any RCTs evaluating CIK cellcombination with TACE for the treatment of hepatocellular cancers. The quality of RCTs meeting inclusion criteria was evaluated and data on short-term and long-term curative ef ects, quality of life, liver function and immunologic function were extracted. For quantitative data, we conducted meta-analysis with ReMan 5.1 software and the GRADE System was used to rate the level of evidence and strength of recommendation. For qualitative data, data mainly adopted descriptive methods. Results：The 9 RCTs involving 870 cases meeting the inclusion criteria were included. The meta-analysis showed significant survival benefit on 0.5-year survival rate （RR=1.51, 95%CI, 1.35-1.69, P〈0.00001） in fa-vor of CIK based therapy. This ef ect was consistent at other prospective dates, including 1-year survival rate （RR=2.30, 95%CI, 1.94-2.72, P〈0.00001）, 2-year survival rate （RR=7.03, 95%CI, 3.83-12.91, P〈0.0001）. Meanwhile, the CIK-based group also demonstrated a significantly prolonged time-to-progression （TTP） （SD=1.62, 95%CI, 1.30-1.94, P〈0.0001） and overal survival （OS） （SD=20.6, 95%CI, 20.2-21.18, P〈0.0001）. Moreover, a favored response rate （RR=CR＋PR） （RR=2, 95%CI, 1.65-2.43, P〈0.00001） and the quality of life improvement rate （KPS） （RR=1.76, 95%CI, 1.26-2.45, P=0.0008） were also observed in patients receiving CIK cells and TACE therapy. Furthermore, patients in the CIK group showed lower AFP （SD=-165.23, 95%CI,-178.51--151.94, P〈0.00001）, ALT （SD=-33.14, 95%CI,-40.30--36.37, P〈0.00001）, and AST （SD=-15.57, 95%CI,-17.05--14.09, P〈0.00001） levels. In terms of T-lymphocyte subsets in peripheral blood, the analysis also showed the percentage of CD3＋, CD4＋cells and the ratio of CD4＋/CD8＋cells in the CIK group increased compared with the non-CIK group. Based on GRADE, the level of evidence was GRADE 2C, and the strength of recommen-dation was 2. Conclusion：CIK cells combined with TACE therapy demonstrated a significant superiority in improving recent and forward curative ef ects, immunity function, quality of life and liver function of HCC patients. Based on GRADE, the level of evidence was GRADE 2C, and the strength of recommendation was 2. In the light of the limitations of this study, large-scale, high-quality clinical trials should be carried out to further confirmed the above conclusion.

Engineered Fabrication of Enamel-Mimetic Materials

Tooth enamel,which is a biological tissue mainly composed of well-aligned hydroxyapatite nanocrystals and an interlaced protein matrix,has remarkable mechanical and aesthetic behaviors.Nevertheless,it is challenging to regenerate enamel naturally,and potential pulp involvement and tooth loss may occur.As the hardest biogenic composite material,enamel has long been regarded as a promising load-bearing material.Thus,understanding the enamel formation process and enamel structural motif mechanisms is important for the design and engineering of high-performance biomimetic composites with high strength and physical resilience.Extensive studies have been conducted on mimicking the microstructure and mechanical properties of tooth enamel,and various enamel-like material synthesis protocols have been developed.In light of the engineering fabrication of enamel-like materials,this review focuses on recent progress in synthetic strategies for enamel-mimetic materials and provides a discussion of the potential applications of these materials.

Introduction to the Special Issue on Advances in Biophotonics and Biomedical Optics:Part II

The 9th Chinese–Russian Workshop on Biophotonics and Biomedical Optics was held online on 28–30 September 2020.The bilateral workshop brought together both Russian and Chinese scientists,engineers,and clinical researchers from a variety of disciplines engaged in applying optical science,photonics,and imaging technologies to problems in biology and medicine.During the workshop,2 plenary lectures,35 invited presentations,5 oral presentations,and 8 internet reports were presented.This special issue selects some papers from the attendees and includes both research and review articles.