一例手足裂畸形6型家系的致病变异鉴定及胚胎植入前遗传学检测

手足裂畸形(split-hand/split-foot malformation,SHFM)是一种严重的先天性肢端畸形,主要临床特征为并指(趾)畸形、指(趾)骨及掌(跖)骨发育不全。本研究报道了一例手足裂畸形胎儿,利用全外显子组测序技术结合Sanger测序的方法筛选候选基因变异位点,并为其家庭成员提供了胚胎植入前遗传学检测(preimplantation genetic testing,PGT)。基因检测结果显示胎儿WNT10B基因存在c.786G>A(p.Trp262*)纯合变异,其父母均为杂合突变携带者;PGT检测结果显示家系的2枚囊胚中,1枚基因型为突变杂合子,1枚基因型为突变纯合子,所有胚胎染色体均为二倍体,移植突变杂合子胚胎后成功达到单胎妊娠。本研究表明WNT10B基因纯合突变可能是导致该家系患手足裂畸形的原因,对于单基因病家系,在明确其致病突变后,通过胚胎植入前遗传学检测可有效避免患儿出生。

Bioinspired micro/nanostructured surfaces prepared by femtosecond laser direct writing for multi-functional applications

manufacturing of biomimetic micro/nanostructures due to its specific advantages including high precision,simplicity,and compatibility for diverse materials in comparison with other methods(e.g.ion etching,sol-gel process,chemical vapor deposition,template method,and self-assembly).These biomimetic micro/nanostructured surfaces are of significant interest for academic and industrial research due to their wide range of potential applications,including self-cleaning surfaces,oil-water separation,and fog collection.This review presents the inherent relationship between natural organisms,fabrication methods,micro/nanostructures and their potential applications.Thereafter,we throw a list of current fabrication strategies so as to highlight the advantages of FLDW in manufacturing bioinspired microstructured surfaces.Subsequently,we summarize a variety of typical bioinspired designs(e.g.lotus leaf,pitcher plant,rice leaf,butterfly wings,etc)for diverse multifunctional micro/nanostructures through extreme femtosecond laser processing technology.Based on the principle of interfacial chemistry and geometrical optics,we discuss the potential applications of these functional micro/nanostructures and assess the underlying challenges and opportunities in the extreme fabrication of bioinspired micro/nanostructures by FLDW.This review concludes with a follow up and an outlook of femtosecond laser processing in biomimetic domains.

Encryption/decryption and microtarget capturing by pH-driven Janus microstructures fabricated by the same femtosecond laser printing parameters

Several natural organism can change shape under external stimuli. These natural phenomena have inspired a vast amount of research on exploration and implementation of reconfigurable shape transformation. The Janus structure is a promising approach to achieve shape transformation based on its heterogeneous chemical or physical properties on opposite sides.However, the heterogeneity is generally realized by multi-step processing, different materials,and/or different processing parameters. Here, we present a simple and flexible method of producing p H-sensitive Janus microactuators from a single material, using the same laser printing parameters. These microactuators exhibit reversible structural deformations with large bending angles of ~31°and fast response(~0.2 s) by changing the p H value of the aqueous environment. Benefited from the high flexibility of the laser printing technique and the spatial arrangements, pillar heights, and bending directions of microactuators are readily controlled,enabling a variety of switchable ordered patterns and complex petal-like structures on flat surfaces and inside microchannels. Finally, we explore the potential applications of this method in information encryption/decryption and microtarget capturing.

TMT Heterogeneity and Firm Performance: The Moderating Effect of Managerial Discretion

Now the top management team and managerial discretion play an important role in driving the firms’development.This paper built a theoretical model to explore the effect of top management team heterogeneity on firm performance,and analyze the moderating role of managerial discretion.Based on the data of 167 listed firms from Shanghai Stock Exchange in 2019,this paper constructs a multiple regression model and tested the hypothesis.The empirical results show that gender heterogeneity,tenure heterogeneity and education level heterogeneity have a negative effect on firms performance.At the same time managerial discretion can partially moderates the relationship between the heterogeneity of top management team and firm performance,in which capital intensity and the firm size play a negative moderating role,and duality play a positive moderating role.According to the research results,this paper also puts forward corresponding suggestions to improve the firm performance.

Soliton molecules,T-breather molecules and some interaction solutions in the(2+1)-dimensional generalized KDKK equation

By employing the complexification method and velocity resonant principle to N-solitons of the(2+1)-dimensional generalized Konopelchenko–Dubrovsky–Kaup–Kupershmidt(KDKK)equation,we obtain the soliton molecules,T-breather molecules,T-breather–L-soliton molecules and some interaction solutions when N≤6.Dynamical behaviors of these solutions are discussed analytically and graphically.The method adopted can be effectively used to construct soliton molecules and T-breather molecules of other nonlinear evolution equations.The results obtained may be helpful for experts to study the related phenomenon in oceanography and atmospheric science.

A Meta-analysis of the Effects of Firm’s Social Capital on Innovation Performance

Despite a surge of studies examining the impact of firm’s social capital on the innovation performance,empirical research shows controversial results.To resolve this problem,this paper conducted a meta-analysis to restudy the impact of the firm’s social capital and its three dimensions on innovation performance based on the previous empirical research results of independent samples.This paper also explored some moderators affecting this relationship from culture,industry,firm and methodology.The results indicated that the firm’s social capital and its three-dimension had positive impact on innovation performance.At the same time,the age of the firm and the cultural context can also affect the impact of social capital on innovation performance to a large extent.Based on these findings,this paper developed recommendations for future research.

Research Hotspot and Frontier Analysis of Business School International Accreditation

International accreditation is the only way for the internationalization of colleges and universities.This article takes 380 articles in the field of business schools international accreditation in the Web of Science database as the research object,and uses the method of scientometrics and VOS viewer knowledge map analysis software to perform co-occurrence analysis on keywords,and finally reveals the research hotspot and development trend of business school international accreditation.

Visualization Analysis of Research on Student Classroom Engagement by Knowledge Mapping

The aim of the paper is to identify and explore leading development situation within the research field related to student classroom engagement.Using knowledge mapping tools,this paper conducted the visualization analysis on internationalliteraturein relation to student classroom engagementfrom the Web of Science databases.By combination of the statistical data and visualizationmapping,this paper studied on the research relationship networks and status for the co-authors'countries/institutions,co-citation documents/journalsand co-occurring keywordsbased on the sample datafromliterature.The results indicate that the number ofpublished papershasincreased obviously and expanded graduallysince 2000.Main countries and institutions of researches were the UnitedStates,Australia,United Kingdom,Canada and China in order,and these countries had intense collaboration.The theoretical basis of the research come from education and teaching,psychology.The hotspots of researches fromthe global literature coveredvarious fields including achievement,motivation,behavior,education,performance.As a result of the multidisciplinary integration,many relevant internationalresearch constantly expanded the research scopes,which promoted the combination and development of theories.

A Review of the Antecedents and Consequences of Digital Maturity

Digital maturity has become a hot topic in various fields.This paper aims to provide an integrative review of digital maturity.This paper summarizes the concept of digital maturity from the perspectives of process,degree and ability.Four categories of antecedents,namely,strategic,cultural,talent and others are gathered.Performance and Non-performance consequences are analyzed.Finally,combining the results of digital maturity,it discusses the current research shortage of digital maturity and prospects for the future research direction.The analysis of antecedents and consequences of digital maturity can provide an integrative framework of existing research on digital maturity,and also provide some reference for the research of related research.

A Systematic Literature Review of Digital Maturity Model Research

Existing literature suggests that higher levels digitalization could promote the organizational development,and research has focused attention on digital maturity from multiple disciplines.The objective of this paper is to find the common research themes and conclusions in digital maturity research.This paper summarizes the concept of digital maturity,then combines the evaluation of digital maturity in multiple fields.Finally,it also discusses the current research shortage of digital maturity and prospects for the future research direction.This study helps to systematically comb the knowledge context of digital maturity,and helps to promote further research of digital maturity.

A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

飞秒激光诱导钛表面可控微纳结构用于水下气泡操纵

针对典型金属材料钛,利用自主搭建的飞秒激光振镜扫描加工系统,加工了具有特定形貌特征的多尺度微纳结构.在此基础上对多尺度微纳结构的可逆润湿性及水下气泡操纵特性进行了实验探究,并从微观界面化学的角度阐释了可逆润湿性的调谐机理.研究结果表明:在飞秒激光烧蚀挤压作用下,钛表面诱导的多尺度微纳结构对原始表面的润湿性具有放大效应,固液接触角减小,水下气泡接触角增大;在辅助加热条件下,固液接触角增大,水下气泡接触角同时减小,气泡在表面完全铺展;随后将超疏水表面置于紫外灯下曝光,多尺度微纳结构上的液体接触角又开始减小,并最终实现了超疏水到超亲水性以及水下超亲气到超疏气的可逆调谐.另外,液体接触角与水下气泡接触角的可逆调谐特性呈现相反的变化趋势,这与固液气三相接触线的移动机制密切相关.本文对实现钛表面微纳结构设计与调控,提高具有可逆润湿性的金属表面在水下气泡操纵与收集,以及污水处理等领域的应用都具有重要意义.

Telomere-dependent and telomereindependent roles of RAP1 in regulating human stem cell homeostasis

RAP1 is a well-known telomere-binding protein, but its functions in human stem cells have remained unclea匚 Here we generated RAP1 -deficient human embryonic stem cells (hESCs) by using CRISPR/Cas9 technique and obtained RAP1-deficient human mesenchymal stem cells (hMSCs) and neural stem cells (hNSCs) via directed differentiation. In both hMSCs and hNSCs, RAP1 not only negatively regulated telomere length but also acted as a transcriptional regulator of RELN by tuning the methylation status of its gene promoter. RAP1 deficiency enhanced self-renewal and delayed senescence in hMSCs, but not in hNSCs, suggesting complicated lineage-specific effects of RAP1 in adult stem cells.Altogether, these results demonstrate for the first time that RAP1 plays both telomeric and nontelomeric roles in regulating human stem cell homeostasis.

Single-nucleus transcriptomics reveals a gatekeeper role for FoxP1 in primate cardiac aging

Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

Hyperthermia differentially affects specific human stem cells and their differentiated derivatives

Dear Editor,The human body operates optimally at a core temperature of 37 degrees Celsius.Homeostasis at this temperature is essential for cellular and physiological functions(Cheshire,2016).However,infectious diseases,inflammation,injury,neoplasia,and elevated climate temperature can cause a regulated rise in body core temperature,i.e.,fever(Pasi-khova et al,2017).Indeed,an acute or chronic increase in temperature leads to detrimental effects on vasculature by altering a number of indices of vascular structure and function(DuBose et al.,1998).

Pseudo core-shell LaCoO3@MgO perovskite oxides for high performance methane catalytic oxidation

Magnesia modified LaCoO3 was prepared by a facile one-step sol-gel method and used for removal of dilute methane.Compared with the conventional doping technique,the obtained LaCoO3@MgO-x exhibits pseudo core-shell structure and shows superior catalytic activity.The methane conversion exceeds90%at 532℃on LaCoO3@MgO-0.1,while only 60%of methane is conversed using the doped perovskite LaCo0.9Mg0.1O3.The high catalytic performance of LaCoO3@MgO-0.1 is mainly attributed to the adjustment of surface acid-base properties by the MgO shell structure.According to density functional theory(DFT)calculation,the methane is more likely to be adsorbed and cracked on LaCoO3@MgO-0.1.The in situ DRIFTS shows that CH3-O-CH3 intermediate specie is formed.The pseudo core-shell structure also enhances the stability and the LaCoO3@MgO-0.1 maintains high activity after working for 100 h.The above results demonstrate that surface modification by magnesia is an effective strategy for improving LaCoO3 catalytic performance.

The effects of icariine concentration on osteoclasts bone resorption induced by titanium particles in vitro

In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.

Comparative genotoxicity of water processed by three drinking water treatment plants with different water treatment procedures

Advanced water treatment is commonly used to remove micropollutants such as pesticides,endocrine disrupting chemicals,and disinfection byproducts in modem drinking water treatment plants.However,little attention has been paid to the changes in the genotoxicity of substances remaining in the water following the different water treatment processes.In this study,samples were collected from three drinking water treatment plants with different treatment processes.The treated water from each process was analyzed and compared for genotoxicity and the formation of organic compounds.The genotoxicity was evaluated by an umu test,and the acute and chronic toxicity was analyzed through Ecological Structure-Activity Relationship(ECOSAR).The results of the umu test indicated that biological activated carbon reduced the genotoxicity by 38%,77%,and 46%in the three drinking water treatment plants,respectively,while chlorination increased the genotoxicity.Gas chromatograph-mass spectrometry analysis revealed that halogenated hydrocarbons and aromatic compounds were major contributors to genotoxicity.The results of ECOSAR were not consistent with those of the umu test.Therefore,we conclude that genotoxicity cannot be determined using ECOSAR.

4E-BP1 counteracts human mesenchymal stem cell senescence via maintaining mitochondrial homeostasis

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders,the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown.Here,we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem celis(hMSCs).Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration,increases mitochondrial reactive oxygen species(Ros)production,and accelerates cellular senescence.Mechanistically,the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes,especially several key subunits of complex III including UQCRC2.Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs.These findings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis,particularly for the mitochondrial respiration complex Il,thus providing a new potential target to counteract human stem cell senescence.

Tunable Fluid-Type Metasurface for Wide-Angle and Multifrequency Water-Air Acoustic Transmission

Efficient acoustic communication across the water-air interface remains a great challenge owing to the extreme acoustic impedance mismatch.Few present acoustic metamaterials can be constructed on the free air-water interface for enhancing the acoustic transmission because of the interface instability.Previous strategies overcoming this difficulty were limited in practical usage,as well as the wide-angle and multifrequency acoustic transmission.Here,we report a simple and practical way to obtain the wide-angle and multifrequency water-air acoustic transmission with a tunable fluid-type acoustic metasurface(FAM).The FAM has a transmission enhancement of acoustic energy over 200 times,with a thickness less than the wavelength in water by three orders of magnitude.The FAM can work at an almost arbitrary water-to-air incident angle,and the operating frequencies can be flexibly adjusted.Multifrequency transmissions can be obtained with multilayer FAMs.In experiments,the FAM is demonstrated to be stable enough for practical applications and has the transmission enhancement of over 20 dB for wide frequencies.The transmission enhancement of music signal across the water-air interface was performed to demonstrate the applications in acoustic communications.The FAM will benefit various applications in hydroacoustics and oceanography.