[Co_(3)]簇基金属有机框架材料实现“一石二鸟”高效催化CO_(2)转化为噁唑烷酮

噁唑烷酮是药物化学中重要的中间体,可以通过炔丙基胺类或氮杂环类化合物与CO_(2)的环化获得。合成一种可以同时催化这两种反应的催化剂是一件有很强吸引力,但极具挑战性的工作。本文合成了一例独特的三维(3D)[CO_(3)]簇金属-有机框架(MOF){(CH_(3)NH_(2)CH_(3))2[CO_(3)(BCP)_(2)]·6H_(2)O·4DMF}n(1)并进行了表征,1表现出良好的溶剂稳定性和热稳定性。催化实验结果表明,1可以高效催化氮杂环或炔丙基胺类化合物与CO_(2)反应来制备噁唑烷酮,并且催化剂对两种反应都具有广泛的底物普适性和良好的循环使用性。对照实验和核磁共振测试表明,1中路易斯酸和路易斯碱位点的共存是高效催化的原因。化合物1作为一种新型催化剂,成功实现了“一石二鸟”高效催化CO_(2)转化为噁唑烷酮。

Global characterization of modifications to the charge isomers of IgG antibody

Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.

FAM64A promotes HNSCC tumorigenesis by mediating transcriptional autoregulation of FOXM1

Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.

A systematic review of steel bridge deck pavement in China

As an important part of steel bridge deck,the engineering quality and service condition of steel bridge deck pavement(SBDP)directly affects the capacity and operational efficiency of the bridge.This paper reviews the history of the development of SBDP in China over the past 20 years from the exploration stage,rapid development stage and prosperity stage.The development and application of SBDP at different stages are discussed in terms of materials,structure,design,performance evaluation,maintenance and rehabilitation,respectively.The advantages and disadvantages of different pavement materials and structures,and the application of different research methods are summarized.The review shows that the improvement of pavement materials and structures and the development of new materials should be further studied on the multi-scale to enhance the durability of pavement materials,so as to extend the service life of pavements.The design method of SBDP related to the synergistic effect of vehicle,pavement and bridge should be established,and the design concept and method standard of rigid base pavement structure should be improved and formulate a complete design standard.In addition,multi-disease intelligent identification system and equipment should be studied to track the entire course of disease development in real time.And it is necessary to develop appropriate algorithms to select and classify the complex data of disease and maintenance history.

基于道德许可理论视角的企业社会责任对员工亲社会行为的影响机制研究

良好的企业社会责任可以通过改变员工的态度及行为,进而对员工绩效和创新行为等方面产生一系列积极影响。然而,以往研究却忽视了企业社会责任对员工道德心态与社会行为的潜在负面影响。基于道德许可理论视角,本文提出企业社会责任对员工在工作场所之外亲社会行为的潜在消极影响。基于双波纵向调研(子研究1)与实验法(子研究2)的混合式研究设计收集数据,分析结果表明:企业积极履行社会责任会使员工产生个人道德许可,减少在工作场所外做出的亲社会行为。本文揭示和验证了企业社会责任的潜在负面影响,拓展了企业社会责任与员工工作场所外行为的研究,为企业与员工更好地履行社会责任,提供了有益的参考建议。

年长员工主观年龄对利他行为的影响:控制感的中介作用和组织支持的调节作用

随着我国社会人口日益老龄化,企业如何有效管理和开发年长员工成为人力资源开发学者和管理人员广泛关注的问题。然而,年龄刻板印象使得部分管理人员忽视了个人生理实际年龄与心理主观感受的差异,从而无法充分发挥年长员工在丰富工作经验、知识诀窍(know how)积累、社会网络资本深厚、适应组织文化等多方面优势。与生理年龄相比,主观年龄反映了个人对年龄的心理感知,更能解释年长员工态度和行为的内源性成因。本研究基于资源保存理论,探讨了主观年龄对年长员工利他行为的作用机制。对三阶段问卷调查数据分析的结果表明,主观年龄年轻化通过控制感,增加年长员工利他行为。组织支持具有显著的调节作用:在高水平组织支持下,主观年龄更年轻的年长员工对生活和工作的控制力越强,利他行为越多。研究结果拓展了主观年龄对年长员工影响机制的前沿研究,对人力资源管理者如何有效开发年长员工资源、实现成功老龄化提供了建议,以期起到抛砖引玉的作用。

何谓获得?员工获得感的内涵与来源探索

获得感是具有新时代中国特色社会主义情境特征的原创性概念。企业是国民经济的细胞,员工个体是社会治理中的基本单位。在全社会人民获得感得到重视和改善的基础上,有针对性地提升员工获得感是企业人力资源开发的重要议题。然而,目前针对企业员工获得感内涵与来源的探索相对较少。本研究采用大数据文本分析的方法,建构和检验了企业员工获得感的主客观维度与细分指标,丰富和拓展了获得感在社会微观层面的研究。本研究基于网页数据爬取的关键词进行大数据分析,通过词汇分类提炼员工获得感的内涵,探索了员工获得感的主客观内涵维度与细分指标。文章探讨了2018和2021年研究发现的差异,反映了基于时代发展的各领域关注度变化。本研究成果预期可为我国企业在社会主义新时代的管理实践提供参考,促进我国更多、更好的研究成果为世界管理理论贡献“中国智慧”。

Toxicity assessment and long-term three-photon fluorescence imaging of bright aggregation-induced emission nanodots in zebrafish

Aggregation-induced emission （AIE） luminogen displays bright fluorescence and has photobleaching resistance in its aggregation state. It is an ideal fluorescent contrast agent for bioimaging. Multiphoton microscopy is an important tool for bioimaging since it possesses the ability to penetrate deep into biological tissues. Herein, we used AIE luminogen together with multiphoton microscopy for long-term imaging of zebrafish. A typical AIE luminogen, 2,3-bis（4-（phenyl（4- （1,Z2-triphenylvinyl） phenyl）amino）phenyl） fumaronitrile （TPE-TPA-FN or TTF）, was encapsulated with 1,2-distearoyl-sn-glycero-3-phosphoethanola-mine-N- [methoxy（polyethylene glycol）-2000] （DSPE-mPEG2000） to form nanodots that exhibited bright three-photon fluorescence under 1,560 nm-femtosecond （fs） laser excitation. The TTF-nanodots were chemically stable in a wide range of pH values and showed no in vivo toxicity in zebrafish according to a series of biological tests. The TTF-nanodots were microinjected into zebrafish embryos, and the different growth stages of the labeled embryos were monitored with a three-photon fluorescence microscope. TTF-nanodots could be traced inside the zebrafish body for as long as 120 hours. In addition, the TTF-nanodots were utilized to target the blood vessel of zebrafish, and three-photon fluorescence angiogram was performed. More importantly, these nanodots were highly resistant to photobleaching under 1,560 nm-fs excitation, allowing long-term imaging of zebrafish.

PLEK2 promotes cancer stemness and tumorigenesis of head and neck squamous cell carcinoma via the c-Myc-mediated positive feedback loop

Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.

Growth substrates alter aboveground plant microbial and metabolic properties thereby influencing insect herbivore performance

The gut microbiome of plant-eaters is affected by the food they eat,but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores.Here,we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems.From a plant metabolomics analysis,we identified 20 plant metabolites that were related to caterpillar feeding performance.In a bioassay,the effects of these plant metabolites on insects'feeding were tested.Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects,while compounds enriched with leaves of plants growing in natural soil decreased feeding.Several microbial groups(e.g.,Sporolactobacillus,Haliangium)detected inside the plant correlated with caterpillar feeding performance and other microbial groups,such as Ramlibacter and Methylophilus,correlated with the gut microbiome.Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders.It illustrates how belowground factors can influence the aboveground properties of plant-animal systems,which has important implications for plant growth and pest control.

Unified convergence analysis of a second-order method of multipliers for nonlinear conic programming

In this paper,we accomplish the unified convergence analysis of a second-order method of multipliers(i.e.,a second-order augmented Lagrangian method)for solving the conventional nonlinear conic optimization problems.Specifically,the algorithm that we investigate incorporates a specially designed nonsmooth(generalized)Newton step to furnish a second-order update rule for the multipliers.We first show in a unified fashion that under a few abstract assumptions,the proposed method is locally convergent and possesses a(nonasymptotic)superlinear convergence rate,even though the penalty parameter is fixed and/or the strict complementarity fails.Subsequently,we demonstrate that for the three typical scenarios,i.e.,the classic nonlinear programming,the nonlinear second-order cone programming and the nonlinear semidefinite programming,these abstract assumptions are nothing but exactly the implications of the iconic sufficient conditions that are assumed for establishing the Q-linear convergence rates of the method of multipliers without assuming the strict complementarity.

Neutrophil-sourced TNF in cancer:deciphering an intricate orchestrator of immunosuppressive communication in the tumor microenvironment

In a recent Cancer Discovery publication,Bianchi et al.unveil a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs).This insight provides fresh perspectives for surmounting such resistance in PDAC.1 PDAC represents a highly aggressive malignancy exhibiting substantial therapeutic resistance,attributable to factors such as intractable genomic aberrations,immunosuppression mediated by myeloid cells,and pro-inflammatory activation of cancerassociated fibroblasts.