Diversity and redundancy of the ripening regulatory networks revealed by the fruitENCODE and the new CRISPR/Cas9 CNR and NOR mutants

Tomato is considered as the genetic model for climacteric fruits,in which three major players control the fruit ripening process:ethylene,ripening transcription factors,and DNA methylation.The fruitENCODE project has now shown that there are multiple transcriptional circuits regulating fruit ripening in different species,and H3K27me3,instead of DNA methylation,plays a conserved role in restricting these ripening pathways.In addition,the function of the core tomato ripening transcription factors is now being questioned.We have employed CRISPR/Cas9 genome editing to mutate the SBP-CNR and NAC-NOR transcription factors,both of which are considered as master regulators in the current tomato ripening model.These plants only displayed delayed or partial non-ripening phenotypes,distinct from the original mutant plants,which categorically failed to ripen,suggesting that they might be gain-of-function mutants.Besides increased DNA methylation genome-wide,the original mutants also have hyper-H3K27me3 in ripening gene loci such as ACS2,RIN,and TDR4.It is most likely that multiple genetic and epigenetic factors have contributed to their strong non-ripening phenotypes.Hence,we propose that the field should move beyond these linear and twodimensional models and embrace the fact that important biological processes such as ripening are often regulated by highly redundant network with inputs from multiple levels.

氧化石墨烯/聚酰胺纳米复合材料研究进展

石墨烯具有优异的光学、电学和力学性质,石墨烯/聚合物纳米复合材料受到了学术界和产业界的共同关注。近年来,氧化石墨烯/聚酰胺纳米复合材料在提高材料性能、拓展下游应用方面取得了突破。文中综述了氧化石墨烯、还原氧化石墨烯和功能化氧化石墨烯与不同聚酰胺复合的研究进展,总结了原位聚合、熔融复合和溶液共混等制备方法,讨论了氧化石墨烯的功能化方法以及纳米复合材料的化学结构、热性能、力学性能、电化学性能及应用,同时对该领域的发展和面临的挑战进行了探讨。

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.

23株非结核分枝杆菌药物敏感性试验分析

目的对自贡市临床分离鉴定的23株非结核分枝杆菌分别进行26种抗生素的药物敏感试验,了解非结核分枝杆菌对不同抗生素的耐药性,为非结核分枝杆菌病临床治疗提供依据。方法采用微孔板阿尔玛蓝测定法(microplate Alamarblue assay,MABA)测试每种药物对每株非结核分枝杆菌的最低抑菌浓度(MIC值),通过MIC值判断该菌对此种抗生素是否耐药。结果非结核分枝杆菌对大部分抗结核药物耐药,并且对部分药物的耐药存在种间差异。其中脓肿分枝杆菌耐药率达84.6%,鸟分枝杆菌与胞内分枝杆菌分别达53.8%与52.3%,堪萨斯分枝杆菌耐药率最低为38%。结论对临床非结核分枝杆菌肺病,快速菌株鉴定及药敏试验是治疗的关键。

2015—2017年四川省自贡市耐多药结核病分级诊疗实施效果初步评价

目的 初步评价2015—2017年四川省自贡市耐多药结核病（MDR-TB）分级诊疗的实施效果。方法 收集2015—2017年四川省自贡市自流井区、大安区、沿滩区和富顺县、荣县、贡井区6个试点区县的结核病患者登记和疫情报告资料。医防联合体定点医疗机构（包括自流井区、大安区、沿滩区）共登记4418例结核病患者,各区县医院定点医疗机构（包括富顺县、荣县、贡井区）共登记4922例结核病患者。对MDR-TB患者的发现诊断、治疗管理和经济负担进行分析。结果 医防联合体定点医疗机构模式和区县医院定点医疗机构模式下,结核病患者中MDR-TB的发现率分别为9.2%（54/587）和5.4%（37/684）;培阳患者开展传统药物敏感性试验的比率分别为93.9%（460/490）和84.1%（402/478）;MDR-TB患者的治疗覆盖率分别为13.0%（7/54）和59.5%（22/37）;差异均具有统计学意义（χ 2值分别为6.83、23.72、21.86,P值均〈0.05）。治疗成功率分别为5/7和77.3%（17/22）,差异无统计学意义（χ 2=0.10,P〉0.05）。MDR-TB患者承担的人均直接经济负担分别为（28006.90±2.83）元和（26395.70±5.15）元,其中人均自付住院费用（住院费用可报销70%）分别占41.8%（11696.53/28006.90）和40.6%（10719.40/26395.70）。 结论 自贡市部分地区实施分级诊疗在MDR-TB诊治中的整体效果较好,建议重点加强转诊和追踪的管理,提高治疗覆盖率,强化医疗支付方式改革。

2018-2021年四川省自贡市结核病流行病学特征分析

目的了解2018-2021年四川省自贡市结核病的流行特征,比较新冠疫情前后结核病的流行情况,为结核病防控提供依据。方法从结核病管理信息系统收集2018年1月1日-2021年12月31日自贡市报告的结核病患者资料,对资料进行描述性流行病学分析。结果2018-2021年自贡市累计报告结核病5289例,4年报告发病率49.29/10万~55.19/10万,平均52.54/10万。2018、2019及2021年,每年均有2个报告发病高峰,而2020年报告发病高峰集中在9月。所有登记报告患者中,男女患者比例为3.14:1(4010:1279),农民为患者的主要职业(占56.06%),结核性胸膜炎(占肺外结核的69.17%)和糖尿病(占合并症的74.32%)分别是患者最主要的肺外结核和合并症类型。自流井区是自贡市发病率最低的区县,初治患者是自贡市结核病患者的主要治疗类型,初治患者与复治患者之比为14.60:1(4950:339),就诊延迟率较高的是干部职员(74.29%)、复治(73.75%)、因症就诊(74.95%)/因症推荐(78.57%)人群。新冠疫情后,自贡市结核病报告发病率降低,实验室阳性检出率也降低。结论中老年男性及农民是自贡市结核病防治的重点人群。新冠疫情对结核病患者的性别构成影响不大,但新冠疫情可能使结核病隐匿患者增加,因此新冠疫情期间应有针对性地加大对结核病的宣传、教育及筛查力度。

肺肉瘤样癌分子病理学与靶向治疗的研究进展

肺肉瘤样癌是指含有肉瘤或肉瘤样分化成分的非小细胞肺癌,其发病率占非小细胞肺癌总数的2%~3%。肺肉瘤样癌分化极差,具有高度侵袭性,对铂类为基础的化疗不敏感,治疗手段有限,一直是临床研究关注的重点和难点。现有研究发现肺肉瘤样癌中存在多种基因突变,包括TP53、EGFR、KRAS、MET和ALK等,以及高PD-L1阳性率,这些分子病理学特征有望成为肺肉瘤样癌靶向治疗的新希望。本文聚焦于肺肉瘤样癌分子病理学与靶向治疗研究进展作一综述。

Theoretical research and experimental validation of quasi-static load spectra on bogie frame structures of high-speed trains

One of the major problems in structural fatigue life analysis is establishing structural load spectra under actual operating conditions.This study conducts theoretical research and experimental validation of quasi-static load spectra on bogie frame structures of high-speed trains.The quasistatic load series that corresponds to quasi-static deformation modes are identified according to the structural form and bearing conditions of high-speed train bogie frames.Moreover,a force-measuring frame is designed and manufactured based on the quasi-static load series.The load decoupling model of the quasi-static load series is then established via calibration tests.Quasi-static load–time histories,together with online tests and decoupling analysis,are obtained for the intermediate range of the Beijing—Shanghai dedicated passenger line.The damage consistency calibration of the quasi-static discrete load spectra is performed according to a damage consistency criterion and a genetic algorithm.The calibrated damage that corresponds with the quasi-static discrete load spectra satisfies the safety requirements of bogie frames.

Changes of protein oxidation,lipid oxidation and lipolysis in Chinese dry sausage with different sodium chloride curing salt content

The effect of sodium chloride(NaCl)curing salt content on protein oxidation,lipid oxidation and lipolysis of Chinese dry sausage was investigated.Two groups Chinese dry sausages with 2%and 4%(m/m)salt content were studied.The degree of protein oxidation increased during the processes in two groups sausages,while the content of phospholipids decreased,neutral lipids and free fatty acids increased.The degree of protein oxidation,lipid oxidation and lipolysis in 4%NaCl content group was higher than those in 2%NaCl content group,while 4%NaCl content group has higher lipase activity.In conclusion,4%NaCl may facilitate the protein oxidation,lipid hydrolysis and oxidation in Chinese dry sausage,and the protein oxidation had strong correlation with lipid oxidation and lipolysis.The results could provide a basis for improving the technology of industrial production.

Development of volatiles and odor-active compounds in Chinese dry sausage at different stages of process and storage

The effect of process and storage on the volatiles and odorant profi le of Chinese dry sausage was evaluated,as well as its physicochemical parameters.Microbial esterification and wine(27.54%–43.35%),and lipid oxidation(11.30%–34.92%)played a key role in flavor profile during process and storage.A significant increase of each volatile was detected during process except gradual decrease of volatiles from spices,while a gradual decrease of each volatile was detected during storage except signifi cant increase of volatiles from lipid oxidation and esterifi cation.15 and 6 odor-active compounds were respectively correlated(P<0.05)with the process and storage time.Level of heptanal,1-octen-3-ol,the ethyl of 2-methylbutanoic,3-methylbutanoic,butanoic,benzoic,hexanoic,heptanoic,octanoic and decanoic acid were best discriminators of process stage,while(E)-2-nonenal,ethyl hexanoate,ethyl heptanoate,and methyl decanoate,were marker compounds of storage time.An objective method was established to evaluate the stages of process and storage for samples.

Identification of α7 nicotinic acetylcholine receptor on hippocampal astrocytes cultured in vitro and its role on inflammatory mediator secretion

The present study found expressions of a7 nicotinic acetylcholine receptor on hippocampal slices and hippocampal astrocytes using double immunofluorescence stainings. Expression of glial fibdllary acidic protein in the cultured hippocampal slices and hippocampal astrocytes significantly increased, and levels of macrophage inflammatory protein la, RANTES, interleukin-1β, intedeukin-6, and tumor necrosis factor-α increased in the supernatant of cultured astrocytes following exposure to 200 nM amyloid 13 protein 1-42. Preconditioning of 10 μM nicotine, a nicotinic acetylcholine receptor agonist, could attenuate the influence of amyloid β protein 1-42 in inflammatory mediator secretion of cultured astrocytes. Experimental findings indicated that α7 nicotinic acetylcholine receptor was expressed on the surface of hippocampal astrocytes, and activated a7 nicotinic acetylcholine receptor was shown to inhibit inflammation induced by amyloid β protein 1-42.

Redox proteomics of tomato in response to Pseudomonas syringae infection

Unlike mammals with adaptive immunity,plants rely on their innate immunity based on pattern-triggered immunity(PTI)and effector-triggered immunity(ETI)for pathogen defense.Reactive oxygen species,known to play crucial roles in PTI and ETI,can perturb cellular redox homeostasis and lead to changes of redox-sensitive proteins through modification of cysteine sulfhydryl groups.Although redox regulation of protein functions has emerged as an important mechanism in several biological processes,little is known about redox proteins and how they function in PTI and ETI.In this study,cysTMT proteomics technology was used to identify similarities and differences of protein redox modifications in tomato resistant(PtoR)and susceptible(prf3)genotypes in response to Pseudomonas syringae pv tomato(Pst)infection.In addition,the results of the redox changes were compared and corrected with the protein level changes.A total of 90 potential redox-regulated proteins were identified with functions in carbohydrate and energy metabolism,biosynthesis of cysteine,sucrose and brassinosteroid,cell wall biogenesis,polysaccharide/starch biosynthesis,cuticle development,lipid metabolism,proteolysis,tricarboxylic acid cycle,protein targeting to vacuole,and oxidation–reduction.This inventory of previously unknown protein redox switches in tomato pathogen defense lays a foundation for future research toward understanding the biological significance of protein redox modifications in plant defense responses.

Model architecture-oriented combat system effectiveness simulation based on MDE

Combat system effectiveness simulation (CSES) is a special type of complex system simulation. Three non-functional requirements (NFRs), i.e. model composability, domain specific modeling, and model evolvability, are gaining higher priority from CSES users when evaluating different modeling methodologies for CSES. Traditional CSES modeling methodologies are either domain-neutral (lack of domain characteristics consideration and limited support for model composability) or domain-oriented (lack of openness and evolvability) and fall short of the three NFRs. Inspired by the concept of architecture in systems engineering and software engineering fields, we extend it into a concept of model architecture for complex simulation systems, and propose a model architecture-oriented modeling methodology in which the model architecture plays a central role in achieving the three NFRs. Various model-driven engineering (MDE) approaches and technologies, including simulation modeling platform (SMP), unified modeling language (UML), domain specific modeling (DSM), eclipse modeling framework (EMF), graphical modeling framework (GMF), and so forth, are applied where possible in representing the CSES model architecture and its components' behaviors from physical and cognitive domain aspects. A prototype CSES system, called weapon effectiveness simulation system (WESS), and a non-trivial air-combat simulation example are presented to demonstrate the methodology.

Microfluidic reactor with immobilized enzyme-from construction to applications:A review

Microfluidic,as the systems for using microchannel(micron-or sub-micron scale)to process or manipulate microflow,is being widely applied in enzyme biotechnology and biocatalysis.Microfluidic immobilized enzyme reactor(MIER)is a tool with great value for the study of catalytic property and optimal reaction parameter in a flourishing and highly producing manner.In view of its advantages in efficiency,economy,and addressable recognition especially,MIER occupies an important position in the investigation of life science,including molecular biology,bioanalysis and biosensing,biocatalysis etc.Immobilization of enzymes can generally improve their stability,and upon most occasions,the immobilized enzyme is endowed with recyclability.In this review,the enzyme immobilization techniques applied in MIER will be discussed,followed by summarizing the novel developments in the field of MIER for biocatalysis,bioconversion and bioanalysis.The preponderances and deficiencies of the current state-of-the-art preparation ways of MIER are peculiarly discussed.In addition,the prospects of its future study are outlined.

Recyclable polymer functionalization via end-group modification and block/random copolymerization

Recyclable polymers offer a great opportunity to address the environmental issues of plastics.Herein,functionalization of recyclable polymers,poly((R)-3,4-trans six-membered ring-fused GBL)(P((R)-M)),were reported via end-group modifications and block/random copolymerizations.Di-n-butylmagnesium was selected to catalyze ring-opening polymerization(ROP)of(R)-M in the presence of a series of functional alcohols as the initiators.Block/random copolymerizations of(R)-M andε-caprolactone(ε-CL),L-lactide(L-LA)and trimethylene carbonate(TMC)were performed to control the onset decomposition temperature(T_(d)),melting temperature(T_(m))and glass transition temperature(T_(g)).These functionalized recyclable polymers would find broad applications as the sustainable plastics.

Fieldwork Test Research of the Impact on Building Physical Environment on Six Types of Atrium Space in Cold Climates

Since the research on verification to passive design strategies in sustainable building is at the initial stage,and its test method and verification conclusion are not scientific enough to validate,this paper proposes the necessity of building physical environmental monitoring to quantitative optimization of passive strategies efficiency from the perspective of architecture design and building environment. Adopting comparative research method,this research chooses six types of atrium space in cold climate in China as a prototype,focusing on building physical environmental performance difference in and between atrium and building main space. Spatial parameters of the atrium space will be divided into four factors: spatial geometry,interfacial properties,internal and external related categories. With subdividing these four factors into sub-factors,this paper makes crosscomparison among the sub-factors to clarify passive strategies effectiveness in atrium. Data comparison analysis shows that Winter atrium passive strategy in cold regions from traditional view is not obvious in practical application,and test data need to be stratified refined in atrium design in case of optimizing passive strategy from building prototype perspective.

Quantifying impacts of climate and human activities on the grassland in the Three-River Headwater Region after two phases of Ecological Project

The Three-River Headwater Region(TRHR)of China is a typical representative of the alpine environment in the Central Asian plateau and the alpine grassland in the world.Grassland degradation is one of its serious eco-logical problems.The purpose of this study is to quantify the joint impacts of climate and human activities on grassland changes in TRHR after two phases of Ecological Conservation and Construction Project(Ecological Project).Grassland vegetation coverage is selected as an indicator for analyzing grassland changes.We adopt Sen+Mann-Kendall trend analysis,residual trend analysis and correlation analysis methods to analyze the trends in spatial-temporal changes and driving factors of grassland in TRHR from 2000 to 2019.The results show that:(1)The grassland has been mainly restored,and the degraded grassland area only accounts for 1.66%of TRHR.After the implementation of the first phase of the Ecological Project,the percentage of restored grassland area has significantly increased from 8.82%to 24.57%,and slightly decreased during the second phase.(2)The establish-ment of national nature reserves and the implementation of the Ecological Project have changed the situation that“the grassland inside the reserve is worse than that outside the reserve”.(3)Grassland restoration is mainly af-fected by the joint effects of climate and human activities.Nevertheless,grassland degradation is mainly affected by human activities such as overgrazing and grassland reclamation.All of these findings can enrich our under-standing of grassland restoration in TRHR.Artificial measures have certain limitations in promoting grassland restoration.Natural restoration should be considered when human beings strengthen ecological conservation and transform their production and life styles.

基质金属蛋白酶-26在细胞性肝癌中的表达水平与患者临床病理特征的关系

目的研究基质金属蛋白酶-26(matrix metalloproteinase 26,MMP-26)在肝癌中的表达,并分析其与患者临床病理特征的关系。方法收集2016年10月至2017年5月手术切除的新鲜肝癌组织与癌旁组织标本12例,采集肝癌患者和健康志愿者外周血各27例,同时调取肝癌蜡块标本52例。采用实时定量聚合酶链反应(quantitative real-timepolymerase chain reaction,q PCR)、免疫组化和Western-blot法检测MMP-26在癌和相应癌旁组织中的表达。分析MMP-26在肝癌中的表达水平与患者临床病理特征的关系。同时采用ELISA法检测肝癌患者及健康自愿者外周血中MMP-26和甲胎蛋白(AFP)水平,并评估其在肝癌诊断中的价值。结果 MMP-26mRNA在肝癌组织中的相对表达量高于其在癌旁组织中的相对表达量(P <0. 05); MMP-26在肝癌组织中的阳性表达率显著高于癌旁组织(P <0. 05);肝癌组织中MMP-26的表达量显著高于癌旁组织(P <0. 05)。MMP-26在肝癌中的表达水平与肝癌大小和TNM分期显著正相关。MMP-26在肝癌患者外周血中表达水平增高,对肝癌的诊断敏感度和特异度分别为81. 5%和74. 1%; AFP对肝癌的敏感度和特异度分别为70. 4%和77. 8%。这二者并联对肝癌的诊断灵敏度为94. 5%,特异度为53. 9%,而二者串联对肝癌的诊断灵敏度为57. 4%,特异度94. 3%。结论 MMP-26在肝癌中高表达,且其异常表达水平与肿瘤进展有关,MMP-26可能是一个可用于肝癌诊断的分子标志物。

Microfluidic field strategy for enhancement and scale up of liquid-liquid homogeneous chemical processes by optimization of 3D spiral baffle structure

Due to the scale effect, the uniform distribution of reagents in continuous flow reactor becomes bad when the channel is enlarged to tens of millimeters. Microfluidic field strategy was proposed to produce high mixing efficiency in large-scale channel. A 3D spiral baffle structure(3SBS) was designed and optimized to form microfluidic field disturbed by continuous secondary flow in millimeter scale Y-shaped tube mixer(YSTM). Enhancement effect of the 3SBS in liquid-liquid homogeneous chemical processes was verified and evaluated through the combination of simulation and experiment. Compared with 1 mm YSTM, 10 mm YSTM with 3SBS increased the treatment capacity by 100 times, shortened the basic complete mixing time by 0.85 times, which proves the potential of microfluidic field strategy in enhancement and scale-up of liquid-liquid homogeneous chemical process.

Research on Two Types of Buffer Zone Impact on Surrounding Office Space Environment in Winter in Cold Climate Zone—a Fieldwork in Architectural Design Institute Building of Tsinghua University,Beijing

Building buffer zone space is not only one of essential approaches for better mental quality of interior building space, but also an important factor that may influence interior thermal comfort and energy consumption. This study aims to analyze regulative advantages of buffer zone to the surrounding functional spaces. Based on a fieldwork test in a typical office building in cold climate zone in Beijing,China,the monitor data show interior physical performance in the Winter. The research selects two types of different buffer zones in the same building. One is a south-faced greenhouse which has large dimension with plenty of vegetation,and the other is a simple atrium in the middle of five floor building with mount of skylights. The factors and their influence to surrounding functional spaces and the whole building are found out from the comparisons of collected data by floor to floor monitor test on both buffer zones at the same time. The comparisons of two types of buffer zones conclude that the greenhouse is more effective to air quality regulation but not so clearly wellperformed to thermal buffering as expected due to the dominate active central heating in the Winter. This fieldwork test results for building performance can be helpful for both architects and engineers in the early phase of sustainable design.