脊髓性肌萎缩症SMN1基因2+0基因型携带者的家系研究

脊髓性肌萎缩症(spinal muscular atrophy, SMA)是一种儿童时期较为常见的神经肌肉病,属于常染色体隐性遗传。绝大多数SMA由运动神经元存活基因1 (survival motor neuron 1, SMN1)的纯合缺失突变所致。而SMN1的2+0基因型个体作为一种特殊的SMA携带者,给携带者筛查以及家系的遗传咨询带来了巨大的挑战。已有研究表明,g.27134T>G和g.27706_27707delAT多态位点变异对于Ashkenazi犹太人群中的2+0基因型个体具有提示作用。为进一步探究这两个多态位点是否在中国人群也具有特异性,本研究纳入了44例家系成员和204例已知SMN1基因拷贝数的对照样本。44例家系成员来自于9个无关的SMN1基因纯合缺失的SMA家系,先证者双亲之一疑似为2+0基因型携带者。利用多重连接探针扩增(multiplex ligation-dependent probe amplification,MLPA)和短串联重复(short tandem repeat, STR)连锁分析进行基因型的鉴定以及多态位点的筛查,最终通过对家系三代成员或多子女家系两代成员的分析确定了9个家系中的10例个体为2+0基因型携带者,多态位点筛查显示1例携带3拷贝SMN1基因的个体同时存在g.27134T>G和g.27706_27707delAT多态位点的变异。因此,本研究通过对2+0基因型携带者的鉴定,为家系遗传病的诊断提供了精准的遗传咨询。g.27134T>G和g.27706_27707delAT多态位点可能与中国人群2+0基因型个体的关联度较低,尚需寻找中国人群特异的多态位点以提高2+0基因型携带者的检出率。

NMD逃逸机制及其在疾病治疗中的应用

无义介导的mRNA降解(nonsense-mediated mRNA decay, NMD)是指在病理或正常生理情况下mRNA上出现了提前终止密码子(premature termination codon, PTC),从而导致mRNA降解。它是一种广泛存在的mRNA质量监控机制。近年来,在多种疾病中发现某些PTC并未触发NMD,这种现象被称为NMD逃逸(NMD escape),然而其确切机制尚不十分清楚。目前公认的两个学说为:(1) PTC通读,即蛋白的翻译可以顺利通过PTC直至正常的终止密码子,产生全长蛋白;(2)翻译的重新启动,即蛋白翻译在PTC下游的潜在起始点重新开始直至终止密码子,产生N端截短蛋白。目前,通过利用PTC通读,越来越多的药物或小分子已被成功用于无义变异相关疾病的治疗。本文主要综述了NMD逃逸的机制及其在疾病治疗中的应用和进展,以期为进一步了解NMD逃逸及其相关应用概况提供参考。

Discriminative explicit instance selection for implicit discourse relation classification

Discourse relation classification is a fundamental task for discourse analysis,which is essential for understanding the structure and connection of texts.Implicit discourse relation classification aims to determine the relationship between adjacent sentences and is very challenging because it lacks explicit discourse connectives as linguistic cues and sufficient annotated training data.In this paper,we propose a discriminative instance selection method to construct synthetic implicit discourse relation data from easy-to-collect explicit discourse relations.An expanded instance consists of an argument pair and its sense label.We introduce the argument pair type classification task,which aims to distinguish between implicit and explicit argument pairs and select the explicit argument pairs that are most similar to natural implicit argument pairs for data expansion.We also propose a simple label-smoothing technique to assign robust sense labels for the selected argument pairs.We evaluate our method on PDTB 2.0 and PDTB 3.0.The results show that our method can consistently improve the performance of the baseline model,and achieve competitive results with the state-of-the-art models.

纳米酶

纳米酶(Nanozymes)是由我国科学家首次提出的新概念,它是一类具有生物催化功能的纳米材料,能够基于特定的纳米结构催化天然酶的底物并作为酶的代替品。自2007年首次报道以来,全球已有来自于55个国家的420多个研究机构证实了纳米酶的普遍规律。纳米酶的发现第一次揭示纳米材料蕴含一种独特的纳米效应———类酶催化效应。纳米酶作为一种新材料,既有纳米材料本身的理化性质,又有类似酶的催化功能,兼具天然酶与人工酶的优势于一身。其中,纳米结构不仅赋予纳米酶高效催化功能,而且使纳米酶比天然酶稳定,易于规模化生产。另外,纳米酶独特的多酶活性将为设计廉价、稳定、各种各样全新的催化级联反应提供功能分子。纳米酶是多学科交叉融合的典范,2022年被IUPAC评为十大化学新兴技术。在全球从事化学、酶学、材料学、生物学、医学、理论计算等多领域科学家的共同推进下,如今纳米酶已经成为新的研究热点。我国科学家在这一新兴领域一直发挥着引领作用,解析了纳米酶的构⁃效关系,将其催化活性提高了约1万倍,实现了超越天然酶的理性设计,创造了全球首个纳米酶产品,出版了纳米酶学英文专著,发布纳米酶术语及中国/国际标准化。更可喜的是,纳米酶新领域汇集了一大批多学科交叉融合的优秀青年科学家,推动纳米酶进入高速发展阶段,纳米酶的种类已经超过1200多种,其催化机制研究也更加深入,应用研究也从当初的检测逐步拓展到纳米酶催化医学、传感检测、绿色合成、新能源、环境治理等多个领域。本文向读者介绍纳米酶自发现以来的主要进展,包括最近发现的天然纳米酶,期待纳米酶从新概念、新材料衍生出新技术、新产品、新商品,服务人类健康,并带动新学科发展。

Review of the influencing factors of secondary organic aerosol formation and aging mechanism based on photochemical smog chamber simulation methods

The formation and aging mechanism of secondary organic aerosol(SOA)and its influencing factors have attracted increasing attention in recent years because of their effects on climate change,atmospheric quality and human health.However,there are still large errors between air quality model simulation results and field observations.The currently undetected components during the formation and aging of SOA due to the limitation of current monitoring techniques and the interactions among multiple SOA formation influencing factors might be the main reasons for the differences.In this paper,we present a detailed review of the complex dynamic physical and chemical processes and the corresponding influencing factors involved in SOA formation and aging.And all these results were mainly based the studies of photochemical smog chamber simulation.Although the properties of precursor volatile organic compounds(VOCs),oxidants(such as OH radicals),and atmospheric environmental factors(such as NOx,SO2,NH3,light intensity,temperature,humidity and seed aerosols)jointly influence the products and yield of SOA,the nucleation and vapor pressure of these products were found to be the most fundamental aspects when interpreting the dynamics of the SOA formation and aging process.The development of techniques for measuring intermediate species in SOA generation processes and the study of SOA generation and aging mechanism in complex systems should be important topics of future SOA research.

Prospect of China's ambient air quality standards

Ambient air quality standards are the core strategic goal of ambient air quality management.Countries worldwide have given importance to research on the development of ambient air quality standards.To understand the history of the development of China’s ambient air quality standards,this study analyzed the background associated with all previous formulations and revisions of the standards,classification of functional areas,standard grading,pollutants,and evolution of the standard limits over the past 40 years.The results show that since the initial release of the“Ambient Air Quality Standard”by China in 1982,it has been supplemented once,revised twice,and modified twice.The first ambient air quality standard specified the standard limits of six pollutants commonly found in ambient air.With the development of ambient air quality management,the number of pollutants has increased to ten.Since the release of the“Ambient Air Quality Standards”in 2012,the ambient air quality in China has significantly improved.However,the proportion of cities meeting these standards is still low.At present,China is suitably positioned to make the standards associated with 24 hr SO2concentrations more stringent such that it meets the values defined in the World Health Organization(WHO)interim target-2 and the WHO air quality guideline(AQG).We further suggested that the SO2standard should be revised promptly.Simultaneously,regions with a relatively high proportion of cities meeting the standard are encouraged to introduce more stringent interim target limits in due course to manage the local ambient air quality.

Developing China's roadmap for air quality improvement:A review on technology development and future prospects

Air pollution control policies in China have been experiencing profound changes,highlighting a strategic transformation from total pollutant emission control to air quality improvement,along with the shifting targets starting from acid rain and NO_(x)emissions to PM_(2.5)pollution,and then the emerging O_(3)challenges.The marvelous achievements have been made with the dramatic decrease of SO_(2)emission and fundamental improvement of PM_(2.5)concentration.Despite these achievements,China has proposed Beautiful China target through 2035 and the goal of 2030 carbon peak and 2060 carbon neutrality,which impose stricter requirements on air quality and synergistic mitigation with Greenhouse Gas(GHG)emissions.Against this background,an integrated multi-objective and multi-benefit roadmap is required to provide decision support for China’s long-term air quality improvement strategy.This paper systematically reviews the technical system for developing the air quality improvement roadmap,which was integrated from the research output of China’s National Key R&D Program for Research on Atmospheric Pollution Factors and Control Technologies(hereafter Special NKP),covering mid-and long-term air quality target setting techniques,quantitative analysis techniques for emission reduction targets corresponding to air quality targets,and pathway optimization techniques for realizing reduction targets.The experience and lessons derived from the reviews have implications for the reformation of China’s air quality improvement roadmap in facing challenges of synergistic mitigation of PM_(2.5)and O_(3),and the coupling with climate change mitigation.

Preface

The serious air pollution problems in China have significantly affected the development of China’s economy and society,especially in key areas such as Beijing-Tianjin-Hebei,Yangtze River Delta,and Pearl River Delta,which has aroused widespread concern throughout society.With the launch of the MOST(Ministry Of Science and Technology)key project for Air Pollution Formation Mechanism and Control Technology during the 13thFive-Year Plan.

Data quality evaluation and calibration of on-road remote sensing systems based on exhaust plumes

In recent years,with rapid increases in the number of vehicles in China,the contribution of vehicle exhaust emissions to air pollution has become increasingly prominent.To achieve the precise control of emissions,on-road remote sensing(RS)technology has been developed and applied for law enforcement and supervision.However,data quality is still an existing issue affecting the development and application of RS.In this study,the RS data from a cross-road RS system used at a single site(from 2012 to 2015)were collected,the data screening process was reviewed,the issues with data quality were summarized,a new method of data screening and calibration was proposed,and the effectiveness of the improved data quality control methods was finally evaluated.The results showed that this method reduces the skewness and kurtosis of the data distribution by up to nearly 67%,which restores the actual characteristics of exhaust diffusion and is conducive to the identification of actual clean and high-emission vehicles.The annual variability of emission factors of nitric oxide decreases by 60%-on average-eliminating the annual drift of fleet emissions and improving data reliability.

Comprehensive evaluation method of urban air quality statistics based on environmental monitoring data and its application

Air quality monitoring is effective for timely understanding of the current air quality status of a region or city.Currently,the huge volume of environmental monitoring data,which has reasonable real-time performance,provides strong support for in-depth analysis of air pollution characteristics and causes.However,in the era of big data,to meet current demands for fine management of the atmospheric environment,it is important to explore the characteristics and causes of air pollution from multiple aspects for comprehensive and scientific evaluation of air quality.This study reviewed and summarized air quality evaluation methods on the basis of environmental monitoring data statistics during the 13th Five-Year Plan period,and evaluated the level of air pollution in the Beijing-Tianjin-Hebei region and its surrounding areas(i.e.,the“2+26”region)during the period of the three-year action plan to fight air pollution.We suggest that air quality should be comprehensively,deeply,and scientifically evaluated from the aspects of air pollution characteristics,causes,and influences of meteorological conditions and anthropogenic emissions.It is also suggested that a threeyear moving average be introduced as one of the evaluation indexes of long-term change of pollutants.Additionally,both temporal and spatial differences should be considered when removing confounding meteorological factors.

Evaluating cost and benefit of air pollution control policies in China:A systematic review

China has put great efforts into air pollution control over the past years and recently committed to its most ambitious climate target.Cost and benefit analysis has been widely used to evaluate the control policies in terms of past performance,future reduction potential,and direct and indirect impacts.To understand the cost and benefit analysis for air pollution control in China,we conducted a bibliometric review of more than 100 studies published over the past two decades,including the current research progress,most commonly adopted methods,and core findings.The control target in cost and benefit analysis has shifted in three stages,from individual and primary pollution control,moving to joint prevention of multiple and secondary pollutants,and then towards synergistic control of air pollution and carbon.With the expansion of the research scope,the integrated assessment model has gradually demonstrated the necessity for long-term ex-anti policy simulation,especially for dealing with complex factors.To ensure long-term air quality,climate,public health,and sustainable economic development,substantial evidence from published studies has suggested that China needs to continue its efforts in the upstream adjustment of the energy system and industrial structure with multi-regional and-sector collaboration.This cost and benefit review paper provides decision-makers with the fundamental information and knowledge gaps in air pollution control strategies in China,and direction for facing future challenges.

Ambient volatile organic compounds pollution in China

Owing to rapid economic and industrial development, China has been suffering from degraded air quality and visibility. Volatile organic compounds （VOCs） are important precursors to the formation of ground-level ozone and hence photochemical smog. Some VOCs adversely affect human health. Therefore, VOCs have recently elicited public concern and given new impetus to scientific interest. China is now implementing a series of polices to control VOCs pollution. The key to formulating policy is understanding the ambient VOCs pollution status. This paper mainly analyzes the species, levels, sources, and spatial distributions of VOCs in ambient air. The results show that the concentrations of ambient VOCs in China are much higher than those of developed countries such as the United States and Japan, especial benzene, which exceeds available standards. At the same time, the ozone formation potential （OFP） and secondary organic aerosol formation potential （SOAFP） of various VOCs are calculated. Aromatics and alkenes have much higher OFPs, while aromatics have higher SOAFP. The OFPs of ambient VOCs in the cities of Beijing, Guangzhou and Changchun are very high, and the SOAFP of ambient VOCs in the cities of Hangzhou, Guangzhou and Changchun are higher.

RHOBTB2 gene associated epilepsy and paroxysmal movement disorder:two cases report and literature review

Background:RHOBTB2 gene is associated with developmental and epileptic encephalopathy-64(DEE-64),which is characterized by epilepsy,developmental delay,microcephaly,unspecific facial dysmorphism,and paroxysmal movement disorders.Most previous studies showed that the phenotypes of RHOBTB2 gene include developmental and epileptic encephalopathy(DEE)and DEE with paroxysmal movement disorders.Only one study showed that patient with RHOBTB2 variant had paroxysmal movement disorders with no epilepsy.Case presentations:Two cases with RHOBTB2 variants are presented here:Case one was diagnosed as DEE,he had recurrent afebrile focal status epilepticus and paroxysmal extrapyramidal symptoms in infancy.Interictal electroencephalogram(EEG)showed focal discharges.Brain magnetic resonance imaging(MRI)showed cortical dysplasia.Epilepsy of case one was refractory.Nevertheless,case two only showed paroxysmal movement disorders alone in adolescence.Video EEG showed focal discharges during an interictal dystonic episode and he brain MRI was normal.Conclusion:The phenotypes of RHOBTB2 gene include DEE,paroxysmal movement disorders,and DEE with paroxysmal movement disorders.RHOBTB2 can be one of the pathogenic genes of paroxysmal movement disorders.

Modeling of spatial and temporal variations of ozone-NO_(x)-VOC sensitivity based on photochemical indicators in China

Comprehensive air quality model with extensions(CAMx)-decoupled direct method(DDM)was used to simulate ozone-NO_(x)-VOCs sensitivity of for May-November in 2016-2018 in China.Based on the relationship between the simulated ozone(O_(3))sensitivity values and the ratio of formaldehyde(HCHO)to NO_(2)(FNR)and the ratio of production rate of hydrogen peroxide(H_(2)O_(2))to production rate of nitric acid(HNO_(3))(P_(H_(2)O_(2))/P_(HNO_(3))),the localized range of FNR and P_(H_(2)O_(2))/P_(HNO_(3))thresholds in different regions in China were obtained.The overall simulated FNR values are about 1.640-2.520,and P_(H_(2)O_(2))/P_(HNO_(3))values are about 0.540-0.830 for the transition regime.Model simulated O_(3)sensitivities or region specific FNR or P_(H_(2)O_(2))/P_(HNO_(3))thresholds should be applied to ensure the accurate local O3 sensitivity regimes.Using the tropospheric column FNR values from ozone monitoring instrument(OMI)satellite data as an indicator with the simulated threshold values,the spatial distributions of O_(3)formation regimes in China are determined.The O_(3)sensitivity regimes from eastern to central China are gradually from VOC-limited,transition to NO_(x)-limited spatially,and moving toward to transition or NO_(x)-limited regime from 2005 to 2019 temporally.

Unconventional piezoelectric coefficients in perovskite piezoelectric ceramics

Piezoelectric ceramics exhibit three conventional piezoelectric coefficients,i.e.,d33,d31,d15,due to their∞mm crystal symmetry.Unconventional piezoelectric coefficients,such as d11,d12,d13,d14,d16,etc.,can only be extracted from piezoelectric single crystals of special symmetry with specific cut direction.Here we demonstrate a rotated poling method to realize unconventional piezoelectric coefficients in perovskite piezoelectric ceramics.This method is elaborated in theory and experimentally proven to be effective.Full nonzero piezoelectric coefficients in the 36 piezoelectric coefficients matrix can be obtained by combining these“quasi(effective)piezoelectric coefficients”with the conventional piezoelectric coefficients,which would expand applications in a wide variety of piezoelectric devices.