血尿酸/血肌酐比值与狼疮性肾炎患者肾脏预后的关系

目的:探索狼疮性肾炎患者血尿酸/血肌酐比值与肾脏预后的关系。方法:连续纳入2010年3月1日—2021年3月30日深圳大学第一附属医院肾内科经肾穿刺活检确诊为狼疮性肾炎患者132例。按血尿酸/血肌酐比值中位数二分组。随访终点事件为血清肌酐翻倍或ESRD。随访截止至2021年9月30日。采用Cox回归分析血尿酸/血肌酐比值与肾脏预后关系,Kaplan-Meier生存曲线比较血尿酸/血肌酐比值组间终点事件发生情况,血尿酸、eGFR分组行血尿酸/血肌酐比值与肾脏预后关系的分层分析,并对结果进行交互检验。结果:经过纳排标准后共有99例狼疮性肾炎患者进行分析,截止至本研究终点,平均随访时间(40.3±27)月,13例患者达到随访终点。单因素Cox回归分析提示血尿酸/血肌酐比值与肾脏预后不良呈负相关(HR=0.403,95%CI 0.261,0.622,P<0.001)。多因素Cox回归分析,校正了性别、年龄、收缩压、血红蛋白、血白蛋白、SLEDAI评分、核碎裂、肾小管萎缩、血管纤维素样坏死、初始治疗方案等多个混杂因素后,结果提示血尿酸/血肌酐比值与肾脏预后不良独立负相关(HR=0.468,95%CI 0.245,0.896,P=0.022)。将eGFR分为<90 ml·min^(-1)·1.73 m-2组和≥90 ml·min^(-1)·1.73 m^(-2)组,将血尿酸分为≤420μmol/L组和>420μmol/L组,行分层分析并对结果进行交互检验,结果提示狼疮性肾炎患者伴或不伴高尿酸血症以及伴或不伴肾功能异常对血尿酸/血肌酐比值与肾脏预后关系无影响。结论:血尿酸/血肌酐比值与狼疮性肾炎患者肾脏预后不良独立负相关,基线肾功能水平和血尿酸水平对血尿酸/血肌酐比值与肾脏预后的关系无影响。

血红蛋白浓度与糖尿病肾病患者肾功能相关性分析

目的:探索非透析糖尿病肾病患者血红蛋白浓度与肾功能水平的相关性及可能的影响因素。方法:选取2010年~2019年我院70例非透析糖尿病肾病患者,实际纳入66例,按血红蛋白浓度二分组比较各组患者人口学、生化指标、eGFR及尿蛋白的差异,采用单因素线性回归分析寻找eGFR的影响因素,多重线性回归分析评估血红蛋白浓度是否为eGFR独立影响因素,交互作用检验行糖化血红蛋白的分层分析。结果:与高血红蛋白组相比,低血红蛋白组血清白蛋白浓度、eGFR及糖化血红蛋白值更低,且差异具有统计学意义(均P<0.05)。单因素分析发现收缩压、血红蛋白、糖化血红蛋白是eGFR的影响因素,多因素分析矫正了性别、年龄等多个混杂因素后提示血红蛋白浓度与eGFR独立正相关。交互分析发现糖化血红蛋白较高人群血红蛋白浓度与eGFR相关性更密切。结论:非透析糖尿病肾病患者血红蛋白浓度与肾功能水平呈独立正相关,特别是在糖化血红蛋白较高的人群中。

Climate change characteristics of Amur River

Unusually severe weather is occurring more frequently due to global climate change. Heat waves, rainstorms, snowstorms, and droughts are becoming increasingly common all over the world, threatening human lives and property. Both temperature and precipitation are representative variables usually used to directly reflect and forecast the influences of climate change. In this study, daily data （from 1953 to 1995） and monthly data （from 1950 to 2010） of temperature and precipitation in five regions of the Amur River were examined. The significance of changes in temperature and precipitation was tested using the Mann-Kendall test method. The amplitudes were computed using the linear least-squares regression model, and the extreme temperature and precipitation were analyzed using hydrological statistical methods. The results show the following： the mean annual temperature increased significantly from 1950 to 2010 in the five regions, mainly due to the warming in spring and winter; the annual precipitation changed significantly from 1950 to 2010 only in the lower mainstream of the Amur River; the frequency of extremely low temperature events decreased from 1953 to 1995 in the mainstream of the Amur River; the frequency of high temperature events increased from 1953 to 1995 in the mainstream of the Amur River; and the frequency of extreme precipitation events did not change significantly from 1953 to 1995 in the mainstream of the Amur River. This study provides a valuable theoretical basis for settling disputes between China and Russia on sustainable development and utilization of water resources of the Amur River.

Novel MSX1 variants identified in families with nonsyndromic oligodontia

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants.Whole-exome sequencing(WES)and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia,and a series of bioinformatics databases were used for variant confirmation and functional prediction.Phenotypic characterization of the members of these families was described,and an in vitro analysis was performed for functional evaluation.Five novel MSX1 heterozygous variants were identified:three missense variants[c.662A>C(p.Q221P),c.670C>T(p.R224C),and c.809C>T(p.S270L)],one nonsense variant[c.364G>T(p.G122*)],and one frameshift variant[c.277delG(p.A93Rfs*67)].Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P,p.R224C,p.G122*,and p.A93Rfs*67 variants compared to the wild type.Three variants(p.Q221P,p.G122*,and p.A93Rfs*67)were classified as pathogenic or likely pathogenic,while p.S270L and p.R224C were of uncertain significance in the current data.Moreover,we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss.Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.

Risk factors related to postoperative recurrence of dermatofibrosarcoma protuberans: A retrospective study and literature review

BACKGROUND Dermatofibrosarcoma protuberans(DFSP)is a rare low-grade malignant soft tissue tumor characterized by rosette-like infiltrative growth.Postoperative recurrence of this tumor is very common.AIM To evaluate the risk factors related to recurrence after wide local excision(WLE)of DFSP and to guide clinical diagnosis and treatment.METHODS The medical records of 44 DFSP patients confirmed by pathology at our hospital from 2012 to 2019 were retrospectively reviewed.The relationship between clinical features,tumor characteristics,treatment,and recurrence risk were analyzed,and the possible risk factors for postoperative tumor recurrence were evaluated.RESULTS There were 44 patients in total,including 21 males and 23 females.The median progression free survival was 36 mo(range,1-240 mo).Twenty patients were treated for the first time,while 24 had previous treatment experience.Forty-two cases were followed for 25.76±22.0 mo,among whom four(9.52%)experienced recurrence after WLE(rate was 9.52%).The recurrence rate in the recurrent group was higher than that in the patients with primary tumor(19.05%vs 0%,P=0.028).Eighteen cases had a history of misdiagnosis(rate was 40.91%).The recurrence rate among patients with previous experience of misdiagnosis was significantly higher than in patients without(68%vs 36.84%,P=0.04).The tumor diameter in patients with a history of treatment was larger than in patients treated for the first time(4.75±0.70 cm vs 2.25±0.36 cm,P=0.004).CONCLUSION To sum up,the clinical manifestations of DFSP are not specific and are easily misdiagnosed,thus commonly causing the recurrence of DFSP.After incomplete resection,the tumor may rapidly grow.Previous recurrence history may be a risk factor for postoperative recurrence,and tumor location may have an indirect effect on postoperative recurrence;however,we found no significant correlation between sex,age,course of the disease,or tumor size and postoperative recurrence.

猕猴脑网络组图谱:包含分区、连接和组织学的多层面全新大脑地图

The rhesus macaque(Macaca mulatta)is a crucial experimental animal that shares many genetic,brain organizational,and behavioral characteristics with humans.A macaque brain atlas is fundamental to biomedical and evolutionary research.However,even though connectivity is vital for understanding brain functions,a connectivity-based whole-brain atlas of the macaque has not previously been made.In this study,we created a new whole-brain map,the Macaque Brainnetome Atlas(MacBNA),based on the anatomical connectivity profiles provided by high angular and spatial resolution ex vivo diffusion MRI data.The new atlas consists of 248 cortical and 56 subcortical regions as well as their structural and functional connections.The parcellation and the diffusion-based tractography were evaluated with invasive neuronal-tracing and Nissl-stained images.As a demonstrative application,the structural connectivity divergence between macaque and human brains was mapped using the Brainnetome atlases of those two species to uncover the genetic underpinnings of the evolutionary changes in brain structure.The resulting resource includes:(1)the thoroughly delineated Macaque Brainnetome Atlas(MacBNA),(2)regional connectivity profiles,(3)the postmortem high-resolution macaque diffusion and T2-weighted MRI dataset(Brainnetome-8),and(4)multi-contrast MRI,neuronal-tracing,and histological images collected from a single macaque.MacBNA can serve as a common reference frame for mapping multifaceted features across modalities and spatial scales and for integrative investigation and characterization of brain organization and function.Therefore,it will enrich the collaborative resource platform for nonhuman primates and facilitate translational and comparative neuroscience research.

Tailoring sulfur-doped and nitrogen-defective carbon nitride nanosheets for efficient photo-controlled radical polymerizations

Despite the challenges that remain,the synergistic adjustment of various microstructures and photochemical parameters of graphitic carbon nitride(g-C_(3)N_(4))in photocatalytic reactions holds promises for improving catalytic efficiency and reducing energy consumption.Herein,sulfur-doped and nitrogen-defective g-C_(3)N_(4)(n-SC_(3)N_(x))nanosheets were designed and elaborately synthesized.The resultant n-SC_(3)N_(x)possessed a precisely defined 2D layer structure with extensive porosity and incremental specific surface area.Enhanced photoinduced electron transfer-reversible addition-fragmentation chain transfer(PET-RAFT)polymerization of vinyl monomers with low dispersity,excellent temporal control and high chain-end fidelity was achieved under mild blue light irradiation in a nondegassed system.Owing to their ultrathin nanostructures with nitrogen defects and sulfur dopants,n-SC_(3)N_(x)was capable of catalyzing RAFT polymerization in aqueous solutions at significantly accelerated rates,which were nearly 8 times faster compared to bulk g-C_(3)N_(4).The ease of separation and efficient reusability in subsequent polymerizations was enabled by the heterogeneous nature of n-SC_(3)N_(x).The appeal of this approach was illustrated by the fact that utilizing a reusable and metal-free photocatalyst in aqueous environments allowed for the synthesis of polymers with molecular weight up to 300 kg mol^(-1) and a dispersity of 1.32.

Subnanometric bimetallic Pt-Pd clusters in zeolites for efficient hydrogen production and selective tandem hydrogenation of nitroarenes

The solvolysis of ammonia borane(AB)and the hydrogenation of nitroarenes represent significant reactions for hydrogen generation and value-added chemical synthesis.The strategic engineering of the catalysts is imperative for surmounting obstacles associated with their stability and catalytic efficiency.In this work,subnanometric bimetallic Pt–Pd clusters were encapsulated within silicalite-1(S-1)zeolites through a ligand-protected in-situ hydrothermal synthesis method.The synergetic effect of bimetallic composition and zeolite confinement markedly enhances the catalytic performance of representative Pt_(0.5)Pd_(0.5)@S-1-H catalyst,affording exceptional turnover frequency(TOF)values of 1,043 and 573 mol_(H_(2))mol_(metal)^(-1)min^(-1)for AB hydrolysis and methanolysis at ambient conditions,respectively,surpassing most of the state-of-the-art Pt-based catalysts.Kinetic and isotopic experiments reveal that the bimetallic catalytic system remarkably boosts the O-H cleavage of water,thereby facilitating the H_(2) production from AB hydrolysis.Remarkably,a conspicuous synergistic effect is demonstrated in the shape-selective tandem hydrogenation of nitroarenes,with the bimetallic catalyst facilitating both AB hydrolysis and nitroarene hydrogenation,giving a high TOF value of 1,260 h^(-1)under atmospheric pressure.This study not only demonstrates the effectiveness of bimetallic nanocatalysts encapsulated in zeolites for hydrogen production from chemical hydrogen storage materials,but also paves the way for the design of catalysts with multifunctional active sites capable of synergistically promoting tandem catalytic processes.

Engineering of cofactor preference and catalytic activity of methanol dehydrogenase by growth-coupled directed evolution

Methanol,produced from carbon dioxide,natural gas,and biomass,has drawn increasing attention as a promising green carbon feedstock for biomanufacturing due to its sustainable and energy-rich properties.Nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(MDH)catalyzes the oxidation of methanol to formaldehyde via NADH generation,providing a highly active C1 intermediate and reducing power for subsequent biosynthesis.However,the unsatisfactory catalytic efficiency and cofactor bias of MDH significantly impede methanol valorization,especially in nicotinamide adenine dinucleotide phosphate(NADP^(+))-dependent biosynthesis.Herein,we employed synthetic NADH and NADPH auxotrophic Escherichia coli strains as growth-coupled selection platforms for the directed evolution of MDH from Bacillus stearothermophilus DSM 2334.NADH or NADPH generated by MDH-catalyzed methanol oxidation enabled the growth of synthetic cofactor auxotrophs,establishing a positive correlation between the cell growth rate and MDH activity.Using this principle,MDH mutants exhibiting a 20-fold improvement in catalytic efficiency(k_(cat)/K_(m))and a 90-fold cofactor specificity switch from NAD^(+)to NADP+without a decrease in specific enzyme activity,were efficiently screened from random and semi-rationally designed libraries.We envision that these mutants will advance methanol valorization and that the synthetic cofactor auxotrophs will serve as versatile selection platforms for the evolution of NAD(P)^(+)-dependent enzymes.

基于多任务学习的同行评审论文接收预测

同行评审论文接收预测是一项具有重要意义的任务,其有效提升了同行评审的效率和质量。以往的同行评审论文接收预测方法大多以单任务的形式研究,并未充分利用论文评分等其它辅助信息,同时也未有效提取同行评审文本的语义特征。针对上述问题,文中提出了一种多任务同行评审文本分析模型BCLJ(BERT-CNN-LSTM-Joint Model,BCLJ)。首先,使用BERT作为词向量获得文本的矩阵表示;然后,引入卷积神经网络(Convolutional Neural Network,CNN)和长短期记忆网络(Long Short-Term Memory Network,LSTM)进行语义特征的提取,并运用注意力机制增强对文本信息的理解能力;最后,利用不同的全连接层进行多任务学习,获得论文接受预测和评分预测两种输出,通过评分预测任务来优化主分类任务。实验结果表明,多任务模型在论文接收预测任务和评分预测任务中表现出色高于其他的基线模型,在论文接收预测任务中准确率达到了0.7117,F1值达到了0.7101,在论文评分预测任务中MSE,RMSE和MAE分别为1.3690,1.1700和0.9324。

二氧化碳到己糖的人工合成

土地短缺及环境恶化导致依赖光合作用的糖制造技术面临诸多挑战.当前人工CO_(2)-糖合成技术在立体选择性转化、降低能量消耗、扩展产物谱等方面亟待突破.本文设计了低ATP消耗、路线短且普适性强的CO_(2)-糖路线,能量转化效率高于传统制糖方法.结合酶工程技术获得了催化性能优异的酶元件,构建了化学-酶转化体系,实现转化CO_(2)合成葡萄糖、阿洛酮糖等己糖分子,具有较高的产物选择性和碳转化率,CO_(2)-糖合成效率为目前报道最高水平.本研究为创制结构多样性糖及其衍生物,解决人类食糖与健康、工业发酵等糖需求提供蓝图和方案.

Directed evolution of a neutrophilic and mesophilic methanol dehydrogenase based on high-throughput and accurate measurement of formaldehyde

Methanol is a promising one-carbon feedstock for biomanufacturing,which can be sustainably produced from carbon dioxide and natural gas.However,the efficiency of methanol bioconversion is limited by the poor catalytic properties of nicotinamide adenine dinucleotide(NAD^(+))-dependent methanol dehydrogenase(Mdh)that oxidizes methanol to formaldehyde.Herein,the neutrophilic and mesophilic NAD^(+)-dependent Mdh from Bacillus stearothermophilus DSM 2334(Mdh_(Bs))was subjected to directed evolution for enhancing the catalytic activity.The combination of formaldehyde biosensor and Nash assay allowed high-throughput and accurate measurement of formaldehyde and facilitated efficient selection of desired variants.Mdh_(Bs)variants with up to 6.5-fold higher K_(cat)/K_(M)value for methanol were screened from random mutation libraries.The T153 residue that is spatially proximal to the substrate binding pocket has significant influence on enzyme activity.The beneficial T153P mutation changes the interaction network of this residue and breaks theα-helix important for substrate binding into two shortα-helices.Reconstructing the interaction network of T153 with surrounding residues may represent a promising strategy to further improve Mdh_(Bs),and this study provides an efficient strategy for directed evolution of Mdh.

NEHASH:high-concurrency extendible hashing for non-volatile memory

Extendible hashing is an effective way to manage increasingly large file system metadata,but it suffers from low concurrency and lack of optimization for non-volatile memory(NVM).In this paper,a multilevel hash directory based on lazy expansion is designed to improve the concurrency and efficiency of extendible hashing,and a hash bucket management algorithm based on groups is presented to improve the efficiency of hash key management by reducing the size of the hash bucket,thereby improving the performance of extendible hashing.Meanwhile,a hierarchical storage strategy of extendible hashing for NVM is given to take advantage of dynamic random access memory(DRAM)and NVM.Furthermore,on the basis of the device driver for Intel Optane DC Persistent Memory,the prototype of high-concurrency extendible hashing named NEHASH is implemented.Yahoo cloud serving benchmark(YCSB)is used to test and compare with CCEH,level hashing,and cuckoo hashing.The results show that NEHASH can improve read throughput by up to 16.5%and write throughput by 19.3%.

Genomic landscapes of Chinese sporadic autism spectrum disordersrevealed by whole-genome sequencing

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.

Effectiveness and impact of the crossborder healthcare model as implemented by non-governmental organizations: case study of the malaria control programs by health poverty action on the ChinaMyanmar border

Background:In the Yunnan province of China,18 counties in six prefectures border Myanmar.Due to its particular combination of geographic features,climate conditions,and cultural landscape,the area provides a suitable environment for the spread of insect-borne diseases such as malaria.In five identified Myanmar Special Regions along the China-Myanmar border,economic development is lagging,people live in extreme poverty,and the healthcare system is fragile.Coupled with political and other reasons,this precludes malaria control work to be effectively carried out in Myanmar,resulting in a heavy burden of the disease.Frequent population movements and favorable conditions for malaria transmission on the border fuel difficulties in controlling and eliminating the spread of the disease in the area.Case presentation:To reduce the prevalence of malaria in the China-Myanmar border area and improve healthcare services for local residents in this particular environment,Health Poverty Action(HPA)has provided malaria aid in the area since the beginning of 2006,as a sub-recipient of the China Global Fund Malaria Programs.In this case study,we examined HPA’s activities as part of its malaria control programs in the area,analyzed and summarized the effectiveness and impact of the cross-border healthcare model as implemented by non-governmental organizations,and put forward suggestions for cross-border health aid models and for the prevention of malaria transmission in the Greater Mekong Subregion.Conclusions:HPA had carried out a great quantity of successful malaria control activities in border areas between China and Myanmar,strengthened the partnership and established the collaboration,coordination and cooperation channels among stakeholders.HPA has laid good groundwork and developed its valuable model that could be highlighted and referenced.

RANS simulations on combustion and emission characteristics of a premixed NH_(3)/H_(2) swirling flame with reduced chemical kinetic model

Ammonia(NH_(3))is considered as a potential alternative carbon free fuel to reduce greenhouse gas emission to meet the increasingly stringent emission requirements.Co-burning NH_(3) and H_(2) is an effective way to overcome ammonia’s relative low burning velocity.In this work,3D Reynolds Averaged Navier-Stokes(RANS)numerical simulations are conducted on a premixed NH_(3)/H_(2) swirling flame with reduced chemical kinetic mechanism.The effects of(A)overall equivalence ratio Φ and(B)hydrogen blended molar fraction XH2 on combustion and emission characteristics are examined.The present results show that when 100%NH_(3)-0%H_(2)-air are burnt,the NO emission and unburned NH3 of at the swirling combustor outlet has the opposite varying trends.With the increase of Φ,NO emission is found to be decreased,while the unburnt ammonia emission is increased.NH_(2)→HNO,NH→HNO and HNO→NO sub-paths are found to play a critical role in NO formation.Normalized reaction rate of all these three sub-paths is shown to be decreased with increased Φ.Hydrogen addition is shown to significantly increase the laminar burning velocity of the mixed fuel.However,adding H_(2) does not affect the critical equivalence ratio corresponding to the maximum burning velocity.The emission trend of NO and unburnt NH_(3) with increased Φ is unchanged by blending H_(2).NO emission with increased X_(H2) is increased slightly less at a larger Φ than that at a smaller Φ.In addition,reaction rates of NH_(2)→HNO and HNO→NO sub-paths are decreased with increased X_(H2),when Φ is larger.Under all tested cases,blending H_(2) with NH_(3) reduces the unburned NH_(3) emission,especially for rich combustion conditions.In summary,the present work provides research finding on supporting applying ammonia with hydrogen blended in low-emission gas turbine engines.

Lessons on malaria control in the ethnic minority regions in Northern Myanmar along the China border, 2007–2014

Background:For many countries where malaria is endemic,the burden of malaria is high in border regions.In ethnic minority areas along the Myanmar-China border,residents have poor access to medical care for diagnosis and treatment,and there have been many malaria outbreaks in such areas.Since 2007,with the support of the Global Fund to Fight AIDS,Tuberculosis and Malaria(GFATM),a malaria control project was introduced to reduce the malaria burden in several ethnic minority regions.Methods:A malaria control network was established during the period from 2007 to 2014.Multiple malaria interventions,including diagnosis,treatment,distribution of LLINs and health education,were conducted to improve the accessibility and quality of malaria control services for local residents.Annual cross-sectional surveys were conducted to evaluate intervention coverage and indicators of malaria transmission.Results:In ethnic minority regions where a malaria control network was established,both the annual malaria incidence(19.1 per thousand per year,in 2009;8.7,in 2014)and malaria prevalence(13.6%in 2008;0.43%in 2014)decreased dramatically during the past 5–6 years.A total of 851393 febrile patients were detected,202598 malaria cases(including confirmed cases and suspected cases)were treated,and 759574 LLINs were delivered to populations at risk.Of households in 2012,73.9%had at least one ITNs/LLINs(vs.28.3%,in 2008),and 50.7%of children less than 5 years and 50.3%of pregnant women slept under LLINs the night prior to their visit.Additionally,malaria knowledge was improved in 68.4%of residents.Conclusion:There has been great success in improving malaria control in these regions from 2007 to 2014.Malaria burdens have decreased,especially in KOK and WA.The continued maintenance of sustainable malaria control networks in these regions may be a long-term process,due to regional conflicts and the lack of funds,technology,and health workers.Furthermore,information and scientific support from the international community should be offered to these ethnic minority regions to uphold recent achievements.

The Splicing Factor PRP31 Is Involved in Transcriptional Gene Silencing and Stress Response in Arabidopsis

Although DNA methylation is known to play an important role in the silencing of transposable elements （TEs） and introduced transgenes, the mechanisms that generate DNA methylation-independent transcrip- tional silencing are poorly understood. Previous studies suggest that RNA-directed DNA methylation （RdDM） is required for the silencing of the RD29A-LUC transgene in the Arabidopsis rosl mutant back- ground with defective DNA demethylase. Loss of function of ARGONAUTE 4 （AGO4） gene, which encodes a core RdDM component, partially released the silencing of RD29A-LUC in the rosl/ago4 double mutant plants. A forward genetic screen was performed to identify the mutants with elevated RD29A-LUC trans- gene expression in the rosl/ago4 mutant background. We identified a mutation in the homologous gene of PRP31, which encodes a conserved pre-mRNA splicing factor that regulates the formation of the U4/ U6.U5 snRNP complex in fungi and animals. We previously demonstrated that the splicing factors ZOP1 and STA1 contribute to transcriptional gene silencing. Here, we reveal that Arabidopsis PRP31 associates with ZOP1, STA1, and several other splicing-related proteins, suggesting that these splicing factors are both physically and functionally connected. We show that Arabidopsis PRP31 participates in transcrip- tional gene silencing. Moreover, we report that PRP31, STA1, and ZOP1 are required for development and stress response. Under cold stress, PRP31 is not only necessary for pre-mRNA splicing but also for regulation of cold-responsive gene expression. Our results suggest that the splicing machinery has multiple functions including pre-mRNA splicing, gene regulation, transcriptional gene silencing, and stress response.

MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution

Organisms and cells,in response to environmental influences or during development,undergo considerable changes in DNA methylation on a genome-wide scale,which are linked to a variety of biological processes.Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly.In this study,we develop a novel approach,named MBRidge,to detect the methylation levels of repertoire CpGs,by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis.A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation(R>0.90)with much less cost(∼10%)in comparison with MethylC-seq.We further applied MBRidge to profiling DNA methylome in T29H,an oncogenic counterpart of T29’s.By comparing methylomes of T29H and T29,we identified 131790 differential methylation regions(DMRs),which are mainly enriched in carcinogenesis-related pathways.These are substantially different from7567 DMRs that were obtained by RRBS and related with cell development or differentiation.The integrated analysis ofDMRsin the promoterand expression of DMR-corresponding genes revealed thatDNAmethylation enforced reverse regulation of gene expression,depending on the distance fromthe proximalDMRto transcription starting sites in both mRNA and lncRNA.Taken together,our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.