发现驱动中医药研究的新范式

发挥中医药原创优势、推动我国生命科学实现创新突破是国家需求,但如何挖掘中医药的原创优势,还需要进一步提升思想认知,用现代科学解读中医药学原理。本文在建国以来中医药实证性研究的基础上,正本清源,传承精华,厘清中医学中未加工事实与理性推演之间的关系,发现其中的科学事实;阐幽明微,守正创新,应用现代科学技术,发现中医理论与效应的独特原创优势,从中医出发为医学与生命科学做贡献,解决生物医药“卡脖子”问题两方面,面向未来,列举例证,发现驱动中医药研究的新范式:在厘清古籍医学事实、明确中医药临床效应的基础上,深入研究中国医学中尚不能被现代医学解释的独特生物学现象和过程,以期揭示新的生理现象、阐释新的病理机制、创建新的治疗策略,更加充分地发挥中医药原创优势,推动我国生物医学实现创新突破。

Methylene blue intercalated vanadium oxide with synergistic energy storage mechanism for highly efficient aqueous zinc ion batteries

With the rise of aqueous multivalent rechargeable batteries,inorganic-organic hybrid cathodes have attracted more and more attention due to the complement of each other’s advantages.Herein,a strategy of designing hybrid cathode is adopted for high efficient aqueous zinc-ion batteries(AZIBs).Methylene blue(MB)intercalated vanadium oxide(HVO-MB)was synthesized through sol-gel and ion exchange method.Compared with other organic-inorganic intercalation cathode,not only can the MB intercalation enlarge the HVO interlayer spacing to improve ion mobility,but also provide coordination reactions with the Zn^(2+)to enhance the intrinsic electrochemical reaction kinetics of the hybrid electrode.As a key component for the cathode of AZIBs,HVO-MB contributes a specific capacity of 418 mA h g^(-1) at 0.1 A g^(-1),high rate capability(243 mA h g^(-1) at 5 A g^(-1))and extraordinary stability(88%of capacity retention after 2000cycles at a high current density of 5 A g^(-1))in 3 M Zn(CF_(3)SO_(3))_(2) aqueous electrolyte.The electrochemical kinetics reveals HVO-MB characterized with large pseudocapacitance charge storage behavior due to the fast ion migration provided by the coordination reaction and expanded interlayer distance.Furthermore,a mixed energy storage mechanism involving Zn^(2+)insertion and coordination reaction is confirmed by various ex-situ characterization.Thus,this work opens up a new path for constructing the high performance cathode of AZIBs through organic-inorganic hybridization.

Fine mapping of a major QTL qHYF_B06 for peanut yield

High yield is a major objective for peanut(Arachis hypogaea L.) breeding worldwide. However, fewer yield-related quantitative trait loci(QTL) have been reported in peanut than in other staple food crops such as rice(Oryza sativa), wheat(Triticum aestivum), and maize(Zea mays). This study aimed to identify stable major-effect QTL associated with pod yield per plant, hundred-pod weight for double-seeded pods,hundred-seed weight, shelling percentage, and pod number per plant, allowing us to predict candidate genes by means of transcriptome and genome sequencing. To this end, we used a population of recombinant inbred lines comprising 192 F9:11families derived from a JH6 × KX01-6 cross to construct a highresolution genetic map(1705.7 c M) consisting of 2273 polymorphic SNPs, with 0.75 c M(on average)between adjacent SNPs. We identified two high-confidence, yield-related QTL, qHYF_A08 and qHYF_B06, explaining 5.78%–31.40% of phenotypic variation and with LOD values of 5.10–24.48, in six environments. qHYF_A08 mainly explained the variation in shelling percentage, whereas qHYF_B06explained variation in hundred-pod weight and hundred-seed weight and accounted for 8.77%–31.40%of the variation in effective pod number per plant, pod number per plant, and shelling percentage. We narrowed down qHYF_B06 to an 890-kb interval using an advanced mapping population.Transcriptome and genome analyses revealed that only Arahy.129FS0 and Arahy.3R9A5K in the candidate mapping interval were differentially expressed between JH6 and KX01-6, with substantial structural variations in their promoter and coding regions. Genotypes of 208 peanut accessions determined using a diagnostic CAPS marker suggested that the two haplotypes of Arahy.3R9A5K were highly associated with hundred-seed weight and hundred-pod weight;this diagnostic CAPs marker could therefore be useful for selecting high-yielding lines during peanut breeding. Overall, our results provide valuable information for cloning alleles with favorable effects on peanut yield.

Generation of seed lipoxygenase-free soybean using CRISPR-Cas9

Beany flavor induced by three lipoxygenases(LOXs, including LOX1, LOX2, and LOX3)restricts human consumption of soybean. It is desirable to generate lipoxygenase-free new mutant lines to improve the eating quality of soybean oil and protein products. In this study, a pooled clustered regularly interspaced short palindromic repeats(CRISPR)-CRISPRassociated protein 9(Cas9) strategy targeting three GmLox genes(GmLox1, GmLox2, and GmLox3) was applied and 60 T_0 positive transgenic plants were generated, carrying combinations of sg RNAs and mutations. Among them, GmLox-28 and GmLox-60 were gmlox1 gmlox2 gmlox3 triple mutants and GmLox-40 was a gmlox1 gmlox2 double mutant.Sequencing of T_1 mutant plants derived from GmLox-28, GmLox-60, and GmLox-40 showed that mutation in the GmLox gene was inherited by the next generation. Colorimetric assay revealed that plants carrying different combinations of mutations lost the corresponding lipoxygenase activities. Transgene-free mutants were obtained by screening the T_2 generation of lipoxygenase-free mutant lines(GmLox-28 and GmLox-60). These transgeneand lipoxygenase-free mutants could be used for soybean beany flavor reduction without restriction by regulatory frameworks governing transgenic organisms.

A facile ionic liquid approach to prepare cellulose fiber with good mechanical properties directly from corn stalks

It is very difficult to directly spin the lignocellulose without pretreatment.Ionic liquids(ILs)are promising solvent to dissolve lignocellulose to prepare cellulose fiber.However,the degree of cellulose polymerization(DP)is reduced when lignocellulose is dissolved in ILs,and the lignin removal rate is low.The elongation at break and tensile strength of the fibers obtained by spinning the lignocellulose dissolved in ILs are poor.In this paper,preparing cellulose fiber directly from lignocellulose based on dissolving corn stalk via[C4mim]Cl-L-arginine binary system is achieved.It shows that the removal rate of lignin can reach 92.35%and the purity of cellulose can reach 85.32%after corn stalk was dissolved at 150℃C for 11.5 h when the mass fraction of arginine is 2.5%.The elongation at break of fiber reached 10.12%and the tensile strength reached 420 MPa.It is mainly due to the fact that L-arginine not only inhibits the degradation of cellulose but also promotes the delignination.Without any pulping or pretreatment,preparing cellulose fibers via direct dissolution and extrusion may provide a simple and effective way to prepare many novel cellulose materials.

The Research on the Analysis and Application of Detecting Underground Civil Air Defense with GPR

On the basis of the principle of Ground Penetrating Radar (GPR) method and geophysical characteristics, this paper discusses in detail detection method of civil air defense distinguished by GPR under the complex geological condition through using the analysis and application in the survey of underground civil air defense as an example. Three dimensional image of the defense clearly reflects its underground structure. Test result has the greatly high detection precision. This example illustrates the effectiveness and practicability of GPR in the respect of detection of the civil air defense and also accumulates experiences for the application of GPR in urban geological survey.

Designing salt stress-resilient crops:Current progress and future challenges

Excess soil salinity affects large regions of land and is a major hindrance to crop production worldwide.Therefore,understanding the molecular mechanisms of plant salt tolerance has scientific importance and practical significance.In recent decades,studies have characterized hundreds of genes associated with plant responses to salt stress in different plant species.These studies have substantially advanced our molecular and genetic understanding of salt tolerance in plants and have introduced an era of molecular design breeding of salt-tolerant crops.This review summarizes our current knowledge of plant salt tolerance,emphasizing advances in elucidating the molecular mechanisms of osmotic stress tolerance,salt-ion transport and compartmentalization,oxidative stress tolerance,alkaline stress tolerance,and the trade-off between growth and salt tolerance.We also examine recent advances in understanding natural variation in the salt tolerance of crops and discuss possible strategies and challenges for designing salt stress-resilient crops.We focus on the model plant Arabidopsis(Arabidopsis thaliana)and the four most-studied crops:rice(Oryza sativa),wheat(Triticum aestivum),maize(Zea mays),and soybean(Glycine max).

Insights into plant salt stress signaling and tolerance

Soil salinization is an essential environmental stressor,threatening agricultural yield and ecological security worldwide.Saline soils accumulate excessive soluble salts which are detrimental to most plants by limiting plant growth and productivity.It is of great necessity for plants to efficiently deal with the adverse effects caused by salt stress for survival and successful reproduction.Multiple determinants of salt tolerance have been identified in plants,and the cellular and physiological mechanisms of plant salt response and adaption have been intensely characterized.Plants respond to salt stress signals and rapidly initiate signaling pathways to re-establish cellular homeostasis with adjusted growth and cellular metabolism.This review summarizes the advances in salt stress perception,signaling,and response in plants.A better under-standing of plant salt resistance will contribute to improving crop performance under saline conditions using multiple engineering approaches.The rhizosphere microbiome-mediated plant salt tolerance as well as chemical priming for enhanced plant salt resistance are also discussed in this review.

调控作物耐碱性关键基因及其机制解析

盐碱胁迫是限制农业生产和作物产量的主要逆境因素之一。近年来,植物响应盐胁迫的分子机制研究取得了较大进展,但是对碱胁迫的分子机制知之甚少,这制约了通过分子设计育种提高作物盐碱胁迫耐受性的研究进程。最近,中国科学院遗传与发育生物学研究所谢旗团队、中国农业大学于菲菲团队和华中农业大学欧阳亦聃团队等8家单位联合攻关,在解析植物耐碱分子机制方面取得突破性进展。他们通过高粱(Sorghumbicolor)基因组关联分析检测到1个负调控耐碱性的主效基因AT1(Alkaline tolerance 1)。AT1及其同源基因的敲除增强了高粱、水稻(Oryza sativa)、谷子(Setaria italica)和玉米(Zea mays)耐碱性,并提高了碱胁迫下的产量。AT1编码非典型G蛋白γ亚基,它通过调控水通道蛋白PIP2;1的磷酸化水平改变细胞内外H_(2)O_(2)的分布,响应碱胁迫引发的氧化应激。该研究揭示了作物适应碱胁迫的新机制,对作物抗碱性育种具有重要意义。

Inhibition of the maize salt overly sensitive pathway by ZmSK3 and ZmSK4

Soil salinity is a worldwide problem that adversely affects plant growth and crop productivity. The salt overly sensitive (SOS) pathway is evolutionarily conserved and essential for plant salt tolerance. In this study, we reveal how the maize shaggy/glycogen synthase kinase 3-like kinases ZmSK3 and ZmSK4, orthologs of brassinosteroid insensitive 2 in Arabidopsis thaliana, regulate the maize SOS pathway. ZmSK3 and ZmSK4 interact with and phosphorylate ZmSOS2, a core member of the maize SOS pathway. The mutants defective in ZmSK3 or ZmSK4 are hyposensitive to salt stress, with higher salt-induced activity of ZmSOS2 than that in the wild type. Furthermore, the Ca^(2+) sensors ZmSOS3 and ZmSOS3-like calcium binding protein 8 (ZmSCaBP8) activate ZmSOS2 to maintain Na^(+)/K^(+) homeostasis under salt stress and may participate in the regulation of ZmSOS2 by ZmSK3 and ZmSK4. These findings discover the regulation of the maize SOS pathway and provide important gene targets for breeding salt-tolerant maize.

Plant abiotic stress response and nutrient use efficiency

Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies.

Unraveling salt stress signaling in plants

Salt stress is a maior environmental factor limiting plant growth and productivity. A better understanding of the mechanisms mediating salt resistance will help researchers design ways to improve crop performance under adverse environmental conditions. Salt stress can lead to ionic stress, osmotic stress and secondary stresses, particularly oxidative stress, in plants. Therefore, to adapt to salt stress, plants rely on signals and pathways that re-establish cellular ionic, osmotic, and reactive oxygen species （ROS） homeostasis. Over the past two decades, genetic and biochemical analyses have revealed several core stress signaling pathways that participate in salt resistance. The Salt Overly Sensitive signaling pathway plays a key role in maintaining ionic homeostasis, via extruding sodium ions into the apoplast. Mitogenactivated protein kinase cascades mediate ionic, osmotic, and ROS homeostasis. SnRK2 （sucrose nonfermenting l-related protein kinase 2） proteins are involved in maintaining osmotic homeostasis. In this review, we discuss recent progress in identifying the components and pathways involved in the plant＇s response to salt stress and their regulatory mechanisms. We also review progress in identifying sensors involved in salt-induced stress signaling in plants.

植物细胞质外体pH感受机制的解析

质外体是植物感受和应答环境胁迫(包括生物和非生物胁迫)的前沿区域。质外体的pH值是被严格调控的重要生理参数。环境胁迫(如细菌病害)等会引起植物细胞质外体碱化现象。然而,质外体pH如何协调根生长与免疫响应?其分子调控机制尚不清楚。最近,南方科技大学生命科学学院郭红卫团队与清华大学-德国马克斯普朗克研究所-科隆大学柴继杰团队以模式植物拟南芥(Arabidopsis thaliana)为研究材料,通过遗传学、细胞生物学、生物化学和结构生物学等综合手段,发现细胞表面小肽-受体复合物可作为质外体pH感受器,感受和应答分子模式触发的免疫(PTI)引发的拟南芥根尖分生组织细胞质外体碱化。该研究揭示了植物根尖分生组织细胞质外体pH感受的蛋白质复合物及响应机制,以及免疫与生长之间的协调机制,加深了人们对植物如何平衡生长与免疫应答生物学反应过程的理解。

Protein kinases in plant responses to drought, salt,and cold stress

Protein kinases are major players in various signal transduction pathways. Understanding the molecular mechanisms behind plant responses to biotic and abiotic stresses has become critical for developing and breeding climate-resilient crops. In this review,we summarize recent progress on understanding plant drought, salt, and cold stress responses, with a focus on signal perception and transduction by different protein kinases, especially sucrose nonfermenting1(SNF1)-related protein kinases(Sn RKs),mitogen-activated protein kinase(MAPK) cascades,calcium-dependent protein kinases(CDPKs/CPKs),and receptor-like kinases(RLKs). We also discuss future challenges in these research fields.

Functional assembly of root-associated microbial consortia improves nutrient efficiency and yield in soybean

Root-associated microbes are critical for plant growth and nutrient acquisition. However, scant information exists on optimizing communities of beneficial root-associated microbes or the mechanisms underlying their interactions with host plants. In this report, we demonstrate that rootassociated microbes are critical influencers of host plant growth and nutrient acquisition. Three synthetic communities(SynComs) were constructed based on functional screening of 1,893 microbial strains isolated from root-associated compartments of soybean plants. Functional assemblage of SynComs promoted significant plant growth and nutrient acquisition under both N/P nutrient deficiency and sufficiency conditions.Field trials further revealed that application of SynComs stably and significantly promoted plant growth, facilitated N and P acquisition, and subsequently increased soybean yield. Among the tested communities, SynCom1 exhibited the greatest promotion effect, with yield increases of up to 36.1% observed in two field sites. Further RNA-seq implied that SynCom application systemically regulates N and P signaling networks at the transcriptional level, which leads to increased representation of important growth pathways, especially those related to auxin responses. Overall,this study details a promising strategy for constructing SynComs based on functional screening,which are capable of enhancing nutrient acquisition and crop yield through the activities of beneficial root-associated microbes.

源自针灸的靶标发现之科学路径:以针刺防治哮喘为例

针灸学如何传承精华,实现守正创新.本文在长期工作积累基础上,系统建立了源自针灸的靶标发现科学路径,包括经验传承、临床疗效、效应调节、生物过程、物质基础、靶标发现,并对未来可期的新药创制进行了展望.

Dynamic changes of phosphatidylinositol and phosphatidylinositol 4-phosphate levels modulate H^(+)-ATPase and Na^(+)/H^(+) antiporter activities to maintain ion homeostasis in Arabidopsis under salt stress

Plant metabolites are dynamically modified and distributed in response to environmental changes.How-ever,it is poorly understood how metabolic change functions in plant stress responses.Maintaining ion ho-meostasis under salt stress requires coordinated activation of two types of central regulators:plasma membrane(PM)H^(+)-ATPase and Na^(+)/H^(+) antiporter.In this study,we used a bioassay-guided isolation approach to identify endogenous small molecules that affect PM H^(+)-ATPase and Na^(+)/H^(+) antiporter activities and identified phosphatidylinositol(PI),which inhibits PM H^(+)-ATPase activity under non-stress conditions in Arabidopsis by directly binding to the C terminus of the PM H^(+)-ATPase AHA2.Under salt stress,the phosphatidylinositol 4-phosphate-to-phosphatidylinositol(PI4P-to-PI)ratio increased,and PI4P bound and activated the PM Na^(+)/H^(+) antiporter.PI prefers binding to the inactive form of PM H^(+)-ATPase,while PI4P tends to bind to the active form of the Na^(+)/H^(+) antiporter.Consistent with this,pis1 mutants,with reduced levels of PI,displayed increased PM H^(+)-ATPase activity and salt stress toler-ance,while the pi4kβ1 mutant,with reduced levels of PI4P,displayed reduced PM Na^(+)/H^(+) antiporter activity and salt stress tolerance.Collectively,our results reveal that the dynamic change between PI and PI4P in response to salt stress in Arabidopsis is crucial for maintaining ion homeostasis to protect plants from un-favorable environmental conditions.

The molecular mechanism of plasma membrane H^(+)-ATPases in plant responses to abiotic stress

Plasma membrane H^(+)-ATPases(PM H^(+)-ATPases)are critical proton pumps that export protons from the cytoplasm to the apoplast.The resulting proton gradient and difference in electrical potential energize various secondary active transport events.PM H^(+)-ATPases play essential roles in plant growth,development,and stress responses.In this review,we focus on recent studies of the mechanism of PM H^(+)-ATPases in response to abiotic stresses in plants,such as salt and high pH,temperature,drought,light,macronutrient deficiency,acidic soil and aluminum stress,as well as heavy metal toxicity.Moreover,we discuss remaining outstanding questions about how PM H^(+)-ATPases contribute to abiotic stress responses.

DNA methylation signature of intergenic region involves in nucleosome remodeler DDM1-mediated repression of aberrant gene transcriptional read-through

The strict and efficient transcription termination is required to prevent production of aberrant read- through transcripts that may cause transcriptional interference at neighboring genes. However, the exact regulatory mechanism remains poorly understood. Through a genetic screening of a LUCIFERASE （LUC） reporter system, we found that Arabidopsis nucleosome remodeler DECREASE IN DNA METHYL- ATION1 （DDM1） is a key component of this regulatory machinery and plays an important role in tran- scription termination, thus limiting transcriptional read-through （TRT）. By whole-genome strand- specific RNA sequencing, we identified and confirmed 43 endogenous TRTs between genes, transposable elements （TEs）, or genes and TEs in the ddml-10 mutant, which mainly occurred at heterochromatin regions. The DNA methylation analysis of these TRT regions revealed that TRT occurred frequently at the intergenic regions with a higher methylation level in wild type comparing to the regions where TRT did not occur. Our results suggest that the level of intergenic DNA methylation may involve in preventing aberrant gene TRT or producing new gene during evolution.

Testing the polar auxin transport model with a selective plasma membrane H^(+)-ATPase inhibitor

Auxin is unique among plant hormones in that its function requires polarized transport across plant cells.A chemiosmotic model was proposed to explain how polar auxin transport is derived by the H^(+)gradient across the plasma membrane(PM)established by PM H^(+)-adenosine triphosphatases(ATPases).However,a classical genetic approach by mutations in PM H^(+)-ATPase members did not result in the ablation of polar auxin distribution,possibly due to functional redundancy in this gene family.To confirm the crucial role of PM H^(+)-ATPases in the polar auxin transport model,we employed a chemical genetic approach.Through a chemical screen,we identified protonstatin-1(PS-1),a selective small-molecule inhibitor of PM H^(+)-ATPase activity that inhibits auxin transport.Assays with transgenic plants and yeast strains showed that the activity of PM H^(+)-ATPases affects auxin uptake as well as acropetal and basipetal polar auxin transport.We propose that PS-1 can be used as a tool to interrogate the function of PM H^(+)-ATPases.Our results support the chemiosmotic model in which PM H^(+)-ATPase itself plays a fundamental role in polar auxin transport.