Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coelicolor M1154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthesize HBMs-a class of the largest and most complex Type-Ⅱpolyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosynthetic pathway toward potent anticancer drugs.

Approximate solution of Volterra-Fredholm integral equations using generalized barycentric rational interpolant

It is well-known that interpolation by rational functions results in a more accurate approximation than the polynomials interpolation.However,classical rational interpolation has some deficiencies such as uncontrollable poles and low convergence order.In contrast with the classical rational interpolants,the generalized barycentric rational interpolants which depend linearly on the interpolated values,yield infinite smooth approximation with no poles in real numbers.In this paper,a numerical collocation approach,based on the generalized barycentric rational interpolation and Gaussian quadrature formula,was introduced to approximate the solution of Volterra-Fredholm integral equations.Three types of points in the solution domain are used as interpolation nodes.The obtained numerical results confirm that the barycentric rational interpolants are efficient tools for solving Volterra-Fredholm integral equations.Moreover,integral equations with Runge’s function as an exact solution,no oscillation occurrs in the obtained approximate solutions so that the Runge’s phenomenon is avoided.

Blockchain-Based Key Management Scheme Using Rational Secret Sharing

Traditional blockchain key management schemes store private keys in the same location,which can easily lead to security issues such as a single point of failure.Therefore,decentralized threshold key management schemes have become a research focus for blockchain private key protection.The security of private keys for blockchain user wallet is highly related to user identity authentication and digital asset security.The threshold blockchain private key management schemes based on verifiable secret sharing have made some progress,but these schemes do not consider participants’self-interested behavior,and require trusted nodes to keep private key fragments,resulting in a narrow application scope and low deployment efficiency,which cannot meet the needs of personal wallet private key escrow and recovery in public blockchains.We design a private key management scheme based on rational secret sharing that considers the self-interest of participants in secret sharing protocols,and constrains the behavior of rational participants through reasonable mechanism design,making it more suitable in distributed scenarios such as the public blockchain.The proposed scheme achieves the escrow and recovery of personal wallet private keys without the participation of trusted nodes,and simulate its implementation on smart contracts.Compared to other existing threshold wallet solutions and keymanagement schemes based on password-protected secret sharing(PPSS),the proposed scheme has a wide range of applications,verifiable private key recovery,low communication overhead,higher computational efficiency when users perform one-time multi-key escrow,no need for trusted nodes,and personal rational constraints and anti-collusion attack capabilities.

Smoking of Carica papaya in Nigeria:The rationale,the public health effects and policies for intervention

Psychoactive substance use is characterized by the habitual use of substances that have significant effects in altering the activities of neurotransmitters in certain regions of the brain.Consequently,these alterations manifest as cognitive,emotional,perceptual and behavioural changes in affected individuals[1].

Experimental study of core MHD behavior and a novel algorithm for rational surface detection based on profile reflectometry in EAST

Microwave reflectometry is a powerful diagnostic that can measure the density profile and localized turbulence with high spatial and temporal resolution and will be used in ITER,so understanding the influence of plasma perturbations on the reflect signal is important.The characteristics of the reflect signal from profile reflectometry,the time-of-flight(TOF)signal associated with the MHD instabilities,are investigated in EAST.Using a 1D full-wave simulation code by the Finite-DifferenceTime-Domain(FDTD)method,it is well validated that the local density flattening could induce the discontinuity of the simulated TOF signal and an obvious change of reflect amplitude.Experimental TOF signals under different types of MHD instabilities(sawtooth,sawtooth precursors and tearing mode)are studied in detail and show agreement with the simulation.Two new improved algorithms for detecting and localizing the radial positions of the low-order rational surface,the cross-correlation and gradient threshold(CGT)method and the 2D convolutional neural network approach(CNN)are presented for the first time.It is concluded that TOF signal analysis from profile reflectometry can provide a straightforward and localized measurement of the plasma perturbation from the edge to the core simultaneously and may be a complement or correction to the q-profile control,which will be beneficial for the advanced tokamak operation.

Erratum regarding Declaration of Competing Interest statements in previously published articles

Declaration of Competing Interest statements were incorrectly included in the published version of the following articles that appeared in previous issues of Materials Reports:Energy.The appropriate Declaration of Competing Interest statements,provided by the authors,are included below.

Practice of Perioperative Rational Use of Antibacterial Drugs Based on Drug Pathway

[Objectives]To establish a new management model for rational use of perioperative antibacterial drugs in surgical departments.[Methods]Based on evidence-based medicine,the department s drug pathway was formulated,and the new mode of rational drug use control was established by using fine pharmaceutical technology intervention,and the intervention effect was evaluated by the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs.[Results]After adopting drug pathway in departments,the intensity of antibacterial drug use,per capita drug costs and the proportion of drugs decreased significantly,and the effect of rational drug use control was remarkable.[Conclusions]The drug pathway provides a new management and control mode for the rational use of perioperative antibacterial drugs in surgical departments of hospitals.Thus,it is worthy of popularization and application.

Exact controllability of rational expectations model with multiplicative noise and input delay

This paper considers the rational expectations model with multiplicative noise and input delay,where the system dynamics rely on the conditional expectations of future states.The main contribution is to obtain a sufficient condition for the exact controllability of the rational expectations model.In particular,we derive a sufficient Gramian matrix condition and a rank condition for the delay-free case.The key is the solvability of the backward stochastic difference equations with input delay which is derived from the forward and backward stochastic system.

The Global Security Initiative: Its Relevance, Rationale and Delivery

Today,our world is undergoing profound changes unseen in a century.Global security landscape is becoming ever more unstable and uncertain.In the face of growing deficits in security,Chinese President Xi Jinping put forward the Global Security Initiative(GSI),offering a clear answer to the question of the times:what kind of security concept does the world need,and how can we achieve common security?It is of great significance to fully grasp the relevance of and the rationale for the GSI,and push for its strategic delivery,so as to contribute to the long-term peace and stability of the world.

The Frontiers and Future Landscape of Research and Education on Value Rationality in Contemporary China

The importance of conducting in-depth research and education on value rationality in the new era is increasingly recognized.Therefore,it is essential to systematically grasp the themes,frontiers,and trends of research in this field,organizing the knowledge system to provide references for future studies.This necessitates clarifying the research achievements of scholars from different disciplines and institutions.Using the CiteSpace visualization analysis method,we can analyze,summarize,and synthesize research networks,hotspots,and knowledge structures,thereby forming a direction for advancing research.Through literature review methods and knowledge graph software analysis,it is believed that value rationality and instrumental rationality represent the rational attitudes individuals adopt when contemplating issues and putting them into practice.They are merely methods and should not be subjected to excessive value judgments.The relationship between value rationality and instrumental rationality is a focal point of societal concern,involving complex interdisciplinary issues with significant theoretical value and practical implications.In the future,the academic community needs to strengthen research collaboration,enhance the expansion of value rationality in various social practice fields,and conduct empirical studies to build consensus for the construction of Chinese society.

Evaluation of the Effectiveness of Community Pharmacy Services on Rational Medication Use in Elderly Patients with Hypertension and Diabetes

Objective:To explore the effect of community pharmacy services on rational medication use in elderly patients with hypertension and diabetes.Methods:Between November 2022 and December 2023,80 elderly patients with hypertension and diabetes were selected and randomly divided into a control group(routine medication guidance)and an observation group(community pharmacy services),with 40 subjects each.The medication effect scores,blood pressure,blood sugar levels,and quality of life scores before and after intervention were compared between the two groups.Results:Comparison of pharmaceutical knowledge,medication compliance,and safe medication behavior scores showed that the observation group had higher scores as compared to the control group(P<0.05);blood pressure(systolic blood pressure,diastolic blood pressure,heart rate)and blood sugar(fasting blood glucose,2 h postprandial blood glucose,glycated hemoglobin)index levels were compared,and the observation group’s index levels were lower than those of the control group(P<0.05);the scores of physical health,mental health,social relationships,and environment in the observation group were higher than those in the control group(P<0.05).Conclusion:Community pharmacy services improved the rational medication effect of elderly patients with hypertension and diabetes,and improved their blood pressure,blood sugar control levels,and quality of life.

Embodiment of Rationality:Philosophical Interpretation of Embodied Cognition

Under the influence of European rationalism,which holds that human rationality is higher than,or at least independent of human sensory cognition,the first generation of cognitive science advocates for disembodied cognition,manifesting the concept of dualism of mind and body.With the development of cognitive science in the 1980s,the second generation of cognitive science redefines the relationship between mind and body,thought and behavior,and reason and feeling and puts forward the concept of embodied cognition,representing monism of mind and body.It is claimed that the formation of concepts,categorical cognition and the evolution of rational thinking are characterized by embodiment,which is the necessary condition and basis for the formation of human rationality.The current study traces the shift of cognitive science from dualism to monism of mind and body and explores the relationship between rationality and sensibility from the perspective of philosophical basis and interpretations,with an aim to achieve a better understanding and thorough interpretation of human rationality.In this heated discussion about embodied cognition,there are still some fundamental questions that need to be further clarified,such as the essence and mechanism of human cognition,the ways that human body participates in cognitive activities,especially imagination and reasoning.The research paradigm of embodied cognition and its relevant theory have not been established and developed yet,and empirical research from interdisciplinary perspectives is far from enough to provide hard evidence for embodied cognition.

Transcriptome Analysis Reveals New Insights into the Respiration Metabolism Mechanism of Different Feeding Rations of Sea Cucumber(Apostichopus japonicus)

Sea cucumber(Apostichopus japonicus)is an excellent model for investigating effects of bottom-dwellers on carbon mig-ration and transformation.However,the molecular mechanism of respiratory metabolism process variation caused by feeding rations is poorly understood.In this study,treatment groups set as 1%(about 0.63g),3%,and 7%of total body weight(named F1,F3 and F7 groups respectively).The potential molecular mechanisms behind the functions of respiratory tree and body wall were investigated by RNA-Seq.A total of 52411 expressed genes were identified from 89342 expressed transcripts.The results showed 759,254 and 334 genes were up-regulated,and 334,445 and 992 genes were down-regulated in respiratory tree of F1 vs.F3,F1 vs.F7 and F3 vs.F7,respectively.Meanwhile,2070,1601 and 896 genes were up-regulated,and 1303,1337 and 1144 genes were down-regulated in body wall between F1 vs.F3,F1 vs.F7 and F3 vs.F7,respectively.Differentially expressed genes were enriched in salivary secretion and ECM-receptor interaction pathways in respiratory tree,and in various types of N-glycan biosynthesis,ribosome and sphingolipid metabolism pathways in body wall.These results suggested respiratory tree and body wall were involved in activation of respiratory metabolisms in response to different feeding rations.Our research provided valuable knowledge for physiological differences in res-piratory metabolism.

Rational Design of Grain Size to Improve Rice Yield and Quality

Grain size, determined by grain length, grain width and grain thickness, is associated with grain yield and quality. Many genes controlling grain size were cloned and their related regulatory mechanisms were clearly clarified. However, whether these genes can be directly introduced into japonica rice for grain size improvement is unknown.

深部煤层气游离气饱和度计算模型及其应用

近几年全国深部煤层气基于精细地质研究和水平井多段加砂压裂取得重大突破,部分井日产气量高达十万方,给煤层气产业重新树立了信心。但是,由于深部煤储层处于高地应力、高地温、高孔隙压力、低渗透率的复杂地质环境,不同深度煤储层典型参数和煤层气赋存方式的分布特征以及对储量和产量的影响亟需揭示。基于Langmuir等温吸附式、亨利定律及物质平衡原理,考虑吸附层和溶解气的影响,建立了深部煤层气游离气饱和度计算模型;以国内鄂尔多斯盆地大宁-吉县区块深部煤层气藏为例,分析不同深度深部煤层气赋存方式及分布特征,并评价游离气饱和度对深部煤层气储量、产量与合理配产的影响。研究认为:当煤层埋深大于溶解饱和对应的深度,游离气才会出现,且随着埋深的增加,游离气饱和度先快速增加后缓慢增加,目标区块埋深1875 m处才出现游离气,在埋深2800 m处游离气饱和度高达90%,游离气的占比高达17.3%。游离气饱和度对深部煤层气储量计算、产气特征和合理配产影响很大,随着游离气饱和度的增大,煤层气储量线性增大,累产气量持续上升但后期上升幅度逐渐变缓,深部煤层气井最优配产增加,井底流压下降速度加快,压裂改造区的内外压差降低,未改造区动用程度增加。目标区块主力开发煤层埋深位于2100~2300 m,游离气饱和度介于48%~68%,游离气占比介于10%~13%,建议气井合理配产介于(4~10)×10^(4)m^(3)/d。研究结果可为深部煤层气进一步开发提供理论依据和方法支撑。

Rational solutions of Painlevé-Ⅱequation as Gram determinant

Under the Flaschka-Newell Lax pair,the Darboux transformation for the Painlevé-Ⅱequation is constructed by the limiting technique.With the aid of the Darboux transformation,the rational solutions are represented by the Gram determinant,and then we give the large y asymptotics of the determinant and the rational solutions.Finally,the solution of the corresponding Riemann-Hilbert problem is obtained from the Darboux matrices.

Estimation of the Actual Evapotranspiration by the SEBAL Method in the Irrigated Rice Perimeter of Zatta (Yamoussoukro—Côte d’Ivoire)

In this study, the SEBAL (Surface Energy Balance Algorithm for Land) model was used to map the spatio-temporal distribution of actual evapotranspiration in the Yamoussoukro department (Côte d’Ivoire). Like other regions of the country, the Yamoussoukro district is confronted with the phenomenon of evapotranspiration (ET). This is a very important component that comes into play in the water balance but also in the calculation of the water needs of agricultural crops. Consequently, its estimation is of paramount importance in research related to the rational management of water resources, particularly agricultural water. The objective of this study was to analyze the spatio-temporal distribution of actual evapotranspiration (AET) as a function of land cover and land use. The methodology used is based on the SEBAL model which uses remote sensing (Landsat 8_OLI/TIRS) and climatic data to estimate actual evapotranspiration and analyze the spatio-temporal distribution of AET. The results reveal that the AET varied from 0 to 5.44 mm/day over the period from December 2019 to February 2020 with an average value of 4.92 mm/day. The highest average values occurred for water bodies (4.90 mm/day) and flooded vegetation (4.88 mm/day) while the lowest values occurred in residential areas (2.04 mm/day). Furthermore, the results show that the difference between the SEBAL model and the FAO-Penman-Monteith method is minimal with an average RMSE of 0.36 mm/day for all the satellite images. This study demonstrates the considerable potential of remote sensing for the characterization and estimation of spatial evapotranspiration in the Zatta irrigated rice-growing area.

Present situation of rational drug use in plateau area

Plateau is characterized by low oxygen,low pressure,strong radiation,cold and dryness,among which low oxygen is the main factor that affects the normal life activities of human body.Altitude hypoxia leads to significant changes in the metabolic characteristics of drugs in vivo,which in turn affects the efficacy and adverse actions of drugs.This paper summarizes the present situation of rational drug use in plateau area and pinpoints the existing problems.Meanwhile,we posit the strategies and measures for realizing rational and precise pharmacotherapy of plateau residents.First,we need to acquire a panoramic view of differential and relative pharmacokinetics and pharmacodynamics in between plateau area and plain area by carrying out comparative studies on drug metabolisms and on comprehensive drug efficacies and mechanisms.Second,we must apply the findings from basic research to clinical practice and formulate guidelines and recommendations of drug use for plateau habitants.Finally,we should eventually achieve precise and individualized drug use for plateau habitants based on their characteristic etiology and pathogenesis.

Analysis on Value Rationality of Traditional Farm Tools in the Taomin Area

This paper introduces the types of traditional farm tools,and analyzes the value rationality of these traditional farm tools:on the one hand,these farm tools have witnessed the farming culture,and they are also a manifestation of local culture in the Taomin area,representing the cultural characteristics and civilization progress of this area.

边界与弹性:新时代教育评价改革的制度逻辑

新时代教育评价改革需要强化制度层面的认知与执行的双向路径,这正好切合于新制度主义理论关于制度研究主要关注的两个维度,一是属认知的制度分析、二是属实践的制度变迁。故此,在新制度主义理论的基础上,新时代教育评价改革需要依循制度“认知-执行”双向路径对应的“边界-弹性”的双层逻辑框架。认知层上,通过制度分析的相关理论分析,发现新时代教育评价改革的制度认知要基于边界逻辑,即执行主体要理清制度价值层面的“多元”价值边界、主体层面的“规范”权责边界、技术层面的“有限”技术边界,以塑造对制度的理性认知;实践层上,通过制度变迁的相关理论分析,发现新时代教育评价改革的制度执行要基于弹性逻辑,即在制度执行前秉持弹性理念、执行中开展弹性实践以及执行后进行弹性评价,以促使新时代教育评价改革充分落地。