Rationally designed amyloid inhibitors based on amyloid-related structural studies

Amyloid proteins correlate with a series of degenerative diseases. Targeting amyloid aggregation has remained a hot topic in therapeutic studies. Numerous inhibitors have been developed, but very few have been approved for marketing. Meanwhile, the growing knowledge of amyloid structural characteristics provides a basis for the rational design of inhibitors. Here we introduce the high-resolution structural findings of amyloid fibrils in recent years and discuss the reported strategies toward rationally designed inhibitors based on amyloid-related structural studies.

Harnessing Interactional Sensory Genes for Rationally Reprogramming Chaotic Metabolism

Rationally controlling cellular metabolism is of great importance but challenging owing to its highly complex and chaotic nature.Natural existing sensory proteins like histidine kinases(HKs)are understood as“sensitive nodes”of biological networks that can trigger disruptive metabolic reprogramming(MRP)upon perceiving environmental fluctuation.Here,the“sensitive node”genes were adopted to devise a global MRP platform consisting of a CRISPR interference-mediated dual-gene combinational knockdown toolbox and survivorship-based metabolic interaction decoding algorithm.The platform allows users to decode the interfering effects of n×n gene pairs while only requiring the synthesis of n pairs of primers.A total of 35 HK genes and 24 glycine metabolic genes were selected as the targets to determine the effectiveness of our platform in a Vibrio sp.FA2.The platform was applied to decode the interfering impact of HKs on antibiotic resistance in strain FA2.A pattern of combined knockdown of HK genes(sasA_8 and 04288)was demonstrated to be capable of reducing antibiotic resistance of Vibrio by 108-fold.Patterns of combined knockdown of glycine pathway genes(e.g.,gcvT and ltaE)and several HK genes(e.g.,cpxA and btsS)were also revealed to increase glycine production.Our platform may enable an efficient and rational approach for global MRP based on the elucidation of high-order gene interactions.A web-based 1-stop service(https://smrp.sjtu.edu.cn)is also provided to simplify the implementation of this smart strategy in a broad range of cells.

Community perspectives on the effectiveness of watershed management institutions in the Himalayas

The sustainability of environmental management initiatives,such as watershed management programs,relies on the presence of effective institutions at the watershed level.However,there needs to be more empirical evidence from evaluating the effectiveness of watershed-level institutions.Therefore,this study presents a pioneering effort to evaluate the effectiveness of Nepal’s first watershed conservation committee at the watershed scale,focusing on the case of the Khageri Khola watershed in Central Nepal.The study involved conducting a household survey,key informant interviews,focus group discussions,and field observations to collect and analyze the data.Descriptive analysis,index value calculation,and chi-square statistics were then employed to summarize the results regarding local respondents’perceptions of twelve institutional characteristics,their rationalities,and their association with socio-demographic variables.The results reveal that the watershed conservation committee was perceived as performing well in managing the watershed.Specifically,good interaction,appropriate scale,technical,environmental,social,organizational,and government rationality were perceived as highly effective,with an average index value of less than 0.36.In contrast,clarity of objectives and economic rationality showed moderate effectiveness,with an average index value ranging from 0.36 to 0.65.However,the results suggested that adaptiveness,compliance capacity,and financial rationality merit increased attention,intending to improve their performance.Further,the results showed the association of socio-demographics with respondents’perceptions of various indicators of institutional characteristics and their rationalities.Therefore,the study provides valuable insights for policymakers,researchers,and development practitioners charged with designing sustainable and effective programs and institutions.To enhance the effectiveness and sustainability of watershed management programs,we recommend establishing a policy-guided institutional mechanism at the watershed scale.This mechanism should be based on various institutional characteristics and rationalities and should consider the extant variability in the socio-demographic and topographic characteristics of the watershed.

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].

Scientific principles for accelerating the Sustainable Development Goals

The Sustainable Development Goals(SDGs)are significantly off-course as we reach the midpoint of their 2030 deadline.From a scientific perspective,the critical challenge in achieving the SDGs lies in the need for more scientific principles to understand the complex socio-ecological systems(SES)and their interactions influencing the 17 SDGs.Here,we propose a scientific framework to clarify the common scientific principles and the rational treatment of diversity under these principles.The framework’s core is revealing the complex mechanisms underlying the achievement of each Sustainable Development Goal(SDG)and SDG interactions.Building upon the identified mechanisms,complex SES models can be established,and the implementation of SDGs can be formulated as a multi-objective optimization problem,seeking a compromise in competition between essential costs and desired benefits.Our framework can assist countries,and even the world in accelerating progress towards the SDGs.

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.

Assessing the Efficacy of Wheat-Soybean Based Intercropping System at Different Plant Densities in Bambili, Cameroon

Wheat is one of the most important cereals in the world, serving as a staple for millions globally. In the wake of the geopolitical crisis between Russia and Ukraine, it has become incumbent for many countries to invest in wheat production. Improving cropping systems for wheat production is paramount. Intercropping cereals with legumes has tremendous advantages. Therefore, this study was designed to optimize wheat production by intercropping it with soybean at different densities. Between March and August 2023, a randomized complete block design trial was conducted in Bambili, North West of Cameroon with treatments T1 (wheat monocrop at 200,000 plants ha−1), T2 (soybean monocrop at 250,000 plants ha−1), T3 (200,000 wheat and 125,000 soybean ha−1), T4 (100,000 wheat and 250,000 soybean ha−1), T5 (200,000 wheat and 250,000 soybean ha−1) and T6 (100,000 wheat and 125,000 soybean ha−1). Results revealed that growth parameters of wheat were not significantly influenced by monocrop or intercrop. The yield of wheat was significantly higher in the monocrop than the intercrop treatments, with slight variation amongst the intercrop treatments. Soybean yield was higher in the monocrop than in the intercrop, with no variations amongst the intercrop treatments. Only the land equivalence ratio (LER) for T5 was greater than 1.0. The competitive ratio for T5 was 0.54 for wheat and 1.90 for soybean, comparatively lower than the other monocrop treatments. Intercropping wheat and soybean at 200,000:250,000 ratio is recommended.

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.

Rationally connected varieties -On a conjecture of Mumford

We establish a conjecture of Mumford characterizing rationally connected complex projective manifolds in several cases.

The Path,Trends,and Approaches of the Civilization Evolution of Rural Marriage Forms

Rural marriage has characteristics such as close relationship with labor production,deep integration of traditional culture,shy and introverted expression of subjective emotions,and illegal and rough marriage.The civilization evolution of rural marriage forms is moving towards a path that is conducive to the development of production and the pursuit of happiness for farmers,the construction of rural spiritual civilization,and the comprehensive development of rural society.This study analyzes the direction of the evolution of rural marriage form civilization,predicts the trend of rural marriage form civilization evolution,and proposes the future path of rural marriage form civilization evolution,including adhering to human’s most original value expectations of marriage life,drawing nourishment from excellent traditional Chinese culture,and continuously adjusting marriage and family policy tools to keep up with changes in the world of life.

The Impact of the“Belt and Road”Initiative on Industrial Structure Upgrading Along the Corridor

The“Belt and Road”initiative functions as a novel impetus for China’s external economic development within the framework of the new normal of economic growth.By leveraging panel data from 30 provinces and regions across China for the period of 2010 to 2020,this research assesses the influence of the“Belt and Road”initiative on the enhancement of the industrial structure along its trajectory.The findings indicate that:the most notable influence on the rationalization and progress of the industrial structure is observed in the eastern region,with the central region following suit,whereas the western region has yet to exhibit a significant transformation.The analysis delves into the role of technological innovation,concluding that the initiative primarily catalyzes optimization and upgrading through the effect of technological advancement.The study advances several pertinent policy recommendations to support and enhance these developments.

Whole Perfect Vectors and Fermat’s Last Theorem

A naïve discussion of Fermat’s last theorem conundrum is described. The present theorem’s proof is grounded on the well-known properties of sums of powers of the sine and cosine functions, the Minkowski norm definition, and some vector-specific structures.

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.

Rationally Design of Near Infrared Light Responsive Micro-Photoelectrodes for In Vivo Sensing of Neurotransmitter Molecules in Mouse Brain

The accurate quantification of neurotransmitter molecules is an indispensable means to reveal the physiological mechanisms of neuro movement in molecular level.However,existing detection strategies cannot fully meet practical needs,and the on-site and in vivo detection of neurotransmitters in brain remains a great challenge.Here,we report the development of a near infrared light responsive photo-electrochemical(PEC)detection method for in vivo quantification of neurotransmitter dopamine in mouse brain.Under guidance of density function theory calculations,a combination strategy of non-metal cation doping and defect engineering is introduced to rationally design the micro-photoelec-trodes with excellent biocompatibility and stability and implements the in vivo PEC detection of dopamine in mouse brain.It opens up a new way for the accurate in vivo detection of biomolecules and allows researchers to make novel inquiries for long-standing questions in a new way.

Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses

A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability.To evaluate its antigenicity relationship with other variants,antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern(VOCs)and variants of interest(VOIs)were cross-tested against pseudotyped variants.The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens,and Omicron(BA.1)-elicited sera did not efficiently neutralize the other variants.However,a Beta or Omicron booster,when administered as the 4th dose 3-months after the 3rd dose of any of the variants,could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1.Further analysis with 280 available antigen–antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity.Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.