ADVANCES IN STUDY OF INTERACTIONS ASSOCIATED WITH RAINSTORM

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Impact of Drug-Drug Interaction between CDK4/6 Inhibitors and Proton Pump Inhibitors on Survival Outcomes in the Treatment of Metastatic Breast Cancer—Real World Data from a Portuguese Center

Introduction: Proton pump inhibitors (PPi) are widely prescribed, including in patients undergoing treatment for advanced breast cancer (ABC). Due to the pharmacokinetic characteristics of the CDK4/6 inhibitor (Ci) palbociclib a drug interaction with PPi was hypothesized. It was shown in a retrospective study that this association was an independent predictive factor for worse progression-free survival (PFS). Objective: To verify the impact of concomitant administration of PPi with Ci on overall survival (OS) and PFS. Material and Methods: This is a retrospective cohort study of patients treated with Ci for HR+HER2-ABC in the period from Feb/2017 to Aug/2020. SPSS software was used for data processing. Univariate analysis was done by the Kaplan-Meier method and log-rank test, and multivariate analysis by COX regression. P-value < 0.05 was considered significant. Results: 80 patients were included. The median age at diagnosis of ABC was 56 years (25 - 75). Treatment with Ci was 1st line for ABC in 68.8%. Choice of Ci was palbociclib in 73.8% (n = 59) and ribociclib in 26.3% (n = 21). The hormone partner was a nonsteroidal aromatase inhibitor in 45.0%, and fulvestrant in 55.0% of cases. 37.5% of patients were on PPi, and 70.0% of them were during the entire treatment (23.3% omeprazole, 73.4% pantoprazole, 3.3% others). Patients taking concomitant PPi and Ci had lower OS (OS-3 years 42.6% vs. 63.4%, p = 0.254) and PFS (PFS med 15 m. vs. 21 m., p = 0.733), although with no statistically significant difference. Discussion: In the sample, there was a numerical difference, without the statistical significance in the use of PPi in the survival of patients under Ci. This difference could be more evident with a longer follow-up and a larger sample size. This study intends to alert to the growing importance of checking for drug interactions. Polymedication, advanced age and the presence of several comorbidities are real problems in patients with ABC. Conclusion: Real-world data from this center demonstrate a negative, non-statistically significant impact of PPi treatment on survival outcomes, in patients treated with Ci for HR+HER2-ABC.

New advances in the science and use of Trichoderma spp.

Trichoderma spp. have been known for their strong abilities to produce extracellular enzymes, especially cellulases and glucanases by T. reesei, and also for their abilities to control plant pathogens. Most notably, a number of lines of evidence indicate that the agriculturally relevant strains are synergistic plant symbionts. As plant symbionts they possess the following characteristics: (a) they infect plant roots but cause the plant to restrict their growth to outer layers of the plant cortex (an exception is the recent discoveries of plant endophytic strains of Trichoderma and Gliocladium ), (b) they produce bioactive plant molecules in the zone of interaction that (c) induce localized systemic resistance to plant diseases and (d) systemic plant resistance to diseases that in some respects is similar to that induced by rhizobacteria, (e) they induce changes in plant proteomes, (f) increase plant growth and yield at least in part by enhancing root growth, and (g) they increase plant nutrient uptake. The increase in plant growth and yields is strongly interactive with plant genotype, at least in maize. There also are very significant increases in the knowledge of events that occur in mycoparasitism that in many respects have features in common with their interactions with plants. They are highly resistant to toxicants and have recently been shown to degrade cyanide and take up, and then degrade, metallocyanides. These discoveries allow new uses for the organisms in managed plant systems, including agriculture. For example, the induced systemic resistance system allows control of fungi, bacteria, Oomycetes and even one virus at sites temporally and spatially distant from the site of application. The abilities of the fungi to resist/degrade toxicants and increase plant growth indicate they will highly useful components in plant-microbe or microbe-only strategies for remediation of soil and water pollution. Finally, there are new uses of their enzyme systems for production of chitin degradation products for use as nutraceuticals or pharmaceuticals.

Novel understanding of Trichoderma interaction mechanisms

Trichoderma- based biofungicides are a reality in commercial agriculture, with more than 50 formulations registered worldwide as biopesticides or biofertilizers. Several research strategies have been applied to identify the main genes and compounds involved in the complex, three-way interactions between fungal antagonists, plants and microbial pathogens. Proteome and genome analyses have greatly enhanced our ability to conduct targeted and genome-based functional studies. We have obtained reproducible 2-D maps of the entire fungal proteome in various conditions of interaction, which permitted the isolation of many proteins related to specific functions. Many differential proteins from several biocontrol strains of Trichoderma spp. during the in vivo interaction with different plants and/or several phytopathogenic fungi have been isolated and analyzed by MALDI-TOF. Relevant genes have been cloned and specifically inactivated, to demonstrate their function in biocontrol and induction of disease resistance. GFP-based reporter systems with interaction-inducible promoters allowed the characterization of regulatory sequences activated by the presence of the pathogen or the plant. From extensive cDNA. and EST libraries of genes expressed during Trichoderma-pathogen-plant interactions, we are identified and determined the role of a variety of novel genes and gene-products, including ABC transporters specifically induced during antagonism with other microbes; enzymes and other proteins that produce or act as novel elicitors of Induced Resistance in plant and promote root growth and crop yield; proteins possibly responsible of a gene-for-gene avirulent interaction between Trichoderma and plants; mycoparasitism-related inducers released from fungal pathogens and that activate biocontrol in Trichoderma; fungal promoters specifically induced during mycoparasitism and plant colonization; plant proteins and a novel phytoalexin induced by the presence of the fungal antagonist; etc. We have also transgenically demonstrated the ability of Trichoderma to transfer heterologous proteins into plants during root colonization. Finally we have used GFP and other markers to monitor the interaction in vivo and in situ between Trichoderma and its host (s) (the fungal pathogen and the plant).

Advanced wastewater treatment with microalgae-indigenous bacterial interactions

Microalgal-indigenous bacterial wastewater treatment(MBWT)emerges as a promising approach for the concurrent removal of nitrogen(N)and phosphorus(P).Despite its potential,the prevalent use of MBWT in batch systems limits its broader application.Furthermore,the success of MBWT critically depends on the stable self-adaptation and synergistic interactions between microalgae and indigenous bacteria,yet the underlying biological mechanisms are not fully understood.Here we explore the viability and microbial dynamics of a continuous flow microalgae-indigenous bacteria advanced wastewater treatment system(CFMBAWTS)in processing actual secondary effluent,with a focus on varying hydraulic retention times(HRTs).The research highlights a stable,mutually beneficial relationship between indigenous bacteria and microalgae.Microalgae and indigenous bacteria can create an optimal environment for each other by providing essential cofactors(like iron,vitamins,and indole-3-acetic acid),oxygen,dissolved organic matter,and tryptophan.This collaboration leads to effective microbial growth,enhanced N and P removal,and energy generation.The study also uncovers crucial metabolic pathways,functional genes,and patterns of microbial succession.Significantly,the effluent NH4 t-N and P levels complied with the Chinese national Class-II,Class-V,Class-IA,and Class-IB wastewater discharge standards when the HRT was reduced from 15 to 6 h.Optimal results,including the highest rates of CO_(2) fixation(1.23 g L^(-1)),total energy yield(32.35 kJ L^(-1)),and the maximal lipid(33.91%)and carbohydrate(41.91%)content,were observed at an HRT of 15 h.Overall,this study not only confirms the feasibility of CFMBAWTS but also lays a crucial foundation for enhancing our understanding of this technology and propelling its practical application in wastewater treatment plants.

Innovative Techniques Unveiled in Advanced Sheet Pile Curtain Design

This thorough review explores the complexities of geotechnical engineering, emphasizing soil-structure interaction (SSI). The investigation centers on sheet pile design, examining two primary methodologies: Limit Equilibrium Methods (LEM) and Soil-Structure Interaction Methods (SSIM). While LEM methods, grounded in classical principles, provide valuable insights for preliminary design considerations, they may encounter limitations in addressing real-world complexities. In contrast, SSIM methods, including the SSI-SR approach, introduce precision and depth to the field. By employing numerical techniques such as Finite Element (FE) and Finite Difference (FD) analyses, these methods enable engineers to navigate the dynamics of soil-structure interaction. The exploration extends to SSI-FE, highlighting its essential role in civil engineering. By integrating Finite Element analysis with considerations for soil-structure interaction, the SSI-FE method offers a holistic understanding of how structures dynamically interact with their geotechnical environment. Throughout this exploration, the study dissects critical components governing SSIM methods, providing engineers with tools to navigate the intricate landscape of geotechnical design. The study acknowledges the significance of the Mohr-Coulomb constitutive model while recognizing its limitations, and guiding practitioners toward informed decision-making in geotechnical analyses. As the article concludes, it underscores the importance of continuous learning and innovation for the future of geotechnical engineering. With advancing technology and an evolving understanding of soil-structure interaction, the study remains committed to ensuring the safety, stability, and efficiency of geotechnical structures through cutting-edge design and analysis techniques.

Numerical estimation of bank-propeller-hull interaction effect on ship manoeu-vring using CFD method

This paper presents a numerical investigation of ship manoeuvring under the combined effect of bank and propeller. The incompressible turbulent flow with free surface around the self-propelled hull form is simulated using a commercial CFD software （ANSYS-FLUENT）. In order to estimate the influence of the bank-propeller effect on the hydrodynamic forces acting on the ship, volume forces representing the propeller are added to Navier-Stokes equations. The numerical simulations are carried out using the equivalent of experiment conditions. The validation of the CFD model is performed by comparing the numerical results to the availa- ble experimental data. For this investigation, the impact of Ship-Bank distance and ship speed on the bank effect are tested with and without propeller. An additional parameter concerning the advance ratio of the propeller is also tested.

Hydro-elastic computational analysis of a marine propeller using two-way fluid structure interaction

Marine propellers have complex geometry and their performance is determined by costly and time consuming open water experiments.Use of numerical techniques helps researchers in effective design of propellers.Several approaches are used that predicted either hydrodynamic and acoustic response or structural response.Two-way fluid-structure interaction(FSI)analysis is a very useful approach providing all three responses which helps in the design,analysis and optimization of a propeller.The objective of this paper is to predict the hydro-elastic response of a propeller using two-way FSI on a 0.2m diameter,DTMB-4119 propeller using ANSYS software.Two-way FSI analysis is carried out using system coupling approach that transfers the data between the structural and fluid solvers.The turbulence effects are captured using the large-eddy simulation(LES)model and the Ffowcs Williams Hawkings(FWH)acoustic model is used for evaluating the sound pressure level(SPL)generated by propeller.Analysis is extended to evaluate the hydro-elastic and acoustic response of the propeller after validating the hydrodynamic performance with the experimental result in the literature.The results from Two-way FSI analysis are in close agreement when compared with the one-way FSI analysis.Two-way FSI can accommodate the peak value of stress and deformation developed during the initial part of the transient solution which is important in the design of propeller.This study reveals that metallic(NAB)propeller can be replaced by a composite propeller.The acoustic response from two-way FSI analysis will be more realistic due to the consideration of hydro-elastic effect of propeller.

基于深度学习的高职院校在线开放课程设计策略研究

深度学习视角下高职院校在线开放课程具有知识整体性、深度参与性、课堂体验性、成果实用性等特征。明确高职院校在线开放课程设计的主线遵循,要坚持以学习者为中心的设计理念,聚焦学习者高阶能力与素质的培养,落实以问题解决为中心的设计导向,提供丰富的学习支持以促进深度交互。在此基础上,基于深度学习视角,从创新课程设计、梳理课程构成要素、变革教学方式、强化学习情境和交互、丰富评价方式等方面,提出高职院校在线开放课程设计的策略。

新质生产力与产业结构高级化:耦合协调及交互作用分析

文章以2011—2022年我国31个省份为研究对象,先运用耦合协调度模型测算新质生产力与产业结构高级化的耦合协调度,并分析二者的时空演变特征,刻画二者之间相互影响、相互作用的关系;再构建空间联立方程模型,研究新质生产力与产业结构高级化的交互作用。研究发现:新质生产力与产业结构高级化存在耦合协调关系,在时序演化上,二者的耦合协调度呈现稳定上升趋势,但东、中、西部地区之间存在差异;在空间演变上,呈现“大连片、小散落”特征。空间计量模型的估计结果表明,新质生产力与产业结构高级化在本省和邻近省份均可实现双向赋能;从新质生产力的不同子系统来看,产业结构高级化对本省和邻近省份的新质生产力及其子系统--绿色生产力、数字生产力均具有促进作用,但对科技生产力的作用不显著。从区域异质性的角度来看,新质生产力能有效赋能全国和东部地区本地和邻近省份的产业结构高级化,但对中部和西部地区的影响不显著。

Split-HaloTag imaging assay for sophisticated microscopy of protein–protein interactions in planta

An ever-increasing number of intracellular multi-protein networks have been identified in plant cells.Split-GFP-based protein–protein interaction assays combine the advantages of in vivo interaction studies in a native environment with additional visualization of protein complex localization.Because of their simple protocols,they have become some of the most frequently used methods.However,standard fluorescent proteins present several drawbacks for sophisticated microscopy.With the HaloTag system,these drawbacks can be overcome,as this reporter forms covalent irreversible bonds with synthetic photostable fluorescent ligands.Dyes can be used in adjustable concentrations and are suitable for advanced microscopy methods.Therefore,we have established the Split-HaloTag imaging assay in plants,which is based on the reconstitution of a functional HaloTag protein upon protein–protein interaction and the subsequent covalent binding of an added fluorescent ligand.Its suitability and robustness were demonstrated using a well-characterized interaction as an example of protein–protein interaction at cellular structures:the anchoring of the molybdenumcofactor biosynthesis complex to filamentous actin.In addition,a specific interactionwas visualized in a more distinctivemannerwith subdiffractional polarizationmicroscopy,Airyscan,and structured illumination microscopy to provide examples of sophisticated imaging.Split-GFPand Split-HaloTag can complement one another,as Split-HaloTag represents an alternative option and an addition to the large toolbox of in vivo methods.Therefore,this promising new Split-HaloTag imaging assay provides a unique and sensitive approach formore detailed characterization of protein–protein interactions using specific microscopy techniques,such as 3D imaging,single-molecule tracking,and super-resolution microscopy.

Diet with high content of advanced glycation end products induces oxidative stress damage and systemic inflammation in experimental mice: protective effect of peanut skin procyanidins

Non-enzymatic glycation reaction in food can produce diet-derived advanced glycation end products(dAGEs),which have potential health risks.Thus,it is of great significance to find efficient substances to improve the negative effects induced by dAGEs on human health.This study investigated the intervening effects of peanut skin procyanidins(PSP)on the dAGEs-induced oxidative stress and systemic inflammation in experimental mice model.Results showed that the accumulation of AGEs in serum,liver,and kidney was significantly increased after mice were fed dAGEs(P<0.05).The expression of advanced glycation product receptor(RAGE)was also significantly increased in liver and kidney(P<0.05).PSP could not only effectively reduce the accumulation of AGEs in serum,liver and kidney of mice,but also reduce the expression of RAGE in liver and kidney of mice.And the levels of pro-inflammatory cytokines interleukin-6(IL-6),tumor necrosis factor(TNF-α),and IL-1βin serum of mice were significantly decreased(P<0.05),while the levels of antiinflammatory factor IL-10 were increased,and the inflammatory injury in mice was improved.In addition,the levels of superoxide dismutase(SOD),glutathione(GSH),catalase(CAT)in liver and kidney of mice were increased(P<0.05),and the level of malondialdehyde(MDA)was decreased(P<0.05),which enhanced the antioxidant capacity of mice in vivo,and improved the oxidative damage of liver and kidney.Molecular docking technique was used to confirm that the parent compound of procyanidins and its main metabolites,such as 3-hydroxyphenylacetic acid,could interact with RAGE,which might inhibit the activation of nuclear transcription factor(NF-κB),and ultimately reduce oxidative stress and inflammation in mice.

水-岩软化作用下巴东组泥岩隧道大断面开挖掌子面稳定性研究

为明确软弱围岩条件下高速铁路隧道大断面机械化施工过程中的掌子面稳定性特征,以郑万铁路巴东隧道穿越巴东组紫红泥岩段为工程背景,对隧道揭露的巴东组紫红泥岩开展不同含水率下的三轴试验,揭示巴东隧道紫红泥岩的水-岩软化特征;在考虑水-岩软化特征的Hoek-Brown强度准则下,构建考虑水-岩软化作用的隧道穿越巴东紫红泥岩地层流-固耦合数值模型,揭示不同地层水位下巴东组紫红泥岩隧道大断面施工掌子面稳定性特征;最终提出“掌子面喷混凝土+掌子面超前锚杆+超前管棚”的组合式超前加固方案。经过试验和模拟计算,结果表明:1)随含水量的增加,巴东隧道紫红泥岩的刚度与抗剪强度显著降低,与既有研究揭示的浅表地层紫红泥岩相比,巴东隧道紫红泥岩具有更高的抗剪强度;2)掌子面后方拱顶沉降、掌子面前方拱顶预收敛、掌子面挤出变形的最大值均随历史水位的升高而增大;3)根据不同地层历史水位条件下开挖面支护力与挤出变形之间的关系,巴东隧道紫红泥岩掌子面稳定性可以分为A(稳定)、B(短期稳定)以及C(不稳定)3类,对于C类掌子面,采用“掌子面喷混凝土+掌子面超前锚杆+超前管棚”的组合式超前加固措施后,掌子面前后方各项变形最大值可以减小60%~90%。

Exploration and Practice of“Guiding Interactive”Teaching in Advanced Geochemistry Courses from the Perspective of Constructivist Theory

The construction of geochemical disciplines has brought new vitality to the development of traditional geology.In the new round of“Double First-Class”discipline construction at Central South University,the course of Advanced Geochemistry has effectively stimulated students’interest in learning and further improved their scientific thinking and research innovation skills through the implementation of“Guiding Interactive”teaching reform measures,which has important theoretical significance and practical value.

基于“高阶互动”的线上线下混合式教学模式的探索与实践——以“仪器分析”教学为例

在“做中学”和“以学生发展为中心”的教学理念指导下,采用“课前浅层互动+课中高阶互动+课后升华互动”的线上线下混合式教学模式与多元化考核相结合的方式,对仪器分析课程实施了教学改革,有效提高了学生应用新技术、现代工具解决问题的能力,以期为其他相关学科提供借鉴。

基于交互式教学法的对外汉语中高级阅读课教学设计

随着全球汉语热的兴起,对外汉语教学在国际教育领域中扮演着越来越重要的角色。而阅读是语言学习中至关重要的一环,尤其是在对外汉语学习中,高级阅读能力对学生的语言水平提升至关重要。基于交互式教学法的对外汉语中高级阅读课教学设计,不仅能提高学生的阅读能力和交流能力,还能激发学生的学习兴趣和积极性。因而研究基于交互式教学法的对外汉语中高级阅读课教学设计有重要的意义。对此,通过阐述交互式教学法与对外汉语教学的契合点,分析交互式教学法在对外汉语中高级阅读课教学中的优势,在此基础上探究基于交互式教学法的对外汉语中高级阅读课教学设计策略,以期为相关教育工作者提供新的思路和方法。

基于混合推进机制的海上防空反导作战推演系统设计

混合推进机制融合了逻辑时间推进和基于自然时间的实时推进两种推进模式,其中逻辑时间推进能提高仿真效率,实时推进能提升仿真逼真度,而混合推进兼具两者优势。本文针对海上防空反导装备体系作战能力评估与战法推演需求,采用分层设计模式,借鉴LVC资源集成方式,设计基于混合推进机制的海上防空反导作战推演系统体系架构,完成系统功能、信息交互设计,给出系统的典型部署方式。利用实装与模拟器拓展作战推演系统的能力,可真实反映作战人员素质和关键武器装备对战争结果的影响,提升防空反导作战仿真推演的置信度。

镍基合金FN3蠕变-疲劳交互试验特性研究

超高参数燃煤电站汽轮机工作条件非常复杂,有必要对复杂应力状况下的新材料力学行为进行评价。对进汽温度大于650℃的先进超超临界燃煤电站用镍基高温合金FN3,在725℃下进行了应变控制蠕变-疲劳交互试验,拉伸峰值应变保载时间为0.5 min和3 min。结合应变变程划分(SRP)模型和M-C模型,从半寿命对应的总应变划分出弹性应变和非弹性应变,将非弹性应变划分为拉向塑性与压向塑性应变、拉向蠕变与压向塑性应变、拉向蠕变与压向蠕变应变以及拉向塑性与压向蠕变应变,提出了各应变分量与失效循环次数的幂函数关系,并拟合各分量的关系参数。对试验结果和断口特征进行了比较分析,结果表明,在相同的应变幅下,随着保载时间的增加,FN3合金蠕变损伤量增加,疲劳失效次数降低。由于析出相的强化作用,合金抵抗裂纹扩展的能力增强,总失效时间增加。研究成果可为先进超超临界汽轮机机组高温部件的选材和使用提供参考。

无人机先进地面站关键技术综述

具有沉浸显示、智能辅助、自然化人机交互等先进控制能力的新型无人机地面站已成为当前无人机控制领域的研究热点。为分析其中的技术脉络,系统性地梳理国内外一系列无人机先进地面站的功能要点及设计理念,在此基础上从无人机地面站指挥控制的观察-判断-决策-行动回路出发,归纳提炼了其技术体系构成,分析指出了其中的任务环境构建、战场态势沉浸式显示、智能化辅助决策和自然化人机交互等关键技术,并对各项技术的主要研究方法进行了深入剖析,还对无人机先进地面站目前存在的挑战和未来发展趋势进行了研判。该研究对新型地面站的研制具有指导和借鉴意义。

平台经济、技术创新与产业结构升级

文章选用2013-2019年我国30个省级行政单位面板数据,利用双向固定效应模型实证分析平台经济与技术创新对产业结构升级的影响。研究发现,平台经济对产业结构合理化和产业结构高级化均有促进作用,但这一促进作用存在区域异质性,东部地区的促进效果最为显著;平台经济与技术创新之间存在交互效应,平台经济对技术创新的促进效应弱于技术创新对平台经济的促进效应;平台经济与技术创新的交互效应可以显著推动产业结构升级。为进一步发挥平台经济和技术创新对产业结构升级的促进效应,政府部门要以技术创新引领平台经济发展、完善平台经济治理体系、加大平台经济和技术创新的融合去缩小产业发展的区域差异。