Vedolizumab serum trough concentrations with and without thiopurines in ulcerative colitis: The prospective VIEWS pharmacokinetics study

BACKGROUND Ulcerative colitis(UC)is a chronic inflammatory condition requiring continuous treatment and monitoring.There is limited pharmacokinetic data on vedolizumab during maintenance therapy and the effect of thiopurines on vedolizumab trough concentrations is unknown.AIM To investigate the exposure-response relationship of vedolizumab and the impact of thiopurine withdrawal in UC patients who have achieved sustained clinical and endoscopic remission during maintenance therapy.METHODS This is a post-hoc analysis of prospective randomized clinical trial(VIEWS)involving UC patients across 8 centers in Australia from 2018 to 2022.Patients in clinical and endoscopic remission were randomized to continue or withdraw thiopurine while receiving vedolizumab.We evaluated vedolizumab serum trough concentrations,presence of anti-vedolizumab antibodies,and clinical outcomes over 48 weeks to assess exposure-response asso-ciation and impact of thiopurine withdrawal.RESULTS There were 62 UC participants with mean age of 43.4 years and 42%were females.All participants received vedolizumab as maintenance therapy with 67.7%withdrew thiopurine.Vedolizumab serum trough concentrations remained stable over 48 weeks regardless of thiopurine use,with no anti-vedolizumab antibodies detected.Pa-tients with clinical remission had higher trough concentrations at week 48.In quartile analysis,a threshold of>11.3μg/mL was associated with sustained clinical remission,showing a sensitivity of 82.4%,specificity of 60.0%,and an area of receiver operating characteristic of 0.71(95%CI:0.49-0.93).Patients discontinuing thiopurine required higher vedolizumab concentrations for achieving remission.CONCLUSION A positive exposure-response relationship between vedolizumab trough concentrations and UC outcomes suggests that monitoring drug levels may be beneficial.While thiopurine did not influence vedolizumab levels,its with-drawal may necessitate higher vedolizumab trough concentrations to maintain remission.

Impact of Pollutant Concentration and Particle Deposition on the Radiative Flow of Casson-Micropolar Fluid between Parallel Plates

Assessing the behaviour and concentration of waste pollutants deposited between two parallel plates is essential for effective environmental management.Determining the effectiveness of treatment methods in reducing pollution scales is made easier by analysing waste discharge concentrations.The waste discharge concentration analysis is useful for assessing how effectively wastewater treatment techniques reduce pollution levels.This study aims to explore the Casson micropolar fluid flow through two parallel plates with the influence of pollutant concentration and thermophoretic particle deposition.To explore the mass and heat transport features,thermophoretic particle deposition and thermal radiation are considered.The governing equations are transformed into ordinary differential equations with the help of suitable similarity transformations.The Runge-Kutta-Fehlberg’s fourthfifth order technique and shooting procedure are used to solve the reduced set of equations and boundary conditions.The integration of a neural network model based on the Levenberg-Marquardt algorithm serves to improve the accuracy of predictions and optimize the analysis of parameters.Graphical outcomes are displayed to analyze the characteristics of the relevant dimensionless parameters in the current problem.Results reveal that concentration upsurges as the micropolar parameter increases.The concentration reduces with an upsurge in the thermophoretic parameter.An upsurge in the external pollutant source variation and the local pollutant external source parameters enhances mass transport.The surface drag force declines for improved values of porosity and micropolar parameters.

Rheological properties and concentration evolution of thickened tailings under the coupling effect of compression and shear

Cemented paste backfill(CPB)is a key technology for green mining in metal mines,in which tailings thickening comprises the primary link of CPB technology.However,difficult flocculation and substandard concentrations of thickened tailings often occur.The rheological properties and concentration evolution in the thickened tailings remain unclear.Moreover,traditional indoor thickening experiments have yet to quantitatively characterize their rheological properties.An experiment of flocculation condition optimization based on the Box-Behnken design(BBD)was performed in the study,and the two response values were investigated:concentration and the mean weighted chord length(MWCL)of flocs.Thus,optimal flocculation conditions were obtained.In addition,the rheological properties and concentration evolution of different flocculant dosages and ultrafine tailing contents under shear,compression,and compression-shear coupling experimental conditions were tested and compared.The results show that the shear yield stress under compression and compression-shear coupling increases with the growth of compressive yield stress,while the shear yield stress increases slightly under shear.The order of shear yield stress from low to high under different thickening conditions is shear,compression,and compression-shear coupling.Under compression and compression-shear coupling,the concentration first rapidly increases with the growth of compressive yield stress and then slowly increases,while concentration increases slightly under shear.The order of concentration from low to high under different thickening conditions is shear,compression,and compression-shear coupling.Finally,the evolution mechanism of the flocs and drainage channels during the thickening of the thickened tailings under different experimental conditions was revealed.

Analysis of Air Exchange System Influence on Thermal and Concentration Modes in the Local Working Area under Radiant Heating Conditions

One of the effective options for energy saving in terms of heat costs for the formation of routine thermal conditions of working areas of large-sized industrial premises is the replacement of traditional convective(water)heating systems with systems,the main part of which are gas infrared emitters.But the mass introduction of such systems based on emitters was held back until recently by the lack of scientific and technical foundations for ensuring not only the routine thermal conditions of local working areas,but also ensuring acceptable concentrations of carbon dioxide,which is formed during the operation of a gas emitter.Solving the latter problem by the method of experimental selection of heating and air exchange modes is practically impossible due to the multivariate nature of possible solutions to this problem.Therefore,the purpose of the work is to analyze the results of theoretical studies of the possibility of ensuring an acceptable level of carbon dioxide concentrations in local working areas during the operation of gas infrared emitters and an air exchange system.Numerical modeling of heat and mass transfer processes under such conditions was performed in a fairly wide range of the main significant factors:air flow rate in the air exchange system from 0.01 to 0.04 kg/s,the position of the air inlet and outlet channels relative to the radiator and the local workplace(height from 0.3 to 4.1 m).It was found that by varying the numerical values of these factors,it is possible to ensure carbon dioxide concentrations in the local working area within the permissible limits of up to 1400 ppm.

A NOx Concentration Prediction Model Based on a Sparse Regularization Stochastic Configuration Network

For accurate prediction of nitrogen oxides(NOx) concentration during the municipal solid waste incineration(MSWI) process, in this paper, a prediction modeling method based on a sparse regularization stochastic configuration network is proposed. The method combines Drop Connect regularization with L1 regularization. Based on the L1 regularization constraint stochastic configuration network output weights, Drop Connect regularization is applied to the input weights to introduce sparsity. A probability decay strategy based on network residuals is designed to address situations where the Drop Connect fixed drop probability affects model convergence. Finally, the generated sparse stochastic configuration network is used to establish the model, and is validated through experiments with standard datasets and actual data from an MSWI plant in Beijing. The experimental results prove that this modeling method exhibits high-precision prediction and generalization ability while effectively simplifying the model structure, which enables accurate prediction of NOx concentration.

Shear Thickening Fluids Based on Additives with Different Concentrations and Molecular Chain Lengths

Shear thickening fluids （STFs） based on additives with different concentrations and molecular chain lengths were investigated. STF samples were prepared with silica and additive dispersed in polyethylene glycol （PEG） 400, where three types of additives with different molecular chain lengths of PEG4000, PEG6000, and PEG10000 were used. For PEG10000, different concentrations, including 0, 1%, 3%, and 5%, were selected to study the influences of additive concentrations. Rheological properties of the samples were measured with a rheometer. The results show that the shear thickening effect was significantly enhanced with the increase of the concentration and the molecular chain length of additives. The mechanism of enhancement was quantitatively explained with the formation of large particles clusters.

A High Breakdown Voltage Thin SOI Device with a Vertically Linearly Graded Concentration Drift Region

As the thickness of an SOI layer varies,a minimum breakdown voltage is reached when the thickness is about 2μm. The vertical electric field of the SOI LDMOS with a drift region which is vertically linearly graded is constant. The vertically linearly graded concentration drift can be achieved by impurity implanting followed by thermal diffusion. In this way,the vertical breakdown voltage of SOI LDMOS with 2μm thickness SOI layer can be improved by 43%. The on-state resistance is lowered by 24 % because of the higher impurity concentration of the SOI surface.

Prediction of SO_2 Concentration in Urban Atmosphere Based on B-P Neural Network

Base on the principle and method of B-P neural network,the prediction model of SO2 concentration in urban atmosphere was established by using the statistical data of a city in southwest China from 1991 to 2009,so as to forecast atmospheric SO2 concentration in a city of southwest China.The results showed that B-P neural network applied in the prediction of SO2 concentration in urban atmosphere was reasonable and efficient with high accuracy and wide adaptability,so it was worthy to be popularized.

INTRODUCTION TO PROF. YANG YUN-KUAN'S THE NEEDLING TECHNIQUE OF MIND REGULATION AND TAOISM CONCENTRATION

The combination of needling technique of Mind Regulation with Taoism Concentration is to promote the propagated sensation along the channels （PSC） and the needling sensation to the affected area in order to activate the potential regulation of human body. Prof. Yang Yun-kuan used this combination to treat some pain diseases, nervous system＇s diseases and intractable chronic diseases and got a better result than the general techniques, This is the introduction to the manipulation of this technique and its clinical application.

语言类型学视角下汉语“看”与现代维吾尔语“kør”的语法化

汉语“看”与现代维吾尔语“kør”属于各自语言体系中的常用基本词汇,它们的使用频率高,语法功能多,在各自语言系统中占比较重要的地位。本文将从汉语“看”和现代维吾尔语“kør”的实义动词用法、体助动词用法及二者语法化三方面进行分析,来探析两种语言之间的共性及各自的独特性,旨在加深“看”和“kør”演变规律的进一步认识。

不同强度运动抑制糖尿病大鼠肾脏PI3K/AKT/mTOR信号通路改善自噬的比较

背景:2型糖尿病损害肾功能。研究表明运动干预可以保护肾脏;鸢尾素可以通过抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路恢复自噬,保护糖尿病肾病患者的肾功能。目的:探讨运动能否通过抑制肾脏磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活来恢复自噬,改善肾损伤,以及分析不同方式运动产生影响的差异。方法:将6周龄的SD大鼠随机分为空白对照组(正常大鼠)和糖尿病组,其中糖尿病组大鼠经过高脂高糖喂养加腹腔注射低剂量1%链脲佐菌素(30 mg/kg)建立2型糖尿病模型。造模成功后再将糖尿病组大鼠随机分成糖尿病模型组、中强度持续运动组和高强度间歇运动组。两个运动组大鼠分别进行8周不同强度运动干预。取材后采用葡萄糖氧化酶法检测大鼠空腹血糖,使用试剂盒检测糖化血红蛋白水平,Elisa法检测血清胰岛素浓度,计算胰岛素抵抗指数,RT-PCR检测肾组织磷脂酰肌醇3-激酶、蛋白激酶B、雷帕霉素靶蛋白、Beclin-1、podocin、nephrin的基因表达量,Western Blot检测肾组织雷帕霉素靶蛋白及自噬标记蛋白LC3-1、LC3-2、Beclin-1的蛋白表达量。结果与结论:①2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著性升高,胰岛素抵抗水平显著上升,胰岛素水平显著下降;两种运动均能使2型糖尿病大鼠空腹血糖和糖化血红蛋白水平极显著下降,胰岛素抵抗水平显著下降,胰岛素水平显著上升;与中强度持续运动组相比,高强度间歇运动组胰岛素水平显著上升。②2型糖尿病大鼠podocin、nephrin基因表达量显著降低;两种不同形式运动均能显著提高其表达;与高强度间歇运动组相比,中等强度持续性运动组足细胞相关蛋白基因表达有进一步上升趋势,但无显著性差异。③2型糖尿病大鼠肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及蛋白的表达量显著增加,自噬标志蛋白Beclin-1、LC3-2表达量以及LC3-2/LC3-1显著降低;两种不同形式运动均能使肾组织磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白蛋白的表达量显著降低,自噬标志蛋白Beclin-1、LC3-2以及LC3-2/LC3-1显著升高;与中等强度持续性运动组相比,高强度间歇运动的磷脂酰肌醇3-激酶、蛋白激酶B、mTORC1的mRNA及雷帕霉素靶蛋白的蛋白表达量有进一步下降的趋势,Beclin-1、LC3-2以及LC3-2/LC3-1有进一步升高的趋势,但仅Beclin-1有显著性差异。④结果说明2型糖尿病肾脏足细胞损伤,自噬受到抑制,与磷脂酰肌醇3-激酶/蛋白激酶B/mTORC1信号通路被异常激活密切相关。高强度间歇运动和中等强度持续性运动可以保护糖尿病肾脏,减少足细胞损伤,促进自噬恢复,这可能与运动抑制磷脂酰肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路过度激活有关。与中等强度持续性运动相比,高强度间歇运动恢复自噬的效果呈更优趋势,但足细胞蛋白表达稍有下降。

Research on Vegetation Recovery of Mountainous Parks in City-and-town Concentration Areas in China

Based on the analysis of features and problems of green lands in mountainous parks in towns concentration areas,the paper has illustrated the significance for vegetations'recovery.By taking Tashan Park in Neijiang City for example,it has investigated the eco-environment and vegetations of this park.The results show that its terrain is precipitous,eco-environment is weak,slope vegetation is less,rocks'exposing rate is high and community structure is simple.In view of the survey results,it has proposed two methods for vegetation recovery that are natural recovery and artificial recovery.In particular,it has explored how to conduct vegetation recovery on green lands of different gradients of slopes by using plants'selection and community disposition.

k-center问题的算法研究综述

k-center问题是设施选址的基础问题,同样是NP难问题,在分配、紧急服务等领域也有着实际的应用。随着问题规模的扩大,原有的算法已不再适用,需要进一步优化或者改进。为了找到求解该问题的高效算法,对现有算法进行研究。对各类求解k-center问题的算法进行梳理,将求解算法划分为精确算法、启发式算法、元启发式算法、近似算法等,从算法原理、改进思路、性能和精度等方面进行对比综述。精确算法在求解小规模k-center问题时可在多项式时间内得到最优解,但是算法效率低,不适用于大规模问题;启发式算法可以在多项式时间内给出相对最优解,但是没有理论保证,无法衡量与最优解的关系;元启发式算法可根据对目前存在的智能优化算法进行改进,给出相对最优解,但是解的质量无法保证;利用近似算法得到的解具有近似比保证,有较大的理论研究价值,但是实用价值较弱。目前求解k-center问题的元启发式算法已取得一定的研究成果,但是在求解时间、求解规模、算法效率等方面仍待突破,这将是未来k-center问题的研究重点。

A Facile Li_(2)TiO_(3) Surface Modification to Improve the Structure Stability and Electrochemical Performance of Full Concentration Gradient Li-Rich Oxides

Full concentration gradient lithium-rich layered oxides are catching lots of interest as the next generation cathode for lithium-ion batteries due to their high discharge voltage,reduced voltage decay and enhanced rate performance,whereas the high lithium residues on its surface impairs the structure stability and long-term cycle performance.Herein,a facile multifunctional surface modification method is implemented to eliminate surface lithium residues of full concentration gradient lithium-rich layered oxides by a wet chemistry reaction with tetrabutyl titanate and the post-annealing process.It realizes not only a stable Li_(2)TiO_(3)coating layer with 3D diffusion channels for fast Li^(+)ions transfer,but also dopes partial Ti^(4+)ions into the sub-surface region of full concentration gradient lithium-rich layered oxides to further strengthen its crystal structure.Consequently,the modified full concentration gradient lithium-rich layered oxides exhibit improved structure stability,elevated thermal stability with decomposition temperature from 289.57℃to 321.72℃,and enhanced cycle performance(205.1 mAh g^(-1)after 150 cycles)with slowed voltage drop(1.67 mV per cycle).This work proposes a facile and integrated modification method to enhance the comprehensive performance of full concentration gradient lithium-rich layered oxides,which can facilitate its practical application for developing higher energy density lithium-ion batteries.

Organochlorine compounds and polycyclic aromatic hydrocarbons in surface sediment from Baiyangdian Lake,North China:Concentrations,sources profiles and potential risk

Organochlorine pesticides （OCPs）, polychlorinated biphenyls （PCBs）, and polycyclic aromatic hydrocarbons （PAHs） were determined in nineteen surface sediment samples collected from Baiyangdian Lake and its inflowing river （Fuhe River） in North China. Total concentrations of OCPs, PCBs and PAHs in sediments ranged from 5.4 to 707.6 ng]g, 2.3 to 197.8 ng/g, and 101.3 to 6360.5 ng]g, respectively. The levels of contaminants in Fuhe River were significantly higher than those in Baiyandian Lake. For hexachlorocyclohexane （HCHs） and dichlorodiphenytrich/oroethanes （DDTs）, α-HCH and p,p＇-DDT were predominant isomers; while for PCBs, PCB 28/31, PCB 40/103, PCB 60, PCB 101, and PCB 118 were predominant congeners. Possible sources derived from historical usage for OCPs and incomplete combustion fuel, wood, and coal and exhaustion of boats or cars for PAHs. Risk assessment of sediment indicated that sediments in Fuhe River were likely to pose potential biological adverse impact.

基于k-center聚类和最近邻中心的公平数据汇总

公平数据汇总是指从每种数据类别中选择有代表性的子集,且满足公平性要求。在大数据时代,每种类别的数据都是海量的,因此公平数据汇总研究具有非常重要的现实意义。为了使公平数据汇总的数据点更具有代表性,提出了基于k-center聚类和最近邻中心的公平数据汇总算法。算法主要包括2个基本步骤:(1)通过k-center聚类,将k个簇中心作为当前汇总结果;(2)选择满足公平约束的原簇中心的最近邻点作为新簇中心。由于更新簇中心时选择的是原簇中心的最近邻点,因此相对随机选择的数据点,最近邻点更具有代表性,是除原始簇中心外的次优代表点。同时,寻找最近邻点作为新的簇中心能最大限度减少公平代价。在2个模拟数据集和6个UCI真实数据集上的对比实验结果表明,所提出的算法在近似因子和公平代价方面都优于对比算法,说明所提出的算法获得的数据汇总更具有代表性。

Dynamics and genetic regulation of macronutrient concentrations during grain development in maize

Nitrogen(N), phosphorus(P), and potassium(K) are essential macronutrients that are crucial not only for maize growth and development, but also for crop yield and quality. The genetic basis of macronutrient dynamics and accumulation during grain filling in maize remains largely unknown. In this study, we evaluated grain N, P, and K concentrations in 206 recombinant inbred lines generated from a cross of DH1M and T877 at six time points after pollination. We then calculated conditional phenotypic values at different time intervals to explore the dynamic characteristics of the N, P, and K concentrations. Abundant phenotypic variations were observed in the concentrations and net changes of these nutrients. Unconditional quantitative trait locus(QTL) mapping revealed 41 non-redundant QTLs, including 17, 16, and 14 for the N, P, and K concentrations, respectively. Conditional QTL mapping uncovered 39 non-redundant QTLs related to net changes in the N, P, and K concentrations. By combining QTL, gene expression, co-expression analysis, and comparative genomic data, we identified 44, 36, and 44 candidate genes for the N, P, and K concentrations, respectively, including GRMZM2G371058 encoding a Doftype zinc finger DNA-binding family protein, which was associated with the N concentration, and GRMZM2G113967encoding a CBL-interacting protein kinase, which was related to the K concentration. The results deepen our understanding of the genetic factors controlling N, P, and K accumulation during maize grain development and provide valuable genes for the genetic improvement of nutrient concentrations in maize.

Trends of surface ozone based on hourly concentrations in the Beijing–Tianjin–Hebei region during 2017–2021

As a typical secondary air pollutant,surface ozone has been monitored routinely since 2013 in China.Most studies on the spatiotemporal variation of ozone have been centered around the daily maximum 8-h average,with little attention paid to the trends of hourly ozone,especially hourly ozone exceedances.Focusing on hourly ozone exceedances and peak values,the spatiotemporal trends of hourly ozone at 77 sites in 13 cities of the Beijing-Tianjin-Hebei(BTH)region during 2017-2021 were analyzed in this study.The number of hours with exceedances(N_(H200))in 2019 was nearly three times that of 2021.On a five-year average,the percentage of cumulative NH200 in June accounted for up to 40.5%of all hourly exceedances.Cities in central Hebei Province had the highest cumulative annual N_(H200).June had the highest average hourly ozone exceeded multiples of 0.158.The top two cities with the highest average exceeded multiple were Tangshan(0.166)and Beijing(0.158).Tangshan and Xingtai ranked as the top two in terms of the mean of the 10 highest daily maximum ozone concentrations(MTDM),with 286.74 and 285.37μg m^(−3),respectively.The gap between the MTDM and the daily maximum of hourly ozone averaged over all sites had narrowed to 97.88μg m^(−3) in 2021,much lower than that in other years,which indicated that the stability and convergence of ozone pollution in BTH region had been enhanced in 2021 to some extent.

CH_4 Concentrations and Emissions from Three Rivers in the Chaohu Lake Watershed in Southeast China

This study was conducted at three rivers of the Chaohu Lake watershed during the summer season of 2008,aiming to investigate the diurnal variations of dissolved CH4 concentrations and emissions,as well as the dynamics of CH4 accumulation emission rates over consecutive 72 h.The results showed that CH4 concentrations in the Fengle,Hangbu,and Nanfei rivers ranged from 56.33-124.79,160.82-341.03,and 213.49-716.81 nmol L-1,respectively,over a daily cycle;while the saturation of CH4 ranged from 188.72-418.07,538.74-1 142.46,and 715.23-2 401.38%,respectively,which indicated that surface waters were in all cases oversaturated with respect to the atmosphere.An obvious diurnal variation pattern of the dissolved CH4 concentrations demonstrated a higher value during daytime but a lower value for night time.Additionally,the highest dissolved CH4 concentrations were detected in the Nanfei River which received substantial urban wastewater discharges.CH4 emissions measured with floating chambers ranged from 5.82-15.46,5.77-8.41,and 13.51-49.25 mg C m-2 h-1 for the Fengle,Hangbu,and Nanfei rivers,respectively,over a daily cycle.Significantly higher CH4 emissions were also observed from the Nanfei River.The accumulative CH4 emissions for each river increased with time,while a decline trend on the accumulation rates was investigated over the consecutive 72 h.

Sludge concentration dynamic distribution and its impact on the performance of UNITANK

UNITANK is a biological wastewater treatment process that combines the advantages of traditional activated sludge process and sequencing batch reactor, which is divided into Tank A, B and C. In this study, the sludge distribution and its impact on performance of UNITANK were carried out in Liede Wastewater Plant （WWTP） of Guangzhou, China. Results showed that there was a strong affiliation between Tank A and B of the system in sludge concentration distribution. The initial sludge concentration in Tank A could present the sludge distribution of the whole system. The sludge distribution was mainly influenced by hydraulic condition. Unsteady sludge distribution had an impact on variations of substrates in reactors, especially in decisive reactor, and this could lead to failure of system. Settler could partially remove substrates such as COD and NO3-N, but there was adventure of sludge deterioration. The rational initial sludge concentration in Tank A should be 4000-6000 mg/L MLSS.