Development and Validation of a UPLC Method for the Determination of Docetaxel and Its Related Substances in Pharmaceutical Dosage Forms, an Antineoplastic Agent

A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.

Robustness Study and Superior Method Development and Validation for Analytical Assay Method of Atropine Sulfate in Pharmaceutical Ophthalmic Solution

Background: The robustness is a measurement of an analytical chemical method and its ability to contain unaffected by little with deliberate variation of analytical chemical method parameters. The analytical chemical method variation parameters are based on pH variability of buffer solution of mobile phase, organic ratio composition changes, stationary phase (column) manufacture, brand name and lot number variation;flow rate variation and temperature variation of chromatographic system. The analytical chemical method for assay of Atropine Sulfate conducted for robustness evaluation. The typical variation considered for mobile phase organic ratio change, change of pH, change of temperature, change of flow rate, change of column etc. Purpose: The aim of this study is to develop a cost effective, short run time and robust analytical chemical method for the assay quantification of Atropine in Pharmaceutical Ophthalmic Solution. This will help to make analytical decisions quickly for research and development scientists as well as will help with quality control product release for patient consumption. This analytical method will help to meet the market demand through quick quality control test of Atropine Ophthalmic Solution and it is very easy for maintaining (GDP) good documentation practices within the shortest period of time. Method: HPLC method has been selected for developing superior method to Compendial method. Both the compendial HPLC method and developed HPLC method was run into the same HPLC system to prove the superiority of developed method. Sensitivity, precision, reproducibility, accuracy parameters were considered for superiority of method. Mobile phase ratio change, pH of buffer solution, change of stationary phase temperature, change of flow rate and change of column were taken into consideration for robustness study of the developed method. Results: The limit of quantitation (LOQ) of developed method was much low than the compendial method. The % RSD for the six sample assay of developed method was 0.4% where the % RSD of the compendial method was 1.2%. The reproducibility between two analysts was 100.4% for developed method on the contrary the compendial method was 98.4%.

Development and validation of an instrument to assess knowledge,attitudes,and practices on digital health among nursing officers

Objective:Validation is an important aspect of an instrument,and it ensures the confidence of researchers to employ the instrument in their studies.This study was conducted to develop and validate an instrument to assess knowledge,attitudes,and practices(KAP) on digital health among nurses since digital health capacity is a major concern in health care that needs to be assessed.Methods:We conducted a methodological study to assess the content validity and reliability of the instrument.First,items were generated through a comprehensive literature review and by obtaining an expert opinion.Second,content and face validity were assessed by a panel of 7 experts.Both the item-level content validity index(I-CVI) and the scale-level content validity index(S-CVI) were established.Moreover,test–retest reliability and internal consistency of the instrument were assessed.Data were analyzed using SPSS version 25.Results:The initial pool consisted of 60 items and after obtaining content,face,and construct validity,51 items remained.Items with an I-CVI <0.78 were considered relevant.The S-CVI for relevancy,clarity,ambiguity,and simplicity were 0.93,0.91,0.94,and 0.92,respectively.Five subcomponents were constructed in each knowledge and attitudes domain,and the test–retest reliability test revealed that the instrument has good reliability,showing correlation coefficient values for the KAP domains and the total questionnaire of 0.76,0.98,0.99,and 0.99,respectively.The independent Cronbach's α for all items was 0.76,indicating good internal consistency.Conclusions:The present study established the acceptable validity and ensured the good reliability and internal consistency of the instrument,which can serve as an assessment tool of KAP on digital health among healthcare professionals.

LID设施布局对城市径流与污染负荷影响评估

关于低影响开发(LID)空间布局对水量水质控制效果影响的研究较为缺乏。针对上述问题,以郑州市中原区为对象,基于SWMM模型原理构建布设LID设施的研究区城市水量水质模型。所提模型依据城市综合径流系数的经验值以及研究区实际情况,将中原区划分为城市建筑高、中、低密集区,并在研究区高、中、低密集子汇水区布设不同比例的LID设施(S1~S5),计算不同雨量级别下不同空间格局下的LID设施对水量水质的控制效果。结果表明:随着雨量级别的增大,LID方案的径流总量削减率、峰值流量削减率和TSS负荷削减率不断减小。在降雨级别为暴雨、大雨和中雨时,在高、中、低密集子汇水区布设占比分别为35%、35%和30%的LID方案(S5),其径流总量削减率超过80%,峰值流量削减率超过70%,且TSS负荷削减率超过50%。从各事件下水量与水质综合指标评估来看,该方案表现最佳。

基于遗传算法的LID设施优化布设

在系统化全域推进海绵城市建设的背景下,低影响开发设施布设对城市雨洪过程具有重要影响。以江苏省宜兴市区为研究对象基于暴雨洪水管理模型SWMM建立研究区雨洪模型,考虑以径流总量削减率、悬浮物负荷削减率、生命周期成本、低影响开发设施占地面积建立综合目标函数,通过权重调整目标参数的优先级,运用遗传算法求解得到不同情景下低影响开发设施的最佳布设方案。结果表明:①在同等权重条件下,生命周期成本对优化计算的影响远大于面积,径流总量削减率与悬浮物负荷削减率影响较小;②位于管道上游的小面积汇水区内低影响开发设施的优化布设易受降雨重现期影响。研究成果可为海绵城市建设中低影响开发设施的优化布设及城市内涝防治研究提供参考。

基于GWO-PSO算法的小尺度地区LID布设优化模型研究

【目的】海绵城市通过低影响开发(LID)雨水系统来降低降雨相关灾害的影响,合理的LID布设方案是开发效果的决定性因素。【方法】通过耦合暴雨洪水管理模型(SWMM)和灰狼粒子群算法(GWO-PSO),建立了小尺度地区LID优化布设模型。GWO-PSO算法中粒子进行了基于社会等级制度的位置策略调整,以此得到更好地寻优性能。模型依据排放口流量,完成参数自动率定,并以洪峰流量为目标,经济成本为约束,求解雨水花园、生物网格、绿色屋顶和透水铺装四种包含相互独立与制约关系的LID设施的优化布设方案。【结果】将该模型应用于某试点小区,在预算182万元的情况下,得到5 a、10 a、20 a和50 a重现期下的布设方案,洪峰削减率分别为61.5%、53.2%、42.4%和31.1%。【结论】结果表明:在小尺度地区进行LID建设时,需要考虑子汇水区面积的影响;对于道路汇水区,需要联系地理位置布设;在低重现期下,各LID设施调控效果均较好,而在高重现期下,绿色屋顶的承受能力最强,且需要更多预算进行削峰。

基于SWMM模型与NSGA-Ⅱ多目标优化的LID布局研究

科学的海绵城市设计方案能够在一定程度上缓解由极端暴雨引发的城市内涝。以北京市海淀区老旧小区为研究对象,将雨洪管理模型(SWMM)与非支配排序遗传算法(NSGA-Ⅱ)相结合,以建设成本费用、总径流削减率以及节点超载时间为优化目标,以各项低影响开发措施(LID)按比例布置的最大面积为约束条件,迭代筛选出Pareto最优曲线,通过分析不同LID措施组合在老旧小区中的雨水排放效率,提出有效的规划建议。研究结果表明:对于单项LID的布置方案,同比例下透水铺装的径流控制效果优于绿色屋顶;LID组合的径流控制效果与建设成本呈正相关,但总径流削减率增长幅度有限,高成本的建设方案并不能达到更优的削减效果,节点超载时间不会持续下降;降雨重现期为10 a时(P=10),该小区LID布局最佳组合为37.12%绿色屋顶+17.7%下沉式绿地+7组雨水罐+9.47%透水铺装。在强降雨条件下耦合SWMM与NSGA-Ⅱ智能算法的多目标优化模型能够为类似社区LID布局设计提供参考。

基于多目标进化算法和SWMM的LID设施空间布局优化研究

针对传统算法无法满足低影响开发(LID)设施空间布局优化模型求解的性能要求的问题,以重庆秀山海绵城市建设区为研究区,基于MATLAB软件的platEMO4.0平台,对比分析了NSGA-Ⅱ、NSGA-Ⅲ、MOEAD、PICEA-g、MOEAPSL、CCMO与CAMOEA7种多目标进化算法对LID设施空间布局优化问题的求解结果与性能评价指标,并提出最佳方案。结果表明:新算法大部分性能指标优于传统算法,其中CCMO算法的多样性与收敛性最佳,而MOEAPSL算法的求解速度最快,搜索能力最强,且最优解数量最多;采用CCMO和MOEAPSL算法可获得研究区不同降雨重现期下的Pareto近似前沿,即LID设施空间布局的最优解集;以径流削减为控制目标的最佳方案在降雨重现期为5~100 a时径流总量控制率为67.23%~76.70%,洪峰流量削减率为66.42%~77.86%,LID单位面积建设成本为203.90~245.23元/m 2。

GAMYB transcription factor LoMYB65 from lily plays a vital role in pollen development

Lily(Lilium spp.)is an important horticultural crop,but its use is limited due to serious pollen contamination problems.There are many studies on pollen development in model plants,but few on flower crops such as lilies.Gibberellin(GA)is a large class of hormones and plays an important role in plant vegetative growth and reproductive development.GAMYB is a group of the R2R3-MYB family upregulated by gibberellin,and plays an important role in anther development.Here,we isolated a novel GAMYB,named LoMYB65,from lily,which was closely related to the AtMYB65 and AtMYB33 in Arabidopsis.Fluorescence quantitative PCR results showed that LoMYB65 was mainly expressed in lily anthers.LoMYB65 could be activated by 288μmol·L^(-1)GA3treatment and the LoMYB65 protein was located in the nucleus and cytoplasm,and had transactivation in yeast and tobacco leaf cells.The conserved motif within 226 amino acids of the C-terminal of LoMYB65 contributed to its transactivation.Overexpression of LoMYB65 caused dwarf phenotype,unnormal tapetum development,less seeds of siliques in transgenic Arabidopsis plants,the transgenic plants showed partly male sterile.Simultaneously,silencing of LoMYB65 with VIGS(Virus Induced Gene Silencing)in lily anthers caused unnormal pollen development and reduced the pollen amount.Overexpression of LoMYB65 in Arabidopsis and silencing of LoMYB65 in lily resulted in decreased pollen counts,so we speculate that LoMYB65 may be dose-dependent.Overall,these findings suggest that LoMYB65 may play an important role in anther development and pollen formation in lily.LoMYB65 may provide a useful candidate gene for pollenless breeding of lily.

传统理水智慧对海绵城市建设的启示与运用--以朗清园居住区LID系统设计为例

对我国造园专著《园冶》中的理水手法进行研究,总结出“疏源之去由,察水之来历”的理水智慧,分析调查现实案例颐和园的水系统情况,论述这一理水智慧的有效性与指导意义。将其运用到新建居住区朗清园LID系统规划设计中,结合现代技术与经验,构建以传统理水手法为基础,科学完整的住区LID系统。

基于InfoWorks ICM模型的城市小区LID组合方案成本效益研究

针对低影响开发(LID)雨水系统建设中存在成本与效益难以平衡的问题,选取甘肃省天水市某居住小区为研究对象,构建InfoWorks ICM一、二维耦合模型,以不同LID组合方案在不同降雨重现期下的径流总量控制率、径流峰值削减率、积水面积削减率、积水量削减率、固体悬浮物(SS)削减率、化学需氧量(COD)削减率为效益表征量,结合LID设施的生命周期成本定量分析成本效益。结果表明:包含绿色屋顶的LID组合方案成本效益偏低,但对于高重现期降雨具有较强的适应能力,更适用于暴雨频发地区;LID组合方案对于积水面积削减率与积水量削减率的成本效益较高,能有效缓解内涝积水,对于COD削减率的成本效益较低,需进一步优化;雨水桶+生物滞留设施+透水铺装作为总成本效益最高的方案,更适用于研究区域LID雨水系统的建设。研究成果对LID雨水系统的优化设计具有重要参考意义。

Analytical Method Development and Validation of Some Biosimilar Drugs by High Performance Thin Layer Chromatography

A simple and rapid HPTLC analytical method has been developed and validated for the determination of Etanercept and Filgrastim in pure form and in marketed formulation. Both the drugs were chromatographed on silica gel 60 F254s HPTLC plates, as stationary phase. The mobile phase optimized for Filgrastim and Etanercept was Water: n-butanol (7.5:2.5 v/v) and Isopropyl alcohol: water (6.5:4.5 v/v), respectively. The chromatogram obtained was scanned at 225 nm and 222 nm for filgrastim and etanercept which resulted in a retention factor of 0.45 ± 0.07 and 0.32 ± 0.03, respectively. The method was validated for parameters like linearity, accuracy, precision, specificity and robustness. Recovery studies were performed at three concentration levels, to demonstrate suitability, accuracy and precision of proposed method. Statistical analysis proved that the proposed method is accurate and reproducible with linearity in the range of 500 to 3000 ng/band for filgrastim and 200 to 1200 ng/band for etanercept. The limit of detection and limit of quantification for filgrastim was found to be 63.418 ng/band and 192.177 ng/band. For etanercept, LOD and LOQ were found to be 33.381 ng/band and 101.153 ng/band, respectively. The proposed method can be employed for the routine analysis of selected biosimilars.

Nutrition impacts of non-solid cooking fuel adoption on under-five children in developing countries

This paper examines the nutrition impacts of using non-solid cooking fuel on under-five children in developing countries.We draw on data from more than 1.12 million children in 62 developing countries from the Demographic and Health Surveys(DHS).Results from both fixed effects(FE)and instrumental variable(IV)estimates show that using non-solid cooking fuel significantly improves the nutrition outcomes of under-five children.Compared with their peers from households mainly using solid fuel,children from households mainly using non-solid fuel exhibit a lower probability of experiencing stunting(by 5.9 percentage points)and being underweight(by 1.2 percentage points).Our further investigation provides evidence for several underlying mechanisms,such as improved indoor air quality,induced reduction in children’s respiratory symptoms,benefits on maternal health,and reduction in maternal time spent on fuel collection or cooking.Heterogenous analyses suggest that the nutrition benefits of using non-solid cooking fuel are more prominent among boys,children above three years old,and those from households of lower socioeconomic status,rural areas,and Southeast Asia.

Development and Validation of an Indirect Whole-Virus ELISA Using a Predominant Genotype VI Velogenic NewCastle Disease Virus Isolated from Lebanese Poultry

Commercial ELISA kits are commonly used to assess the levels of chicken antibodies against NewCastle Disease Virus (NDV) and trace a field strain infection. Nevertheless, the specificity of these kits vis-à-vis endemic strains in Lebanon remains in question. This study developed an in-house indirect ELISA system to evaluate the level of chicken antibodies against a predominant velogenic NDV strain belonging to Genotype VI. A checkerboard analysis comprised a five-factorial multivariate experiment to optimize the protocol: coating antigen concentration, blocking buffer utilization, serum and conjugate dilution levels, and OD reading wavelength. The developed test was optimized and then validated through parallel testing of the sera of 20 broilers and 5 layers using standard serological assays. There was a strong correlation between the developed ELISA results and those obtained with the Hemagglutination Inhibition test (P < 0.01), and a commercial NDV ELISA kit (P < 0.05). The specificity, sensitivity, and reproducibility of the developed ELISA suggest that it can be used as the test of choice for the assessment of chicken antibody titers against locally circulating velogenic NDV strains, specifically those belonging to Genotype VI. It also offers better help in the serological detection of birds’ exposure to the said strains.

Conventional Geothermal Systems and Unconventional Geothermal Developments: An Overview

This paper provides an overview of conventional geothermal systems and unconventional geothermal developments as a common reference is needed for discussions between energy professionals. Conventional geothermal systems have the heat, permeability and fluid, requiring only drilling down to °C, normal heat flow or decaying radiogenic granite as heat sources, and used in district heating. Medium-temperature (MT) 100°C - 190°C, and high-temperature (HT) 190°C - 374°C resources are mostly at plate boundaries, with volcanic intrusive heat source, used mostly for electricity generation. Single well capacities are °C - 500°C) and a range of depths (1 m to 20 Km), but lack permeability or fluid, thus requiring stimulations for heat extraction by conduction. HVAC is 1 - 2 m deep and shallow geothermal down to 500 m in wells, both capturing °C, with °C are either advanced by geothermal developers at <7 Km depth (Enhanced Geothermal Systems (EGS), drilling below brittle-ductile transition zones and under geothermal fields), or by the Oil & Gas industry (Advanced Geothermal Systems, heat recovery from hydrocarbon wells or reservoirs, Superhot Rock Geothermal, and millimeter-wave drilling down to 20 Km). Their primary aim is electricity generation, relying on closed-loops, but EGS uses fractures for heat exchange with earthquake risks during fracking. Unconventional approaches could be everywhere, with shallow geothermal already functional. The deeper and hotter unconventional alternatives are still experimental, overcoming costs and technological challenges to become fully commercial. Meanwhile, the conventional geothermal resources remain the most proven opportunities for investments and development.

Development and technology status of energy storage in depleted gas reservoirs

Utilizing energy storage in depleted oil and gas reservoirs can improve productivity while reducing power costs and is one of the best ways to achieve synergistic development of"Carbon Peak–Carbon Neutral"and"Underground Resource Utiliza-tion".Starting from the development of Compressed Air Energy Storage(CAES)technology,the site selection of CAES in depleted gas and oil reservoirs,the evolution mechanism of reservoir dynamic sealing,and the high-flow CAES and injection technology are summarized.It focuses on analyzing the characteristics,key equipment,reservoir construction,application scenarios and cost analysis of CAES projects,and sorting out the technical key points and existing difficulties.The devel-opment trend of CAES technology is proposed,and the future development path is scrutinized to provide reference for the research of CAES projects in depleted oil and gas reservoirs.

Construction and Implementation of OBE-based Practical Course for Software System Development with Solid Foundation and Continuous Improvement

Software engineering is a highly practical major,and students need a lot of hands-on practice to transform the theoretical contents learned in class into the practical ability to solve practical problems,so practical courses are an essential and important part in the process of training talents in software engineering.From the point of view of cultivating talents in software engineering,this paper expounds the important position of practical courses in software engineering in the process of cultivating talents,analyzes the problems in the existing practical courses,and puts forward the construction ideas and characteristics of practical courses in software engineering which strengthen the foundation,advance steadily,and face the output.Taking the practical course for software system development as an example,this paper introduces in detail the concrete implementation process,achievements,existing problems and countermeasures of the course.

Embryonic Development and Eclosion Season of New Species Berastagia (Lepidoptera: Pyralidae) from Taiwan

This paper describes a new species of the snout moth Berastagia tainanica sp. nov. (Lepidoptera: Pyralidae) from Taiwan. From 2009 to 2016, a biology study was conducted on population dynamics and embryonic development. Spring season is the peak of the eclosion of overwintering larvae or pupae. The average longevity of adult was 14.8 ± 6.2 days (N = 174), the average number of eggs laid was 259 ± 3 eggs/moth (N = 2), the hatching rate of eggs was 95.4% (N = 262), and the average hatching time of eggs was 99.6 ± 18.6 hours (N = 68). The average body length of males was 5.64 mm ± 0.91 mm (N = 30), and the average body length of females was 6.28 mm ± 0.84 mm (N = 30). This finding indicates that female snout moths are larger than males (Global R = 0.058, P = 0.012). The snout moth eclosion rate was 16.9 moths/100 pods in the first year (2010/2011, N = 2,224 pods) and 10.9 moths/100 pods in the second year (2014/2015, N = 6,382 pods). The pod borer rate was 31.8% (N = 707) and the seed borer rate was 41.2% (N = 3,628) in the first year, whereas the pod borer rate was 76.2% (N = 6,382) in the second year.

BMPRⅡ^(+)neural precursor cells isolated and characterized from organotypic neurospheres:an in vitro model of human fetal spinal cord development

Roof plate secretion of bone morphogenetic proteins(BMPs)directs the cellular fate of sensory neurons during spinal cord development,including the formation of the ascending sensory columns,though their biology is not well understood.Type-ⅡBMP receptor(BMPRⅡ),the cognate receptor,is expressed by neural precursor cells during embryogenesis;however,an in vitro method of enriching BMPRⅡ^(+)human neural precursor cells(hNPCs)from the fetal spinal cord is absent.Immunofluorescence was undertaken on intact second-trimester human fetal spinal cord using antibodies to BMPRⅡand leukemia inhibitory factor(LIF).Regions of highest BMPRⅡ^(+)immunofluorescence localized to sensory columns.Parenchymal and meningeal-associated BMPRⅡ^(+)vascular cells were identified in both intact fetal spinal cord and cortex by co-positivity with vascular lineage markers,CD34/CD39.LIF immunostaining identified a population of somas concentrated in dorsal and ventral horn interneurons,mirroring the expression of LIF receptor/CD118.A combination of LIF supplementation and high-density culture maintained culture growth beyond 10 passages,while synergistically increasing the proportion of neurospheres with a stratified,cytoarchitecture.These neurospheres were characterized by BMPRⅡ^(+)/MAP2ab^(+/–)/βⅢ-tubulin^(+)/nestin^(–)/vimentin^(–)/GFAP^(–)/NeuN^(–)surface hNPCs surrounding a heterogeneous core ofβⅢ-tubulin^(+)/nestin^(+)/vimentin^(+)/GFAP^(+)/MAP2ab^(–)/NeuN^(–)multipotent precursors.Dissociated cultures from tripotential neurospheres contained neuronal(βⅢ-tubulin^(+)),astrocytic(GFAP+),and oligodendrocytic(O4+)lineage cells.Fluorescence-activated cell sorting-sorted BMPRⅡ^(+)hNPCs were MAP2ab^(+/–)/βⅢ-tubulin^(+)/GFAP^(–)/O4^(–)in culture.This is the first isolation of BMPRⅡ^(+)hNPCs identified and characterized in human fetal spinal cords.Our data show that LIF combines synergistically with high-density reaggregate cultures to support the organotypic reorganization of neurospheres,characterized by surface BMPRⅡ^(+)hNPCs.Our study has provided a new methodology for an in vitro model capable of amplifying human fetal spinal cord cell numbers for>10 passages.Investigations of the role BMPRⅡplays in spinal cord development have primarily relied upon mouse and rat models,with interpolations to human development being derived through inference.Because of significant species differences between murine biology and human,including anatomical dissimilarities in central nervous system(CNS)structure,the findings made in murine models cannot be presumed to apply to human spinal cord development.For these reasons,our human in vitro model offers a novel tool to better understand neurodevelopmental pathways,including BMP signaling,as well as spinal cord injury research and testing drug therapies.

基于SolidWorks的钢丝绳参数化建模系统

针对空间结构复杂的钢丝绳,设计和建模过程较繁琐的问题,对SolidWorks进行二次开发,实现钢丝绳快速参数化建模。该方法首先对特定型号钢丝绳参数方程和扫掠所需法平面圆进行计算,对计算结果进行编程化处理,基于Visual Studio编程平台,利用VB.net语言和对应API函数,实现钢丝绳快速参数化建模。以弯曲状6×7+IWS钢丝绳为例,对钢丝法平面圆的参数方程推导过程进行了详细介绍,一键绘制了弯曲状6×7+IWS钢丝绳模型,对所建模型进行有限元分析,验证所得此建模方法所建模型精确可靠,可提高钢丝绳建模效率,具有一定实用性。