Licorice-saponin A3 is a broad-spectrum inhibitor for COVID-19 by targeting viral spike and anti-inflammation

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016μM.The mechanism was related to binding with Y453 of RBD determined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quantum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)pathways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

基于离散数值分析技术的海上风电机组安装施工规划模拟研究

海上风电机组安装主要包括多船舶联合施工、单船自运输安装施工两种方式。海上风电场建设中,风电机组安装施工费用占有较大比重,进行整体施工规划分析可以为宏观决策提供量化依据。鉴于此,采用离散数值分析模拟技术,以实际工程项目施工限制条件和风浪流数据为计算参数,对项目总工期和怠机时长等进行数值模拟,以比较上述两种模式的施工效率优劣。结果表明,相对航行距离在359.26 km前,单船模式施工累计耗时高于多船模式,超过该距离后,多船模式逐渐高于单船模式;多船模式怠机抵抗性能整体上优于单船模式。

海上风电机组塔筒门洞结构多参数优化分析

研究海上风电塔架门洞结构多参数优化设计技术,有助于提高塔架门洞设计准确性,减少塔筒工程量。根据海上风力发电机组的底段塔架门洞的结构,利用Workbench软件DX模块开发一套参数化建模优化分析流程,可根据不同的塔架和门洞几何参数,自动建立有限元分析模型,并自动获取门框极限应力、门洞焊缝极限应力、门洞焊缝疲劳损伤值,搭建优化模型,确定各个输入变量的合理变化范围,设定门洞结构优化约束条件及优化目标,选择合适优化算法,完成优化分析。通过多参数优化分析可以指导塔架门洞各个输入参数调整方向,明确塔架门洞各个输入参数对强度指标和模型重量的敏感程度,更加直观地看到每个输入参数对结果的影响情况等。有助于后续设计参数调整。研究成果可以为塔架门洞设计提供指导依据,有利于工程项目塔架减重降本。

Mechanism of Huanglian Detoxification Soup Relieving Postherpetic Neuralgia by Enhancing IL-2 Levels in Rats

[Objectives]To explore the mechanism of Huanglian detoxification soup improving pain behavior by affecting serum IL-2 levels in postherpetic neuralgia(post herpes neuralgia,PHN)model rats.[Methods]20 PHN rats were randomly divided into model group(PHN group)and detoxification decoction group(n=10).In the group,10%Huanglian detoxification soup(0.4 mL/0.1 kg)was given once in the morning and evening for 14 d.The PHN group was filled with an equal volume of 0.9%sodium chloride solution.Tail vein serum inflammatory factor interleukin-2(IL-2),IL-βand IL-6 levels were measured using ELISA kits at 7 and 21 d.[Results]IL-2 increased at 14 and 21 d in IL group,while IL-βand IL-6 decreased compared with the PHN group(P<0.05).[Conclusions]Huanglian detoxification soup may raise IL-2 levels after VZV infection to promote the differentiation of cells of the immune system,so as to relieve the pain caused by IL-βand IL-6 inflammatory factors.

Simultaneous determination of 35 constituents and elucidation of effective constituents in a multi-herb Chinese medicine formula Xiaoer-Feire-Kechuan

Xiaoer-Feire-Kechuan(XFK) is an 11-herb Chinese medicine formula to treat cough and pulmonary inflammation.The complicated composition rendered its chemical analysis and effective-component elucidation.In this study,we combined quantitative analysis and bioactivity test to reveal the antiinflammatory constituents of XFK.First,UPLC-DAD and UHPLC/Q-Orbitrap-MS methods were established and validated to quantify 35 analytes(covering 9 out of 11 herbs) in different XFK formulations.Parallel reaction monitoring mode built in Q-Orbitrap-MS was used to improve the sensitivity and selectivity.Then,anti-inflammatory activities of the 35 analytes were analyzed using in vitro COX-2 inhibition assay.Finally,major analytes forsythosides H,I,A(8-10),and baicalin(15)(total contents varied from 21.79 to 91.20 mg/dose in different formulations) with significant activities(inhibitory rate ≥ 80%) were proposed as the anti-inflammatory constituents of XFK.The present study provided an effective strategy to discover effective constituents of multi-herb formulas.

Intestinal Absorption of Ergostane and Lanostane Triterpenoids from Antrodia cinnamomea Using Caco-2 Cell Monolayer Model

Antrodia cinnamomea is a precious medicinal mushroom.It exhibits promising therapeutic effects on cancer,intoxication,hypertension,hepatitis,and inflammation.Its major bioactive constituents are ergostane and lanostane triterpenoids.In this study,we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A.cinnamomea.The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method.In the case of pure compounds,ergostanes 5(25R-antcin H),6(25Santcin H)and 10(25R-antcin B)could readily pass through the Caco-2 cell layer,whereas lanostanes 13(dehydroeburicoic acid)and 14(eburicoic acid)could hardly pass through.When the cells were treated with A.cinnamomea extract,antcins A,B,C,H and K(1–6 and 9–11)were absorbed via passive transcellular diffusion,and showed high PAB and PBA values(>2.5×10^(-5) cm/s).Meanwhile,the lanostanes dehydrosulphurenic acid(8),15a-acetyldehydrosulphurenic acid(12),13 and 14 exhibited poor permeability.Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats.This study could also be helpful in predicting the intestinal absorption of A.cinnamomea in human.

Identification and determination of (+)-sesamin in Semen Cuscutae by capillary GC and GC-MS

(+)-Sesamin was found in Semen Cuscutae for the first time. A rapid and simple approach for the analysis of(+)-sesamin in different sources of Semen Cuscutae is proposed, which used GC-FID for the determination of(+)-sesamin and CC-MS for its identification. The result suggested that this approach could be used to identify Semen Cuscutae from various sources based on the different content of(+)-sesamin in them.

Chloride Assisted Growth of Aluminum Nitride Nanobelts and Their Enhanced Dielectric Responses

Aluminum nitride （AlN） nanobelts were successfully synthesized in high yield through a chloride assisted vapor-solid process. X-ray diffraction, transmission electron microscopy, and selected area electronic diffraction demonstrate that the as-prepared nanobelts are pure, structurally uniform and single crystalline, and can be indexed to hexagonal wurtzite structure. The micro observations show that there exist no defects in the obtained nanobelts. The growth direction of the nanobelts is along [0001]. The frequency spectra of the relative dielectric constant and of the dielectric loss were measured in the frequency range of 50 Hz to 5 MHz. Analysis of these spectra indicates that the interface in samples has great influence on the dielectric behavior of samples. As compared with AlN micropowders, AlN nanobelts have much higher relative dielectric constant, especially at low frequencies at room temperature.

Preliminary Study on Rooting Promotion Activity of 33 Species of Plant Extracts

[ Objective ] The paper was to study the rooting promotion activity of plant extracts, so as to lay the foundation for development of natural source of roo- fing reagent with high efficiency, safety and environment friendship. [Method] Using mung bean rooting method, the rooting promotion effects of 33 plant extracts on mung bean section were studied. [Result] When the concentration was 1 mg/mL, Eupatorium adenophorum （stem and leaf）, Cryptomeriafortunei （stem and leaf）, Pinus yunnanensis （stem）, Pinus yunnanensis （leaf）, Rhododendron simsii （leaf）, Pinus armandii （leaf）, Litchi chinensis （pericarp）, P/nus armandiifruit （fruit） and Alnus cremastogyne （leaf） showed strong promotion effect on rooting of mung bean sections, and the rooting promotion rate reached over 100% ; the roo- ting promotion effect ofE. adenophorum （stem and leaf） was the strongest, reaching（1068.42 ＋7.87）%, which was extremely higher than the extracts of other plants. [Conclusion] E. adenophorum （stem and leaf）, C. fortunei （stem and leaf）, P. yunnanens/s （stem）, P. yurmanens/s （leaf）, R. simsii （leaf）, P. armandii （leaf）, L. chinensis （pericarp）, P. armandiifruit （fruit） and A. cremastogyne （leaf） all contained substances with st/ong rooting promotion effect, which could be further used for development of natural rooting reagent.

Metabolites identification and quantification of antcin H in mice tumors after oral administration of the anticancer mushroom Antrodia camphorata

Objective： Antrodia camphorata （AC）, a precious medicinal mushroom in Taiwan, is popularly used for adjuvant cancer therapy. This paper aims to clarify the metabolites which are present in tumor tissues after oral administration of AC in Sarcoma-180 tumor-bearing mice, as well as their contents in tumors. Methods： Tumors of Sarcoma-180 tumor-bearing mice were obtained at 1 h and 4 h after oral administration of AC extract, and the metabolites in the tumor homogenate samples were characterized using UHPLC-orbitrap/MS analysis. Then, a fully validated LC-MS/MS method was developed for quantitative analysis of the most abundant compounds in tumor tissues, namely （25R/S）-antcin H. Results： A total of 33 compounds were characterized in tumor homogenate samples including 28 prototypes of triterpenoids and 5 metabolites. Among them, （25R）-antcin H and （25S）-antcin H had the highest contents of 2.03 and 0.66 μg/g tumor tissues for the 1 h group, and 2.04 and 0.59 μg/g tumor tissues for the 4 h group, respectively. It was obvious that （25R）-antcin H had higher tumor affinity than （25S）-antcin H, since the content of （25R）-antcin H was lower than that of （25S）-antcin H in AC extract （P 〈 0.01）. Conclusion： Triterpenoids can enter tumor tissues after oral administration of AC. Particularly, （25R）-antcin H showed higher exposure to tumor than （25S）-antcin H. These compounds could contribute to the anticancer activities of AC.

中医药治疗小儿厌食症的研究进展

该文总结分析近年来中医药治疗小儿厌食症的相关研究,发现小儿厌食症的病因病机涉及先天与后天因素,病变责之于脾胃,病机关键为脾胃不和,纳运失常;临床证型包括邪热不清证、湿滞中焦证、肝气犯胃证、伤食积滞证等;治疗方法主要包括推拿、针刺、穴位贴敷等外治法,经典方药、自拟方、中成药口服及中医食疗等内治法,以及内外合治法。

Review of advanced road materials, structures, equipment, and detection technologies

As a vital and integral component of transportation infrastructure,pavement has a direct and tangible impact on socio-economic sustainability.In recent years,an influx of groundbreaking and state-of-the-art materials,structures,equipment,and detection technologies related to road engineering have continually and progressively emerged,reshaping the landscape of pavement systems.There is a pressing and growing need for a timely summarization of the current research status and a clear identification of future research directions in these advanced and evolving technologies.Therefore,Journal of Road Engineering has undertaken the significant initiative of introducing a comprehensive review paper with the overarching theme of“advanced road materials,structures,equipment,and detection technologies”.This extensive and insightful review meticulously gathers and synthesizes research findings from 39 distinguished scholars,all of whom are affiliated with 19 renowned universities or research institutions specializing in the diverse and multidimensional field of highway engineering.It covers the current state and anticipates future development directions in the four major and interconnected domains of road engineering:advanced road materials,advanced road structures and performance evaluation,advanced road construction equipment and technology,and advanced road detection and assessment technologies.

基于PISA方法的大直径单桩水平承载特性

单桩基础作为海上风电机组的重要支撑结构,其水平承载能力关系到海上风电机组能否安全高效地运行。基于PISA设计方法,对大连庄河某海上风电场址32号桩嵌固深度、桩径、壁厚对单桩水平承载特性影响规律开展研究。结果表明:1)增加嵌固深度和桩径,可有效提高单桩水平承载能力,减小桩身水平变形;2)增加壁厚可小幅提升单桩水平承载能力,减少单桩水平变形,但改善效果极为有限;3)相较于传统p-y曲线法,PISA设计方法在保证安全变形前提下,可以设计更小的桩径或嵌固深度,有效降低单桩重量。

Efficacy and safety of Lianhuaqingwen capsules in high-risk common type COVID-19 pneumonia:A multicenter retrospective study

Objective:To evaluate the clinical safety and efficacy of Lianhuaqingwen(LHQW)capsules in patients with high-risk common type COVID-19 pneumonia.Methods:A retrospective multicenter study on 383 high-risk common type COVID-19 pneumonia cases was conducted.Patients were categorized as the standard treatment(SDT)group(n=168)and the LHQW+SDT group(n=215).The primary endpoint was the rate of symptom(fever,fatigue,coughing)recovery and the secondary endpoints included the time to symptom recovery,the proportion of patients with improvement in chest CT images,the proportion of patients with clinical cure,the timing and rate of negative conversion of SARS-CoV-2 RNA assay.Results:The recovery rate was significantly higher in the LHQW+SDT group as compared with the SDT group(89.7%vs.72.0%,P<0.01).The combined use of LHQW+SDT also showed shorter time for symptom recovery,as well as shorter time for individual symptom of fever,fatigue and coughing recovery than use of SDT alone.A higher proportion of patients in the LHQW+SDT group with improvements in chest CT images and clinical cure(77.7%vs.57.1%,P<0.01)but the proportion of patients deteriorating to severe cases(1%vs.25%,P<0.01)in this group was significant lower than those in the SDT group.No significant difference in negative conversion rate of viral assay results was observed(76.8%vs.75.0%,P>0.05).No serious adverse events were reported.Conclusions:LHQW capsules could be recommended to ameliorate clinical symptoms and reduce the rate of deteriorating to severe cases for high-risk common type COVID-19 pneumonia.

《牛津高中英语》Project板块教学设计与反思——以Unit 2 Let’s Talk Teens为例

针对《牛津高中英语》Project板块常常被忽略、简化及教学重心被误解为阅读,功能被削弱的事实,结合必修一Unit 2 Let’s Talk Teens案例,探讨该板块的教学设计。提出Project板块的教学设计思路,即服务单元主题,锚定核心素养;强化课前探究,构建实施“支架”;分析范例语篇,实现以“动”生成。认为教师应充分发挥Project板块的实践性和综合性的优势,实现育人价值。

用小波变换讨论地震中的多普勒现象

地震中多普勒效应可以确定地震的破裂面等,说明对多普勒效应的研究有实际意义,但目前确定地震中是否存在多普勒效应的方法并不成熟。在研究多普勒效应空间分布规律的基础上,提出用小波变换确定地震中是否存在多普勒效应的方法。选择位于汶川地震断层滑动前方的若干台站对台站最初时段的地震记录进行小波变换时,发现随着震中距的增加,小波谱高频幅值明显大于小波谱低频幅值;说明虽然存在介质对地震波的吸收衰减作用,但多普勒效应的存在仍使得小波谱高频幅值增大。选择与汶川地震断层垂直方位的若干台站对台站最初时段的地震记录进行小波变换时,发现随着震中距的增加,小波谱高频幅值迅速降低,震中距大到一定程度后低频部分的小波谱幅值会明显大于高频部分的小波幅值;说明在该方向上,介质对地震波的高频吸收衰减起主要作用,没有发生多普勒效应。

用随机有限断层方法模拟2016-11-13新西兰M_W7.8地震

在未来大地震发震构造已知的前提下,提出用经验公式确定大地震断层长度、宽度、地震矩和滑动分布等参数,并用随机有限断层方法预测未来大地震。用随机有限断层方法模拟2016-11-13新西兰M W7.8地震的12个基岩台站地震动时程和反应谱,并用模拟的频谱幅值与记录频谱幅值平均比值确定模拟误差。结果表明,在周期为0~10 s的范围内,模拟误差在0.92~1.08之间,不同频率模拟误差的标准差变化范围不超过1。95%的置信区间宽度随频率无明显变化,模拟结果反映了地震动记录的平均效果。用准随机方法重新获取新西兰大地震断层初始破裂点和位错滑动分布,模拟地震动并计算模拟误差随频率的变化,得到与最初模型相似的结论,从而进一步证实了本文提出的获取震源参数并用随机有限断层方法预测未来大地震的可靠性,且其特别适用于大地震远场模拟。

用相干体属性开展断层识别

利用地震属性可以提高三维地震解释的精度和速度,并且节约成本,有利于矿井安全生产。在重点对相干体属性做出阐述和分析的基础上,以永城煤矿为研究区,首先正确合理选用相干体属性的最优参数,然后将相干体属性应用于实例获取数据体,再从属性数据体中提取出沿层切片,最后对地震数据进行相干体处理后得到了地震剖面。与不经相干处理的的地震原始剖面相比较,经相干处理的地震剖面更清晰地反映了地层和断层。相干体方法是有前途的地震剖面解释方法。

半潜式浮式风机系统湿拖过程动力响应研究

研究浮式风力机系统整体湿拖的运动及拖缆张力,建立浮式风力机系统的水动力模型,基于三维势流理论计算浮式基础的水动力。考虑风、浪、流环境载荷,计算拖航过程浮式基础运动、风机法兰倾角、机舱加速度、拖缆张力等关键参数,分析缆长、有义波高、谱峰周期等参数对计算结果的影响。结果表明,在给定的环境参数范围内,浮式风机运动符合限制条件;拖缆越短相同环境参数下拖缆张力越大,600 m及以上缆长的拖缆张力相对稳定,受波浪参数影响较小。最后给出不同缆长作业的波浪参数限制条件,为浮式风机整体湿拖作业提供参考。

Irregular surface of carotid atherosclerotic plaque is associated with ischemic stroke: a magnetic resonance imaging study

Objective To determine the association between the irregularity of carotid plaque surface using multidimensional magnetic resonance imaging(MRI) of ipsilateral acute cerebral infarction(ACI) cases. Methods Patients with recent cerebrovascular symptoms(stroke or transient ischemic attack < 2 weeks) and atherosclerotic plaque in at least one carotid artery were diagnosed by B-mode ultrasound imaging(intima-media thickness ≥ 1.5 mm) and recruited for the present study. Irregular surface was defined when plaque surface was uneven with high and low fluctuation or plaque with surface ulceration. The irregularity of carotid plaque surface was determined on axial or oblique images alone(single-dimension) and on both axial images and oblique images(multidimensions), separately. Univariate and multivariate logistic regression analyses were performed to calculate the odds ratio(OR) and the corresponding 95% CI of the irregular plaque surface in discriminating the presence of ipsilateral ACI. Results A total of 217 included subjects(mean age: 60.7 ± 10.2 years, 149 men) were recruited and 89(41.0%), 88(40.6%) and 118(54.4%) of them exhibited irregular plaque surface on axial, oblique and multidimensional MR images, respectively. The OR of irregularity of the plaque surface was determined by multidimensional MRI to be 5.88(95% CI: 3.16–10.96, P < 0.001) in discriminating the presence of ipsilateral ACI. Following adjustment for clinical confounding factors, this association remained statistically significant(OR = 5.65, 95% CI: 2.53–12.60, P < 0.001). The analysis included further adjustment for the presence of lipid-rich necrotic core, intraplaque hemorrhage and stenosis and the results included that this association also remained statistically significant(OR = 6.08, 95% CI: 2.52–14.68, P < 0.001). Conclusions The irregular plaque surface was determined by multidimensional MRI as an independent indicator for ipsilateral acute cerebral infarction.