基于Tei指数评价蒽环类药物对急性白血病患儿心脏毒性的研究

目的应用超声技术监测急性白血病患儿使用蒽环类药物后的心功能,以期得到心功能早期变化的指标。方法按照入组与排除标准选取2018年3月至2020年12月昆明医科大学附属儿童医院白血病患儿,记录其常规心脏超声指标和组织多普勒,并应用TeiS、TeiRL、TeiM和TeiT评估心脏收缩功能的变化。结果正常组和用药前实验组常规心脏超声指标中LVEF的均值都在60%以上,FS、SV及EDV均在正常范围,常规指标、TDI和Tei指数无统计学意义(P>0.05);实验组累积剂量为200和250 mg/m^(2)组的TeiM与用药前存在显著差异(P<0.05);200和250 mg/m^(2)组与用药前的TeiRL存在显著差异(P<0.05);200和250 mg/m^(2)组与用药前的TeiT存在显著差异(P<0.05)。结论Tei指数可作为白血病患儿应用蒽环类药物后左右心功能的早期改变较敏感监测指标。

Fracture propagation and evolution law of indirect fracturing in the roof of broken soft coal seams

Indirect fracturing in the roof of broken soft coal seams has been demonstrated to be a feasible technology.In this work,the No.5 coal seam in the Hancheng block was taken as the research object.Based on the findings of true triaxial hydraulic fracturing experiments and field pilot under this technology and the cohesive element method,a 3D numerical model of indirect fracturing in the roof of broken soft coal seams was established,the fracture morphology propagation and evolution law under different conditions was investigated,and analysis of main controlling factors of fracture parameters was conducted with the combination weight method,which was based on grey incidence,analytic hierarchy process and entropy weight method.The results show that“士”-shaped fractures,T-shaped fractures,cross fractures,H-shaped fractures,and“干”-shaped fractures dominated by horizontal fractures were formed.Different parameter combinations can form different fracture morphologies.When the coal seam permeability is lower and the minimum horizontal principal stress difference between layers and fracturing fluid injection rate are both larger,it tends to form“士”-shaped fractures.When the coal seam permeability and minimum horizontal principal stress between layers and perforation position are moderate,cross fractures are easily generated.Different fracture parameters have different main controlling factors.Engineering factors of perforation location,fracturing fluid injection rate and viscosity are the dominant factors of hydraulic fracture shape parameters.This study can provide a reference for the design of indirect fracturing in the roof of broken soft coal seams.

The“depict”strategy for discovering new compounds in complex matrices:Lycibarbarspermidines as a case

The comprehensive detection and identification of active ingredients in complex matrices is a crucial challenge.Liquid chromatography coupled with high-resolution mass spectrometry(LC-HRMS)is the most prominent analytical platform for the exploration of novel active compounds from complex matrices.However,the LC-HRMS-based analysis workflow suffers from several bottleneck issues,such as trace content of target compounds,limited acquisition for fragment information,and uncertainty in interpreting relevant MS2 spectra.Lycibarbarspermidines are vital antioxidant active ingredients in Lycii Fructus,while the reported structures are merely focused on dicaffeoylspermidines due to their low content.To comprehensively detect the new structures of lycibarbarspermidine derivatives,a“depict”strategy was developed in this study.First,potential new lycibarbarspermidine derivatives were designed according to the biosynthetic pathway,and a comprehensive database was established,which enlarged the coverage of lycibarbarspermidine derivatives.Second,the polarity-oriented sample preparation of potential new compounds increased the concentration of the target compounds.Third,the construction of the molecular network based on the fragmentation pathway of lycibarbarspermidine derivatives broadened the comprehensiveness of identification.Finally,the weak response signals were captured by data-dependent scanning(DDA)followed by parallel reaction monitoring(PRM),and the efficiency of acquiring MS2 fragment ions of target compounds was significantly improved.Based on the integrated strategy above,210 lycibarbarspermidine derivatives were detected and identified from Lycii Fructus,and in particular,170 potential new compounds were structurally characterized.The integrated strategy improved the sensitivity of detection and the coverage of low-response components,and it is expected to be a promising pipeline for discovering new compounds.

Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in patients.As a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological processes.However,it remains elusive whether and how YAP may control autophagy activation during ischemia-reperfusion.Methods:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy activation.Both an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of regulation.Results:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of hepatocytes.Liver-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with 3-methyladenine.In addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of hepatocytes.Targeting Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

The Effect of Self-Investment on Hoarding Tendency of Chinese College Students:Role of Psychological Connections

Because of factors such as energy and time one invests in an object,the stronger the connection,value,and reluc-tance to lose said object individual will have.Hoarding behavior arises when individuals incorporate a strong attachment with themselves to an object.The purpose of this study is to examine the effect of self-investment on hoarding tendency and the roles of possession-self link and liking level in this connection.A hypothetical model of the relationship between self-investment,possession-self link,liking level,and hoarding tendency was tested.A convenience sampling method was used to survey 450 college students in Yunnan Province on either a paper-based or online self-report scale.The data were collected using self-investment,possession-self link,and liking level questionnaires,as well as the Saving Inventory Revised.Results showed positive relationship between the study variables,ranging from 0.37 to 0.87.College students’self-investment had a direct positive pre-dictive effect on hoarding tendency;self-investment,in turn,indirectly predicted hoarding tendency through the mediating effect of possession-self link;and individual liking level of items had a moderating effect for self-invest-ment on the possession-self link.This study shows how self-investment affects the hoarding tendency of college students,and the results of this study also help demonstrate the value of self-investment and possession-self link in optimizing students’hoarding tendency and thus promoting good psychological status.

以去氢弯孢霉素NMR结构解析讲授本科生波谱分析课程

以去氢弯孢霉素核磁共振波谱(NMR)解析为例,讲授本科化学和药学相关专业波谱分析课程NMR解析。去氢弯孢霉素结构包含苯环、双键、酚羟基、羰基和酯基等常见基团,NMR信号几乎无重叠、辨识度高,非常适合作为核磁共振波谱结构解析中化学位移、耦合常数和二维核磁共振波谱的授课内容。

The Influence of Body Investment on Depression in Chinese College Students:A Moderated Mediating Effect

An individual’s perception,attitude,feeling and behavior about their body are important factors for mental health(depression).This study aims to explore the impact of body investment on depression,and the role of self-efficacy and self-esteem in this connection.A hypothetical model about the relationship between body investment,selfefficacy,self-esteem and depression was tested.Using convenient sampling methods,a self-rated cross-sectional survey comprised of paper-based and online modes was conducted among 1,164 college students in Yunnan Province,China from July 2021 to August 2021.The data collection used the body investment scale,self-efficacy scale,self-esteem scale and depression scale.The results show that there is a low to moderate positive correlation(ranging between-0.11 and-0.59)between the research variables.The body investment of college students has a negative predictive effect(B=16.23,SE=0.65)on depression.This connection is also regulated by the mediating role of self-esteem and self-efficacy.All these factors explain 37.83%variability of research participation.These findings show how body investment affects the depressive state of college students.Further,these results help to demonstrate that self-efficacy and self-esteem are academically important for optimizing students’depression,so as to promote a good mental state.

Screening of Potent Inhibitor of H1N1 Influenza NS1 CPSF30 Binding Pocket by Molecular Docking

The swine flu, H1N1 virus was outbroken in Mexico and the United States in April 2009 and then rapidly spread worldwide. The World Health Organization declared that the outbreak of influenza is caused by a new subtype of influenza H1N1 influenza virus. And researchers have isolated some oseltamivir resistance strains in 2009 swine flu which makes the imminency of research and development of new anti influenza drug. The CPSF30 binding pocket of effector domain in NS1 protein is very important in the replication of influanza A virus and is a new attractive anti flu drug target. But up to now there is no antiviral drug target this pocket. Here we employ molecular docking to screening of about 200,000 compounds. We find four novel compounds with high binding energy. Binding comformation analysis revealed that these small molecules can interact with the binding pocket by some strong hydrophobic interaction. This study find some novel small molecules can be used as lead compounds in the development of new antiinfluenza drug based on CPSF30 pocket.

On Self and Other

In the philosophy of mind, the essential qualities of self and selfhood have been discussed widely. According to Zahavi （2015, 149）, ＂the notion of an experiential self is the precondition of any plausible account of intersubjectivity.＂ In Zahavi （2015）, he elaborates two influential views on selfhood and offers a phenomenological perspective from which he argues that selfhood is both a built-in feature of experience and socially constructed. In the following paper, we would further investigate the essential qualities of self in the line with Zahavi （2015） and provide a complementary quality of self from a phenomenological view, namely, the predictability of the expressive phenomena of subjects. We would also explore the intersubjective relationship between others and self and discuss the sharing phenomenon of empathy.

Application of a quantitative ^1H NMR method for rapid extraction and determination of the content of paeonol in Cynanchum paniculatum

Cynanchum paniculatum(Bunge) Kitagawa is usually used as an herbal medicine for treating many diseases. Paeonol is the main active component, and its content is the key indicator for quality control of C. paniculatum. In the present study, we developed a rapid, accurate and precise method for quantitation of paeonol in C. paniculatum using 1 H NMR spectra. The deuterated solvent of methanol-d4 enabled satisfactory separation of the signals to be integrated in 1 H NMR spectrum. H-6(δ 7.78) of 1 H NMR spectrum of C. paniculatum was selected as the feature signal for quantitation, and trimesic acid(TMA) was selected as an internal standard. Validation of the quantitative method was performed in terms of linearity, specificity, repeatability and stability. This is the first time to report quantitative 1 H NMR(qHNMR) applied to determine the content of paeonol in C. paniculatum and showed a wider linearity range than the reported quantitation of paeonol in others. The simple extraction of paeonol from C. paniculatum was rapid and will prompt the application of the developed method. This work implied that qHNMR represented a feasible alternative to HPLC-based methods for quantitation of paeonol in C. paniculatum, and it was suitable for the quality control of C. paniculatum.

The antioxidant activity and total phenolic and total flavonoid contents of Pyracantha fortuneana fruit can be improved by solid-state fermentation with Rhizopus oryzae and Penicillium commune

The fruits of Pyracantha fortuneana(Maxim.)Li were fermented with pure fungi to improve their antioxidant capacity.The antioxidant activities of fermented and non-fermented P.fortuneana fruits were estimated by 1,1-diphenyl-2-picrylhydrazyl(DPPH)and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate)(ABTS)radical scavenging activities,as well as ferric ion reducing antioxidant power(FRAP).The total phenolic content(TPC)and total flavonoid content(TFC)were also determined.Additionally,the changes caused by fermentation were characterized by proton nuclear magnetic resonance spectroscopy(1H NMR).The results showed that P.fortuneana fruits fermented with Rhizopus oryzae and Penicillium commune exhibited stronger antioxidant activity compared with the non-fermented material.Correlation analysis indicated that the increased activity might be ascribed to the improvement of TPC.Chemical characterization of 1H NMR implied that the increased TPC and antioxidant activity might be attributed to some of the phenolic and flavonoid glycosides hydrolyzed to new components during fermentation.The present study was the first report of the fermentation of P.fortuneana fruit with pure fungal strains and suggested that fermentation of P.fortuneana fruits with R.oryzae and P.commune was an effective alternative approach to increase antioxidant,and P.fortuneana fruit fermented by R.oryzae and P.commune might be the new alternative of natural antioxidants.

Plasma non-transferrin-bound iron uptake by the small intestine leads to intestinal injury and intestinal flora dysbiosis in an iron overload mouse model and Caco-2 cells

Iron overload often occurs during blood transfusion and iron supplementation, resulting in the presence of non-transferrin-bound iron(NTBI) in host plasma and damage to multiple organs, but effects on the intestine have rarely been reported. In this study, an iron overload mouse model with plasma NTBI was established by intraperitoneal injection of iron dextran. We found that plasma NTBI damaged intestinal morphology, caused intestinal oxidative stress injury and reactive oxygen species(ROS) accumulation,and induced intestinal epithelial cell apoptosis. In addition, plasma NTBI increased the relative abundance of Ileibacterium and Desulfovibrio in the cecum, while the relative abundance of Faecalibaculum and Romboutsia was reduced. Ileibacterium may be a potential microbial biomarker of plasma NTBI. Based on the function prediction analysis, plasma NTBI led to the weakening of intestinal microbiota function, significantly reducing the function of the extracellular structure. Further investigation into the mechanism of injury showed that iron absorption in the small intestine significantly increased in the iron group. Caco-2 cell monolayers were used as a model of the intestinal epithelium to study the mechanism of iron transport. By adding ferric ammonium citrate(FAC, plasma NTBI in physiological form) to the basolateral side, the apparent permeability coefficient(Papp) values from the basolateral to the apical side were greater than 3×10^(-6)cm s^(-1). Intracellular ferritin level and apical iron concentration significantly increased, and SLC39A8(ZIP8) and SLC39A14(ZIP14) were highly expressed in the FAC group.Short hairpin RNA(sh RNA) was used to knock down ZIP8 and ZIP14 in Caco-2 cells. Transfection with ZIP14-specific sh RNA decreased intracellular ferritin level and inhibited iron uptake. These results revealed that plasma NTBI may cause intestinal injury and intestinal flora dysbiosis due to the uptake of plasma NTBI from the basolateral side into the small intestine, which is probably mediated by ZIP14.

Novel resonant pressure sensor based on piezoresistive detection and symmetrical in-plane mode vibration

In this paper,a novel resonant pressure sensor is developed based on electrostatic excitation and piezoresistive detection.The measured pressure applied to the diaphragm will cause the resonant frequency shift of the resonator.The working mode stress–frequency theory of a double-ended tuning fork with an enhanced coupling beam is proposed,which is compatible with the simulation and experiment.A unique piezoresistive detection method based on small axially deformed beams with a resonant status is proposed,and other adjacent mode outputs are easily shielded.According to the structure design,high-vacuum wafer-level packaging with different doping in the anodic bonding interface is fabricated to ensure the high quality of the resonator.The pressure sensor chip is fabricated by dry/wet etching,high-temperature silicon bonding,ion implantation,and wafer-level anodic bonding.The results show that the fabricated sensor has a measuring sensitivity of~19 Hz/kPa and a nonlinearity of 0.02%full scale in the pressure range of 0–200 kPa at a full temperature range of−40 to 80°C.The sensor also shows a good quality factor>25,000,which demonstrates the good vacuum performance.Thus,the feasibility of the design is a commendable solution for high-accuracy pressure measurements.

钇掺杂锆酸钡中点/线缺陷结构及氧扩散机理的分子动力学模拟

钇掺杂锆酸钡具有优异的化学稳定性和离子电导率,是固体氧化物燃料电池电解质最有吸引力的候选材料之一.本文采用经典分子动力学模拟方法首次研究点缺陷和线缺陷共存的锆酸钡体系,分别得到钇掺杂剂和氧空位浓度以及刃位错对体系结构和氧传输性质的影响.结果表明,钇掺杂剂浓度过高或者过低,都不利于氧传导;无论有无刃位错缺陷, 30%钇掺杂锆酸钡体系的氧离子扩散系数更高.在1073.15 K的温度下,掺杂剂浓度小于30%时,刃位错的存在会加速氧离子扩散,这一现象可以通过刃位错、氧空位以及氧离子之间的富集-慢跑传输机制来解释.因此,在固体电解质的实际应用中,锆酸钡的掺杂剂浓度不能太高,并且可以考虑制造线缺陷来提高离子电导率.