Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling

Microtubule-associated serine/threonine kinase(MASTL)functions to regulate chromosome condensation and mitotic progression.Therefore,aberrant MASTL expression is commonly implicated in various human cancers.This study analyzed MASTL expression in gastric cancer vs.adjacent normal tissue for elucidating the association with clinicopathological data from patients.This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro.The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN,GEPIA,and Oncomine online databases.Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells.RT-qPCR,Western blotting,cell viability,cell counting,flow cytometric apoptosis and cell cycle,and colony formation assays were performed.MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue,and the MASTL expression was associated with advanced tumor stage,Helicobacter pylori infection and histological subtypes.On the other hand,knockdown of MASTL expression significantly reduced tumor cell viability and proliferation,and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis.At protein level,knockdown of MASTL expression enhanced levels of cleaved PARP1,cleaved caspase-3,Bax and p-ERK1/2 expression,but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells.MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression,whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis.Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

Optimal Formula of Angelica sinensis Ameliorates Memory Deficits in β-amyloid Protein-induced Alzheimer's Disease Rat Model

Objective:Angelica(A.)sinensis is used as a traditional medical herb for the treatment of neurodegeneration,aging,and inflammation in Asia.A.sinensis optimal formula(AOF)is the best combination in A.sinensis that has been screened to rescue the cognitive ability in P-amyloid peptide(Ap25-35)-treated Alzheimer’s disease(AD)rats.The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms.

Synchronization of High-order Discrete-time Linear Complex Networks with Time-varying Delays

Synchronization of high-order discrete-time complex networks with undirected topologies is studied and the impacts of time delays are investigated. Firstly,by the state decomposition,synchronization problems are transformed into asymptotic stability ones of multiple lower dimensional time-delayed subsystems. Then,linear matrix inequality( LMI) criteria for synchronization are given,which can guarantee the scalability of complex networks since they only include three LMI constraints independent of the number of agents. Moreover,an explicit expression of the synchronization function is presented,which can describe the synchronization behavior of all agents in complex networks. Finally,a numerical example is given to demonstrate the theoretical results,where it is shown that if the gain matrices of synchronization protocols satisfy LMI criteria for synchronization,synchronization can be achieved.

Resveratrol ameliorates diabetic myocardial injury through HSF1-mediated ferroptosis

Objective:To observe the effect of resveratrol on the injury of diabetic cardiomyocytes and its effect on HSF1 mediated iron death.Methods:the diabetic cardiomyopathy model was established by high glucose induced H9c2,and H9c2 was exposed to normal glucose concentration as a control.Then the intervention was performed with the corresponding drugs.The cell proliferation level was detected by CCK8 method,the concentrations of LDH,SOD,MDA and iron ions were detected by kit method,and the expression levels of HSF1,apoptotic proteins(Bax and Bcl-2)and iron death marker proteins(ACSL4,GPX4 and SLC7A11)were detected by Western blot;Results:compared with the blank group,the cell activity,SOD activity,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein in the model group decreased significantly,and the LDH activity,MDA content,Bax and ACSL4 protein expression,Bax/Bcl-2 ratio and Fe^(2+)content increased significantly(P<0.01).Compared with the model group,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein increased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)decreased significantly in the resveratrol group(P<0.01).After the intervention,the activity of H9c2 cells,the activity of SOD,the expression of HSF1,Bcl-2,GPX4 and SLC7A11 protein decreased significantly,and the activity of LDH,the content of MDA,the expression of Bax and ACSL4 protein,the ratio of Bax/Bcl-2 and the content of Fe^(2+)increased significantly in si-hsf1 group(P<0.01);Conclusion:resveratrol can inhibit cell iron death and improve high glucose induced cardiomyocyte injury by up regulating the expression of HSF1.

Study on the preparation and quality standard of Callicarpa nudiflora film

Objective:To screen the best prescription and technology of Callicarpa nudiflora film,and to study and establish the quality standard of the flim.Methods:The orthogonal test was used to investigate the effect of PVA content,glycerin content,ethanol and water ratio on the comprehensive score of the coating agent;the general inspection method and content determination method were used to control the quality of Callicarpa nudiflora film,and the quality standard of the film was established.Results:The best formulation was selected as polyvinyl alcohol 6.0g,glycerin 2ml,ethanol:water 1:1.The appearance,stability,heat and cold resistance of the film were good,and the quality standard of the film was established.Conclusion:The formulation is simple and feasible,and the quality control method of the film is stable and feasible.

Novel Coil Winding Method to Realize Pot Heated Evenly

To solve the problem about the inhomogeneous thermal effect of pot heated by coils along the circumference, a novel coil winding method is proposed and compared with the general winding method in the paper. First, based on the Biot-Savart law and Ampere＇s rule, the magnetic induction generated by a straight current carrying conductor and a current loop is discussed, respectively. Then the novel coil winding method is developed by adjusting the location of inhomogeneous joints. The joints are periodically scattered along the circumferential direction and symmetrically designed around the central axis.Numerical results show that the quite non-uniform temperature in the base of pot at the circular direction is effectively improved by using the proposed winding method. The potential danger produced by high temperature at some region of coils plate is minimized.It is energy-efficient and safe for residential appliances.

医学评估量表用户手册撰写框架的定性系统评价

目的系统评价医学评估量表用户手册的撰写框架。方法计算机检索PubMed、Embase、The Cochrane Library、中国知网、万方、维普数据库,学科范围限制为生物医学卫生领域,检索时间从建库至2021年1月,纳入量表用户手册的相关文献或仅提及量表用户手册名称的文献,辅以补充检索相应参考文献和量表官网,由两名研究员独立提取信息,采用主题综合法形成量表用户手册的撰写框架。结果共纳入31篇文献,涉及31个评估量表用户手册,各手册撰写框架不同,包括前言、背景、工具概要、使用方法、条目介绍、案例分析、附件和参考文献8个部分,其中条目介绍的报告频率最高(68%)。结论医学领域评估量表的用户手册撰写框架尚无统一标准,但各手册均以条目介绍、结果解释及结论等内容为主,辅以工具研发背景等内容,开发者可根据目标人群特征拟定框架,开发不同详略程度和表述风格的用户手册,以提高手册使用效率。

Interaction between cyclooxygenase-2,Snail,and E-cadherin in gastric cancer cells

AIM:To investigate the mechanisms of how cyclooxygenase-2(COX-2)regulates E-cadherin in gastric cancer cells.METHODS:COX-2 expression in human gastric cancer cell lines SGC-7901,BGC-823,MGC-803 and AGS were measured at the mRNA and protein level.COX-2 rich cell line SGC-7901 was chosen for subsequent experiments.siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB),Snail,and E-cadherin in gastric cancer cells.Gene expression was determined by Western blot and real-time polymerase chain reaction.To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2(PGE2)on E-cadherin,gastric cancer cells were treated with celecoxib or PGE2,in the presence of NF-κB specific siRNA.RESULTS:Highest expression level of COX-2 was found in SGC-7901 cells,both at mRNA and protein levels.siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail,but an increased expression of E-cadherin in SGC-7901 cells.siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells.However,COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells.Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin.In contrast,treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin.However,siRNAmediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.CONCLUSION:COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.

Overexpression of MiR-633 Suppresses the Tumorigenicity of Gastric Cancer Cells and Induces Apoptosis by Targeting MAPK1

Objective MicroRNA(miRNA/miR)-633 is dysregulated in several types of cancers and is involved in tumorigenesis.However,the function and role of this miRNA in gastric cancer(GC)are not fully understood.The aim of the present study was to evaluate miR-633 expression in GC cell lines and in GC tissue vs.adjacent normal tissue,and to determine its association with clinicopathological data.This work was extended to investigate the effects of miR-633 overexpression on tumor cells in vitro.Methods Reverse transcription-quantitative PCR(RT-qPCR)was used to detect and compare the expression level of miR-633 in GC cells,as well as in GC and normal adjacent tissue samples.The clinical significance of miR-633 was also analyzed.MiR-633 lentivirus(LV-miR-633)and negative control lentivirus(LV-NC)were generated and used to transduce SGC-7901 and HGC-27 GC cells in order to analyze the effect of miR-633 on their phenotype.The effects of miR-633 overexpression on GC cell proliferation,apoptosis,migration and invasion were investigated.The target gene of miR-633 was predicted,then confirmed using a dual luciferase reporter gene assay,RT-qPCR and Western blotting.Results MiR-633 was significantly downregulated in GC cell lines,as well as in GC tissue compared with adjacent normal tissue.Moreover,miR-633 expression was associated with the tumor/node/metastasis(TNM)stage,invasion depth,Borrmann classification and lymph node metastasis(P<0.05).Compared with the LV-NC group,transduction with LV-miR-633 reduced the proliferation,the number of clones,the wound healing rate,the number of invading cells and the number of cells in the G1 phase of the cell cycle(P<0.01).LV-miR-633 also increased the apoptosis rate(P<0.01).The expression level of mitogen-activated protein kinase(MAPK)1,high-mobility group box 3(HMGB3),claudin 1(CLDN1)and MAPK13 were downregulated in LV-miR-633-transduced cells(P<0.01).The dual luciferase reporter assay confirmed that the 3′-untranslated region of MAPK1 was the target site of miR-633(P<0.01).Conclusion MiR-633 acts as a tumor suppressor in GC,and its expression level is associated with TNM stage,invasion depth,Borrmann type and lymph node metastasis.Overexpression of miR-633 inhibits the proliferation and migration of GC cells and induces apoptosis and cell cycle arrest at the in G1 phase.In addition,miR-633 negatively regulates the expression of MAPK1,HMGB3,CLDN1 and MAPK13 and directly targets MAPK1.

Numerical Analysis of Artificial Electron Heating Effects on Polar Mesospheric Winter Echoes

In this paper,an analytical model is used to analyze the modulated polar mesospheric winter echoes(PMWE).The winter parameters were introduced to simulate the effects of different parameters during the artificial electron heating of PMWE.The important role of the charged dust particle in the creation of PMWE is confirmed again.It is found that during the heating of PMWE,the increases of the dust size,dust charge,electron temperature,initial electron density,and ion-neutral collision frequency cause the increase of the electron density irregularity,and hence the PMWE strength.However,with increasing the dust density,the electron density irregularity and the PMWE strength decrease.

Ka波段高效率扩展互作用振荡器的电路设计（英文）

设计并讨论了一种高效率的基于梯形结构的扩展互作用振荡器(EIO)。优化了提升器件效率的关键因素包括间隙数目、频率分隔度、间隙长度、特性阻抗R/Q和品质因数Qe,从而实现有效电子束调制并避免模式竞争。本文初步设计了适用于高互作用效率的EIO电路。

Estimating submarine groundwater discharge and associated nutrient inputs into Daya Bay during spring using radium isotopes

Daya Bay, a semi-enclosed bay in the South China Sea, is well known for its aquaculture, agriculture, and tourism. In recent years, many environmental problems have emerged, such as the frequent(almost yearly) occurrence of harmful algal blooms and red tides. Therefore,investigations of submarine groundwater discharge(SGD) and associated nutrient inputs to this bay have important theoretical and practical significance to the protection of the ecological system. Such a study was conducted using short-lived radium isotopes ^(223)Ra and ^(224)Ra. The estimated SGD fluxes were 2.89 × 10~7 m^3/d and 3.05 × 10~7 m^3/d based on ^(223)Ra and ^(224)Ra, respectively. The average SGD flux was about 35 times greater than that of all the local rivers. The SGD-associated dissolved inorganic nitrogen(DIN) and dissolved inorganic phosphorus(DIP)fluxes ranged from 1.95 × 10~6 to 2.06 × 10~6 mol/d and from 5.72 × 10~4 to 6.04 × 10~4 mol/d, respectively. The average ratio of DIN to DIP fluxes in SGD was 34, much higher than that in local rivers(about 6.46), and about twice as large as the Redfield ratio(16). Our results indicate that SGD is a significant source of nutrients to the bay and may cause frequent occurrence of harmful algal blooms. This study provides baseline data for evaluating potential environmental effects due to urbanization and economic growth in this region.

Plasma simulation to analyze velocity distribution characteristics of pseudospark-sourced electron beam

Pseudospark-sourced electron beam is a promising candidate for driving vacuum electronic devices to generate millimeter wave and terahertz wave radiation as it has a very high combined beam current density. However, the inherent velocity spread of the beam, which is difficult to measure in experiment, has a great influence on the operating frequency and efficiency of the vacuum electronic device. In this paper, the velocity distribution characteristics of the electron beam produced by a single-gap hollow cathode electron gun are numerically studied and a three-dimensional kinetic plasma simulation model of a single-gap hollow cathode electron gun is built by using particle in cell and Monte Carlo collision methods in Vorpal. Based on the simulation model, the time-dependent evolution of the plasma formation inside the hollow cathode and electron beam generation process are observed. It is demonstrated that the pseudospark-sourced electron beam has a relatively large velocity spread. The time-dependent velocity distribution of the beam is analyzed, and the dependence of the beam velocity distribution under various operating conditions such as anode–cathode potential difference, gas pressure, and cathode aperture size are also studied.

Clinical significance and influencing factors of linked color imaging technique in real-time diagnosis of active Helicobacter pylori infection

Background:Determining the Helicobacter pylori (H. pylori) infection state during the gastroscopic process is important but still challenging. The linked color imaging (LCI) technique might emphasize the mucosal color change after H. pylori infection, which might help the diagnosis. In the present study, we aimed to compare the LCI technique with traditional white light imaging (WLI) endoscopy for diagnosing active H. pylori infection.Methods:We collected and analyzed gastroscopic images from 103 patients in our hospital from November 2017 to March 2018, including both LCI and WLI modes. All images were randomly disordered and independently evaluated by four endoscopists who were blinded to the H. pylori status of patients. In addition, the H. pylori state was determined by both rapid urease test and pathology staining. The sensitivity, specificity, positive prediction value (PPV), and negative prediction value (NPV) were calculated for the detection of H. pylori infection. Moreover, the kappa value and interclass correlation coefficient (ICC) were used to evaluate the inter-observer variety by SPSS 24.0 software.Results:Of the 103 enrolled patients, 27 of them were positive for H. pylori infection, while the 76 patients were negative. In total, 388 endoscopic images were selected, including 197 WLI and 191 LCI. The accuracy rate for H. pylori evaluation in the corpus LCI group was significantly higher than other groups (81.2% vs. 64.3%-76.5%, χ2 = 34.852, P < 0.001). Moreover, the corpus LCI group had the optimal diagnostic power with the sensitivity of 85.41% (95% confidence interval [CI]: 76.40%-91.51%), the specificity of 79.71% (95% CI: 74.38%-84.19%), the PPV of 59.42% (95% CI: 50.72%-67.59%), and the NPV of 94.02% (95% CI: 89.95%-96.56%), respectively. The kappa values between different endoscopists were higher with LCI than with WLI (0.433-0.554 vs. 0.331-0.554). Consistently, the ICC value was also higher with LCI than with WLI (0.501 [95% CI: 0.429-0.574] vs. 0.397 [95% CI: 0.323-0.474]). We further analyzed the factors that might lead to misjudgment, revealing that active inflammation might disturb WLI judgment (accuracy rate: 58.70% vs. 76.16%, χ2 = 21.373, P < 0.001). Atrophy and intestinal metaplasia might affect the accuracy of the LCI results (accuracy rate: 66.96% vs. 73.47%, χ2 = 2.027;68.42% vs. 73.53 %, χ2 = 1.594, respectively);however, without statistical significance (P = 0.154 and 0.207, respectively).Conclusions:The application of LCI at the corpus to identify H. pylori infection is reliable and superior to WLI. The inter-observer variability is lower with LCI than with WLI.

Effects of keto acid supplements on Chinese patients receiving maintenance hemodialysis:a prospective,randomized,controlled,single-center clinical study

Background:The effects of keto acid(KA)supplements on Chinese patients receiving maintenance hemodialysis(MHD)are unclear.This study aimed to evaluate the effects of KA supplementation on nutritional status,inflammatory markers,and bioelectric impedance analysis(BIA)parameters in a cohort of Chinese patients with MHD without malnutrition.Methods:This was a prospective,randomized,controlled,single-center clinical study conducted in 2011 till 2014.Twenty-nine patients with MHD were randomly assigned to a control(n=14)or a KA(n=15)group.The control group maintained a dietary protein intake of 0.9 g/kg/day.The KA group received additional KA supplement(0.1 g/kg/day).BIA was used to determine the lean tissue mass,adipose tissue mass,and body cell mass.The patients,nutritional status,dialysis adequacy,and biochemical parameters were assessed at the ends of the third and sixth months with t test or Wilcoxon rank-sum test.Results:The daily total energy intake for both groups was about 28 kcal/kg/day.After 6 months,the Kt/V(where K is the dialyzer clearance of urea,t is the dialysis time,and V is the volume of the distribution of urea)was 1.33±0.25 in KA group,and 1.34±0.25 in the control group.The median triceps skin-fold thickness in KA group was 12.00 and 9.00 mm in the control group.In addition,the median hand-grip strength in KA group was 21.10 and 25.65 kg in the control group.There were no significant differences between the groups with respect to the anthropometry parameters,dialysis adequacy,serum calcium and phosphorus levels,inflammatory markers,and amino-acid profiles,or in relation to the parameters determined by BIA.Both groups achieved dialysis adequacy and maintained nutritional status during the study.Conclusions:In this cohort of Chinese patients with MHD,the patients in the control group whose dietary protein intake was 0.9 g/kg/day and total energy intake was 28 kcal/kg/day,maintained well nutritional status during study period.The KA supplement(0.1 g/kg/day)did not improve the essential amino acid/non-essential amino acid ratio,nor did it change the patients5 mineral metabolism,inflammatory parameters,or body compositions.

Chemical Constituents with Antihyperlipidemic Activities from Desmodium triquetrum

Objective To study the chemical constituents from Desmodium triquetrum and their antihyperlipidemic activities. Methods The constituents of D. triquetrumwere isolated and purified using various column chromatographies. Their chemical structures were elucidated using extensive spectroscopic methods. The lipid-lowering effects of the isolates were evaluated in HepG2 cells. Results Nine compounds were obtained from the ethanol extract of D. triquetrum and determined to be 6＇-O-cis-p-coumaroyl- 3,5-dihydroxyphenyl-β-D-glucopyranoside （1）, tadehaginoside （2）, rutin （3）, quercetin-3-O-β-D-glucopyranoside （4）, quercetin-3-O-β-D-galactopyranoside （5）, 6-O-（E）-p-hydroxy-cinnamoyl-β-glucose （6）, 6-O-（E）-p-hydroxy-cinnamoyl-α-glucose （7）, kaempferol-3-O-β-D-rutinoside （8）, and 3-O-β-D-galacopyranosyl （6-1）-α-L- rhamnosyl quercetin （9）. Compounds 1 and 2 significantly reduced the intracellular content of total cholesterols and triglycerides. Conclusion Compound 1 is a new phenolic compound and exhibits potent anti-hyperlipidemic activity. Additionally, compounds 6 and 7 are isolated from D. triquetrum for the first time.

High Tensile Strength and Superelasticity of Directionally Solidified Ti_(30)Ni_(30)Fe_(10)Hf_(10)Nb_(20) Eutectic High Entropy Alloy

Superelasticity has been widely used in various fields.High elastic limit simultaneously with large superelasticity is urgent in the critical applications.In this study,we have employed the high entropy alloy(HEA)concept to develop a new TiHfNiFe-Nb eutectic HEA(EHEA)based on the TiNi-Nb eutectic alloy.The results show the directional catkin-like microstructure with the fiber eutectic in the center and the lamella eutectic in the outside form along the directional solidification direction when the growth rate is 60 mm/h.The corresponding specimens display the high strength of 1409 MPa and superelasticity of 3.1%in tension at room temperature,which is attributed to the synergetic effect of high entropy,preferred orientation,ordered body-centered cubic(B2)phase and disordered body-centered cubic phase in the eutectic structure.This work sheds light on designing the high-performance superelastic function materials with EHEAs.

Anti-inflammatory activities of gentiopicroside against iNOS and COX-2 targets

Objective: To isolate high-purity gentiopicroside from the Chinese herbal Gentiana officinalis and investigate its anti-inflammatory activity against iNOS and COX-2 targets.Methods: The purity and structures of gentiopicroside were determined by HPLC, IR, NMR, and MS. The anti-inflammatory effects of gentiopicroside were investigated by in vivo, in vitro, and molecular experiments.Results: In vitro experiment results showed that gentiopicroside inhibited nitric oxide(NO), prostaglandin E2(PGE2), and interleukin-6(IL-6) production in mouse macrophages RAW 264.7 stimulated by lipopolysaccharide. In vivo experiment found that xylene-induced mouse ear swelling was inhibited by gentiopicroside with an inhibition rate of 34.17%. Molecular docking of cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(i NOS) with gentiopicroside showed that hydrogen bonds(H-bonds) were formed between the sugar fragments in gentiopicroside structure with Tyr355, Ser353, Leu352, Ser530,Arg120, and His90 of COX-2, and Glu377, Asp382, Tyr373, Tyr347, Gln263, Asn370, and Gly371 of i NOS.Thus, gentiopicroside had a lower docking score and displayed satisfactory anti-inflammatory activities.Conclusion: These results suggested that the mechanism of anti-inflammatory activity of gentiopicroside was associated with the downregulation of inflammatory cytokines, such as NO, PGE2, and IL-6, and the suppression of iNOS and COX-2. Therefore, gentiopicroside is a potential and selective iNOS and COX-2 inhibitor.