普拉洛芬联合玻璃酸钠治疗中重度干眼的短期疗效

目的:评估普拉洛芬滴眼液联合玻璃酸钠滴眼液对中重度干眼治疗的短期临床疗效及对患者心理状况的影响。方法:选取2018-01/12于我院眼科就诊并治疗的中重度干眼患者318例,采用随机数字表法将患者分为试验组(238例)和对照组(80例),其中对照组采用玻璃酸钠滴眼液治疗,试验组采用普拉洛芬滴眼液联合玻璃酸钠滴眼液治疗。治疗前、治疗后7、14、28d问卷调查患者的自觉症状及体征评分,检查结膜充血程度、泪膜破裂时间、角膜荧光素染色及泪液分泌情况,评估患者焦虑和抑郁程度。结果:在患者的自觉症状及体征评分、结膜充血程度、泪膜破裂时间、角膜荧光素染色及泪液分泌方面,试验组在治疗后7d即有显著改善,且随着治疗时间的延长,效果更加显著,对照组在治疗后14d或28d逐渐好转;同一治疗时间点,试验组疗效均明显优于对照组(P<0.05)。治疗后随着病情的好转,患者的焦虑或抑郁症状得到改善,试验组治疗后7d即有明显好转,对照组治疗后14d或28d逐渐好转;同一治疗时间点,相比对照组,试验组患者的焦虑或抑郁程度均显著减轻(P<0.05)。结论:普拉洛芬滴眼液联合玻璃酸钠滴眼液治疗干眼症起效快且疗效显著,患者自觉症状及体征显著改善,结膜充血和角膜荧光素染色减轻,泪膜破裂时间延长,泪液分泌量增加,患者焦虑或抑郁程度显著好转。

透明角膜隧道切口超声乳化摘除术治疗白内障的疗效及对SDES评分和BUT的影响

目的:分析透明角膜隧道切口超声乳化摘除术治疗白内障的疗效及对患者主观干眼症状问卷评分(SDES)和泪膜破裂时间(BUT)的影响。方法:选取2015-06/2019-01在本院接受白内障手术的117例139眼白内障患者,按随机数字表法分为A组(65例72眼)、B组(52例67眼);两组均接受超声乳化摘除术,A组使用2.2mm微切口,B组使用3.0mm切口;比较两组一般手术情况、SDES、BUT及疗效指标[最佳矫正视力(BCVA)、等效球镜(SE)和角膜内皮细胞密度(ECD)]。结果:两组超声时间、累计释放能量、手术时间及术后并发症无差异(P>0.05);术后两组干眼症状评分较术前显著上升,BUT较术前1d有下降趋势,至术后3mo时SDES评分、BUT恢复至术前水平;但A组术后1d,1wk时的干眼评分显著低于B组,BUT显著高于B组(P<0.05);且两组术后BCVA(LogMAR)、ECD、SE较术前均显著下降,但组间无差异(P>0.05)。结论:透明角膜切口白内障超声乳化摘除术治疗白内障疗效可靠,且2.2mm微切口术后泪膜功能更佳。

颅内段颈内动脉狭窄与眼部动脉血流状态及视网膜血管形态的相关性

目的:探讨颅内段颈内动脉狭窄与眼部动脉血流状态及视网膜血管形态的相关性。方法:选取2017-01/2018-06因疑似脑缺血来我院就诊的患者251例,根据颈内动脉狭窄程度分为无狭窄组(39例)、轻度狭窄组(80例)、中度狭窄组(83例)、重度狭窄组(49例)。比较四组患者眼部动脉血流动力学指标及视网膜血管管径,分析眼部血流参数与颅内段重度颈内动脉狭窄的相关性及诊断价值。结果:重度狭窄组患者眼动脉(OA)、视网膜中央动脉(CRA)、睫状后动脉(PCA)的血管血流参数收缩峰流速(PSV)和舒张峰流速(EDV)均低于其他三组,且PSV、EDV与重度狭窄组患者颈内动脉狭窄率呈显著负相关,其中PCA PSV、PCA EDV对颅内段重度颈内动脉狭窄诊断最佳临界值分别为11.26、5.21cm/s。结论:颅内段颈内动脉狭窄与眼部动脉PSV、EDV呈显著负相关,其中PCA PSV、PCA EDV对于颅内段颈内动脉狭窄最敏感。

Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

AIM: To investigate the role of diarylpropionitrile(DPN), a selective agonist of estrogen receptor β(ERβ), in liver cirrhosis with portal hypertension(PHT) and isolated hepatic stellate cells(HSCs).METHODS: Female Sprague-Dawley rats were ovariectomized(OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin(HE) and Masson's trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction(q RT-PCR). Collagengel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance(IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of Rho A and ROCK Ⅱ, and even suppressed ROCK Ⅱ activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase(e NOS) and phosphorylated e NOS, and promoted the activities of protein kinase G(PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK Ⅱ activity in activated HSCs. Finally, in vivo /in vitro experiments demonstrated that MLC activity was inhibited by DPN.CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver Rho A/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to reduced portal pressure. Therefore, DPN represents a relevant treatment choice against PHT in cirrhotic patients, especially postmenopausal women.

Down-regulated γ-catenin expression is associated with tumor aggressiveness in esophageal cancer

AIM:To evaluate the significance ofγ-catenin in clinical pathology,cellular function and signaling mechanism in esophageal squamous cell carcinoma(ESCC).METHODS:The mRNA expression ofγ-catenin was detected by real-time quantitative reverse transcription-polymerase chain reaction in 95 tissue specimens and evaluated for association with the clinicopathologic characteristics and survival time of patients with ESCC.siRNAs against humanγ-catenin were used to inhibitγ-catenin expression.Hanging drop aggregation assay and dispase-based dissociation assay were performed to detect the effect ofγ-catenin on ESCC cell-cell adhesion.Transwell assay was performed to determine cell migration.Luciferase-based transcriptional reporter assay(TOPflash)was used to measureβ-catenindependent transcription in cells with reducedγ-catenin expression.The expression and subcellular localizations ofβ-catenin and E-cadherin were examined using Western blot and immunofluorescence analysis.RESULTS:γ-catenin mRNA expression was significantly associated with tumor histological grade(P=0.017)in ESCC.Kaplan-Meier survival analysis showed thatγ-catenin expression levels had an impact on the survival curve,with lowγ-catenin indicating worse survival(P=0.003).The multivariate Cox regression analysis demonstrated thatγ-catenin was an independent prognostic factor for survival.Experimentally,silencingγ-catenin caused defects in cell-cell adhesion and a concomitant increase in cell migration in both KYSE150 and TE3 ESCC cells.Analysis of Wnt signaling revealed no activation event associated withγ-catenin expression.Totalβ-catenin and Triton X-100-insolubleβ-catenin were significantly reduced in theγ-catenin-specific siRNA-transfected KYSE150 and TE3 cells,whereas Triton X-100-solubleβ-catenin was not altered.Moreover,knocking downγ-catenin expression resulted in a significant decrease of E-cadherin and Triton X-100-insoluble desmocollin-2,along with reducedβ-catenin and E-cadherin membrane localization in ESCC cells.CONCLUSION:γ-catenin is a tumor suppressor in ESCC and may serve as a prognostic marker.Dysregulated expression ofγ-catenin may play important roles in ESCC progression.

Skp2-RNAi suppresses proliferation and migration of gallbladder carcinoma cells by enhancing p27 expression

AIM:To explore the role of S-phase kinase-associated protein-2(Skp2)in gallbladder carcinoma and to identify whether depletion of Skp2 by Skp2-RNAi could attenuate proliferation and migration of gallbladder carcinoma.METHODS:Skp2-RNAi was transduced into cells of the gallbladder carcinoma cell line GBC-SD,using a lentiviral vector.The effect of Skp2-RNAi on the proliferation,migration,invasion and cell cycle of GBC-SD cells was studied using in vitro assays for cell proliferation,colony formation,wound healing and cell cycle.The expression of Skp2 and p27 was detected by real-time polymerase chain reaction and Western immunoblotting.The effect of Skp2-RNAi on the proliferation of GBC-SD cells in vivo was investigated by tumorigenicity experiments in nude mice.RESULTS:Lentivirus-mediated RNAi reduced the expression of Skp2 in cultured cells.The expression of the p27 protein increased along with the down-regulation of Skp2,although no significant difference was found in p27 mRNA expression.Flow cytometry revealed that Skp2-RNAi transfection significantly increased the proportion of cells in the S phase and significantly decreased the proportion of cells in the G 2 /M phase.No significant difference in the frequency of cells in the G0/G1 phase was observed.The results from the cell proliferation,colony formation and wound healing assays revealed that Skp2-RNAi transfection markedly inhibited the proliferation and migration of GBC-SD cells in vitro.Additionally,tumorigenicity experiments showed that suppression of Skp2 significantly decreased the weights of the tumors(0.56 ± 0.11 and 0.55 ± 0.07 g in the control and Scr-RNAi groups vs 0.37 ± 0.09 and 0.35 ± 0.08 g in the Skp2-RNAi-L and Skp2-RNAi-H groups).CONCLUSION:The expression of Skp2 in GBC-SD cells was inhibited following Skp2-RNAi transfection.Silencing of the Skp2 gene inhibited proliferation,migration and invasiveness of GBC-SD cells by mechanisms dependent on enhanced expression of the p27 protein.

Hydrological response to climate change and human activities:A case study of Taihu Basin,China

Climate change and human activities have changed a number of characteristics of river flow in the Taihu Basin.Based on long-term time series of hydrological data from 1986 to 2015,we analyzed variability in precipitation,water stage,water diversion from the Yangtze River,and net inflow into Taihu Lake with the Mann-Kendall test.The non-stationary relationship between precipitation and water stage was first analyzed for the Taihu Basin and the Wuchengxiyu(WCXY)sub-region.The optimized regional and urban regulation schemes were explored to tackle high water stage problems through the hydrodynamic model.The results showed the following:(1)The highest,lowest,and average Taihu Lake water stages of all months had increasing trends.The total net inflow into Taihu Lake from the Huxi(HX)sub-region and the Wangting Sluice increased significantly.(2)The Taihu Lake water stage decreased much more slowly after 2002;it was steadier and higher after 2002.After the construction of Wuxi urban flood control projects,the average water stage of the inner city was 0.16e0.40 m lower than that of suburbs in the flood season,leading to the transfer of flooding in inner cities to suburbs and increasing inflow from HX into Taihu Lake.(3)The regional optimized schemes were more satisfactory in not increasing the inner city flood control burden,thereby decreasing the average water stage by 0.04e0.13 m,and the highest water stage by 0.04e0.09 m for Taihu Lake and the sub-region in the flood season.Future flood control research should set the basin as the basic unit.Decreasing diversion and drainage lines along the Yangtze River can take an active role in flood control.

Estrogen improves the hyperdynamic circulation and hyporeactivity of mesenteric arteries by alleviating oxidative stress in partial portal vein ligated rats

AIM:To evaluate the effects of estrogen(E2) on systemic and splanchnic hyperdynamic circulation in portal hypertensive rats.METHODS:Fifty castrated female Sprague-Dawley rats were divided into five groups:sham operation(SO),partial portal vein ligation(PPVL) + placebo(PLAC),PPVL + E2,PPVL + ICI and PPVL + E2 + ICI. Hemodynamic measurements were performed using ultrasonography. Mesenteric arteriole contractility in response to norepinephrine was determined using a vessel perfusion system. Oxidative stress in the mesenteric artery was investigated by in situ detection of the superoxide anion(O2) and hydrogen peroxide(H2O2) concentrations.RESULTS:Treatment with E2 resulted in a significant decrease of portal pressure(P < 0.01) and portal venous inflow(P < 0.05),and higher systemic vascular resistance(P < 0.05) and splanchnic arteriolar resistance(P < 0.01) in PPVL + E2 rats compared to PPVL+ PLAC rats. In the mesenteric arterioles of PPVL +E2 rats,the dose-response curve was shifted left,and the EC50was decreased(P < 0.01). E2 reduced O2 production and H2O2concentration in the mesenteric artery. However,ICI182,780 reversed the beneficial effects of E2,therefore,the systemic and splanchnic hyperdynamic circulation were more deteriorated in ICI182,780-treated rats.CONCLUSION:Treatment with estrogen improved the systemic and splanchnic hyperdynamic circulation in PPVL rats,in part due to the alleviation of oxidative stress.

Gender differences in vascular reactivity of mesenteric arterioles in portal hypertensive and non-portal hypertensive rats

BACKGROUND Portal hypertension(PHT)is primarily caused by an increase in resistance to portal outflow and secondarily by an increase in splanchnic blood flow.Vascular hyporeactivity both in systemic circulation and in the mesenteric artery plays a role in the hyperdynamic circulatory syndrome.AIM To explore gender differences and the role of endogenous sex hormones in PHT and vascular reactivity of mesenteric arterioles in rats.METHODS Cirrhosis and PHT were established by subcutaneous injection of carbon tetrachloride(CCl4)in both male and female integral and castrated rats(ovariectomized[OVX]in female rats,orchiectomy[ORX]in male rats).The third-order branch of the mensenteric artery was divided and used to measure vascular reactivity to vasoconstrictors.RESULTS No significant difference in portal pressure was observed between integral and castrated male PHT rats(15.2±2.1 mmHg vs 16.7±2.7 mmHg,P>0.05).The portal pressure in integral female PHT rats was lower than that in OVX female PHT rats(12.7±2.7 mmHg vs 16.5±2.4 mmHg,P<0.05).In PHT rats,the concentration response curves of the mesenteric arterioles to norepinephrine were shifted to the right,and the maximal responses(Emax)values were decreased and effective concentrations causing half maximum responses(EC50)values were increased,compared to those of non-PHT rats,both in male and female rats.Compared to non-PHT integral male rats,the sensitivity of the mesenteric arterioles of non-PHT ORX male rats to norepinephrine was decreased(P>0.05).However,there was no difference between integral and ORX male rats with PHT.In integral female PHT rats,the concentration response curves were shifted to the left(P<0.05),and the Emax values were increased and EC50 values were decreased compared to OVX female PHT rats.CONCLUSION Clear gender differences were observed in mesenteric vascular reactivity in CCl4-induced cirrhotic and PHT rats.Conservation of estrogen can retain the sensitivity of the mesenteric arterioles to vasoconstrictors and has a protective effect on splanchnic vascular function in PHT.

Desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats

BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.

Sequential chemotherapy and icotinib as first-line treatment for advanced epidermal growth factor receptor-mutated non-small cell lung cancer

BACKGROUND Icotinib could have potential effect and tolerability when used sequentially with chemotherapy for advanced epidermal growth factor receptor(EGFR)-mutated non-small cell lung cancer(NSCLC).AIM To evaluate the efficacy and safety of chemotherapy followed by icotinib maintenance therapy as first-line treatment for advanced EGFR-mutated NSCLC.METHODS This multicenter,open-label,pilot randomized controlled trial enrolled 68 EGFRmutated stage IIIB/IV NSCLC patients randomized 2:3 to the icotinib alone and chemotherapy+icotinib groups.RESULTS The median progression-free survival in the icotinib alone and chemotherapy+icotinib groups was 8.0 mo(95%CI:3.84-11.63)and 13.4 mo(95%CI:10.18-16.33),respectively(P=0.0249).No significant differences were found in the curative effect when considering different cycles of chemotherapy or chemotherapy regimen(all P>0.05).CONCLUSION A sequential combination of chemotherapy and EGFR-tyrosine kinase inhibitor is feasible for stage IV EGFR-mutated NSCLC patients.

Diagnosing anomalous characteristics of atmospheric water cycle structure during seasonal-scale drought events:A case study in middle and lower reaches of Yangtze River

Anomalous characteristics of the atmospheric water cycle structure are highly significant to the mechanisms of seasonal-scale meteorological droughts.They also play an important role in the identification of indicative predictors of droughts.To better understand the causes of seasonal meteorological droughts in the middle and lower reaches of the Yangtze River(MLRYR),characteristics of the atmospheric water cycle structure at different drought stages were determined using standardized anomalies.The results showed that the total column water vapor(TCWV)was anomalously low during drought occurrence periods.In contrast,there were no anomalous signals at the drought persistence and recovery stages in the MLRYR.Moreover,there was no significant temporal correlation between the TCWV anomaly and seasonal-scale drought index(the 3-month standardized precipitation index(SPI_(3))).During drought events,water vapor that mainly originated from the Bay of Bengal was transported southwest of the MLRYR.Meanwhile,the anomalous signal of water vapor transport was negative at the drought appearance stage.At the drought persistence stage,the negative anomalous signal was the most significant.Water vapor flux divergence in the MLRYR showed significant positive anomalous signals during drought events,and the signal intensity shifted from an increasing to a decreasing trend at different drought stages.In addition,a significant positive correlation existed between the anomaly of water vapor flux divergence and regional SPI_(3).Overall,water vapor flux divergence is more predictive of droughts in the MLRYR.

A 4-aminonaphthalimide based environmentally sensitive fluorescence probe

A simply synthesized 4-aminonaphthalimide derivative 1 expresses both polarity and viscosity sensitive fluorescence spectra,indicating its potential usage as an environmentally sensitive fluorescence probe. By comparing the fluorescence behavior of 1 with that of a known 4-aminonaphthalimide derivative 2,it was found that the substitution of the 4-amino group has profound influence on the environmentally sensitive fluorescence properties of 4-aminonaphthalimide.

Protein-coding genes combined with long noncoding RNA as a novel transcriptome molecular staging model to predict the survival of patients with esophageal squamous cell carcinoma

Background:Esophageal squamous cell carcinoma(ESCC)is the predominant subtype of esophageal carcinoma in China.This study was to develop a staging model to predict outcomes of patients with ESCC.Methods:Using Cox regression analysis,principal component analysis(PCA),partitioning clustering,Kaplan-Meier analysis,receiver operating characteristic(ROC)curve analysis,and classification and regression tree(CART)analysis,we mined the Gene Expression Omnibus database to determine the expression profiles of genes in 179 patients with ESCC from GSE63624 and GSE63622 dataset.Results:Univariate cox regression analysis of the GSE63624 dataset revealed that 2404 protein-coding genes(PCGs)and 635 long non-coding RNAs(lncRNAs)were associated with the survival of patients with ESCC.PCA categorized these PCGs and lncRNAs into three principal components(PCs),which were used to cluster the patients into three groups.ROC analysis demonstrated that the predictive ability of PCG-lncRNA PCs when applied to new patients was better than that of the tumor-node-metastasis staging(area under ROC curve[AUC]:0.69 vs.0.65,P<0.05).Accord-ingly,we constructed a molecular disaggregated model comprising one lncRNA and two PCGs,which we desig-nated as the LSB staging model using CART analysis in the GSE63624 dataset.This LSB staging model classified the GSE63622 dataset of patients into three different groups,and its effectiveness was validated by analysis of another cohort of 105 patients.Conclusions:The LSB staging model has clinical significance for the prognosis prediction of patients with ESCC and may serve as a three-gene staging microarray.

非对称Au@CdSe异质纳米棒的二次谐波增强

本工作对比研究了金纳米棒、金-银纳米棒及非对称Au@CdSe异质纳米棒中等离激元增强的二次谐波性质.通过精确控制镉离子的浓度,制备了顶端生长和侧边生长的非对称Au@CdSe异质纳米棒,并实现了等离激元共振波长的调控.由于非对称的结构和局域场增强效应,相比于金纳米棒,非对称Au@CdSe异质纳米棒的二次谐波增强倍数最大可达617.7.此外,二次谐波激发谱表明在金纳米棒和侧边生长的Au@CdSe异质纳米棒中存在着由金的带间跃迁引起的谐波能量转移.而由于银的存在,谐波能量转移在金-银纳米棒和顶端生长的Au@CdSe异质纳米棒中可以忽略.非对称Au@CdSe异质纳米棒中等离激元增强的二次谐波在传感、生物光谱等领域都具有潜在应用.

P300/CBP-associated factor(PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer

Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational modifications.However,whether and how Fascin is regulated by acetylation remains unclear.This study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor metastasis.Methods:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their colocalization.An in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF expression.An in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor metastasis.Live-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium formation.The clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using immunohistochemistry.Results:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by PCAF.Using the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF knockdown.Functionally,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic function.Moreover,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opposite effect.In the filipodium shaft,K471-acetylated Fascin displayed rapid dynamic exchange,suggesting that it remained in its monomeric form owing to its weakened actinbundling activity.Clinically,high levels of AcK471-Fascin in ESCC tissues were strongly associated with prolonged overall survival and disease-free survival of ESCC patients.Conclusions:Fascin interacts directly with PCAF and is acetylated at lysine 471 in ESCC cells.Fascin-K471 acetylation suppressed ESCC cell migration and tumor metastasis by reducing filopodium formation through the impairment of its actin-bundling activity.

Liquiritin ameliorates metabolic and endocrine alterations in a mouse model of polycystic ovary syndrome

Objective::Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties;however, limited information is available regarding its therapeutic potential in PCOS.Methods::Female C57BL/6 mice were randomly assigned into four groups ( n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed. Results::Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone ( P < 0.001) and dehydroepiandrosterone sulfate ( P < 0.05) in the PCOS group. Histomorphological inspection of ovaries from the liquiritin group revealed fewer cystic dilated follicles than in the PCOS group. Moreover, liquiritinsignificantly ( P < 0.01) decreased Cyp17a1, Cyp19a1, Fshr, Hsd3b2, Runx2, and Ccn2 mRNA expression compared to letrozole-induced PCOS. Conclusion::Liquiritin may be safe and helpful in ameliorating PCOS-associated hyperandrogenemia and hyperglycemia. However, clinical trials investigating different liquiritin dosages are needed to confirm these findings.

A tassel-type multilayer flexible probe for invasive neural recording

Invasive neural probes are one of the most critical components in the intracortical neural signal recording system.However,they can cause brain damage and tissue response during and after implantation.Thus,neural probes with high flexibility,biocompatibility,and simple implantation methods are required in brain research.Here we present a novel approach to fabricating a multilayer flexible tassel-type neural probe using low-cost maskless laser direct-write lithog-raphy,combined with straightforward release and assembly methods to prepare a whole implantation system.The probe has 32 recording electrodes with an area of 8×8μm^(2),arranged into two rows of different depths and 16 separated shanks,aiming at the neural signal recording in an extensive range.Polyimide and gold are used as the insulating and conductive layers,respectively.With the help of a polyethylene glycol(PEG)coating,the tassel structure was mechanically enhanced for successful implantation,and our morphology characterization showed that the diameter of the coated probe was less than 50μm.Mechanical property tests also proved that it had the necessary stiffness for brain implantation.Afterwards,electrochemical tests were carried out,which showed that the probe had a rather low impedance after a simple gold electroplating.Finally,in vivo experiments demonstrated our probe can be successfully used in neural recording.