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Transforming the agricultural development mode and accelerating the transformation of the “resource and ecologically sound agriculture” production system means transforming an extensive agricultural production mode, which features high consumption, low output, and high pollution, in accordance with the objective requirements of accelerating the transformation of the economic development mode and promoting the construction of a “resource and ecologically sound society”. It means relying on scientific, technological, and institutional innovation to improve resource utilization and protect the ecological environment, promoting the transformation of traditional agriculture into modern “resource and ecologically sound agriculture” by popularizing resource-conserving and eco-friendly technologies and thereby realizing the common development of people and nature as well as the sustainable use of resources, demonstrating its economic, social, ecological, humanitarian, and circulatory function, producing harmonious economic, social, ecological, human, and source-saving benefits. The final objective is to establish the “resource and ecologically sound agriculture” production system with low input, low energy consumption, low pollution, and high output. The production system includes a “resource and ecologically sound agriculture” industrial system, the agriculture standardization production system with guaranteed quality of agricultural products at its core, the system of agricultural non-point sources pollution prevention and control with the core of ecological environment protection, the system of disaster prevention and mitigation by means of the construction of irrigation and water conservation, and the protective system of biological species resources through biological germplasm resources protection.

Hepatocellular carcinoma (HCC) is an aggressive tumor type which results in poor prognosis. ALBI and Child-Pugh score have been widely applied for predicting prognosis in patients with liver diseases. We conducted a systematic review to compare the prognostic ability of ALBI versus Child-Pugh in HCC patients. PubMed, EMBASE and Cochrane Library were explored. The data were extracted from every study. Studies investigating HCC patients and comparing the predicting ability between ALBI and Child-Pugh were analyzed. This systematic review revealed that ALBI showed better discriminative ability than Child-Pugh for predicting the prognosis in HCC patients. However, the predictive abilities of two scores should be improved. Except for the most common used serum biomarker AFP for diagnosis and surveillance of HCC, recent studies have also explored all aspects of HCC through genome-wide sequencing, exome sequencing, RNA sequencing and genome-wide methylation analysis which provide essential clues for genotyping of HCC. Further studies should explore biomarkers by advanced techniques to validate new prognostic tools for early diagnosis and prognosis of HCC. Moreover, multicenter prospective studies should be carried out to compare the prognostic values of predictive indicators in HCC population in the future.

In the development of human society, each transformation in the development mode could be considered as a new hallmark of human civilization and economic development, as well as an internal catalyst for economic structure changes. China has relatively low resources per capita because of a huge population. Therefore, it is a pressing task for China to accelerate the transformation of agricultural development to build up a new agricultural pattern featuring “low input, low energy consumption, low pollution, and high output” under the direction of constructing a “resource and ecologically sound society” and thereby realizing the multiple goals of the sustainable development of a national economy, which consist of ensuring national food security, environmental protection, resource conservation, an income increase for farmers, and agricultural efficiency.

As the world has stepped into the information age from an industrial one, the information wave characterized by computer multimedia technology, optical fiber, and communication satellite technology has swept the globe. Similarly, modern information technologies are permeating the field of agriculture. And the combination of technology and information resources will greatly alter the appearance and production lifestyle of rural areas. It is crucial to find a breakthrough in building a modern commercialized rural service system from rural informatization, aiming to accelerate the transformation of the agricultural development mode and to remold traditional agriculture, which means China must establish a rural information service network system, platform, and mode.

Institutional economics holds that institutions play an important role in the development of agriculture. On the one hand, institutions act as an endogenous variable together with other elements to promote the development of the agricultural economy. On the other hand, institutions function as an exogenous variable to guarantee, stimulate, block, or induce other factors. From the perspective of the entire development process of agriculture, the development mode corresponding to each stage of agriculture is supported by corresponding institutions. Every transformation of the agricultural development mode is inseparable from institutional innovations, because it provides not only the necessary incentives and restraint mechanism for agricultural production businesses, but also the appropriate institutional environment for agricultural development.

Under current resource and environmental constraints, China must establish a system for the agro-scientific and technological innovations to achieve the following goals: to speed up the advancement of sci-tech and promote agricultural mechanization; to speed up agricultural labor-saving technology to better allocate human capital and boost labor productivity; to speed up resource-conserving technology to increase land productivity and resource utilization ratio; and to speed up environmental protection technology to reduce non-point agricultural source pollution and protect farmland environment. These measures will enable technological innovations to be an internal impetus to accelerate the transformation of agricultural development mode in the construction of a “resource and ecologically sound society”, which represents the most fundamental way to transform Chinese agricultural development as well as a prerequisite for advancing the development of a “resource and ecologically sound society”.

The transformation of the agricultural development mode is a new proposition for China’s modern agricultural development and a profound revolution in the history of agricultural development in China. Before the “agricultural development mode” was put forward at the Third Plenary Session of the 17th CPC Central Committee, the 15th National Congress of the Party had proposed the concept of “transforming the economic growth mode” and subsequently the concept of “agricultural growth mode”. Many scholars believe that the content of “agricultural growth mode” includes: resource intensity concentrated on per unit land area, the satisfaction of growth targets, the utilization efficiency of production factors, the driving force behind the growth mechanism, and the regional characteristics of growth mode. The transformation of agricultural growth mode is essentially a process of technological progress and the optimal allocation of resources. The major impact of the system on economic growth will determine the allocation of resources and economic efficiency. The Third Plenary Session of the 17th CPC Central Committee pointed out that the transformation of agricultural development mode should be accelerated in accordance with the requirements of high yields, good quality and high efficiency, ecological protection, and safety. Then why should we transform agricultural development mode? What are the connotations? Is the transformation of agricultural development mode endogenous or exogenous? What are the constraints? These are timely topics that urgently need to be explored before China realizes modern transformation in agriculture.

A series of novel orange-red emitting tungstate phosphors, Ca3La2W2O12 (CLWO):xSm3+ (0.005 ≤ x ≤ 0.30) were successfully prepared through the solid-state method at high temperature. The space group is hexagonal R 3 ‾ m. Under 600 nm monitoring, a large charge transfer band from 250 to 340 nm composed of the electron transition of O2-–Sm3+ and O2-–W6+ and represented the strongest excitation at 300 nm. CLWO:Sm3+ emitted orange-red light at 600 nm (4G5/2–6H7/2) under the strongest excitation of 300 nm. The intensity ratio of the electric-dipole and magnetic-dipole of all the samples were bigger than 1. With the Sm3+-doped concentration increasing, the upward tendency of ratio values originated from the increased degree of lattice distortion. The calculated Rc (21.32 A) and Q (3.78) represented the dipole–dipole interaction to account for the concentration quenching. With the temperature changing from 300 to 400 K, the chromaticity coordinates of samples just have a tiny difference (Δx = 1.02 × 10−4, Δy = 1.01 × 10−4). The thermal activation energy was calculated to be 0.42 eV and T0.5 > 480 K. The color purity of all the phosphors reached 98.9%. Ultimately, a white light-emitting diode (w-LED) was fabricated by coating trichromatic (red, blue, and green) phosphors on a near-ultraviolet chip. The fabricated w-LED revealed a high color rendering index (Ra = 91, R9 = 41) and a good chromaticity coordinate (0.320, 0.363) in the white area. Thus, these orange-red phosphors CLWO:Sm3+ with high thermal stability and high color purity can be potentially used in w-LED applications.

The endotoxin lipopolysaccharide (LPS)-induced pulmonary endothelial barrier disruption is a key pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the molecular mechanisms underlying LPS-impaired permeability of pulmonary microvascular endothelial cells (PMVECs) are not fully understood. Gap junctions, particularly Connexin40 (Cx40), are necessary for the maintenance of normal vascular function. In this study, we for the first time investigated the role of Cx40 in LPS-impaired permeability of PMVECs and provided potential therapeutic approaches based on mechanistic findings of Cx40 regulation by LPS stimuli. Rat PMVECs were isolated, cultured and identified with cell morphology, specific markers, ultrastructural characteristics and functional tests. Western blot analysis demonstrated that Cx40 is the major connexin highly expressed in PMVECs. Furthermore, by inhibiting Cx40 in a time-dependent manner, LPS impaired gap junction function and induced permeability injury of PMVECs. The key role of Cx40 decline in mediating detrimental effects of LPS was further confirmed in rescue experiments through Cx40 overexpression. Mechanistically, LPS stress on PMVECs inhibited the protein kinase C (PKC) pathway, which may synergize with the inflammatory nuclear factor kappaB (NFκB) signaling activation in suppressing Cx40 expression level and phosphorylation. Moreover, through pharmacological PKC activation or NFκB inhibition, Cx40 activity in PMVECs could be restored, leading to maintained barrier function under LPS stress. Our findings uncover a previously unrecognized role of Cx40 and its regulatory mechanisms in impaired endothelial integrity under endotoxin and inflammation, shedding light on intervention approaches to improve pulmonary endothelial barrier function in ALI and ARDS.

We investigated the clinical value of fractional flow reserve (FFR) for the prognostic evaluation of patients with percutaneous coronary intervention. We enrolled 120 patients who were admitted to the hospital to undergo percutaneous coronary intervention for acute coronary syndromes between May 2014 and June 2015. The 120 patients were divided into two groups, the observation group and the control group, according to the post-surgery level of FFR. Each cohort contained 60 patients. These patients were divided into the occurrence group (n=45) and the non-occurrence group (n=75), classified according to the occurrence of major adverse cardiovascular events (MACE). There were no statistically significant differences in the comparison of the occurrence rate of MACE within 30 days after surgery, such as lethal or non-lethal myocardial infarction or non-lethal cerebrovascular events, between the observational group and the control group (P>0.05). For the observation group, the 1-year survival cases were 56 with a survival rate of 93.3%, and 2-year survival cases were 50 with a survival rate of 83.3%. In the control group, the 1-year and 2-year survival cases were respectively 55 and 49 (survival rate of 91.7 and 81.7%). The occurrence rates of hyperlipidemia and ratio of patients with a history of smoking and drinking in the occurrence group were significantly higher than those in the non-occurrence group (P0.05), but the post-treatment FFR in the occurrence group was significantly lower than that in the non-occurrence group (P

Background: Myopia has emerged as a major health issue in the world, due to the sight-threatening pathologies associated with high myopia. Even though previous studies have implicated that myopia is determined by a complex interaction of environmental and genetic factors, the pathogenesis of this disease remains unclear. Methods: Here we utilized plasma from patients with myopia, myopic animal models including the adenomatous polyposis coli (APC) gene mutation mouse model, and the form deprivation induced mouse model of myopia. Findings: Using these systems, we demonstrated that the over-activation of canonical Wnt pathway is associated with myopia. Moreover, inhibition of canonical Wnt signaling in mouse models markedly reduced axial elongation, resulting in myopia regression. Interpretation: Together, these results suggest that dysregulation of canonical Wnt signaling is a characteristic of myopia and suggest that targeting Wnt signaling pathways has potential as a therapeutic strategy for myopia. Funding Statement: This study was supported by the Natural Science Foundation of Fujian (No. 2019J05007, ZL); National Basic Research Program of China (Project 973) (No.2011CB50460); National Key Program of China (No. 2018YFA0107304); and National Natural Science Foundation of China (No.81870627). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Approval was received from the Human Ethics committee of Xiamen Eye Center Affiliated to Xiamen University, in accordance with the Declaration of Helsinki. Informed consents were obtained from all subjects after explanation of the nature and possible consequences of the study. Mice were used, treated, and cared for in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research and the Guidelines of the Animal Experimental Committee of Xiamen University.

The attachment of cell-surface carbohydrates to proteins mediated by the amino acids serine or threonine (O-glycan) is involved in tumor metastasis; the roles of O-glycans vary depending on their structure, but the detailed mechanisms by which O-glycans trigger signaling to control tumor metastasis are largely unknown. In this study, we found that the reduced expression of core 3 synthase correlated with metastasis to lymph nodes and distant organs, resulting in poor prognosis for colorectal cancer (CRC) patients. Mechanically, we revealed that mucin-type core 3 O-glycan was synthesized at the membrane-tethered MUC1 N terminus because of core 3 synthase expression in colon cancer cells. This further inhibited the translocation of MUC1-C to the nucleus, initiated p53 gene transcription that was dependent on the inhibition of MUC1-C nucleus translocation, activated p53-mediated miR-200c expression and resulted in mesenchymal-epithelial transition (MET). Inhibition of MUC1 via small interfering RNA (siRNA) in re-expressed core 3 synthase colon cancer cells further inhibited MUC1-C nucleus translocation, increased p53 and miR-200c expression, and enhanced MET. However, inhibition of p53 via siRNA or miR-200c via miR-200c inhibitor in re-expressed core 3 synthase colon cancer cells promoted the epithelial-mesenchymal transition (EMT) in a reversible manner. Core 3 synthase mRNA levels and the p53 mRNA levels or miR-200c levels in the colon cancerous samples were positively correlated. Our findings suggest a novel mechanism linking mucin-type core 3 O-glycan to the EMT-MET plasticity of CRC cells via MUC1/p53/miR-200c-dependent signaling cascade and shed light on therapeutic strategies to treat this malignancy.

Vascular endothelial permeability transition does not cause significant lesions, but enhanced permeability may contribute to the development of vascular and other diseases, including atherosclerosis, hypertension, heart failure and cancer. Therefore, elucidating the effect of Particulate Matter 2.5 (PM2.5) on vascular endothelial permeability could help prevent disease that might be caused by PM2.5. Our previous study and the present one revealed that PM2.5 significantly increased the permeability of vascular endothelial cells and disrupted the barrier function of the vascular endothelium in Sprague Dawley (SD) rats. We found that the effect occurred mainly through induction of signal transducer and activator of transcription 3 (STAT3) phosphorylation, further transcriptional regulation of microRNA21 (miR-21) and promotion of miR-21 expression. These changes post-transcriptionally repress tissue inhibitor of metalloproteinases 3 (TIMP3) and promote matrix metalloproteinases 9 (MMP9) expression. This work provides evidence that PM2.5 exerts direct inhibitory action on vascular endothelial barrier function and might give rise to a number of vascular diseases.

Angiogenesis provides nutrients and oxygen to promote tumor growth and affords a channel that facilitates tumor cell entry into the circulation. Andrographolide (Andro) possess anti-tumor activity; however, its direct effect on angiogenesis still needs to be clarified. In this study, our experiments revealed that Andro significantly inhibited vascular growth in chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumor angiogenesis was also suppressed by Andro. Additionally, we found that cell proliferation, migration and tube formation of vascular endothelial cells was inhibited by Andro treatment in vitro. The effect was primarily mediated through inhibition of miR-21-5p expression and further targeting of TIMP3. This work provides evidence that Andro directly inhibits angiogenesis and might be an effective anti-angiogenic therapeutic drug for cancer treatment.

We successfully treated a patient who was diagnosed of having hypertrophic obstructive cardiomyopathy after the aortic valve replacement surgery for the concomitant aortic stenosis. We report this first in kind new procedure exclusively developed in our center, Liwen procedureTM (percutaneous intramyocardial septal radiofrequency ablation), for patients with left ventricular outflow tract obstruction in spite of maximal medical therapy. The procedure was performed under transthoracic echo guidance. We discussed the technical details, safety, and effectiveness with corresponding images. The patient did well one year after the procedure without LVOT obstruction or arrhythmia.

Pulmonary fibrosis involves the formation of inappropriate scar tissue in the lungs, but what drives fibrosis is unclear. Sialidases (also called neuraminidases) cleave terminal sialic acids from glycoconjugates. In humans and mice, pulmonary fibrosis is associated with desialylation of glycoconjugates and upregulation of sialidases. Of the four mammalian sialidases, we previously detected only NEU3 in the bronchoalveolar lavage fluid from mice with bleomycin-induced pulmonary fibrosis. In this report, we show that NEU3 upregulates extracellular accumulation of the profibrotic cytokines IL-6 and IL-1β, and IL-6 upregulates NEU3 in human peripheral blood mononuclear cells, suggesting that NEU3 may be part of a positive feedback loop potentiating fibrosis. To further elucidate the role of NEU3 in fibrosis, we used bleomycin to induce lung fibrosis in wild-type C57BL/6 and Neu3(−/−) mice. At 21 days after bleomycin, compared with male and female C57BL/6 mice, male and female Neu3(−/−) mice had significantly less inflammation, less upregulation of other sialidases and the profibrotic cytokine active transforming growth factor β1, and less fibrosis in the lungs. Our results suggest that NEU3 participates in fibrosis and that NEU3 could be a target to develop treatments for fibrosis.

In this paper, we propose a novel thermal face recognition based on physiological information. The training phase includes preprocessing, feature extraction and classification. In the beginning, the human face can be depicted from the background of thermal image using the Bayesian framework and normalized to uniform size. A grid of 22 thermal points is extracted as a feature vector. These 22 extracted points are used to train Linear Support Vector Machine Classifier (linear SVC). The classifier calculates the support vectors and uses them to find the hyperplane for classification. A feature vector of testing image is inputted to the classifier for face recognition. Our contribution is that the proposed method firstly applies temperature information in face recognition. Experimental results prove the effectiveness of the proposed method.

MicroRNA-663 (miRNA-663) regulates the expression of transforming growth factor β1 (TGF-β1), which participates in the pathogenesis of myocardial fibrosis. Therefore, microRNA-663 may also serve a role in myocardial fibrosis. The present study aimed to determine whether miRNA-663 participates in myocardial fibrosis via interaction with TGF-β1. In the present study, the expression of miRNA-663 was significantly downregulated, whereas that of TGF-β1 was significantly upregulated in the endomyocardial biopsies of patients with myocardial fibrosis compared with those in control necropsies. Pearson's correlation analysis revealed that the expression levels of miRNA-663 were negatively correlated with those of TGF-β1 in patients with myocardial fibrosis, but not in the controls. Receiver operating characteristic curve analysis demonstrated that the downregulation of miRNA-663 distinguished patients with myocardial fibrosis from controls. In the AC16 human cardiomyocyte cell line, miRNA-663 overexpression resulted in downregulated TGF-β1 expression, whereas exogenous TGF-β1 treatment exhibited no significant effects on miRNA-663 expression. These results indicate that miRNA-663 may participate in myocardial fibrosis, possibly through interaction with TGF-β1.

The mechanism of age‐related decline in the angiogenic potential of the myocardium is not yet fully understood. Our previous report revealed that the aging of cardiac microvascular endothelial cells (CMECs) led to changes in their expression of receptor Trk isoforms: among the three isoforms (TrkB‐FL, TrkB‐T1 and TrkB‐T2), only the truncated TrkB‐T1 isoform continued to be expressed in aged CMECs, which led to decreased migration of CMECs in aging hearts. Thus far, how BDNF induces signalling through the truncated TrkB‐T1 isoform in aged CMECs remains unclear. Here, we first demonstrated that aged CMECs utilize BDNF–TrkB‐T1 signalling to recruit Willin as a downstream effector to further activate the Hippo pathway, which then promotes migration. These findings suggest that the aging process shifts the phenotype of aged CMECs that express TrkB‐T1 receptors by transducing BDNF signals via the BDNF–TrkB‐T1–Willin–Hippo pathway and that this change might be an important mechanism and therapeutic target of the dysfunctional cardiac angiogenesis observed in aged hearts.

Supplemental material, Supplemental_Material for User testing of the psychometric properties of pictorial-based disability assessment Longshi Scale by healthcare professionals and non-professionals: a Chinese study in Shenzhen by Yulong Wang, Shanshan Guo, Jiejiao Zheng, Qing Mei Wang, Yuling Zhang, Zhenwen Liang, Lihai Zhang, Yi Yang, Haohan Zhai, Miaoling Chen, Yuzhen Wang, Yawei Li, Xing Lyu, Xuhui Li, Hongli Geng, Xiaolong Zhu, Fei Yu, Jian Yuan, Jing Zhou, Fang Liu, Haoming Luo, Jianjun Long, Wensheng Chen, Hua Li, Guanqi Fu, Chunxiu Zhou, Jiehong Zhang, Yao Wang, Yongyang Huo, Xiujun Ke, Yuanyuan Zeng, Jiayu Liu, Hailan Xing, Huixiang Xiao, Rui Jiao, Miao Wu, Qiang Tang and Xun Luo in Clinical Rehabilitation

Organic additives are extensively used as ingredients in biodegradable mulch films. They are swiftly released into the environment, which may have an ecotoxicological impact on plant growth and development, as well as on soil microbial community abundance and function. Herein, a method based on the application of microwave-assisted extraction (MAE) and dispersive liquid–liquid microextraction (DLLME) was developed to analyze eighty organic additives by gas chromatography-mass spectrometry in poly(butylene adipate terephthalate) (PBAT) biodegradable mulch films. This was a comprehensive study, including the identification of organic additives, optimization of MAE and DLLME methods, analysis of isocyanate conversion, and evaluation of the matrix effect (ME). Under the optimized experimental conditions, this method exhibited excellent detection capabilities for organic additives, except for 5 kinds of isocyanates and their reaction products, with coefficients of determination R2 > 0.999 and lack of fit P > 0.05 in linear regression parameters. A negligible ME was observed. The relative recoveries were 93.0–109.8%, and the repeatability and reproducibility varied within the ranges of 2.06–8.76% and 2.38–10.23%, respectively. The limits of detection and limits of quantitation were 0.0008–0.0586 μg g−1 and 0.003–0.195 μg g−1, respectively. The developed method was further successfully applied to the analysis of organic additives in PBAT biodegradable mulch films from four different manufacturers. Interestingly, the Venn diagram and principal component analysis showed that different manufacturing origins display obvious characteristic differences in the organic additive types and concentrations.

PurposeTo evaluate the surgical outcome of levator resection with suspensory ligament of the superior fornix (SLSF) suspension in severe congenital ptosis with poor levator function (LF).Patients and methodsThe medical records of 25 patients who underwent levator resection with SLSF suspension between March 2011 and January 2013 were retrospectively reviewed. All of the patients had severe congenital ptosis (>4 mm) and poor LF (

Recently, we demonstrated that melatonin reduced protein kinase RNA (PKR)-like ER kinase (PERK)-eukaryotic initiation factor 2 alpha (eIF2α)-activating transcription factor-4 (ATF4)-mediated myocardial endoplasmic reticulum (ER) stress and apoptosis during myocardial ischemia-reperfusion (MI/R) injury. However, the underlying mechanisms are still not clear. Myocardial reperfusion injury salvage kinase (RISK) pathway as well as survivor activating factor enhancement (SAFE) pathway are two pivotal intrinsic pro-survival signaling cascades. In this study, we performed in vivo and in vitro experiment to investigate the ameliorative effect of melatonin on ER stress with a focus on RISK and SAFE pathways interaction. Male C57Bl/6 mice received melatonin (300 μg/25 g/day, 3 days before MI/R surgery; 300 μg/25 g, 25 min before the onset of ischemia) pre-treatment with or without the administration of LY294002 (a PI3K/Akt inhibitor), U0126 (an ERK1/2 inhibitor) or AG490 (a STAT3 pathway inhibitor). H9c2 cells were pre-treated with melatonin (100 μM, 8 h) in the presence or absence of LY294002, U0126 or AG490. Compared with the I/R-injured group, melatonin effectively reduced myocardial apoptosis, oxidative stress and improved cardiac function. In addition, melatonin pre-treatment also increased the phosphorylation of Akt, GSK-3β, ERK1/2 and STAT3 and reduced PERK-eIF2α-ATF4-mediated ER stress. However, these effects were blocked by LY294002, U0126 or AG490. Additionally, either LY294002 or U0126 treatment could inhibit STAT3 phosphorylation, whereas AG490 administration also reduced both Akt and ERK1/2 phosphorylation, indicating an interplay exists between RISK and SAFE pathways in melatonin's cardioprotective effect. In summary, our study demonstrates that RISK and SAFE pathways mediate the cardioprotective effect of melatonin against MI/R injury. Melatonin pre-treatment attenuates PERK-eIF2α-ATF4-mediated ER stress and apoptosis during MI/R injury via RISK and SAFE pathways interaction.

The aim of the present study was to investigate the role and molecular mechanism of human IgD (hIgD) on the proliferation of human Burkitt lymphoma Daudi cells in vitro. Logarithmically growing Daudi cells were treated with hIgD for different time periods, and cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. The expressions of Daudi surface markers and IgD receptor (IgDR) as well as cell cycle and apoptosis were measured by flow cytometry analysis. Our results showed that hIgD stimulation induced proliferation and IgDR expression and reduced the apoptosis of Daudi cells. Treatment with hIgD promoted progression of the cell cycle at the G1/S transition, and this was accompanied by upregulation of c-myc, cyclin D3, and CDK6 as well as downregulation of p16 mRNA and protein levels. Moreover, hIgD treatment also upregulated the expression of tyrosine phosphorylation of 70 kDa protein (IgDR) and p-Lyn. Taken together, these results indicate that hIgD can induce Daudi cell proliferation through activating IgDR to initiate the tyrosine phosphorylation signaling cascade to accelerate the G1/S transition.

Background & Aims Multidrug resistance-associated protein 2 (MRP2) excretes conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2 leads to jaundice in patients. Studies in rodents indicate that Radixin plays a critical role in determining Mrp2 canalicular membrane expression. However, it is not known how human hepatic MRP2 expression is regulated in cholestasis. Methods We assessed liver MRP2 expression in patients with obstructive cholestasis caused by gallstone blockage of bile ducts, and investigated the regulatory mechanism in HepG2 cells. Results Western blot detected that liver MRP2 protein expression in obstructive cholestatic patients (n=30) was significantly reduced to 25% of the non-cholestatic controls (n=23). Immunoprecipitation identified Ezrin but not Radixin associating with MRP2 in human livers, and the increased amount of phospho-Ezrin Thr567 was positively correlated with the amount of co-precipitated MRP2 in cholestatic livers, whereas Ezrin and Radixin total protein levels were unchanged in cholestasis. Further detailed studies indicate that Ezrin Thr567 phosphorylation plays an important role in MRP2 internalization in HepG2 cells. Since increased expression of PKCα, δ and e were detected in these cholestatic livers, we further confirmed that these PKCs stimulated Ezrin phosphorylation and reduced MRP2 membrane expression in HepG2 cells. Finally, we identified GP78 as the key ubiquitin ligase E3 involved in MRP2 proteasome degradation. Conclusions Activation of liver PKCs during cholestasis leads to Ezrin Thr567 phosphorylation resulting in MRP2 internalization and degradation where ubiquitin ligase E3 GP78 is involved. This process provides a mechanistic explanation for jaundice seen in patients with obstructive cholestasis.

To determine the effect of andrographolide (Andro) on angiogenesis of human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with different concentrations of Andro and the cell viability was detected with Cell Counting Kit-8 (CCK-8). HUVECs were treated with half lethal dose (IC50) of Andro. Matrigel was used to make capillary formation of HUVECs and the effect of Andro on capillary formation was evaluated by calculating the percentage of capillary formation. Moreover, the effects of Andro and the supernatant from cultured A549 tumor cells on capillary formation were evaluated by calculating the percentage of capillary formation. The effect of Andro on the expression of matrix metalloproteinase-9 (MMP-9) was determined with Western blot. Results: The cell viability of HUVECs decreased with the increase of Andro concentrations. IC50 was 20 μmol/L. The capillary formation of HUVECs was inhibited when treated with 20 μmol/L Andro for 24 hours. Moreover, Andro was able to antagonize the promotion of the capillary formation induced by the supernatant from cultured tumor cells. Andro could suppress the expression of MMP-9 and antagonize the capillary formation. Conclusion: Andro inhibits the capillary formation of HUVECs and can antagonize the promotion of angiogenesis induced by the supernatant from cultured tumor cells.目的：探讨穿心莲内酯(andrographolide，Andro)对人脐带静脉内皮细胞(human umbilical vein endothelial cells，HUVECs)成管能力的影响。方法：将不同体积浓度的Andro溶液作用于HUVECs，采用细胞计数试剂盒-8(Cell Counting Kit-8，CCK-8)检测细胞存活率。采用半数致死量(IC50)的Andro溶液作用于HUVECs，采用Matrigel胶使HUVECs成管，通过计算成管率来评估Andro溶液对HUVECs成管能力的影响。此外，将A549细胞分泌物与Andro溶液同时处理HUVECs，检测其成管情况。采用Western印迹检测Andro溶液对基质金属蛋白酶-9(matrix metalloproteinase-9，MMP-9)表达水平的影响。结果：Andro溶液可抑制HUVECs的增殖，且呈浓度依赖性；Andro溶液对HUVECs的IC50为20 μmol/L。选取20 μmol/L的Andro溶液作用于HUVECs 24 h，发现Andro溶液显著抑制HUVECs的成管能力。另外，A549细胞分泌物促进HUVECs成管作用，而Andro溶液拮抗肿瘤细胞分泌物对HUVECs成管的促进作用，降低MMP-9的表达。结论：Andro能够抑制HUVECs成管，而且能够拮抗肿瘤细胞分泌物对HUVECs成管的促进作用，从而抑制血管新生。.

Rationale: No medical intervention has been identified that decreases acute kidney injury and improves renal outcome at 1 year after cardiac surgery. Objectives: To determine whether administration of nitric oxide reduces the incidence of postoperative acute kidney injury and improves long-term kidney outcomes after multiple cardiac valve replacement requiring prolonged cardiopulmonary bypass. Methods: Two hundred and forty-four patients undergoing elective, multiple valve replacement surgery, mostly due to rheumatic fever, were randomized to receive either nitric oxide (treatment) or nitrogen (control). Nitric oxide and nitrogen were administered via the gas exchanger during cardiopulmonary bypass and by inhalation for 24 hours postoperatively. Measurements and Main Results: The primary outcome was as follows: oxidation of ferrous plasma oxyhemoglobin to ferric methemoglobin was associated with reduced postoperative acute kidney injury from 64% (control group) to 50% (nitric oxide group) (relative risk [RR], 0.78; 95% confidence interval [CI], 0.62-0.97; P = 0.014). Secondary outcomes were as follows: at 90 days, transition to stage 3 chronic kidney disease was reduced from 33% in the control group to 21% in the treatment group (RR, 0.64; 95% CI, 0.41-0.99; P = 0.024) and at 1 year, from 31% to 18% (RR, 0.59; 95% CI, 0.36-0.96; P = 0.017). Nitric oxide treatment reduced the overall major adverse kidney events at 30 days (RR, 0.40; 95% CI, 0.18-0.92; P = 0.016), 90 days (RR, 0.40; 95% CI, 0.17-0.92; P = 0.015), and 1 year (RR, 0.47; 95% CI, 0.20-1.10; P = 0.041). Conclusions: In patients undergoing multiple valve replacement and prolonged cardiopulmonary bypass, administration of nitric oxide decreased the incidence of acute kidney injury, transition to stage 3 chronic kidney disease, and major adverse kidney events at 30 days, 90 days, and 1 year.

Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4+ T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4+ T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4+ T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr394). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4+ T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr394) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4+ T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

One popular approach for working on video datasets is to use face tracks [1, 2], face sequence containing faces of one person, for matching instead of single face as in static image datasets. In this article, we propose face track retrieval using sparse representation. At first, every image of face tracks is normalized to uniform size. Then, feature is extracted utilizing Discrete Wavelet Transform (DWT). In training part, Online Dictionary Learning (ODL) [3] is exploited to compute dictionary and sparse matrix for sparse representation. On the other hand, in testing part, dictionary and sparse matrix are utilized to calculate the L2 distance for identifying the face. Experimental results demonstrate the effectiveness of the proposed technique.

Background Berberine (BBR), a Chinese traditional herbal medicine, has many pharmacologic benefits such as anti-inflammation and anti-oxidation. It is widely used in clinical treatment of cardiovascular diseases such as hypertension. However, the mechanism of how BBR attenuates hypertension through affecting central neural system is not clear. Purpose This study was designed to determine whether chronic infusion of BBR into the hypothalamic paraventricular nucleus (PVN) attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway. Methods Two-kidney, one-clip (2K1C) renovascular hypertensive rats were randomly assigned and treated with bilateral PVN infusion of BBR (2μg/h) or vehicle (artificial cerebrospinal fluid) via osmotic minipumps for 28 days. Results 2K1C rats showed higher mean arterial pressure (MAP) and PVN Fra-like activity, plasma levels of norepinephrine (NE), PVN levels of NOX2, NOX4, Erk1/2 and iNOS, and lower PVN levels of copper/zinc superoxide dismutase (Cu/Zn-SOD). Chronic infusion of BBR reduced MAP, PVN Fra-like activity and plasma levels of NE, reduced NOX2, NOX4, Erk1/2, iNOS and induced Cu/Zn-SOD in the PVN. Conclusions These results suggest that BBR attenuates hypertension and sympathoexcitation via the ROS/Erk1/2/iNOS pathway in 2K1C renovascular hypertensive rats.

High levels of NaCl in the diet are associated with both cardiac and renal fibrosis, but whether salt intake affects pulmonary fibrosis has not been examined.To test the hypothesis that salt intake might affect pulmonary fibrosis.Mice were fed low, normal, or high salt diets for 2 weeks, and then treated with oropharyngeal bleomycin to induce pulmonary fibrosis, or oropharyngeal saline as a control.As determined by collagen staining of lung sections, and protein levels and cell numbers in the bronchoalveolar lavage (BAL) fluid at 21 days after bleomycin, the high salt diet did not exacerbate bleomycin-induced fibrosis, while the low salt diet attenuated fibrosis. For the bleomycin-treated mice, staining of the post-BAL lung sections indicated that compared to the regular salt diet, high salt increased the number of Ly6c-positive macrophages and decreased the number of CD11c and CD206-positive macrophages and dendritic cells. The low salt diet caused bleomycin-induced leukocyte numbers to be similar to control saline-treated mice, but reduced numbers of CD45/collagen-VI positive fibrocytes. In the saline controls, low dietary salt decreased CD11b and CD11c positive cells in lung sections, and high dietary salt increased fibrocytes.Together, these data suggest the possibility that a low salt diet might attenuate pulmonary fibrosis.

Background & Aims Bile acid transporters maintain bile acid homeostasis. Little is known about the functions of some transporters in cholestasis or their regulatory mechanism. We investigated the hepatic expression of solute carrier organic anion transporter family member 3A1 (SLCO3A1, also called OATP3A1) and assessed its functions during development of cholestasis. Methods We measured levels of OATP3A1 protein and messenger RNA and localized the protein in liver tissues from 22 patients with cholestasis and 21 patients without cholestasis, using real-time quantitative polymerase chain reaction, immunoblot, and immunofluorescence analyses. We performed experiments with Slco3a1-knockout and C57BL/6J (control) mice. Mice and Sprague-Dawley rats underwent bile duct ligation (BDL) or a sham operation. Some mice were placed on a 1% cholic acid (CA) diet to induce cholestasis or on a control diet. Serum and liver tissues were collected and analyzed; hepatic levels of bile acids and 7-α-C4 were measured using liquid chromatography/mass spectrometry. Human primary hepatocytes and hepatoma (PLC/PRF/5) cell lines were used to study mechanisms that regulate OATP3A1 expression and transport. Results Hepatic levels of OATP3A1 messenger RNA and protein were significantly increased in liver tissues from patients with cholestasis and from rodents with BDL or 1% CA diet–induced cholestasis. Levels of fibroblast growth factor 19 (FGF19, FGF15 in rodents) were also increased in liver tissues from patients and rodents with cholestasis. FGF19 signaling activated the Sp1 transcription factor and nuclear factor κB to increase expression of OATP3A1 in hepatocytes; we found binding sites for these factors in the SLCO3A1 promoter. Slco3a1-knockout mice had shorter survival times and increased hepatic levels of bile acid, and they developed more liver injury after the 1% CA diet or BDL than control mice. In hepatoma cell lines, we found OATP3A1 to take prostaglandin E2 and thyroxine into cells and efflux bile acids. Conclusions We found levels of OATP3A1 to be increased in cholestatic liver tissues from patients and rodents compared with healthy liver tissues. We show that OATP3A1 functions as a bile acid efflux transporter that is up-regulated as an adaptive response to cholestasis.

The classical model of innovation behind closed doors is slowly but surely being challenged by the Open Innovation model that is reshaping the way organizations bring new products and services into the market. This paper reports on the results of an International Space University (ISU) Team Project (TP) focused on the potential, limitations and conditions of success of Open Innovation in the space sector using ISU׳s international, interdisciplinary, intercultural (3Is) approach. Open Innovation can be defined as “the process of strategically managing the sharing of ideas and resources among entities to co-create value”. Conventional approaches to technology development for space, such as spin-offs or spin-ins, are no longer sufficient to fully describe the interactions between organizations in today׳s Research and Development (R&D) landscape. Traditionally, conducting space technology development and launching space missions required massive infrastructure investments, long lead times and large teams of experts. However, internal R&D, dedicated marketing departments and closely guarded intellectual property are no longer the only way to achieve success. Smaller, nimbler teams, significant use of crowdfunding, a more aggressive approach to managing risk and a great motivation to leverage intellectual property are just some of their defining characteristics. By using a case study methodology focused on asteroid mining supported by a critical literature review, the project team highlighted the potential of Open Innovation in space by identifying its most promising applications as well as its limitations.

// Yangyang Shang 1,* , Qiong Pan 1,* , Lei Chen 1,* , Jun Ye 1 , Xiaoli Zhong 1 , Xiaohuan Li 1 , Linkuan Meng 1 , Jin Guo 1 , Yin Tian 1 , Yonghong He 1 , Wensheng Chen 1 , Zhihong Peng 1 and Rongquan Wang 1 1 Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P. R. China * These authors have contributed equally to this study Correspondence to: Zhihong Peng , email: // Rongquan Wang, email: // Keywords : Achaete scute-like 2, CDX2, transcriptional regulation, colorectal carcinoma, differentiation Received : March 26, 2015 Accepted : August 13, 2015 Published : August 17, 2015 Abstract The role of Achaete scute-like 2 (Ascl2) in colorectal cancer (CRC) cell differentiation is unknown. LS174T, HT-29 and Caco-2 cells have high Ascl2 expression, while Lovo and SW480 cells have low Ascl2 expression. LS174T and HT-29 cells with Ascl2 knockdown were transfected with caudal type homeobox 2 (CDX2) promoter constructs and used for luciferase assays and chromatin immunoprecipitation (ChIP) assays. Ascl2 knockdown promoted differentiation of CRC cells into a goblet cell phenotype, as determined by increased expression of MUC2, TFF3, and CDX2. Ascl2 knockdown activated CDX2 expression through a transcriptional mechanism via direct binding of Ascl2 to the proximal E-box of the CDX2 promoter. Ascl2 over-expression in Lovo and SW480 cells inhibited a goblet cell phenotype, as determined by reduced CDX2 and MUC2 expression. Inverse correlations between Ascl2 and CDX2, and Ascl2 and MUC2 mRNA levels, as well as Ascl2 and CDX2 protein levels were observed in CRC cancerous samples. This study demonstrates CDX2 repression by Ascl2 and highlights a role for Ascl2 in CRC cell differentiation. These findings suggest that the Ascl2/CDX2 axis may serve as a potential therapeutic target in colorectal cancer.

Berberine (BBR) confers cardioprotective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also reduces MI/RI. We hypothesize that BBR may protect against MI/RI by modulating Notch1/Hes1-Phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signaling. In this study, male Sprague-Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 μmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Caspase-3 expression. However, the anti-apoptotic effect conferred by BBR was blocked by Notch1 siRNA, Hes1 siRNA or LY294002 (the specific inhibitor of Akt signaling) in the cultured cardiomyocytes. In summary, our results demonstrate that BBR treatment attenuates MI/RI by modulating Notch1/Hes1-PTEN/Akt signaling.

A proficiency testing scheme (CNAS T0419) is described involving 217 laboratories in China as participants using their regular analytical methods for the determination of lead and arsenic in foundation cream cosmetics. The metrological comparability of results from various approaches was tested using simple linear regression analysis and analysis of variance as valid techniques. There were no significant differences in the values obtained after elimination of outliers by the Grubbs test. The normality of the distribution of the results submitted by the participants was examined with the one-sample Kolmogorov–Smirnov test. The distribution characteristics of result points for the paired samples were investigated using the Youden plot, which could greatly simplify the data analysis process. The assigned values of test materials for proficiency assessment were derived directly from the reported results of the participating laboratories. The measurement capabilities of laboratories for determining heavy metals, especially lead and arsenic in complex matrices were objectively assessed using z-scores, which could readily be used to compare each participant's value relative to the others and enabled the outlier laboratories to find out the dominant error sources such as systematic and random variations. The percentages of acceptable results of between- and within-laboratories were 86.0% and 84.2% for lead, and 84.6% and 83.6% for arsenic, respectively.

Ascl2, a basic helix-loop-helix transcription factor, is a downstream target of WNT signaling that controls the fate of intestinal cryptic stem cells and colon cancer progenitor cells. However, its involvement in colon cancer and downstream molecular events is largely undefined; in particular, the mechanism by which Ascl2 regulates the plasticity of epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) programs in colon cancer cells remains unknown. In this study, we systematically demonstrate that Ascl2 loss of function in colon cancer cells promotes MET by derepressing the expression of microRNA (miR)-200s (i.e. miR-200b, miR-200a, miR-429, miR-200c, and miR-141) and further activating their expression through a transcriptional mechanism that involves direct binding to the most proximal E-box (E-box2) in the miR-200b-a-429 promoter. Activation of miR-200s due to Ascl2 deficiency led to the inhibition of ZEB1/2 expression and the alteration of epithelial and mesenchymal features. Transfection of miR-200b, miR-200a, and miR-429 inhibitors into Ascl2-deficient colon cancer cells promoted the epithelial-mesenchymal transition in a reversible manner. Transfection of miR-200a or miR-429 inhibitors into Ascl2-deficient colon cancer cells increased cellular proliferation and migration. Ascl2 mRNA levels and the miR-200a, miR-200b, miR-200c, miR-141, or miR-429 levels in the colon cancerous samples were inversely correlated. These results provide the first evidence of a link between Ascl2 and miR-200s in the regulation of EMT-MET plasticity in colon cancer.

Purpose The purpose is to investigate the mechanism of subconjunctival fibrosis caused by benzalkonium chloride (BAC), which is the most common preservative in ophthalmic preparations. Methods The left eyes of male Sprague-Dawley rats were topically treated with 0.01% BAC or PBS twice daily for 1 month. Primary conjunctival fibroblasts (CFs) were exposed for 24 hours to 0.00005% BAC, 0.000075% BAC, 0.000075% BAC + LY2157299 (a selective transforming growth factor β receptor type I inhibitor); 0.000075% BAC + NS-398 (a selective cyclooxygenase-2 inhibitor) and PBS, respectively. The pathological changes of the bulbar conjunctival tissue of rats were examined using hematoxylin-eosin (HE), Van Gieson's (vG), periodic acid-Schiff (PAS) stains, or immunohistochemisty (IHC). The expression of the extracellular matrix (ECM), the transforming growth factor β (TGF-β) signaling pathway-related molecules, and cyclooxygenase-2 (COX-2) in bulbar conjunctival tissues and CFs were detected using Western blot (WB) and quantitative real-time RT-PCR (qRT-PCR). Results Rats treated with 0.01% BAC exhibited a slight increase of the fibroblast density and a more compact collagen deposition in the bulbar subepithelial connective tissues in comparison with rats treated with PBS. Western blot and qRT-PCR analyses showed that the expression of ECM, TGF-β signaling pathway-related molecules, and COX-2 were markedly increased in the bulbar conjunctival tissues of rats exposed to 0.01% BAC and in CFs exposed to 0.00005% and 0.000075% BAC. In conjunctival fibroblasts, BAC-induced ECM expression was clearly decreased by LY2157299, while the BAC-induced activation of the TGF-β1/Smad3 signaling pathway was greatly attenuated by NS-398. Conclusions Subconjunctival fibrosis BAC-induced is a consequence of excessive ECM production of CFs through the COX-2-modulated activation of a TGF-β1/Smad3 signaling pathway.

Vascular insulin resistance and oxidative stress contribute to endothelial dysfunction and hypertension. The present study investigated whether chronic treatment with purified Tartary buckwheat flavonoids fraction (TBF) prevents the development of hypertension via improving vascular insulin sensitivity and reducing oxidative stress. Six-week-old male spontaneously hypertensive rats (SHRs) and their normotensive Wistar-Kyoto (WKY) control rats were subjected to different dosages of TBF for 8 weeks. Blood pressure, mesenteric arteriolar vasorelaxation, superoxide anion (O2-) generation, NAD(P)H oxidase activity, and insulin-stimulated Akt/endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production were determined. The SHRs had higher systolic blood pressure, systemic insulin resistance, and impaired vasodilator actions of insulin and the insulin signaling pathway in mesenteric arterioles when compared with the WKY rats. TBF treatment at a dosage of 100 mg kg-1 day-1 significantly reduced systolic blood pressure and increased vasodilator response to insulin in the SHRs. Additionally, TBF treatment significantly reduced phosphorylation of insulin receptor substrate 1 (IRS-1) at serine 307 and increased insulin-stimulated Akt/eNOS activation in the SHRs. Furthermore, TBF treatment reduced the overproduction of basal O2- in association with a reduction of NAD(P)H oxidase activity in mesenteric arterioles of the SHRs. Finally, quercetin was identified as the predominant active component of TBF in attenuating the development of hypertension with regard to reducing vascular oxidative stress, regulating the vascular insulin signaling pathway and restoring vasodilator response to insulin in the SHRs. In conclusion, TBF possesses protective effects against hypertension through attenuating vascular insulin resistance and oxidative stress.

Immunoglobulin IgD might play an important role in autoimmune diseases, but the function of IgD has remained elusive, despite multiple attempts to define its biological function. Fibroblast-like synoviocytes (FLSs) are specialized cells of the synovium that play a key role in the pathogenesis of rheumatoid arthritis (RA). In this study we explored the possible roles of excessive IgD expression on the function of FLSs from RA patients (RA-FLSs). We showed that IgD Fc receptor (IgDR) was constitutively expressed on FLSs, and was significantly elevated in RA-FLSs compared with FLSs prepared from synovial tissues of healthy controls (HC-FLSs). Furthermore, IgDR was mainly detected on the cell surface and in the cytoplasm. We further detected the intrinsic binding affinity of IgD to IgDR on HC-FLSs with an equilibrium dissociation constant (KD) of 0.067 nmol/L. Incubation of RA-FLSs with IgD (1-10 μg/mL) for 48 h dose-dependently promoted the expression of IgDR, and stimulated the production of inflammatory cytokines and chemokines, such as IL-1β, IL-6, monocyte chemotactic protein (MCP)-1, TNF-α and receptor activator of nuclear factor-κB ligand (RANKL), thus potentially contributing to IgD-IgDR crosslinking. Moreover, incubation with IgD (0.1-10 μg/mL) for 48 h dose-dependently enhanced viability for both HC-FLSs and RA-FLSs. Our results demonstrate that IgDR is expressed on RA-FLSs and contributes to the activation of FLSs, and suggest that IgD-IgDR is a potential novel immunotherapeutic target for the management of RA.

An innovative natriuretic peptide analog named CNAAC (structurally consisting of the C-terminus and ring of ANP and the N-terminus of CNP) that has been shown to exhibit potent vasodilatory, diuretic, and hypotensive effects in our previous study was evaluated for the treatment of left ventricular dysfunction following myocardial infarction. The temporal relaxation effect and metabolic status of CNAAC were determined. A myocardial ischemic model was established. Rats were randomly divided into Sham, MI, MI-ANP, MI-CNP, MI-VNP, and MI-CNAAC groups. Humoral factors were measured; echocardiography and hemodynamics methods were employed to assess the cardiac function at the fourth week after modeling. The results showed that CNAAC had a potent relaxant effect and longer duration of action than ANP, CNP, or VNP. The stability of CNAAC in blood was higher than other three NPs. Four weeks of NP administration ameliorated diastolic and systolic dysfunction, the hypertrophic index, myocardial fibrosis, and infarct size; it also restored the abnormal changes in humoral factors. These results demonstrate that CNAAC has a potent cardioprotective effect against left ventricular dysfunction after myocardial infarction. The results may lay the foundation for the clinical application of this newly designed NP chimera in the treatment and prevention of heart failure.

Multidrug resistance (MDR) remains a major clinical obstacle in the treatment of gastric cancer (GC) since it causes tumor recurrence and metastasis. The transcription factor activator protein-2α (AP-2α) has been implicated in drug-resistance in breast cancer; however, its effects on MDR of gastric cancer are far from understood. In this study, we aimed to explore the effects of AP-2α on the MDR in gastric cancer cells selected by vincristine (VCR). Decreased AP-2α levels were markedly detected by RT-PCR and Western blot in gastric cancer cell lines (BGC-823, SGC-7901, AGS, MKN-45) compared with that in the gastric epithelial cell line (GES-1). Furthermore, we found that the expression of AP-2α in SGC7901/VCR or SGC7901/adriamycin (ADR) cells was lower than in SGC7901 cells. Thus, a vector overexpressing AP-2α was constructed and used to perform AP-2α gain-of-function studies in SGC7901/VCR cells. The decreased IC50 values of the anti-cancer drugs in sensitive and resistant cells after transfect with pcDNA3.1/AP-2α were determined in SGC7901/VCR cells by MTT assay. Moreover, flow cytometry analysis indicated that overexpressed AP-2α induced cell cycle arrest in the G0/G1 phase and promoted cell apoptosis of VCR-selected SGC7901/VCR cells. RT-PCR and Western blot demonstrated that overexpressed AP-2α can significantly induce the down-regulation of Notch1, Hes-1, P-gp and MRP1 in SGC7901/VCR cells. Similar effects can be observed when Numb (Notch inhibitor) was introduced. In addition, the intracellular ADR accumulation was markedly detected in AP-2α overexpressed or Numb cells. In conclusion, our results indicate that AP-2α can reverse the MDR of gastric cancer cells, which may be realized by inhibiting the Notch signaling pathway.