Search

Rui-zhe Li,1 Yun-yun Li,1,2 Hui Qin,1 Shan-shan Li1 1Department of Pathology, School of Basic Medical Sciences, Zhengzhou University and First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of China; 2Department of Stomatology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of ChinaCorrespondence: Shan-shan LiDepartment of Pathology, School of Basic Medical Sciences, Zhengzhou University and First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, People’s Republic of ChinaTel +86 138 3815 6395Fax +86 371 6796 6155Email lss_path@sina.comBackground: ACTL6A, a regulatory subunit of ATP-dependent chromatin-remodeling complexes SWI/SNF, has been identified as a central oncogenic driver in many tumor types.Materials and Methods: We used immunohistochemistry (IHC) to detect ACTL6A expression in esophageal squamous cell carcinoma (ESCC) tissues. Then, the effect of ACTL6A on proliferation and DNA synthesis was explored by using cell counting kit 8 (CCK8) and EdU retention assays. The potential oncogenic mechanism of ACTL6A in ESCC cells was also analyzed by flow cytometry and Western blotting. We further established an ESCC xenograft mouse model to validate the in vitro results.Results: ACTL6A expression, localized in cancer cell nuclei, was markedly higher in ESCC tissues than in the corresponding noncancerous tissues (P< 0.001) and was positively associated with tumor size, histological differentiation, T stage and tumor-node-metastasis (TNM) stage. Kaplan–Meier analysis revealed that high ACTL6A expression was significantly associated with poor overall survival (OS) (P = 0.008, HR= 2.562, 95% CI: 1.241– 5.289), and decision curve analysis (DCA) demonstrated that ACTL6A could increase the clinical prognostic efficiency of the original clinical prediction model. Further in vitro experiments showed that ACTL6A knockdown led to inhibition of cell proliferation and DNA synthesis in ESCC cell lines, while overexpression of ACTL6A had the opposite effects. ACTL6A knockdown resulted in G1 phase arrest, with downregulation of cyclin D1, CDK2 and S6K1/pS6 pathway proteins and upregulation of p21 and p27, while overexpression of ACTL6A facilitated the entry of more cells into S phase with upregulated cyclin D1, CDK2 and S6K1/pS6 pathway proteins and downregulated p21 and p27. Finally, a xenograft mouse model of ESCC cells validated the results in vitro.Conclusion: ACTL6A expression may affect the proliferation and DNA synthesis of ESCC cells by facilitating ESCC cell cycle redistribution via the S6K1/pS6 pathway. Therefore, ACTL6A may potentially become an alternative therapeutic target for ESCC.Keywords: ACTL6A, esophageal squamous cell carcinoma, cell cycle, proliferation, pS6

A visible-light-induced and iron-catalyzed oxidative radical addition/cyclization cascade reaction of N-(o-cyanoaryl)acrylamides with dimethyl sulfoxide has been developed. The method exhibits a wide substrate scope and an excellent functional-group tolerance, thus providing an efficient and convenient access to a variety of methylated quinoline-2,4-diones.

Indoor transmission of COVID-19 is highly probable. Multiple sources have verified that the SARS-CoV-2 can be detected within toilets, and people can be infected in restrooms. There is a huge gap in the coronavirus transmission mechanism in restrooms. Understanding it can help to flatten the curve of the infected cases as well as prevent other viruses transmitted in/by the sewage system or human body fluid. Previous studies have shown how simple actions in daily life (coughing, sneezing, or toilet flushing) contribute to virus transmission. This paper quantitatively and visually demonstrates that male urination, which is also a daily action, can agitate virus particles within the toilet and raise them, which may be the main promoter of cross-infection of COVID-19 in restrooms. Adopting numerical and experimental methods, we demonstrate that male urination can cause strong turbulent flow with an averaged urine impinging velocity of 2.3 m/s, which can act as an agitator to raise the virus particles. The climbing velocity of the airflow can be 0.75 - 1.05 m/s. The observed upwards flow will disturb and spread any lurking virus particles (not limited to SARS-CoV-2). Experiments demonstrated that the concentration of the airborne particle could be tripled during male urination. Corresponding precautions are offered as well to prepare the public to consciously act properly when and after using facilities in restrooms for preventing emerging and re-emerging pandemics not limited to the current COVID-19, contributing to the sustainability of human society.

Leonurus japonicus Houtt, a Chinese traditional herbal medicine, has been widely used to cure gynecological diseases, such as incomplete abortion and menoxenia. Leonurine, a major active alkaloid compound only be found in Leonurus japonicus Houtt, has been successfully extracted and purified. Recent evidence has shown that leonurine can regulate a variety of pathologic processes including oxidative stress, inflammation, fibrosis, apoptosis, and multiple metabolic disorders. Here, we have reviewed the pharmacological actions and biological functions of leonurine, with a focus on the role of leonurine in the amelioration of various pathological processes. Insights into the related signaling pathways and molecular mechanisms have strengthened our understanding on the function of leonurine in the alleviation of multiple pathological states. Our summary of the existing researches should help direct future research into the basic science and clinical applications in related diseases.

Nuclear receptor binding SET domain 2 (NSD2)-mediated metabolic reprogramming has been demonstrated to regulate oncogenesis via catalyzing the methylation of histones. The present study aimed to investigate the role of NSD2-mediated metabolic abnormality in pulmonary arterial hypertension (PAH). Monocrotaline (MCT)-induced PAH rat model was established and infected with adeno-associated virus carrying short hairpin RNA (shRNA) targeting NSD2. Hemodynamic parameters, ventricular function, and pathology were evaluated by microcatheter, echocardiography, and histological analysis. Metabolomics changes in lung tissue were analyzed by LC–MS. The results showed that silencing of NSD2 effectively ameliorated MCT-induced PAH and right ventricle dysfunction, and partially reversed pathological remodeling of pulmonary artery and right ventricular hypertrophy. In addition, the silencing of NSD2 markedly reduced the di-methylation level of H3K36 (H3K36me2 level) and inhibited autophagy in pulmonary artery. Non-targeted LC–MS based metabolomics analysis indicated that trehalose showed the most significant change in lung tissue. NSD2-regulated trehalose mainly affected ABC transporters, mineral absorption, protein digestion and absorption, metabolic pathways, and aminoacyl-tRNA biosynthesis. In conclusion, we reveal a new role of NSD2 in the pathogenesis of PAH related to the regulation of trehalose metabolism and autophagy via increasing the H3K36me2 level. NSD2 is a promising target for PAH therapy.

Background The MYBL2 gene, a highly conserved member of the Myb transcription-factor family, has been implicated in the genesis and progression of many types of tumors. Methods We analyzed the expression of MYBL2 and Ki67 in tissue samples of esophageal squamous-cell carcinoma (ESCC) patients by immunohistochemistry. We further analyzed the effect of MYBL2 on cell proliferation and DNA replication using a CCK8 assay, 5-ethynyl-2'-deoxyuridine-retention assay, flow-cytometry analysis, real-time quantitative PCR, Western blot, and a xenograft model of ESCC cells in nude mice. Results MYBL2 expression was significantly higher in ESCC tissue when compared to the adjacent normal tissue (P=0.007). MYBL2 was found to be positively correlated with Ki67 (γ=0.286, P=0.003). Furthermore, Kaplan-Meier curves indicated that MYBL2 expression in ESCC tissue was associated with poor patient outcome (P

A virus-laden particle movement from urinal flushing is simulated. Similar to the toilet-induced flushing, results indicate that the trajectory of the particles triggered by the urinal flushing manifests an external spread type. Even more alarmingly, the particle can reach 0.84 m (man's thigh) in 5.5 s when compared with the diffusion performance of the toilet-induced one (around 0.93 m in 35 s). A more violent climbing tendency is discovered in this Letter. Wearing masks should be made mandatory in public washrooms, and anti-diffusion improvements of facilities in public washrooms are urgently needed, especially in the current "SARS-CoV-2" crisis.

Both the Notch1 and Keap1–Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1–Nrf2 crosstalk in myocardial ischemia–reperfusion injury is unclear. In this study, we established hypoxia–reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1–Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1–Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1–Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.

Mitochondrial quality control is a new target for myocardial protection. Notch signaling plays an important role in heart development, maturation, and repair. However, the role of Notch in the myocardial mitochondrial quality control remains elusive. In this study, we isolated myocardial cells from rats and established myocardial ischemia reperfusion injury (IRI) model. We modulated Notch1 expression level in myocardial cells via infection with recombinant adenoviruses Ad-N1ICD and Ad-shN1ICD. We found that IR reduced myocardial cells viability, but Notch1 overexpression increased the viability of myocardial cells exposed to IRI. In addition, Notch1 overexpression improved ATP production, increased mitochondrial fusion and decreased mitochondrial fission, and inhibited mitophagy in myocardial cells exposed to IRI. However, N1ICD knockdown led to opposite effects. The myocardial protection role of Notch1 was related to the inhibition of Pink1 expression and Mfn2 and Parkin phosphorylation. In conclusion, Notch1 exerts myocardial protection and this is correlated with the maintenance of mitochondrial quality control and the inhibition of Pink1/Mfn2/Parkin signaling.

Developing coordination polymers (CPs) as sensors and exploring their sensing performance are crucial for extending the application of CPs. Herein, we prepared a Cd(II) – citric acid coordination polymer via a hydrothermal method, and explored its efficient sensing for the metal ions and organic molecules. The luminescence sensing experiments demonstrate that its luminescent intensities and peak positions are largely dependent on the solvent molecules and metal ions.

Histone lysine methylation plays an important role in the regulation of ventricular remodelling. NSD2 is involved in many types of tumours through enhancing H3K36me2 expression. However, the role of NSD2 in the regulation of histone lysine methylation during ventricular remodelling remains unclear. In this study, we established cardiac hypertrophy model in C57BL/6 mice by transverse aortic constriction and found that histone lysine methylation participated in ventricular remodelling regulation via the up‐regulation of H3K27me2 and H3K36me2 expression. In addition, we constructed transgenic C57BL/6 mice with conditional knockout of NSD2 (NSD2−/−) in the myocardium. NSD2−/− C57BL/6 mice had milder ventricular remodelling and significantly improved cardiac function compared with wild‐type mice, and the expression of H3K36me2 but not H3K27me2 was down‐regulated. In conclusion, NSD2 promotes ventricular remodelling mediated by the regulation of H3K36me2.

AIM: To present the rationale, design, methodology, and the baseline data of the Beijing Desheng Diabetic Eye Study (BDDES), and to determine the prevalence of diabetic retinopathy (DR) and possible risk factors in patients with type 2 diabetes mellitus (T2DM) in an urban community of Beijing, China. METHODS: Community-based prospective cohort study of persons diagnosed with T2DM aged 30y or older. The main variables of interest are the presence and progression of DR as determined by the standardized ETDRS grading of seven fields fundus photographs. The presence and severity of DR were analyzed for possible correlations to non-genetic and genetic dispositions. RESULTS: A total of 1438 participants with data available for analysis, the prevalence of any DR was 35.4%. The prevalence of mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy was 27.7%, 2.6%, 0.5% and 4.5%, respectively. By multiple logistic regression analysis, risk factors for the presence of any DR included male (P=0.031), lower income level (P=0.011), lower education background (P=0.022), longer duration of diabetes (P=0.001), younger age at diabetic onset (P=0.001), higher systolic blood pressure (P=0.007), higher glycosylated hemoglobin A1c levels (P=0.001), high albuminuria (P=0.03), and use of insulin (P

Three novel networks, namely, {[Co(HL)2]}n (1), {[Co(L)(H2O)]·[Co3/2(L)(OH-Hbdc)(H2O)2]·H2O}n (2), and [Ni(L)(H2O)5]·DMF·4H2O (3), where H2L = 4′-pyridin-4-yl-biphenyl-3,5-dicarboxylic acid and OH-H2bdc = 5-hydroxyisophthalic acid, have been hydrothermally synthesized and characterized. Compound 1 is a two-dimensional (2D) layered structure of Co2+ ions coordinated with incompletely deprotonated HL− ligands. Compound 2 is a crystal in the triclinic space group P and shows a very rare 2D + 2D heterogeneous framework built from 3-connected {63} hcb layers and 4-connected {44·62} sql layers. Compound 3 is a 0-D molecular complex crystallized in the chiral space group P212121, which suggests that symmetry breaking can be driven by the solvent-assisted homochiral helix without any chiral building blocks. In addition, their heterogeneous catalytic oxidation activities toward methyl orange (MO), methyl blue (MB), neutral red (NR), methylene blue (MEB), and safranine T (ST) and the mechanisms in the presence of H2O2 have been investigated in detail in aqueous solutions. The results show that the photocatalytic efficiency of NR is the highest for compounds 1–3.

The NAC (standing for no apical meristem [NAM], Arabidopsis transcription activation factor [ATAF] and cup-shaped cotyledon [CUC]) proteins pertain to one of the plant-specific transcription factor families that play important roles in plant development, abiotic stress resistance and signalling transduction. In the present study, the genomic features of the NAC genes in cucumber were analysed in depth using in silico tools. To reveal a tissue-specific, abiotic stress and hormone-responsive expression profile of CsNAC genes, RT-qPCR was performed under different treatments. Phylogenetic analyses and genome-wide annotation indicated that 82 high-confidence CsNAC genes were clustered into 13 sub-groups with uneven distribution in the cucumber genome. Furthermore, the CsNAC genes exhibited different tissue-specific expression patterns in 10 tissues under normal growth conditions, while 13 (16%) and 28 (34%) genes displayed preferential expression in roots and flowers, respectively. Moreover, CsNAC genes were more sensitive to salinity than other stresses; however, their responses were relatively rapid and transient to nutrition deprivation. Several CsNAC genes, including CsNAC35, which is an orthologue of the known stress-responsive Arabidopsis RD26, were identified as highly responsive to abiotic stresses and hormones. Overall, our findings revealed the genomic landscape and expression profiling of the CsNAC genes in response to multiple stresses and hormones, offering clues for further function analyses and molecular breeding.

Currently, a novel coronavirus named "SARS-CoV-2" is spreading rapidly across the world, causing a public health crisis, economic losses, and panic. Fecal-oral transmission is a common transmission route for many viruses, including SARS-CoV-2. Blocking the path of fecal-oral transmission, which occurs commonly in toilet usage, is of fundamental importance in suppressing the spread of viruses. However, to date, efforts at improving sanitary safety in toilet use have been insufficient. It is clear from daily experience that flushing a toilet generates strong turbulence within the bowl. Will this flushing-induced turbulent flow expel aerosol particles containing viruses out of the bowl? This paper adopts computational fluid dynamics to explore and visualize the characteristics of fluid flow during toilet flushing and the influence of flushing on the spread of virus aerosol particles. The volume-of-fluid (VOF) model is used to simulate two common flushing processes (single-inlet flushing and annular flushing), and the VOF-discrete phase model (DPM) method is used to model the trajectories of aerosol particles during flushing. The simulation results are alarming in that massive upward transport of virus particles is observed, with 40%-60% of particles reaching above the toilet seat, leading to large-scale virus spread. Suggestions concerning safer toilet use and recommendations for a better toilet design are also provided.

How to prevent the flushing-induced plume without changing people's daily habits? Enlightened by thoughts of redesigning the restroom, this article provides a redesigned toilet using liquid-curtain-based strategy and verifies its advantages from the computational fluid dynamics. Two favorable effects are spotted: (1) the liquid curtain can suppress the upward virus particles (only 1% viruses can be lifted out of the toilet) and (2) the flow distribution caused by the liquid curtain can deliver virus particles into the sewage efficiently.

Visible light-induced difluoromethylation of N-arylacrylamides to afford difluoromethylated 2-oxindoles and quinoline-2,4-diones with difluoromethyl 2-pyridyl sulfones as radical precursors has been disclosed. This method provides convenient access to a variety of 2-oxindoles and quinoline-2,4-diones under mild conditions via a proposed tandem radical addition/cyclization process along with good tolerance to various functional groups. In addition, preliminary experimental studies have revealed that water is a key factor in difluoromethylation and the reaction involves an oxidative quenching cycle of the photocatalyst.

Aims To evaluate the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). Materials and methods We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, and Web of Science from inception to 28 February 2018 and identified eligible randomized controlled trials. The following data were extracted from each study: first author, year of publication, sample size, patient characteristics, study design, intervention drug, control drug, follow-up time, and incident bone fracture events. A meta-analysis was conducted using Review Manager 5.3 software to calculate the odds ratio (OR) and 95% confidence intervals (CI) for dichotomous variables. Results A total of 38 studies with 39 795 patients with T2DM were included. There were 241 incident bone fracture cases (107 in the GLP-1 RAs group and 134 in the control group). Compared with patients who received placebo and other anti-diabetic drugs, those who received GLP-1 RAs treatment showed a pooled OR of 0.71 (95% CI, 0.56-0.91) for bone fracture. Subgroup analysis showed that treatments with liraglutide and lixisenatide were associated with significantly reduced risk of bone fractures (ORs, 0.56; 95% CI, 0.38-0.81 and 0.55; 95% CI, 0.31-0.97, respectively). However, other GLP-1 RAs did not show superiority to placebo or other anti-diabetic drugs. Moreover, these beneficial effects were dependent on the duration of GLP-1 RAs treatment, only a GLP-1 RAs treatment period of more than 52 weeks could significantly lower the risk of bone fracture in patients with T2DM (OR, 0.71; 95% CI, 0.56-0.91). Conclusions Compared with placebo and other anti-diabetic drugs, liraglutide and lixisenatide were associated with a significant reduction in the risk of bone fractures, and the beneficial effects were dependent on the duration of treatment.

Higher visual centers could modulate visually-guided ocular growth, in addition to local mechanisms intrinsic to the eye. There is evidence that such central modulations could be species (even subspecies)-dependent. While the mouse has recently become an important experimental animal in myopia studies, it remains unclear whether and how visual centers modulate refractive development in mice, an issue that was examined in the present study. We found that optic nerve crush (ONC), performed at P18, could modify normal refractive development in the C57BL/6 mouse raised in normal visual environment. Unexpectedly, sham surgery caused a steeper cornea, leading to a modest myopic refractive shift, but did not induce significant changes in ocular axis length. ONC caused corneal flattening and re-calibrated the refractive set-point in a bidirectional manner, causing significant myopic (-3 D, 54.5%) or hyperopic (+3 D, 18.2%) shifts in refractive error in most (totally 72.7%) animals, both due to changes in ocular axial length. ONC did not change the density of dopaminergic amacrine cells, but increased retinal levels of dopamine and DOPAC. We conclude that higher visual centers are likely to play a role in fine-tuning of ocular growth, thus modifying refractive development in the C57BL/6 mouse. The changes in refractive error induced by ONC are accounted for by alternations in multiple ocular dimensions, including corneal curvature and axial length.

Hypoxia plays a key role in tumour initiation and metastasis; one of the mechanisms is to induce epithelial-mesenchymal transition (EMT). Signal transducer and activator of transcription 3 (STAT3) is involved in EMT by regulating the transcriptional regulators of E-cadherin, the biomarker of EMT. Until now, however, few studies have focused on the effects of STAT3 in hypoxia-induced EMT in tumour cells. The goal of this study was to investigate the roles of STAT3 in hypoxia-induced EMT in oesophageal squamous cell carcinoma (ESCC). The ESCC cells, TE-1 and EC-1, were incubated in normoxia, or in CoCl2, which was used to mimic hypoxia. With CoCl2, the ESCC cells showed increased migration and invasion abilities, accompanied with upregulation of HIF-1α, STAT3, and vimentin, and downregulation of E-cadherin. Knockdown of STAT3 inhibited EMT of ESCC cells and downregulated HIF-1α in vitro and in vivo. In ChIP assays, STAT3 bound to the promoter of HIF-1α, suggesting that STAT3 regulates transcription of HIF-1α. In conclusion, hypoxia induces EMT of ESCC, and STAT3 regulates this process by promoting HIF-1α expression.

Background: 3,4-dihydroxycinnamic acid and its derivatives exhibit numerous biologic activities. Such activities have not previously been reported for 3,5-dihydroxycinnamic acid derivatives. In this study, ten derivatives of 3,5- dihydroxycinnamic acid were synthesized and their anti-inflammatory activities were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema. Molecular biological studies have shed lights on their anti-inflammatory mechanism. Methods: Anti-inflammatory activities of ten new synthesized derivatives of 3,5-dihydroxycinnamic acid were tested in 12-O-tetradecanoylphorbol 13-acetate-induced mouse ear edema, and their anti-inflammatory mechanism was studied by ELISA, real-time RT-PCR, MPO assay and AA-induced mouse ear edema. Results: Compound 7 showed a pronounced anti-inflammatory effect and the inhibition rate was 65.6% at a dose of 1.6mg/ear. This compound acted by reducing mRNA and protein synthesis of tumor necrosis factor-α, interleukins 1β and 6, and also by decreasing the levels of activated neutrophil infiltrates. Furthermore, compound 7 significantly suppressed arachidonic acid-induced edema as well. Cell-based assays showed that compound 7 inhibited the production of cyclooxygenase- 2-catalyzed prostaglandin E2 from lipopolysaccharide-treated RAW 264.7 cells, and also inhibited 5-lipoxygenase production from A23187-treated RBL-1 cells, and consequently reduced leukotriene B4 production. Conclusion: This investigation revealed that some of the derivatives of 3,5-dihydroxycinnamic acid exhibit a more pronounced anti-inflammatory effect than 3,4-dihydroxycinnamic acid. Therefore, 3,5-dihydroxycinnamic acid derivatives, especially compound 7, represent potential value for antiinflammatory drug development.

Increasing amounts of evidence demonstrated that accumulative reactive oxygen species (ROS) and apoptosis of human endometrial stromal cells (ESCs) are closely associated with endometrial dysfunction induced by oxidative stress, which plays an important role in the pathological process of multiple gynecological and reproduction-related diseases. SCM-198, an alkaloid active component of Leonurus japonicas Houtt, has been reported to have anti-oxidative activity. However, the specific mechanisms of SCM-198 in the prevention of endometrial damage remain unknown. In the present study, we assessed the effect of SCM-198 on hydrogen peroxide (H2O2)-induced oxidative injury in ESCs. ESCs were pretreated with SCM-198 for 4 h and then challenged with H2O2. Morphology changes, apoptosis rate, and intracellular ROS production were measured to assess the level of oxidative injury. Flow cytometry and western blot analysis were performed to detect the expression levels of Bax, Bcl-2, active-caspase-3, and mitogen-activated protein kinases pathways. Classic inflammation cytokines were measured by real-time polymerase chain reactions. Our results showed that SCM-198 attenuated apoptosis and ROS generation of ESCs induced by H2O2. H2O2 induced the apparent apoptotic characteristics, including fragmentation of DNA, upregulation of Bax/Bcl2, activation of caspase-3, and secretion of inflammation cytokines, which were all ameliorated by SCM-198. Furthermore, H2O2-induced apoptosis-related ERK1/2 pathway activation was restrained by SCM-198 pretreatment. These findings suggested that SCM-198 could protect ESCs from oxidative injury, mainly by inhibiting oxidative stress and reducing apoptosis.

A luminescent Pr3+-coordination polymer based on functional linear tetrazole-carboxylic acid and an auxiliary ligand, {[Pr(TBCA)(BPA)·2H2O]}n (1) (HTBCA = 4′-(1H-tetrazol-5-yl)-biphenyl-4-carboxylic acid, H2BPA = 2,2′-biphenyldicarboxylic acid), has been solvothermally synthesized and characterized by single crystal XRD, infrared spectroscopy, elemental analysis, and powder X-ray diffraction. Structural analysis reveals that 1 is a 1D coordination polymer with chains approximately parallel to the a-axis, linked by H-bonding interactions to form a 3-D arrangement. The uptake results for six dyes with different size and different charges revealed that 1 can adsorb neutral red and hardly adsorb the other dyes.

A channel of nanometre size is an important platform for nanofluidic investigations. In this work, we show that a single solid nanopore can be generated by hydrogen fluoride etching of the outside wall of commercially available fused silica capillary. The geometry, size and the singleness were characterized by various means, including scanning electron microscope, electrolyte conductance measurement and a fluorescent microscope. The generation principle is also discussed. The nanopore thus generated features in low aspect ratio and exhibits typical nanofluidic effects such as ion concentration polarization, rectification and molecular translocation.

Letter to the editor

During the progression of osteoarthritis, dysregulation of extracellular matrix (ECM) anabolism, abnormal generation of reactive oxygen species, and proteolytic enzymes have been shown to accelerate the degradation process of cartilage. The purpose of the current study was to investigate the functional role of bromodomain-containing protein 4 (BRD4) in hydrogen peroxide (H2 O2 )-stimulated chondrocyte injury and delineate the underlying molecular mechanisms. We observed that the expression BRD4 was markedly elevated in rat chondrocytes after H2 O2 stimulation. Additionally, inhibition of BRD4 using small interfering RNA or JQ1 (a selective potent chemical inhibitor) led to repression of H2 O2 -induced oxidative stress, as revealed by a decrease in the reactive oxygen species production accompanied by a decreased malondialdehyde content, along with increased activities of antioxidant markers superoxide dismutase, catalase, and glutathione peroxidase on exposure of chondrocytes to H2 O2 . Meanwhile, depletion of BRD4 led to repress the oxidative stress-induced apoptosis of chondrocytes triggered by H2 O2 accompanied by an increase in the expression of anti-apoptotic Bcl-2 and a decrease in the expression of pro-apoptotic Bax and caspase 3 as well as attenuated caspase 3 activity. Moreover, knockdown of BRD4 or treatment with JQ1 markedly attenuated ECM deposition, reflected in a marked upregulation of proteoglycans collagen type II and aggrecan as well as downregulation of ECM-degrading enzymes matrix metalloproteinase 13 and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). More importantly, inhibition of BRD4-activated NF-E2-related factor 2 (Nrf2)-heme oxygenase-1 signaling. Mechanistically, the protective effect of BRD4 inhibition on H2 O2 -stimulated apoptosis and cartilage matrix degeneration was markedly abrogated by Nrf2 depletion. Altogether, we concluded that the protective effect of BRD4 inhibition against oxidative stress-mediated apoptosis and cartilage matrix degeneration occurred through Nrf2-heme oxygenase-1 signaling, implying that BRD4 inhibition may be a more effective therapeutic strategy against osteoarthritis.

Purpose Retinal dopamine has been long implicated in the signaling pathway regulating eye growth, as evidenced by its reduced levels in myopic eyes in various species. We examined whether and how retinal dopamine levels were changed in a C57BL/6 mouse model of experimental myopia. Methods Form-deprivation myopia (FDM) was induced in C57BL/6 mice by wearing monocular occluder for 4 weeks. Refractive errors were measured using an infrared photorefractor. Retinal dopamine/DOPAC and vitreal DOPAC levels were assessed by high-performance liquid chromatography (HPLC). Extracellular dopamine concentrations were examined by Western blot analysis of dopamine transporter (DAT) expression levels. The intactness of retinal dopaminergic system was evaluated by counting tyrosine hydroxylase (TH) immunoreactive cells, measuring the areas occupied by processes of these cells, and quantifying retinal TH expression at both protein and transcription levels. Results Form-deprivation myopia was successfully induced in C57BL/6 mice with the refractive status of deprived eyes being significantly different from fellow eyes. Unlike most of the previous results obtained in other myopic animal models, however, no significant changes in retinal dopamine, DOPAC, DAT, and vitreal DOPAC levels were detected in deprived eyes, either in the daytime or at night. Furthermore, neither the number of dopaminergic amacrine cells, the area size occupied by the processes of these cells, nor retinal TH expression, were altered in deprived eyes. Conclusions The retinal dopamine system remains intact in C57BL/6 mice with FDM, and retinal dopamine levels are not associated with the development of FDM in this mouse strain.

Xue Bai,1 Yun-yun Li,1,2 Hong-yan Zhang,1 Feng Wang,1 Hong-liu He,1 Jin-chao Yao,1 Ling Liu,1 Shan-shan Li1 1Department of Pathology, Basic Medical College of Zhengzhou University, 2Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Abstract: Epithelial–mesenchymal transition (EMT) is thought to be a crucial event during the early metastasis of tumor cells. Transforming growth factor (TGF)-β1 is involved in the process of EMT in a variety of human malignancies. Matrix metalloproteinase (MMP)-9 plays an important role in tumor invasion and metastasis, and its expression is regulated by various growth factors, including TGF-β1, in different cell types. To date, the role of MMP-9 in TGF-β1-induced EMT in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to elucidate the mechanism underlying MMP-9-mediated TGF-β1 induction of EMT in ESCC. We analyzed the expression of MMP-9, E-cadherin, and vimentin, in ESCC cells (EC-1), before and after the treatment with exogenous TGF-β1 or a broad spectrum MMP inhibitor, GM6001. Additionally, we analyzed the activity of MMP-9 in these cells and performed MMP-9 knockdown experiments. The results obtained in this study demonstrated that the treatment of EC-1 cells with TGF-β1 can induce EMT, together with the upregulation of vimentin and downregulation of E-cadherin expression in a time-dependent manner. The treatment with GM6001 was shown to attenuate TGF-β1-induced EMT. Furthermore, the exposure of EC-1 cells to TGF-β1 increased the expression and activity of MMP-9, while MMP-9 knockdown blocked TGF-β1-induced EMT and inhibited cell invasiveness and migration. Additionally, treatment with the recombinant human MMP-9 was shown to induce EMT and enhance ESCC cell invasion and metastasis. The obtained data suggest that the regulation of MMP-9 by TGF-β1 may represent a novel mechanism underlying TGF-β1-induced EMT in ESCC. Keywords: epithelial–mesenchymal transition, esophageal squamous cell carcinoma, matrix metalloproteinase-9, transforming growth factor-β1

Background: hypertension is a modifiable and very important risk factor in chronic renal disease (CKD), and medication adherence (MA) is critical in reaching the treatment goals. Improvement of MA for antihypertensive agents and its impact on blood pressure (BP) in CKD practice settings are not well studied. Methods: In a prospective, controlled open-label studies, the authors have evaluated the four year MA for antihypertensive agents on progress of renal disease and risk of development of cardiovascular disease in 546 hypertension patients with CKD from 2006 to 2014 with targeted nurse-physician intervention. Before randomization Outpatient BP measurements were averaged as high (>140/ 90 mm Hg) . Blood pressure ,serum creatinine(Cr) and potassium were monitored every 14 days in the period of follow-up by physician and healthcare nurse so that every patient is able to perforce self-monitoring BP at home and medication possession ratio(MPR) of target systolic blood pressure Results: By the end of four year,MPR in observation group is 94% and in other is 38%, mean blood pressure in good MA group was 126/76±9/7 mmHg and in control was 146/88±19/12 mmHg, Cr clearance increased from 51±2.0 to 64±3.0 ml/min (p0.05)in the controls. 20 patients had got ACS ,28 patients stroke,38 patients had got pneumonia, 11 patients renal dialysis and nine patient died (6 in SCD and 2 in heart failure and 1 in pneumonia) in controls ,but six patient had stroke ,11 pneumonia, 3 patient renal dialysis and four patients died (2 in SCD and 2 in non-cardio causes) in the treatment group, but incidence of hyperkalaemia was similar between two groups. Conclusions: Good MA is associated with a greater controlled hypertension, better protection of heart and kidney and may decrease mortality than the poor MA.

One new Cd-based Metal-Organic Framework (MOF), {[Cd(cpnc)(H2O)]}n (1), has been synthesized and characterized based on a bidentate carboxylate ligand, H2cpnc, (H2cpnc = (6-(4-carboxyphenyl) nicotinic acid). The Cd cations were connected by cpnc2− ligands to form a rare 6-c rob 3D network. In addition, the effects of different organic reagents and ions on the fluorescence properties of the compound 1 have been studied. The luminescence titration experiments show that a significant quenching of fluorescence intensity can be observed after addition of Fe3+ and K2Cr2O7.