Recent advances of m6A methylation modification in esophageal squamous cell carcinoma.

In recent years, with the development of RNA sequencing technology and bioinformatics methods, the epigenetic modification of RNA based on N6-methyladenosine (m6A) has gradually become a research hotspot in the field of bioscience. m6A is the most abundant internal modification in eukaryotic messenger RNAs (mRNAs). m6A methylation modification can dynamically and reversibly regulate RNA transport, localization, translation and degradation through the interaction of methyltransferase, demethylase and reading protein. m6A methylation can regulate the expression of proto-oncogenes and tumor suppressor genes at the epigenetic modification level to affect tumor occurrence and metastasis. The morbidity and mortality of esophageal cancer (EC) are still high worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common tissue subtype of EC. This article reviews the related concepts, biological functions and recent advances of m6A methylation in ESCC, and looks forward to the prospect of m6A methylation as a new diagnostic biomarker and potential therapeutic target for ESCC.

Circular RNAs and esophageal cancer.

As a new kind of RNA, circular RNA (circRNA) is a endogenous non-coding RNA with circular structure, which has the characteristics of universality, stability, conservatism and specificity. CircRNA can specifically bind to microRNAs (miRNAs) in the form of competitive endogenous RNA, thus directly or indirectly regulating the expression of related genes. In addition to the role of sponge, circRNA also regulates parental gene expression, transcriptional translation and protein modification; and it can be used as a biomarker to develop potential diagnosis and treatment methods and evaluate prognosis. Due to changes in dietary habits and genetic factors, the morbidity and mortality of esophageal cancer (EC) in the world are still high, and are prone to early metastasis. Although the diagnosis and treatment techniques have been improved in recent years, the early diagnosis of EC is not common, and the 5-year survival rate of patients is still very low. This article reviews the function and significance of circRNA and discusses the research progress of circRNA as biomarkers in EC.

A Survey of Surgical Patient's Perception about Anesthesiologist in a Large Scale Comprehensive Hospital in China.

Objectives This study aim to evaluate patient's perception about anesthesiologists' job roles and investigate their expectations for anesthesia care.Methods We designed a self-administered questionnaire for this cross-sectional survey study and delivered questionnaire forms to adult in-patients who were scheduled for elective surgery before pre-operative anesthetic visit the day before surgery. We collected information of respondents' demographic data, education background, health literacy and previous experience of anesthesia, perception of anesthesiologist's job, the expectation on anesthesia care. Descriptive analyses, χ [2] test and multiple linear regression analysis were used for data analysis. Results Of 550 participants, 521（94.7%）completed the questionnaire. In these respondents, 335 (64.3%) considered anesthesiology as an independent medical discipline, 225 (43.2%) believed that anesthesiology department was an independent clinical department, and 243 (46.6%) recognized anesthesiologists as qualified doctors. Only 21.5% of them knew that anesthesiologists also work in the intensive care unit and 26.9% of them knew that anesthesiologists also work in pain clinic as well. Younger patients (ß=-0.044, P<0.001), those with higher education (ß=1.200, P<0.001), or with better health literacy (ß=0.781, P=0.005) had significant more knowledge about the job roles of anesthesiologists. Most patients demanded pre-anesthetic visit (80.5%), expected availability of preoperative anesthetic clinic (74.1%), wished to receive more information about anesthesia (91.3%) and anesthesiologist (77.4%).Conclusions Patients' perception about anesthesiologists might be limited. Efforts should be made on education about anesthesia, especially for elderly patients and those under-educated patients. Preoperative anesthetic clinic is expected by most in-patients.

Ultrasound-guided Selective Cervical Nerve Root Block Plus Superficial Cervical Plexus Block for Minimally Invasive Parathyroidectomy.

Objective To explore the efficacy and safety of ultrasound-guided cervical root block (CRB) in patients undergoing minimally invasive parathyroidectomy (MIP).Methods We enrolled 35 patients with hyperparathyroidism undergoing MIP in Peking Union Medical College Hospital.C4-7 nerve roots were identified in ultrasound imaging by the shape of the transverse process.A 50 mm insulated needle was gently introduced by an in-plane approach toward the posterior edge of the nerve root located at the inside of the posterior tubercle.After careful aspiration,a total of 3-4 ml of a mixture of 0.5% ropivacaine and 1% lidocaine was slowly injected.The superficial block was administered at the midpoint of the posterior border of the sternocleidomastoid by injecting 5-6 ml of the same mixture.The patients were administrated with dexmedetomidine during the surgery.All patients were assessed for sensory following the procedure and for pain after the surgery.Results Totally 35 patients successfully received MIP under ultrasound-guided CRB plus superficial block.There was no conversion to general anesthesia,no toxic reaction of local anesthetics,and no intravertebral injection.Hoarseness occurred in 6 patients (17.1%) and Horner syndrome occurred in 3 patients (8.6%).The median cold sensory visual analogue scale score was 1.2 [0,5] points at 10 minutes after the procedure.Patient's satisfaction score was 9.5 points.Conclusion Ultrasound-guided CRB plus superficial block can achieve accurate and safe anesthesia,and it provides lasting analgesic effect during and after MIP.

Influence of Anesthetic Brochure on Patient's Information Gain, Preoperative Anxiety, Trust, and Satisfaction.

Objective To assess the impacts of anesthetic brochure on anesthetic information gain, preoperative anxiety, trust to anesthesiologists, and satisfaction to the preanesthesia visit for patients undergoing general anesthesia. Methods Totally 134 patients scheduled for elective thyroid surgery under general anesthesia in Peking Union Medical College Hospital were assigned to two groups using the random number table method, among whom 68 patients received brochure before preoperative visit (brochure group) and 66 patients did not (control group). Questionnaires with items for evaluating patient's information gain, preoperative anxiety and trust were completed after preanesthetic visit. Patient's satisfaction with preanesthetic visit was evaluated on the second postoperative day. Results Compared with the control group, patients in the brochure group had significantly higher information gain scores (7.2±1.8 vs. 5.2±2.1, P<0.001) and satisfaction scores (25.0±3.4 vs. 22.7±3.1, P<0.001). There was no significant difference in anxiety scores and trust scores between these two groups. Conclusion Preoperative anesthetic brochure-assisted education can improve information gain and satisfaction among patients undergoing general anesthesia; however, it can not remarkably alter patient's preoperative anxiety and trust.

Genome-wide DNA methylation analysis reveals different methylation patterns in Chinese indigenous sheep with different type of tail.

Background: The study was aimed to analyze the difference of genome-wide DNA differential methylation in Lanzhou Large-tailed sheep, Altay sheep and Tibetan sheep, which the typical breeds with different type tails, as to screen the differentially methylated genes (DMGs) that affect the type of tails. Methods: In this study, three Lanzhou Large-tailed sheep, three Altay sheep and three Tibetan sheep were detected by whole genome bisulfite sequencing (WGBS). The degree of genome-wide DNA methylation, differentially methylated regions (DMRs) and DMGs were analyzed. The candidate genes affecting the tail type of sheep were identified by GO and KEGG pathway enrichment analysis of DMGs. Results: we identified 68,603 different methylated regions (DMCs) and 75 differentially methylated genes (DMGs) associated with these DMCs. Functional analysis showed that these DMGs were mainly enriched in biological process, cellular component and molecular function, Some of the genes in these pathways are involved in fat metabolism: NFATC4, LPIN2, MGAT2 and MAT2B. Conclusion: Our results may help to further understand the epigenetic regulation mechanisms of deposition of fat in the tail of sheep and provide new basic data for the study of local sheep.

2:1 multiplexing function in a simple molecular system.

1-[(Anthracen-9-yl)methylene] thiosemicarbazide shows weak fluorescence due to a photo-induced electron transfer (PET) process from the thiosemicarbazide moiety to the excited anthracene. The anthracene emission can be recovered via protonation of the amine as the protonated aminomethylene as an electron-withdrawing group that suppresses the PET process. Similarly, chelation between the ligand and the metal ions can also suppress the PET process and results in a fluorescence enhancement (CHEF). When solvents are introduced as the third control, a molecular 2:1 multiplexer is constructed to report selectively the inputs. Therefore, a molecular 2:1 multiplexer is realized in a simple molecular system.

AT-specific DNA binding of binuclear ruthenium complexes at the border of threading intercalation.

The binuclear ruthenium complex [µ-bidppz(phen)(4)Ru(2)](4+) has been extensively studied since the discovery of its unusual threading intercalation interaction with DNA, a binding mode with extremely slow binding and dissociation kinetics. The complex has been shown to be selective towards long stretches of alternating AT base pairs, which makes it interesting, for example, as a model compound for anti-malaria drugs due to the high AT content of the genome of the malaria parasite P. falciparum. We have investigated the effect of bridging ligand structure on threading intercalation ability and found that length and rigidity as well as the size of the intercalated ring system are all factors that affect the rate and selectivity of the threading intercalation. In particular, we discovered a new DNA-threading compound, [µ-dppzip(phen)(4)Ru(2)](4+), which appears to be just at the border of being capable of threading intercalation and displays even greater selectivity for AT-DNA than the parent compound, [µ-bidppz(phen)(4)Ru(2)](4+).

Construction of magnetic bifunctional ß-cyclodextrin nanocomposites for adsorption and degradation of persistent organic pollutants.

Herein, we report a novel magnetic bifunctional ß-cyclodextrin nanocomposite (Fe3O4@ß-CD-CDI) based on metal coordination, which may be used for adsorption and degradation of persistent organic pollutants in aqueous solution. More importantly, N,N'-carbonyldiimidazole (CDI) functionalized ß-CD ligand (ß-CD-CDI) was assembled on the surface of Fe3O4 by Zn-N interaction. The results of kinetic and isothermal adsorption model investigation indicated that the adsorption rate and capacity of Fe3O4@ß-CD-CDI were better than other materials, suggesting the effective accessibility of adsorption sites. We further confirmed that Fe3O4@ß-CD-CDI can be used as heterogeneous catalyst to remove BPA through Fenton-like reaction in the presence of hydrogen peroxide (H2O2). Moreover, the material effectively alleviated the secondary pollution owing to the existence of ß-CD inner cavity. This study indicated that the magnetic Fe3O4@ß-CD-CDI material has great potential applications in wastewater purification containing persistent organic pollutants.

Novel porous magnetic nanospheres functionalized by ß-cyclodextrin polymer and its application in organic pollutants from aqueous solution.

Magnetic ß-cyclodextrin (ß-CD) porous polymer nanospheres (P-MCD) was fabricated by one-pot solvent thermal method using ß-CD immobilized Fe3O4 magnetic nanoparticles with tetrafluoroterephthalonitrile as the monomer. Compared with the ß-CD polymerization method reported in the literature,_ENREF_1 the synthetic route is effective and simple, thereby overcoming the harsh conditions that require nitrogen protection and always maintain anhydrous and oxygen-free. Moreover, the immobilization of ß-CD on magnetic nanoparticles is combined with the cross-linking polymerization of the cross-linker, leading to a good synergistic effect on the removal of contaminants. Meanwhile, the dispersibility of the magnetic carrier enhances the dispersion of the ß-CD porous polymer in the aqueous phase, and improves the inclusion adsorption performance and the adsorption process. P-MCD exhibited superior adsorption capacity and fast kinetics to MB. The maximum adsorption capacity of MB for P-MCD was 305.8 mg g -1, which is more than ß-CD modified Fe3O4 magnetic nanoparticles (Fe3O4@ß-CD). Moreover, the material had a short equilibrium time (5 min) for MB, high recovery and good recyclability (the adsorption efficiency was still above 86% after five repeated uses).

Luminescent dipyridophenazine-ruthenium probes for liposome membranes.

Ruthenium complexes with dipyridophenazine (dppz) type ligands have several characteristics that make them good candidates for use as luminescence probes for hydrophobic environments. Most studies have concerned DNA intercalation, but also lipid membrane fluidity and liposome orientation have been assessed. We report here dipyridophenazine derivatives ([Ru(phen)2dppz]2+) substituted with one or two alkyl ether chains of different lengths aimed at finding the optimum substitution for a high quantum yield when bound to a phospholipid membrane bilayer. The orientation of membrane bound molecules is studied using flow linear dichroism (LD) with phospholipid vesicles as membrane models. LD, excitation anisotropy, steady state luminescence and excited-state lifetime measurements are used to quantitatively investigate the insertion and orientation of the complexes in the vesicles. All complexes are inserted with their long axis of the dppz moiety mainly parallel to the lipid chains, and the degree of orientation is comparable to that of the orientation probe retinoic acid. The ruthenium "head group" with its positive charge functions as a buoy at the water-membrane interface while the hydrophobic chain part embeds the complex down into the bilayer. The complex with two hexyl ether substituents (named D6) has the optimal chain length regarding membrane insertion and orientation, and together with the highest quantum yield, is the best luminescence membrane probe in the two series.

Oximated ruthenium tris-bipyridyl complex: synthesis and luminescent response specifically for ClO(-) in water containing multiple ions.

Hypochlorite has been widely and essentially used as the disinfecting agent of water in our daily life. Rapidly, specifically, quantitatively and simply monitoring ClO(-) in water remains to be investigated and is of importance. For this purpose a novel complex bis(2,2'-bipyridine)(4'-methyl-2,2'-bipyridyl-4-carbaldehyde oxime)ruthenium chloride (Ru-C[double bond, length as m-dash]N-OH) was prepared. In water, reaction of complex Ru-C[double bond, length as m-dash]N-OH and ClO(-) results in bis(2,2'-bipyridine)(4'-methyl-2,2'-bipyridyl-4-carboxylic acid)ruthenium (Ru-CO2H) and thereby offers an efficient luminescence response. This was ascertained to be a specific oxidation reaction of complex Ru-C[double bond, length as m-dash]N-OH with ClO(-), and can be used for quantitatively monitoring aqueous ClO(-). The product of the oxidation reaction of complex Ru-C[double bond, length as m-dash]N-OH and ClO(-) was isolated and assigned to Ru-CO2H. The luminescent emission spectra of complex Ru-C[double bond, length as m-dash]N-OH in the presence of ClO(-) demonstrated that the coexistence of F(-), Cl(-), Br(-), I(-), HCO3(-), HSO4(-), H2PO4(-), S2O3(2-), SO3(2-), CO3(2-), PO4(3-), HPO4(2-), NO3(-), AcO(-), Li(+), Na(+), K(+), Ca(2+), Mg(2+), Zn(2+), Co(2+), Fe(3+), Ni(2+), Pb(2+), Hg(2+), Mn(2+) and Cu(2+) did not interfere in the quantitative change of the intensity of the luminescent emission.

An efficient ruthenium tris(bipyridine)-based luminescent chemosensor for recognition of Cu(II) and sulfide anion in water.

A novel efficient luminescent chemosensor based on a 1,4,7,10-tetraazacyclododecane (cyclen)-tethered Ru(bpy)3(2+) derivative (Ru-cyclen) has been synthesized and characterized. It displays an ON-OFF-type luminescence change with excellent selectivity towards Cu(II) amongst 16 metal ions in 100% aqueous solution. The binding stoichiometry of Ru-cyclen with Cu(2+) was established by Job plot analysis and mass spectral evidence. Furthermore, the in situ generated Ru-cyclen-Cu ensemble recovered luminescence in the presence of S(2-), indicating an 'OFF-ON'-type sensing process. Similar phenomena were not observed with other common anions and biothiols, making it a high selective sulfide probe. Finally, the sensing mechanism is confirmed to be displacement approach by NMR, mass and emission spectrometry.

Slow threading intercalation of monomeric Ru(II) complexes with 10,13-diarylsubstituted dppz ligands.

Threading intercalation is an unusual DNA binding mode that displays extremely slow dissociation kinetics, which is an important feature for cytotoxicity, making threading intercalating compounds interesting as model compounds in the search for new DNA binding drugs. This type of binding has for ruthenium complexes previously only been observed for complexes containing 11-substituted dipyridophenazine ligands. In this work we have synthesized and investigated the DNA binding properties of two new 10,13-diarylsubstituted dipyridophenazine ruthenium complexes, using spectroscopic techniques, and found that this substitution pattern provides a new strategy for development of drugs with slow dissociation kinetics. However, the nature of the aryl substituents largely affects the binding properties of the complexes as it was found that a dithienyl substituted complex exhibit slow dissociation kinetics characteristic for threading intercalation while its diphenyl substituted analogue seems to bind DNA by partial intercalation of one phenyl substituent resulting in faster dissociation.

Lipophilic ruthenium complexes with tuned cell membrane affinity and photoactivated uptake.

Ruthenium dipyridophenazine (dppz) complexes are virtually non-emissive in aqueous solutions but show strong luminescence in hydrophobic environments, making them interesting as molecular probes in cellular imaging. We show by luminescence spectroscopy that by substituting the dppz ligand with alkyl ether chains of increasing length the complexes can be tuned from preferential intercalation into DNA to insertion in model phospholipid membranes. Confocal laser scanning microscopy (CLSM) on methanol fixed CHO-K1 cells show an analogous distribution in the cell, where the least hydrophobic complex exclusively stains the nucleus whereas the more hydrophobic ones seem to predominantly stain membrane structures in the cytoplasm. In live cells CLSM show that initially only the more hydrophobic derivatives stain the plasma membrane. However, brief further exposure to the laser light causes permeabilization of the membrane and accumulation of extracellular ruthenium complexes in internal cellular structures, similarly to the distribution found in fixed cells.

Synthesis and DNA threading properties of quaternary ammonium [Ru(phen)2(dppz)]2+ derivatives.

Ruthenium complexes with one dipyrido[3,2-a:2'-3'-c]phenazine (dppz) ligand, e.g. [Ru(phen)(2)(dppz)](2+) (phen=phenanthroline), shows strong binding to double helical DNA and are well-known DNA "light-switch" molecules. We have here investigated four new [Ru(phen)(2)(dppz)](2+) derivatives with different bulky quaternary ammonium substituents on the dppz ligand to find relationships between molecular structure and intercalation kinetics, which is considered to be of importance for antitumor applicability. Linear dichroism spectroscopy shows that the enantiomers of the new complexes exhibit very similar binding geometries (intercalation of dppz moiety between adjacent DNA base pairs) as the enantiomers of the parent [Ru(phen)(2)(dppz)](2+) complex. Absorption spectra and luminescence properties provide further evidence for a final intercalative binding mode which has to be reached by threading of a bulky moiety between the strands of the DNA. Delta-enantiomers of all the new complexes show much slower association and dissociation kinetics than that of a reference complex without a cationic substituent. Kinetics were not very different whether the bulky quaternary group was derived from hexamethylene tetramine or 1,4-diazabicyclo-(2,2,2)octane (DABCO) or whether it had one or two positive charges. However, a complex in which the hexamethylene tetramine substituent is attached via a phenyl group showed a lowered association rate, in addition to an improved quantum yield of luminescence. A second positive charge on the DABCO substituent resulted in a much slower dissociation rate, suggesting that the distance from the Ru-centre and the amount of charge are both important for threading intercalation kinetics.