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Quasichemical theory (QCT) provides a framework that can be used to partition the influence of the solvent surrounding an ion into near and distant contributions. Within QCT, the solvation properties of the ion are expressed as a sum of configurational integrals comprising only the ion and a small number of solvent molecules. QCT adopts a particularly simple form if it is assumed that the clusters undergo only small thermal fluctuations around a well-defined energy minimum and are affected exclusively in a mean-field sense by the surrounding bulk solvent. The fluctuations can then be integrated out via a simple vibrational analysis, leading to a closed-form expression for the solvation free energy of the ion. This constitutes the primitive form of quasichemical theory (pQCT), which is an approximate mathematical formulation aimed at reproducing the results from the full many-body configurational averages of statistical mechanics. While the results from pQCT from previous applications are reasonable, the accuracy of the approach has not been fully characterized and its range of validity remains unclear. Here, a direct test of pQCT for a set of ion models is carried out by comparing with the results of free energy simulations with explicit solvent. The influence of the distant surrounding bulk on the cluster comprising the ion and the nearest solvent molecule is treated both with a continuum dielectric approximation and with free energy perturbation molecular dynamics simulations with explicit solvent. The analysis shows that pQCT can provide an accurate framework in the case of a small cation such as Li+. However, the approximation encounters increasing difficulties when applied to larger cations such as Na+, and particularly for K+. This suggests that results from pQCT should be interpreted with caution when comparing ions of different sizes. [ABSTRACT FROM AUTHOR]

Proton transfers are involved in many chemical processes in solution and in biological systems. Although water molecules have been known to transiently facilitate proton transfers, the possibility that water molecules may serve as the “storage site” for proton in biological systems has only been raised in recent years. To characterize the structural and possibly the dynamic nature of these protonated water clusters, it is important to use effective computational techniques to properly interpret experimental spectroscopic measurements of condensed phase systems. Bearing this goal in mind, we systematically benchmark the self-consistent-charge density-functional tight-binding (SCC-DFTB) method for the description of vibrational spectra of protonated water clusters in the gas phase, which became available only recently with infrared multiphoton photodissociation and infrared predissociation spectroscopic experiments. It is found that SCC-DFTB qualitatively reproduces the important features in the vibrational spectra of protonated water clusters, especially concerning the characteristic signatures of clusters of various sizes. In agreement with recent ab initio molecular dynamics studies, it is found that dynamical effects play an important role in determining the vibrational properties of these water clusters. Considering computational efficiency, these benchmark calculations suggest that the SCC-DFTB/molecular mechanical approach can be an effective tool for probing the structural and dynamic features of protonated water molecules in biomolecular systems. [ABSTRACT FROM AUTHOR]

The properties of two improved versions of charge-on-spring (COS) polarizable water models (COS/G2 and COS/G3) that explicitly include nonadditive polarization effects are reported. In COS models, the polarization is represented via a self-consistently induced dipole moment consisting of a pair of separated charges. A previous polarizable water model (COS/B2), upon which the improved versions are based, was developed by Yu, Hansson, and van Gunsteren [J. Chem. Phys. 118, 221 (2003)]. To improve the COS/B2 model, which overestimated the dielectric permittivity, one additional virtual atomic site was used to reproduce the water monomer quadrupole moments besides the water monomer dipole moment in the gas phase. The molecular polarizability, residing on the virtual atomic site, and Lennard-Jones parameters for oxygen-oxygen interactions were varied to reproduce the experimental values for the heat of vaporization and the density of liquid water at room temperature and pressure. The improved models were used to study the properties of liquid water at various thermodynamic states as well as gaseous water clusters and ice. Overall, good agreement is obtained between simulated properties and those derived from experiments and ab initio calculations. The COS/G2 and COS/G3 models may serve as simple, classical, rigid, polarizable water models for the study of organic solutes and biopolymers. Due to its simplicity, COS type of polarization can straightforwardly be used to introduce explicit polarization into (bio)molecular force fields. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Based on career construction theory, this study examined the relationships between career adaptability, organizational success, and individual career success with the moderating effect of career identity. Using a time-lagged survey design, we tested the proposed model on a sample of 1,652 employees from 20 Chinese companies. The results showed that career adaptability was negatively related to turnover intention but positively associated with supervisor-rated job performance, career satisfaction, and yearly income. In addition, the relationship between career adaptability and turnover intention was significantly positive for employees with low levels of career identity. Moreover, the positive relationship between career adaptability and career satisfaction was stronger for employees with high levels of career identity, and the relationship between career adaptability and yearly income was significantly positive for employees with high levels of career identity. We discuss the research implications for the development of career adaptability and career counseling. [ABSTRACT FROM AUTHOR]

This paper considers the global regularity to the 3D incompressible MHD equations with large initial data in bounded domains. Let µ, ν, u, and b denote the viscosity coefficient, magnetic diffusivity, velocity field, and magnetic field, respectively. We construct new systems for (u - b) and (u + b) to overcome the difficulties caused by the large initial data. It is shown that (u, b)H1 is globally bounded as long as ∥(u0 - b0)∥ H1 + |µ - ν|(µ + ν)-1 or ∥(u0 + b0)∥ H1 + |¿ - ν|(&#181 + ν)-1 is sufficiently small, which indicates that the Navier-Stokes equations can be regularized by the magnetic field. [ABSTRACT FROM AUTHOR]

Background: In the recent years, laparoscopic splenectomy and esophagogastric devascularization (LSD) for liver cirrhosis and portal hypertension rapidly gained the interest of hepatobiliary surgeons due to its minimal invasion. This study aimed to gather and analyze available data from the observational studies that have compared LSD and open splenectomy and esophagogastric devascularization (OSD) for liver cirrhosis and portal hypertension.Materials and Methods: All the studies comparing LSD and OSD for liver cirrhosis and portal hypertension were searched on the available databases, including the Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang Database, and China Biomedical Database. Data were analyzed using Review Manager software version 5.0.Results: After the literature search, a total of 17 studies were included in the meta-analysis, which involved 1093 patients: 552 in the laparoscopic group and 541 in the open group. The laparoscopic group was shown to have a lower overall postoperative complication rate (0.43; 95% confidence interval [CI; 0.29-0.64]) than the open group (P < .0001), which was not associated with heterogeneity between the studies. The laparoscopic group was shown to have a lower intraoperative blood loss (-320.62; 95% CI [-552.35 to -88.9]), shorter time of oral intake (-29.08 hours; 95% CI [-35.28 to -22.88]), and shorter hospital stay (95% CI [-6.19 to -2.19]) than those of the open group (P < .00001). The operative time of the laparoscopic group was 42.16 minutes longer (95% CI [32.20-52.11]) compared with the open group (P < .00001). There was no significant difference of hospitalization costs between the studies.Conclusion: This meta-analysis demonstrated that laparoscopic left lateral resection is a safe and feasible option associated with a reduced overall complication rate. The current evidence suggested that it could be performed routinely in liver centers. [ABSTRACT FROM AUTHOR]

Rural school consolidation has significantly changed the landscape of rural education in China. Based on a study carried out in nine provinces, this article analyzes the effect of this policy initiative. It has led to increased school dropout rates in rural schools. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is a ubiquitous cellular messenger molecule in the cardiovascular, nervous, and immune systems. Mitochondrion is the main area where endogenous NO is synthesized by inducible NOS enzymes in mammalian cells. Thus, real-time monitoring NO in mitochondria is very meaningful for NO chemical biology. Although a variety of fluorescent probes for NO have been successfully developed, they are not suited for detecting mitochondrial NO because none of them can specifically localize in mitochondria. Herein, Mito-Rh-NO, the first mitochondria-targetable "turn-on" fluorescent probe for NO, has been developed through attaching a triphenylphosphonium to a rhodamine spirolactam. The characteristics of this probe are as following: (1) Mito-Rh-NO exhibits high sensitivity toward NO. In solution, Mito-Rh-NO responds to NO by significant fluorescence enhancement up to 60-fold, and its NO detection limit is as low as 4.0 nM. (2) The NO sensing of Mito-Rh-NO is highly selective, which will not interfere with the other reactive oxygen and nitrogen species. (3) Mito-Rh-NO has a low cytotoxic effect: after being treated with 10 μM Mito-Rh-NO for 24 h, the survival rate is higher than 90%. (4) Mito-Rh-NO specifically localizing in mitochondria: colocalization experiment of Mito-Rh-NO and Rh 123, a typical mitotracker, shows the merged fluorescent microcopy image with a high Pearson's colocalization coefficient 0.92 and overlap coefficient 0.99. (5) Mito-Rh-NO demonstrates high applicability for real-time monitoring of mitochondrial NO in live cells. Both the exogenous NO released by the donor NOC13 and endogenous NO generated in cells under stimulation have been visualized under confocal microscopy. [ABSTRACT FROM AUTHOR]

Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. [ABSTRACT FROM AUTHOR]

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1-KCNEx complexes. Mutations in either KCNQ1 or KCNE1 genes result in diseases in brain, heart, and the respiratory system. In addition to complexities arising from existence of five KCNE subunits, KCNE1 to KCNE5, recent studies in heterologous systems suggest unorthodox stoichiometric dynamics in subunit assembly is dependent on KCNE expression levels. The resultant KCNQ1-KCNE channel complexes may have a range of zero to two or even up to four KCNE subunits coassembling per KCNQ1 tetramer. These findings underscore the need to assess the selectivity of small-molecule KCNQ1 modulators on these different assemblies. Here we report a unique small-molecule gating modulator, ML277, that potentiates both homomultimeric KCNQ1 channels and unsaturated heteromultimeric (KCNQ1)4(KCNE1)n (n < 4) channels. Progressive increase of KCNE1 or KCNE3 expression reduces efficacy of ML277 and eventually abolishes ML277-mediated augmentation. In cardiomyocytes, the slowly activating delayed rectifier potassium current, or IKs, is believed to be a heteromultimeric combination of KCNQ1 and KCNE1, but it is not entirely clear whether IKs is mediated by KCNE-saturated KCNQ1 channels or by channels with intermediate stoichiometries. We found ML277 effectively augments IKs current of cultured human cardiomyocytes and shortens action potential duration. These data indicate that unsaturated heteromultimeric (KCNQ1)4(KCNE1)n channels are present as components of IKs and are pharmacologically distinct from KCNE-saturated KCNQ1-KCNE1 channels. [ABSTRACT FROM AUTHOR]

To evaluate the effect of acupuncture on hemiparesis and quality of life for adults with brain astrocytoma grade II, we conducted a randomized, observer-blinded clinical trial. Fifty-eight patients were randomized to standard rehabilitation (SR) therapy without acupuncture (n = 20), SR plus standard acupuncture (SA) (n = 19), and SR plus individualized acupuncture (IA) (n = 19). SA points were PC6, SP6, HT1, LU5, BL40, and ST36, while a special concept called "connecting and regulation Ren and Du" and "Jin-3-needling" served as IA. This treatment was individualized according to the clinical syndrome. The outcome was measured by the Barthel Index (BI), the Fugl-Meyer scale (FM), and the EORTC Core Quality of Life Questionnaire (QLQ-C30) with the Brain Cancer Module (BCM20). IA + SR reached significantly higher BI scores than SA + SR, which reached significantly higher BI scores than SR. IA + SR was significantly superior to SA + SR and to SR at the 8th week for the scores of FM motor and sensory assessments and most QLQ-C30-BCM20 items. In conclusion, the individualized acupuncture concept of "connecting and regulating Ren and Du" combined with "Jin-3-needling" offers a promising possibility for the treatment of hemiparesis due to astrocytoma, but further evaluation is mandatory. [ABSTRACT FROM AUTHOR]

A lysosome-specific and two-photon fluorescent probe, Lyso-NINO, demonstrates high selectivity and sensitivity toward NO, lower cytotoxicity, and perfect lysosomal localization. With the aid of Lyso-NINO, the first capture of NO within lysosomes of macrophage cells has been achieved using both two-photon fluorescence microscopy and flow cytometry. [ABSTRACT FROM AUTHOR]

Fluorescence resonance energy transfer (FRET) is an important photophysical mechanism which finds many applications in biophotonics, particularly in biological sensing and imaging. It is well known, there are two major factors that determine the efficiency of FRET. One is the distance between the donor and the acceptor, and the other is the overlap of the donor's emission and the acceptor's absorption spectra. However, while the distance-modulation of FRET is very popular, the spectral-overlap-modulation draws much less attention. In this talk, I would like to illustrate the importance of the strategy of spectral-overlapmodulation. The presentation will inc]ude our works on the construction of highly efficient FRET systems featuring the short and rigid linker between the donor and acceptor moieties, and several typical examples of spectral-overlap-modulation strategy applied in the development of ratiometric sensors. [ABSTRACT FROM AUTHOR]

In the original 1,3,5,7-tetraphenyl aza-BODIPY, replacing the phenyl rings with thiophene achieved significant bathochromic shifts. One of the target molecules, DPDTAB, emitting strong NIR fluorescence with a quantum yield of 0.46 in acetonitrile, is a very competitive NIR fluorophore. [ABSTRACT FROM AUTHOR]

Cyenopyrafen and its geometric isomer were synthesized by various methods, and the structures were characterized by ¹H NMR. 13C NMR, IR, elemental analyses and X-ray diffraction analyses. The bioassay tests showed that cyenopyrafen exhibited a higher acaricidal activity than its isomer. Cyenopyrafen can be isomerized from the Z form in the presence of a base. [ABSTRACT FROM AUTHOR]

The author examines the role of education in integrating and connecting the Naxi with the Han, grounded in a historical narrative of the Naxi, a minority group in southern China. He stresses that although most Naxi people can speak fluent Chinese, they still keep a sense of ethnic differentiation. The author shows that assimilation is an autonomous and tacit choice led by the ruling class and intellectuals but does not serve as an ultimate end for pursuing group survival and cultural distinctiveness.

Ammonium aminodiboranate ([NH4][BH3NH2BH3]) is a long-sought isomer of diammoniate of diborane ([NH3BH2NH3][BH4]) and ammonia borane (NH3BH3) dimer. Our results show that [NH4][BH3NH2BH3] is stable in tetrahydrofuran at -18 °C and decomposes rapidly to NH3BH2NH2BH3 and H2 at elevated temperatures. The decomposition pathway is dictated by the dihydrogen bonding between Hδ+ on NH4+ and Hδ- on BH3, as confirmed by theoretical calculations. This is in contrast to the interconversion between [NH3BH2NH3][BH4] and (NH3BH3)2, although all three have dihydrogen bonds and the same stoichiometry. [ABSTRACT FROM AUTHOR]

The topological control hypothesis presented by Bostick and Brooks [Proc. Natl. Acad. Sci. U.S.A.2007, 104, 9260] has sought to explain binding selectivity in potassium channels based on the premise that a universal measure of ion solvation in different environments is provided by its average coordination structure in bulk water. This leads to the view that ion selectivity is predominantly controlled by the number of ligands coordinating the ion and that the chemical type of those ligands plays a minor role. The significance of the topological control hypothesis and its ability to predict ion selectivity in protein binding sites are examined. It is shown that the framework encounters increasing difficulties when different protein binding sites with similar coordination numbers are considered. [ABSTRACT FROM AUTHOR]

Eleven new thiazol-containing 1H-1,2,4-triazole derivatives were designed and synthesized by utilizing 3,3-dimethylbutan-2-one as starting material. Their structures were characterized by IR, ¹H NMR, 13C NMR, and elemental analysis. Furthermore, some compounds' structures were confirmed with MS and X-ray diffraction and the biological activities of these compounds were evaluated, including in vitro fungicidal and plant-growth regulatory activities. The primary bioassay results indicated that these compounds showed low antifungal activities while exhibited promising plant-growth regulatory activities. [ABSTRACT FROM AUTHOR]

The standard self-consistent-charge density-functional-tight-binding (SCC-DFTB) method (Phys. Rev. B1998, 58, 7260) is derived by a second-order expansion of the density functional theory total energy expression, followed by an approximation of the charge density fluctuations by charge monopoles and an effective damped Coulomb interaction between the atomic net charges. The central assumptions behind this effective charge−charge interaction are the inverse relation of atomic size and chemical hardness and the use of a fixed chemical hardness parameter independent of the atomic charge state. While these approximations seem to be unproblematic for many covalently bound systems, they are quantitatively insufficient for hydrogen-bonding interactions and (anionic) molecules with localized net charges. Here, we present an extension of the SCC-DFTB method to incorporate third-order terms in the charge density fluctuations, leading to chemical hardness parameters that are dependent on the atomic charge state and a modification of the Coulomb scaling to improve the electrostatic treatment within the second-order terms. These modifications lead to a significant improvement in the description of hydrogen-bonding interactions and proton affinities of biologically relevant molecules. [ABSTRACT FROM AUTHOR]

This paper examines the role of schooling in constructing identity of Naxi secondary students in Lijiang, southwest China. The study shows that the school assigns an identity of the Chinese nation to Naxi students, while it also plays a role in forming their ethnic identity. The school curriculum, teachers' teaching, and interactions among students influence the identity construction of Naxi students. A qualitative method was designed to collect data for this study. [ABSTRACT FROM AUTHOR]

An important challenge in the analysis of mechanochemical coupling in molecular motors is to identify residues that dictate the tight coupling between the chemical site and distant structural rearrangements. In this work, a systematic attempt is made to tackle this issue for the conventional myosin. By judiciously combining a range of computational techniques with different approximations and strength, which include targeted molecular dynamics, normal mode analysis, and statistical coupling analysis, we are able to identify a set of important residues and propose their relevant function during the recovery stroke of myosin. These analyses also allowed us to make connections with previous experimental and computational studies in a critical manner. The behavior of the widely used reporter residue, Trp501, in the simulations confirms the concern that its fluorescence does not simply reflect the relay loop conformation or active-site open/close but depends subtly on its microenvironment. The findings in the targeted molecular dynamics and a previous minimum energy path analysis of the recovery stroke have been compared and analyzed, which emphasized the difference and complementarity of the two approaches. In conjunction with our previous studies, the current set of investigations suggest that the modulation of structural flexibility at both the local (e.g., active-site) and domain scales with strategically placed ‘hotspot’ residues and phosphate chemistry is likely the general feature for mechanochemical coupling in many molecular motors. The fundamental strategies of examining both collective and local changes and combining physically motivated methods and informatics-driven techniques are expected to be valuable to the study of other molecular motors and allosteric systems in general. [ABSTRACT FROM AUTHOR]

Although the major structural transitions in molecular motors are often argued to couple to the binding of Adenosine triphosphate (ATP), the recovery stroke in the conventional myosin has been shown to be dependent on the hydrolysis of ATP. To obtain a clearer mechanistic picture for such ‘mechanochemical coupling’ in myosin, equilibrium active-site simulations with explicit solvent have been carried out to probe the behavior of the motor domain as functions of the nucleotide chemical state and conformation of the converter/relay helix. In conjunction with previous studies of ATP hydrolysis with different active-site conformations and normal mode analysis of structural flexibility, the results help establish an energetics-based framework for understanding the mechanochemical coupling. It is proposed that the activation of hydrolysis does not require the rotation of the lever arm per se, but the two processes are tightly coordinated because both strongly couple to the open/close transition of the active site. The underlying picture involves shifts in the dominant population of different structural motifs as a consequence of changes elsewhere in the motor domain. The contribution of this work and the accompanying paper [36] is to propose the actual mechanism behind these ‘population shifts’ and residues that play important roles in the process. It is suggested that structural flexibilities at both the small and large scales inherent to the motor domain make it possible to implement tight couplings between different structural motifs while maintaining small free-energy drops for processes that occur in the detached states, which is likely a feature shared among many molecular motors. The significantly different flexibility of the active site in different X-ray structures with variable level arm orientations supports the notation that external force sensed by the lever arm may transmit into the active site and influence the chemical steps (nucleotide hydrolysis and/or binding). [ABSTRACT FROM AUTHOR]

A polarizable model for simulation of liquid methanol, compatible with the COS/G2 water model, has been developed using the Charge-on-Spring (COS) technique. The model consists of three point charges, with one polarizable center on the oxygen atom. The Lennard–Jones parameters on the oxygen atom together with the molecular polarizability were varied to reproduce the experimental heat of vaporization and density of liquid methanol at ambient conditions. We examined the energies of various methanol dimers in the gas phase and compared them with values obtained from ab initio calculations. The model was then used to study the thermodynamic, dynamic, structural, and dielectric properties of liquid methanol as well as of a methanol–water mixture. A microscopic picture of the structure of pure liquid methanol and of the methanol–water mixture is provided. Good agreement was found between the results from our model simulations and available experimental and ab initio calculation data. In particular, the experimental dielectric permittivity of 32 could be reproduced, which had been shown to be difficult when using nonpolarizable models. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1494–1504, 2006 [ABSTRACT FROM AUTHOR]

The article reports on science research based on applied sciences and engineering which discusses about detection and isolation of free cancer cells from ascites and peritoneal lavages using optically induced electrokinetics (OEK). Topics include detection of free gastric cancer cells in peritoneal lavages and ascites plays a vital role in gastric cancer; and OEK microfluidic method for label-free separation and characterization of patient gastric cancer cells.

In this paper, we study the global existence for classical solutions to the 3D isentropic compressible Navier–Stokes equations in a cuboid domain. Compared to the Cauchy problem studied in Hoff (1995 J. Differ. Equ. 120 215–54), Hoff (2005 J. Math. Fluid Mech. 7 315–38), Huang et al (2012 Commun. Pure Appl. Math. 65 549–85), some new thoughts are applied to obtain upper bounds for density. Precisely, through piecewise estimation and some time-depending a priori estimates, we establish time-uniform upper bounds for density under the assumption that the initial energy is small. The initial vacuum is allowed. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic splenectomy for massive splenomegaly secondary to liver cirrhosis and portal hypertension in patients with an extremely low platelet count (< 1 × 109/l) presents several challenges. The posterolateral laparoscopic splenectomy approach may be a feasible and safe technique for these patients. Aim: To evaluate the feasibility and safety of the posterolateral laparoscopic splenectomy approach in patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension. Material and methods: In the period from January 2013 to December 2016, 11 patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension underwent posterolateral laparoscopic splenectomy in our institution. Pre-, peri-, and postoperative medical managements were reviewed retrospectively. Results: Patients' median platelet count was 0.7 × 109/l at the time of inpatient admission. The median operating time was 75 min, and the median intraoperative blood loss was 30 ml. One patient underwent intraoperative transfusion. The median duration of postoperative hospital stay was 5 days. No intra- or postoperative complications ensued, all patients were followed for 12-32 months (median: 24 months), and none had postoperative complications. Conclusions: The posterolateral laparoscopic splenectomy approach is a feasible, safe technique in the treatment of patients with platelet counts < 1 × 109/l secondary to liver cirrhosis and portal hypertension. [ABSTRACT FROM AUTHOR]

The atomic force microscope (AFM) is one of the most powerful tools for high-resolution imaging and high-precision positioning for nanomanipulation. The selection of the scanning area of the AFM depends on the use of the optical microscope. However, the resolution of an optical microscope is generally no larger than 200 nm owing to wavelength limitations of visible light. Taking into consideration the two determinants of relocation—relative angular rotation and positional offset between the AFM probe and nano target—it is therefore extremely challenging to precisely relocate the AFM probe to the initial scan/manipulation area for the same nano target after the AFM probe has been replaced, or after the sample has been moved. In this paper, we investigate a rapid automated relocation method for the nano target of an AFM using a coordinate transformation. The relocation process is both simple and rapid; moreover, multiple nano targets can be relocated by only identifying a pair of reference points. It possesses a centimeter-scale location range and nano-scale precision. The main advantages of this method are that it overcomes the limitations associated with the resolution of optical microscopes, and that it is label-free on the target areas, which means that it does not require the use of special artificial markers on the target sample areas. Relocation experiments using nanospheres, DNA, SWCNTs, and nano patterns amply demonstrate the practicality and efficiency of the proposed method, which provides technical support for mass nanomanipulation and detection based on AFM for multiple nano targets that are widely distributed in a large area. [ABSTRACT FROM AUTHOR]

Separation and structural identification of lipids remain a major challenge for contemporary lipidomics. Regioisomeric lipids differing only in position(s) of unsaturation are often not differentiated by conventional liquid chromatography-mass spectrometry approaches leading to the incomplete, or sometimes incorrect, assignation of molecular structure. Here we describe an investigation of the gas phase separations by differential-mobility spectrometry (DMS) of a series of synthetic analogues of the recently described 1-deoxysphingosine. The dependence of the DMS behavior on the position of the carbon-carbon double bond within the ionized lipid is systematically explored and compared to trends from complementary investigations, including collision cross-sections measured by drift tube ion mobility, reaction efficiency with ozone, and molecular dynamics simulations. Consistent trends across these modes of interrogation point to the importance of direct, through-space interactions between the charge site and the carbon-carbon double bond. Differences in the geometry and energetics of this intramolecular interaction underpin DMS separations and influence reactivity trends between regioisomers. Importantly, the disruption and reformation of these intramolecular solvation interactions during DMS are proposed to be the causative factor in the observed separations of ionized lipids which are shown to have otherwise identical collision cross-sections. These findings provide key insights into the strengths and limitations of current ion-mobility technologies for lipid isomer separations and can thus guide a more systematic approach to improved analytical separations in lipidomics. [ABSTRACT FROM AUTHOR]

The Epstein-Barr virus (EBV) is highly associated with nasopharyngeal carcinoma (NPC), and it regulates some microRNAs (miRNAs) that are involved in the development of cancer. The role of EBV in the deregulation of cellular miRNAs and how this affects the progression of NPC remain to be investigated. An analysis of the miRNA profile in an EBV-infected cell line revealed that miRNA 203 (miR-203) was downregulated. miR-203 is expressed specifically in epithelial cells. This downregulation of miR-203 was further verified and functionally analyzed. miR-203 was downregulated substantially in epithelial cells and NPC tissues that were latently infected with EBV. Downregulation of miR-203 also occurred during the early stage of EBV infection. Furthermore, the viral oncoprotein, latent membrane protein 1 (LMP1), was responsible for downregulation of miR-203. Removal of the latent EBV genome or suppression of LMP1 resulted in restoration of miR-203 expression. EBV-LMP1 mediated the downregulation of miR-203 at the primary transcript level. E2F3 and CCNG1 were identified as target genes of miR-203. Ectopic expression of miR-203 inhibited EBV-induced S-phase entry and transformation in vivo. Overexpression of the targets overcame the effects of miR-203 mimics on the cell cycle, and the expression of target genes in tumor models was inhibited by miR-203. Inhibitors of Jun N-terminal protein kinase (JNK) and NF-κB blocked miR-203 downregulation. These results imply that EBV promotes malignancy by downregulating cellular miR-203, which contributes to the etiology of NPC. [ABSTRACT FROM AUTHOR]

In the crystal structure of the title compound, C12H14N4O3, the dihedral angle between the phenyl and imidazole rings is 76.55 (7)°. The nitrite O atoms of the ( E)-2-nitriminoimidazolidin-1-yl group act as the acceptors of three N—H...O hydrogen bonds from the N atom of the imidazole ring, resulting in a one-dimensional chain. C—H...O hydrogen-bonding interactions are also observed in this complex, extending the structure into a two-dimensional supramolecular sheet. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopy splenectomy has been a preferred choice over open surgery, but limited studies dealing with laparoscopy splenectomy plus pericardial devascularization (LSPD) for elderly patients are available. Aim: To assess the safety and long-term efficacy of spleen bed LSPD for elderly patients with portal hypertension. Material and methods: A total of 132 elderly patients (age > 60 years) suffering from portal hypertension were operated on in the department. The patients were divided into 2 groups: those undergoing LSPD, and those undergoing open splenectomy plus pericardial devascularization (OSPD). Results and outcomes were compared retrospectively. Results: The clinical characteristics of the patients belonging to the two groups were studied. No significant difference between the characteristics of patients was reported and the clinical data revealed similarities in their characteristics. There was no significant difference in time taken for performing the operation (p > 0.05). The LSPD group showed less blood loss; started oral intake early; and the duration of post-operative hospital stay was also shorter (p < 0.05). Incidence rates of portal vein thrombosis; pancreatic leakage; pleural effusion; pulmonary infection; and delayed wound healing were also found to be lower in the LSPD group as compared to the OSPD group (p < 0.05). During a follow-up period of 6–70 months, no significant differences were found in the data for the two methods with respect to the incidence of rebleeding; hepatic encephalopathy; and survival (p > 0.05). Conclusions: It was concluded that spleen bed LSPD is a safe and feasible procedure for treating elderly patients. It had a better clinical effect than that of OSPD. [ABSTRACT FROM AUTHOR]

Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQI or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as lKS and lKr- The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyo-cytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of lKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if lks is reduced. Using a unique specific chemical activator lkr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an lkr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. [ABSTRACT FROM AUTHOR]

To develop sensitive and selective CN −chemosensors, a new imidazole-functionalized polyfluorene ( P1) was designed and obtained conveniently, the fluorescence of which could be completely quenched by Cu 2+ions at the concentration as low as 0.20 ppm in diluted solutions. By utilizing the much higher stability constant of the complex of CN −and Cu 2+, the quenched fluorescence of the solution of P1by Cu 2+ions could recover upon the addition of trace CN −anions, with the detection limit down to 0.31 ppm, making P1a novel, sensitive and selective cyanide probe. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cavernous hemangioma is an extremely rare benign tumor that is difficult to diagnose on an imaging examination, and its histopathological examination has rarely been reported.Case Presentation: Herein, we present the case of a 63-year-old man who was admitted to the hospital due to left upper abdominal pain and defecation unformed for more than 2 years. None of the positive results obtained from the physical examination could explain his symptoms. The imaging examination indicated a multilocular cyst with septa in the head of the pancreas. The patient underwent a pancreaticoduodenectomy, and the pathologic diagnosis was pancreatic cavernous hemangioma. The histopathological examination showed that the lesion was positive for benign vascular markers, such as CD31, CD34 and F8, and negative for lymphocyte markers, such as D2-40. Moreover, it was also positive for ERG and cytokeratin markers, CAM5.2 and AE1/AE3, indicating the complexity of its components, and Ki-67 negativity revealed its benign nature.Conclusions: Pancreatic cavernous hemangioma has a complex composition that may be reflected not only in the imaging examination but also in the immunohistochemical detection, and it may achieve a good outcome by surgical excision. [ABSTRACT FROM AUTHOR]

Introduction: The safety and feasibility of laparoscopic splenectomy plus selective esophagogastric devascularization (LSSD) via the spleen bed for cirrhotic portal hypertension have not been well studied. Aim: To assess the safety and feasibility of LSSD via the spleen bed for patients with cirrhotic portal hypertension. Material and methods: From June 2012 to December 2017, 423 patients suffering from portal hypertension and hypersplenism with liver cirrhosis underwent surgery in our department. One hundred and sixty-seven of these patients received totally LSSD, and the others received open splenectomy and esophagogastric devascularization (OSD). The characteristics, intraoperative and postoperative details and complications of the two groups were compared. Results: The operations were successfully performed in all patients. Intraoperative blood loss volume and blood transfusion were similar between the two groups (all p-values > 0.05). Postoperative length of hospital stay and time to oral intake were significantly shorter, but operation time was longer in the LSSD group compared with the OSD group (all p < 0.05). However, postoperative portal vein diameter was significantly smaller in the LSSD group (p < 0.001). The postoperative grade of varices was significantly lower in the LSSD group (p = 0.030). No significant differences were detected between the two groups regarding postoperative liver function, but the incidences of pancreatic leakage, pleural effusion, and wound infections were higher in the OSD group (all p < 0.05). Conclusions: LSSD via the spleen bed is safe and feasible for liver cirrhosis and portal hypertension. [ABSTRACT FROM AUTHOR]

Introduction. Many studies have reported increased intimal thickness around the catheter tip after catheterization. Caveolin-1 is a protein in the endothelial cell that acts as a shear sensor causing vascular remodeling. This study aimed to elucidate the suitability of different catheter locations and determine the role of caveolin-1 in canine models. Materials and Methods. Tunneled silicone 14.5-F catheters were inserted into the left jugular vein and right femoral vein in 8 dogs. The dogs were separated into 2 groups by catheter location and were followed up for 28 days. All dogs underwent extracorporeal circulation 3 times a week. After animal sacrifice, histological and immunohistochemical assays were performed to measure specific cell populations. Results. There were higher catheter dysfunction rates and lower blood flow rates in the right femoral vein group compared to the left jugular vein group. There was intimal hyperplasia around the catheter tip in both groups with no significant difference between the two groups. There were caveolin-1 expression in the intimal layer of venous wall around the catheter tip location sites in both groups. Conclusions. These findings indicate that different catheter tip locations may influence catheter function and specific targeting of caveonlin-1 could be a strategy of possible future novel therapies for catheter-related vein stenosis. [ABSTRACT FROM AUTHOR]

Pingyangmycin is an anticancer drug known as bleomycin A5 (A5), discovered in the Pingyang County of Zhejiang Province of China. Bleomycin (BLM) is a mixture of mainly two compounds (A2 and B2), which is on the World Health Organization's list of essential medicines. Both BLM and A5 are hydrophilic molecules that depend on transporters or endocytosis receptors to get inside of cells. Once inside, the anticancer activities rely on their abilities to produce DNA breaks, thus leading to cell death. Interestingly, the half maximal inhibitory concentration (IC50) of BLMs in different cancer cell lines varies from nM to μM ranges. Different cellular uptake, DNA repair rate, and/or increased drug detoxification might be some of the reasons; however, the molecules and signaling pathways responsible for these processes are largely unknown. In the current study, we purified the A2 and B2 from the BLM and tested the cytotoxicities and the molecular mechanisms of each individual compound or in combination with six different cell lines, including a Chinese hamster ovary (CHO) cell line defective in glycosaminoglycan biosynthesis. Our data suggested that glycosaminoglycans might be involved in the cellular uptake of BLMs. Moreover, both BLM and A5 shared similar signaling pathways and are involved in cell cycle and apoptosis in different cancer cell lines. [ABSTRACT FROM AUTHOR]

Bell's palsy is a kind of peripheral neural disease that cause abrupt onset of unilateral facial weakness. In the pathologic study, it was evidenced that ischemia of facial nerve at the affected side of face existed in Bell's palsy patients. Since the direction of facial nerve blood flow is primarily proximal to distal, facial skin microcirculation would also be affected after the onset of Bell's palsy. Therefore, monitoring the full area of facial skin microcirculation would help to identify the condition of Bell's palsy patients. In this study, a non-invasive, real time and full field imaging technology - laser speckle imaging (LSI) technology was applied for measuring facial skin blood perfusion distribution of Bell's palsy patients. 85 participants with different stage of Bell's palsy were included. Results showed that Bell's palsy patients' facial skin perfusion of affected side was lower than that of the normal side at the region of eyelid, and that the asymmetric distribution of the facial skin perfusion between two sides of eyelid is positively related to the stage of the disease (P< 0.001). During the recovery, the perfusion of affected side of eyelid was increasing to nearly the same with the normal side. This study was a novel application of LSI in evaluating the facial skin perfusion of Bell's palsy patients, and we discovered that the facial skin blood perfusion could reflect the stage of Bell's palsy, which suggested that microcirculation should be investigated in patients with this neurological deficit. It was also suggested LSI as potential diagnostic tool for Bell's palsy. [ABSTRACT FROM AUTHOR]

Background: Depression and diabetes have been recognized as major public health issues in China, however, no studies to date examined the factors associated with the development of depression in patients with diabetes in China. This study aimed to estimate the prevalence of co-morbid depression among adults with type 2 diabetes mellitus (DM) and to examine the influence factors of co-morbid depression in a group of patients with type 2 DM. Methods: The study was conducted from March l to May 31, 2012, in the Department of Endocrinology of the First Affiliated Hospital of the General Hospital of the People's Liberation Army (PLA). A systematic random sample of 412 type 2 DM patients aged over 18 years was selected. A structured questionnaire was used for collecting the information about socio-demographic data, lifestyle factors and clinical characteristics. Depression and social support was evaluated by using the Chinese version of Beck Depression Inventory (BDI) and Social Support Rate Scale (SSRS), respectively. Weights and heights were measured. Hemoglobin A1c (HbA1c) was abstracted from each patient directly after the interview. Results: Of the total sample, 142 patients had depression according to the BDI scores (BDI scores ≥14), the prevalence of co-morbid depression in this study population was 5.7 % (142/2500). Of which, 56 had major depression (BDI ≥ 21), and 86 had moderate depression (BDI ≥ 14&BDI < 21). Logistic regression analysis indicated that a high HbA1c level, a high BMI, low quality health insurance, and being single, were significantly associated with the development of depression. However, a family history of diabetes and a high social support level are likely protective factors. Conclusions: The prevalence of co-morbid depression was 5.7 % among Chinese subjects with type 2 DM in this study. High HbA1c level, high BMI score, being single, low social support level, and low quality health insurance were associated with the presence of depression. These findings support a recommendation for routine screening and management in China for depression in patients with diabetes, especially for those in primary care, to reduce the number of the depressed or the misrecognized depressed diabetic patients. [ABSTRACT FROM AUTHOR]

In this paper, the translational motion and self-rotational behaviors of the Raji cells, a type of B-cell lymphoma cell, in an optically induced, non-rotational, electric field have been characterized by utilizing a digitally programmable and optically activated microfluidics chip with the assistance of an externally applied AC bias potential. The crossover frequency spectrum of the Raji cells was studied by observing the different linear translation responses of these cells to the positive and negative optically induced dielectrophoresis force generated by a projected light pattern. This digitally projected spot served as the virtual electrode to generate an axisymmetric and non-uniform electric field. Then, the membrane capacitance of the Raji cells could be directly measured. Furthermore, Raji cells under this condition also exhibited a self-rotation behavior. The repeatable and controlled self-rotation speeds of the Raji cells to the externally applied frequency and voltage were systematically investigated and characterized via computer-vision algorithms. The self-rotational speed of the Raji cells reached a maximum value at 60 kHz and demonstrated a quadratic relationship with respect to the applied voltage. Furthermore, optically projected patterns of four orthogonal electrodes were also employed as the virtual electrodes to manipulate the Raji cells. These results demonstrated that Raji cells located at the center of the four electrode pattern could not be self-rotated. Instead any Raji cells that deviated from this center area would also self-rotate. Most importantly, the Raji cells did not exhibit the self-rotational behavior after translating and rotating with respect to the center of any two adjacent electrodes. The spatial distributions of the electric field generated by the optically projected spot and the pattern of four electrodes were also modeled using a finite element numerical simulation. These simulations validated that the electric field distributions were non-uniform and non-rotational. Hence, the non-uniform electric field must play a key role in the self-rotation of the Raji cells. As a whole, this study elucidates an optoelectric-coupled microfluidics-based mechanism for cellular translation and self-rotation that can be used to extract the dielectric properties of the cells without using conventional metal-based microelectrodes. This technique may provide a simpler method for label-free identification of cancerous cells with many associated clinical applications. [ABSTRACT FROM AUTHOR]

We present a multipoint "virtual dispenser" to draw femtolitre droplets from a dielectric fluidic thin film using pulse-voltage-triggered optically induced electrohydrodynamic instability (PVTOEHI). The "virtual dispenser" generates instability nucleation sites by controlling the optically induced lateral electrical stress and thermocapillary flow inside an optoelectronics chip. A time scale analysis shows that the electrohydrodynamic (EHD) instability phenomenon is present; however, its external manifestation is suppressed by OEHI. We observed two droplet dispensing mechanisms which correspond to different EHD states: Taylor cone formation and optically induced EHD jet. The EHD states transition could be realized by adjusting the pulse voltage parameters to alter the morphology of dispensed micron-scale polymer droplets, which could then be formed into organized arrays of microlenses with controllable diameter and curvature based on surface tension effect. [ABSTRACT FROM AUTHOR]

In this article the authors discuss the evolution and the principles of ion selectivity in channels and transporters. They mention that robust ion selectivity could be achieved in loosely restricted flexible binding site in which classical notions such as snug-fit mechanism does not apply. The authors also conclude that it is possible for two different mechanisms to support ion selectivity and that real protein structures will always be useful in identifying principles of ion selectivity.

Proton transfers are fundamental to chemical processes in solution and biological systems. Often, the well-known Grotthuss mechanism is assumed where a series of sequential ‘proton hops’ initiates from the donor and combines to produce the net transfer of a positive charge over a long distance. Although direct experimental evidence for the sequential proton hopping has been obtained recently, alternative mechanisms may be possible in complex molecular systems. To understand these events, all accessible protonation states of the mediating groups should be considered. This is exemplified by transfers through water where the individual water molecules can exist in three protonation states (water, hydronium, and hydroxide); as a result, an alternative to the Grotthuss mechanism for a proton transfer through water is to generate a hydroxide by first protonating the acceptor and then transfer the hydroxide toward the donor through water. The latter mechanism can be most generally described as the transfer of a "proton hole" from the acceptor to the donor where the ‘hole’ characterizes the deprotonated state of any mediating molecule. This pathway is distinct and is rarely considered in the discussion of proton-transfer processes. Using a calibrated quantum mechanical/molecular mechanical (QM/MM) model and an effective sampling technique, we study proton transfers in two solution systems and in Carbonic Anhydrase II. Although the relative weight of the ‘proton hole’ and Grotthuss mechanisms in a specific system is difficult to determine precisely using any computational approach, the current study establishes an energetics motivated framework that hinges on the donor/acceptor pKa values and electrostatics due to the environment to argue that the ‘proton hole’ transfer is likely as important as the classical Grotthuss mechanism for proton transport in many complex molecular systems. [ABSTRACT FROM AUTHOR]

Motivated by the long-term goal of understanding vectorial biological processes such as proton transport (PT) in biomolecular ion pumps, a number of developments were made to establish combined quantum mechanical/molecular mechanical (QM/MM) methods suitable for studying chemical reactions involving significant charge separation in the condensed phase. These developments were summarized and discussed with representative problems. Specifically, free energy perturbation and boundary potential methods for treating long-range electrostatics were implemented to test the robustness of QM/MM results for protein systems. It was shown that consistent models with sufficient sampling were able to produce quantitatively satisfactory results, such as pKa for titritable groups in the interior of T4-lysozyme, while an inconsistent treatment of electrostatics or lack of sufficient sampling may produce incorrect results. Modifications were made to an approximate density functional theory (SCC-DFTB) to improve the description of proton affinity and hydrogen-bonding, which are crucial for the treatment of PT in polar systems. Test calculations on water autoionization showed clearly that both improvements are necessary for quantitatively reliable results. Finally, the newly established SCC-DFTB/MM-GSBP protocol was used to explore mechanistic issues in carbonic anhydrase (CA). Preliminary results suggest that PT in CA occurs mainly through short water wires containing two water molecules in a thermally activated fashion. Although longer water wires occur with similar frequencies, PT along those pathways, on average, has substantially higher barriers, a result not expected based on previous studies. The fluctuations of water molecules peripheral to the water wire were found to make a larger impact on the PT energetics compared to polar protein residues in the active site, which are largely pre-organized and therefore have less tendency to reorganize during the reaction. [ABSTRACT FROM AUTHOR]