Theoretical Study on the Thermal Decomposition Mechanism of Fe(EDTA)- and Fe(EDTMP).

The decomposition mechanisms of Fe(EDTA)- and Fe(EDTMP)- complexes, widely used in various industrial applications, were investigated through a theoretical approach. Despite their structural similarities, the phosphonic acid and carboxylic acid groups in these complexes lead to vastly different decomposition behaviors. Fe(EDTA)-, stabilized by delocalized π bonds in carboxylic acid groups, exhibited higher stability than that of Fe(EDTMP)-, which has only σ bonds in phosphonic acid groups. Interaction Region Indicator (IRI) analysis revealed that the steric hindrance of Fe(EDTMP)- was stronger than that of Fe(EDTA)-. Ab initio molecular dynamics simulations revealed that Fe(EDTMP)- undergoes rapid decomposition due to the ease of breaking P-C bonds and the repulsion between phosphonic acid groups. In contrast, Fe(EDTA)- decomposes more slowly. These findings suggest the incorporation of phosphonic acid groups for easier degradation pathways when designing organic acid molecules. Understanding these mechanisms provides a basis for developing strategies for wastewater treatment in industrial settings.

Radiation-hardened silicon photonic passive devices on a 3 µm waveguide platform under gamma and proton irradiation.

Silicon photonics is considered to be an ideal solution as optical interconnect in radiation environments. Our previous study has demonstrated experimentally that radiation responses of device are related to waveguide size, and devices with thick top silicon waveguide layers are expected to be less sensitive to irradiation. Here, we design radiation-resistant arrayed waveguide gratings and Mach-Zehnder interferometers based on silicon-on-insulator with 3 µm-thick silicon optical waveguide platform. The devices are exposed to 60Co γ-ray irradiation up to 41 Mrad(Si) and 170-keV proton irradiation with total fluences from 1×1013 to 1×1016 p/cm2 to evaluate performance after irradiation. The results show that these devices can function well and have potential application in harsh radiation environments.

Development of Reliable, High Performance WLCSP for BSI CMOS Image Sensor for Automotive Application.

To meet the urgent market demand for small package size and high reliability performance for automotive CMOS image sensor (CIS) application, wafer level chip scale packaging (WLCSP) technology using through silicon vias (TSV) needs to be developed to replace current chip on board (COB) packages. In this paper, a WLCSP with the size of 5.82 mm × 5.22 mm and thickness of 850 µm was developed for the backside illumination (BSI) CIS chip using a 65 nm node with a size of 5.8 mm × 5.2 mm. The packaged product has 1392 × 976 pixels and a resolution of up to 60 frames per second with more than 120 dB dynamic range. The structure of the 3D package was designed and the key fabrication processes on a 12" inch wafer were investigated. More than 98% yield and excellent optical performance of the CIS package was achieved after process optimization. The final packages were qualified by AEC-Q100 Grade 2.

Activation of ATP-sensitive potassium channels facilitates the function of human endothelial colony-forming cells via Ca2+ /Akt/eNOS pathway.

Accumulating data, including those from our laboratory, have shown that the opening of ATP-sensitive potassium channels (KATP ) plays a protective role in pulmonary vascular diseases (PVD). As maintainers of the endothelial framework, endothelial colony-forming cells (ECFCs) are considered excellent candidates for vascular regeneration in cases of PVD. Although KATP openers (KCOs) have been demonstrated to have beneficial effects on endothelial cells, the impact of KATP on ECFC function remains unclear. Herein, this study investigated whether there is a distribution of KATP in ECFCs and what role KATP play in ECFC modulation. By human ECFCs isolated from adult peripheral blood, KATP were confirmed for the first time to express in ECFCs, comprised subunits of Kir (Kir6.1, Kir6.2) and SUR2b. KCOs such as the classical agent nicorandil (Nico) and the novel agent iptakalim (Ipt) notably improved the function of ECFCs, promoting cell proliferation, migration and angiogenesis, which were abolished by a non-selective KATP blocker glibenclamide (Gli). To determine the underlying mechanisms, we investigated the impacts of KCOs on CaMKII, Akt and endothelial nitric oxide synthase pathways. Enhanced levels were detected by western blotting, which were abrogated by Gli. This suggested an involvement of Ca2+ signalling in the regulation of ECFCs by KATP . Our findings demonstrated for the first time that there is a distribution of KATP in ECFCs and KATP play a vital role in ECFC function. The present work highlighted a novel profile of KATP as a potential target for ECFC modulation, which may hold the key to the treatment of PVD.

HCFU inhibits cervical cancer cells growth and metastasis by inactivating Wnt/ß-catenin pathway.

BACKGROUND: 1-hexylcarbamoyl-5-fluorouracil (HCFU), also known as carmofur, is an effective chemotherapeutic agent applied to several cancers. This study was aimed to explore the functional effects of HCFU on cervical cancer cells and tried to uncover its possible mechanism. METHODS: Two immortalized cervical cancer cell lines (HeLa and Caski) and primary cervical cancer cells prepared from two cervical cancer patients were used in this study. Cell viability, apoptosis, colony formation, migration, invasion, and the expressions of cell growth- and metastasis-associated factors were respectively assessed following 0-1 µg/mL of HCFU treatment for 0-48 h. Besides, the expressions of main factors in Wnt/ß-catenin signaling pathway were detected following HCFU administration. RESULTS: As a result, HCFU significantly suppressed HeLa and Caski cells viability but promoted apoptosis, both in time- and dose-dependent manner (P < 0.05 or P < 0.01). Besides, HCFU reduced these two cell lines colony formation capacity, migration and invasion (P < 0.05, P < 0.01 or P < 0.001). In primary cervical cancer cells, cell viability was reduced (P < 0.05 or P < 0.01), the expressions of Cyclin D1, MMP2 and MMP9 were down-regulated, while the expression of E-Cadherin was up-regulated after HCFU treatment. Further, HCFU down-regulated the expressions of intranuclear ß-catenin, c-Myc, and TCF-1, but has no impacts on intracytoplasmic ß-catenin expression in HeLa cells and primary cervical cancer cells. CONCLUSION: This study demonstrated an anti-growth and anti-metastasis role of HCFU in cervical cancer cells. HCFU suppressed cervical cancer possibly via blocking Wnt/ß-catenin signaling pathway. This article is protected by copyright. All rights reserved.

Endoscopic Endonasal Surgery to Resect a Solitary Trigeminal Neurofibroma Involving the Infratemporal Fossa: A Case Report.

Trigeminal neurofibromas are rarely reported, and even rarer when involving the infratemporal fossa. We describe the case of a 58-year-old man incidentally found through magnetic resonance imaging to have a tumor situated mainly in the infratemporal fossa. The tumor derived from the third branch of the trigeminal nerve and was totally removed by endoscopic endonasal surgery. Final pathology confirmed a diagnosis of neurofibroma. The patient had no intraoperative or postoperative complications except for numbness of the face. During the 6 years of follow-up, there has been no tumor progress or recurrence. We consider that endoscopic endonasal surgery is feasible in treating trigeminal neurofibromas involving the infratemporal fossa.

[Clinical characteristics of patients with reflux esophagitis exhibiting gallbladder heat attacking the stomach or stagnant heat of the liver and stomach syndrome].

OBJECTIVE: To compare the characteristics of the traditional Chinese medicine (TCM) syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with reflux esophagitis (RE), in terms of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and helicobacter pylori (HP) infection. METHODS: Patients with RE were enrolled from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from June 2007 to December 2009 and patients exhibiting the syndrome of gallbladder heat attacking the stomach or stagnant heat of the liver and stomach were collected. The patients were requested to complete clinical questionnaires. The general data, characteristics of clinical symptoms, combination of gallbladder conditions, esophageal mucosal inflammation, gastric bile reflux under endoscopy and HP infection of the two patterns were compared. RESULTS: The average age of the selected patients with gallbladder heat attacking the stomach was older than that of the patients with stagnant heat of the liver and stomach (P<0.01) and the accompanying clinical signs and symptoms were more severe (P<0.01). The incidence of gallbladder diseases in patients with gallbladder heat attacking the stomach was higher than that of the patients with stagnant heat of the liver and stomach (P<0.01). The extent of the esophageal mucosal inflammation under endoscopy as well as the gastric bile reflux and the incidence of HP infection was also more severe (P<0.01). CONCLUSION: There are significant differences in several regards between the syndromes of gallbladder heat attacking the stomach and stagnant heat of the liver and stomach in patients with RE. These characteristics may provide sound evidence for differentiation of signs and symptoms for this disease.

Hypoxia induces the dysfunction of human endothelial colony-forming cells via HIF-1α signaling.

Endothelial injury is considered as a trigger of pulmonary vascular lesions in the pathogenesis of hypoxic pulmonary hypertension (HPH). Although endothelial colony-forming cells (ECFCs) have vascular regeneration potential to maintain endothelial integrity, hypoxia-induced precise alteration in ECFCs function remains controversial. This study investigated the impact of hypoxia on human ECFCs function in vitro and the underlying mechanism. We found that hypoxia inhibited ECFCs proliferation, migration and angiogenesis. Compared with no treatment, the expression of hypoxia inducible factor-1α (HIF-1α) in hypoxia-treated ECFCs was increased, with an up-regulation of p27 and a down-regulation of cyclin D1. The over-secreted vascular endothelial growth factor (VEGF) was detected, with the imbalanced expression of fetal liver kinase 1 (flk-1) and fms related tyrosine kinase 1 (flt-1). Hypoxia-induced changes in ECFCs could be reversed by HIF-1α inhibitor KC7F2. These data suggest that HIF-1α holds the key in regulating ECFCs function which may open a new perspective of ECFCs in HPH management.

[Micro-Raman spectra for gastritis and gastric ulcer tissues].

Micro-Raman spectroscopy was employed to identify gastritis tissues and gastric ulcer tissues. The primary spectral differences between the two types of samples include, for gastric ulcer tissues, (1) the intensity of the peak at 781 cm(-1) ascribed to cytosine decreases, while the peaks ascribed to adenine and thymine respectively at 793 and 823 cm(-1) become stronger; (2) the bands of amide I and amide III at 1654 and 1320-1270 cm(-1) respectively, characteristic of alpha-helix structural protein, lose their intensities, and the tryptophan band at 1332 cm(-1) and phenylalanine band at 1003 cm(-1) reduced significantly, while the tryptophan marker at 1554 cm(-1) up shiftes to 1556 cm(-1) with increasing intensity; (3) a blue shift of 1073 cm(-1) line, the characteristic Raman band of lipid, and a reduction in the ratio of 1303 cm(-1) assigned to in-phase CH2 twisting motion to 1268 cm(-1) from =CH in-plane deformation were observed; (4) statistic analysis shows that the ratio of Raman intensities at bands 1449 cm(-1) originating from CH2 group to 1660 cm(-1) from amide I provides a promising standard to distinguish the two tissues.

[Optimal extraction of Dingxiang jiangqi granules].

OBJECTIVE: To screen and optimize the extraction of Dingxiangjiangqi granules. METHOD: The extraction route was screened by using pharmacodynamic experiment and the extraction conditions were optimized by orthogonal design and taking extract yield, content of naringin and tetrahydropalmatine as indexes. RESULT: The pharmacodynamic result showed that aqueous extract had the best effect to cure the esophagitis of rats and the optimized extraction technique was adding 12 times water, extracting 0. 5 hour for 3 times. CONCLUSION: The optimum extraction was simple, reasonable, stable and useful for further development.

Computational studies on the binding mechanism between triazolone inhibitors and Chk1 by molecular docking and molecular dynamics.

Chk1, a serine/threonine protein kinase that participates in transducing DNA damage signals, is an attractive target due to its involvement in tumor initiation and progression. As a novel Chk1 inhibitor, the triazolone's bioactivity mechanism is not clear. In this study, we carried out an integrated computational study that combines molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations to identify the key factors necessary for the bioactivities. With the aim of discerning the structural features that affect the inhibitory activity of triazolones, MK-8776, a Chk1 inhibitor that reached the clinical stage, was also used as a reference for simulations. A comparative analysis of the triazolone inhibitors at the molecular level offers valuable insight into the structural and energetic properties. A general feature is that all the studied inhibitors bind in the pocket characterized by residues Leu14, Val22, Ala35, Glu84, Tyr85, Cys86, and Leu136 of Chk1. Moreover, introducing hydrophobic groups into triazolone inhibitors is favorable for binding to Chk1, which is corroborated by residue Leu136 with a relatively large difference in the contribution between MK-8776 and five triazolones to the total binding free energies. A hydrogen bond between the polar hydrogen atoms at R1 and Cys86 can facilitate proper placement of the inhibitor in the binding pocket of Chk1 that favors binding. However, the introduction of hydrophilic groups into the R2 position diminishes binding affinity. The information provided by this research is of benefit for further rational design of novel promising inhibitors of Chk1.

Predicting the ecotoxicity of ionic liquids towards Vibrio fischeri using genetic function approximation and least squares support vector machine.

Ionic liquids (ILs) are widely used in industrial production for their unique physicochemical properties, and they are even regarded as green solvents. However, the recent study showed ILs might pose a potential risk to aquatic ecosystems. In the present work, the quantitative structure-activity relationship (QSAR) models, including genetic function approximation (GFA) and least squares support vector machine (LSSVM) were developed for predicting the ecotoxicity of ILs towards the marine bacterium Vibrio fischeri based on the descriptors calculated from cations and anions. Five descriptors were selected by GFA and used to develop the linear model. From the discussion of descriptors, the cation structure was the main factor to the toxicity, which mainly depended on the size, lipophilic, and 3D molecular structure of cations. In order to capture the nonlinear nature, the LSSVM model was also built for more accurately predicting the ecotoxicity. The GFA and LSSVM models were performed the rigorous internal and external validation, further verifying these models with excellent robustness and predictive ability. Therefore, both of models can be used for the prediction of the ecotoxicity of newly synthesized and untested ILs, and can provide reference information and theoretical guidance for designing and synthesizing safer and more eco-friendly ILs.

Study on the agonists for the human Toll-like receptor-8 by molecular modeling.

Toll-like receptor-8 agonists could be promising candidates for vaccine adjuvants, especially for neonatal vaccines. In this study, we established reliable models and explored valuable information which could explain the known experimental facts at the molecular level. Firstly, we divided the whole dataset into four splits and obtained many dependable models based on the simplified molecular input line entry system (SMILES). Secondly, the whole dataset was divided into three splits and other reliable comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models were established. Thirdly, we validated the prediction ability of these models using various validation methods for the test set. Lastly, for a better understanding of the binding modes between agonists and Toll-like receptor-8, molecular docking was applied to reveal the structural factors that impact the activity of agonists towards Toll-like receptor-8. Furthermore, molecular dynamics simulation was employed to further validate the docking results. The results obtained from molecular modeling support each other, which not only provides models to predict the activities of agonists but also leads to a better understanding of the essential features that should be considered when designing novel agonists with desired activities.

Studies of the interaction between demeclocycline and human serum albumin by multi-spectroscopic and molecular docking methods.

This study was designed to examine the interaction of demeclocycline (DMCTC) with human serum albumin (HSA) by multi-spectroscopic and molecular docking methods. The inner filter effect was corrected before we calculated the binding parameters. Fluorescence and UV-vis spectroscopy revealed that DMCTC induced the fluorescence quenching of HSA though a static quenching procedure. Thermodynamic analysis by Van Hoff equation found enthalpy change (ΔH) and entropy change (ΔS) were -53.01 kJ mol(-1) and -65.13 J mol(-1)K(-1), respectively, which indicated hydrogen bond and van der Waals force were the predominant force in the binding process. According to fluorescence resonance energy transfer (FRET), the specific binding distances between Trp-214 (donor) and DMCTC (acceptor) were 3.18 nm. Through site marker competitive experiments, subdomain IIA of HSA has been assigned to possess the high-affinity binding site of DMCTC. The three dimensional fluorescence showed that the conformation of HSA was changed after its complexation with DMCTC, and the alternations of protein secondary structure were quantitatively calculated from FT-IR with reduction of α-helices content about 4.8%, ß-sheet from 30.3% to 21.6% and with increases of ß-turn from 15.6% to 22.2%. Furthermore, the binding details between DMCTC and HSA were further confirmed by molecular docking studies, which revealed that DMCTC was bound at subdomain IIA through multiple interactions, such as hydrophobic effect, polar forces and π-π interactions. Moreover, the coexist metal ions such as Al(3+), Fe(3+), Cu(2+), Cr(3+) and Cd(2+) can decrease the binding constants of DMCTC-HSA.

Monodisperse Low-Bandgap Macromolecule-Based 5,5'-Bibenzo[c][1,2,5]thiadiazole Swivel Cruciform for Organic Solar Cells.

A novel low bandgap star-like macromolecule was synthesized and applied as electron donor material in the bulk heterojunction solar cells, in which the 5,5'-bibenzo[c][1,2,5]thiadiazole was used as the central node, in conjunction with four conjugated donor-acceptor arms. Compared with the corresponding small molecule with first generation arms, the macromolecule with second generation branches exhibited significantly enhanced photovoltaic device performances (blended with PC71BM as the active layer) due to dramatically improved short-circuit current density (Jsc) and fill factor (FF). The improvement in Jsc and FF can be attributed to the more broad absorption and the more favorable phase separation when comparing a monodisperse macromolecule with the second generation arms (SFTBT) with a small molecule with first generation branches (DFTBT).

Spiro-fluorene based 3D donor towards efficient organic photovoltaics.

A novel 3D donor material (SF8TBT) based on spiro-fluorene has been developed. Compared with the corresponding 1D linear molecule, the OPVs of this 3D donor exhibited power conversion efficiencies of 4.82%, much higher than that of 1D small molecules (1.69%).

AtCPK23 functions in Arabidopsis responses to drought and salt stresses.

Calcium-dependent protein kinases (CDPKs) are unique serine/threonine kinases in plants and there are 34 CDPKs in Arabidopsis genome alone. Although several CDPKs have been demonstrated to be critical calcium signaling mediators for plant responses to various environmental stresses, the biological functions of most CDPKs in stress signaling remain unclear. In this study, we provide the evidences to demonstrate that AtCPK23 plays important role in Arabidopsis responses to drought and salt stresses. The cpk23 mutant, a T-DNA insertion mutant for AtCPK23 gene, showed greatly enhanced tolerance to drought and salt stresses, while the AtCPK23 overexpression lines became more sensitive to drought and salt stresses and the complementary line of the cpk23 mutant displayed similar phenotype as wild-type plants. The results of stomatal aperture measurement showed that the disruption of AtCPK23 expression reduced stomatal apertures, while overexpression of AtCPK23 increased stomatal apertures. The alteration of stomatal apertures by changes in AtCPK23 expression may account, at least in partial, for the modified Arabidopsis response to drought stress. In consistent with the enhanced salt-tolerance by disruption of AtCPK23 expression, K(+) content in the cpk23 mutant was not reduced under high NaCl stress compared with wild-type plants, which indicates that the AtCPK23 may also regulate plant K(+)-uptake. The possible mechanisms by which AtCPK23 mediates drought and salt stresses signaling are discussed.