Facet-dependent activation of oxalic acid over hematite nanocrystals under the irradiation of visible light for efficient degradation of pollutants.

Naturally occurring hematite has been widely studied in the Fenton-like system for water pollutant remediation due to its abundance and non-toxicity. However, its inadequate catalytic activity results in difficulty in effectively degrading pollutants in the catalytic degradation system that it constitutes. Thus, we constructed a photochemical system composed of hematite with {001} facet of high activity facet and low-cost and non-toxic oxalic acid (OA) for the removal of various types of pollutants. The removal rate for the degradation of metronidazole, tetracycline hydrochloride, Rhodamine B, and hexavalent chromium by hematite nanoplate with the exposed {001} facet activating OA under visible light irradiation was 4.75, 2.25, 2.33, and 2.74 times than that by the exposed {110} facet, respectively. Density functional theory (DFT) calculation proved that the OA molecule was more easily adsorbed on the {001} facet of hematite than that on the {110} facet, which would favor the formation of the more Fe(III)-OA complex and reactive species. In addition, the reactive site of metronidazole for the attraction of radicals was identified on the basis of the DFT calculation on the molecular occupied orbitals, and the possible degradation pathway for metronidazole included carbon chain fracture, hydroxyethyl-cleavage, denitrogenation, and hydroxylation. Thus, this finding may offer a valuable direction in designing an efficient iron-based catalyst based on facet engineering for the improved activity of Fenton-like systems such as OA activation.

2D WO3-x Nanosheet with Rich Oxygen Vacancies for Efficient Visible-Light-Driven Photocatalytic Nitrogen Fixation.

Oxygen vacancy modulation holds great promise for enhancing the photocatalytic activity for efficient nitrogen fixation under mild conditions. In this work, the two-dimensional WO3-x nanosheets with rich oxygen vacancies were prepared using solvothermal synthesis. The WO3-x nanosheets (rich oxygen vacancies) display nice photocatalytic activity for N2 reduction to ammonia with a high yield rate of 82.41 µmol·gcat-1·h-1 under irradiation of visible light (420 nm), which is 3.59 times higher than that of the WO3-x nanoparticles (poor oxygen vacancies). Electron spin resonance (ESR), N2 adsorption-desorption isotherms, and transient photocurrent responses in the N2 or Ar atmosphere experiments proved that the rich oxygen vacancies, which are induced by the nanosheet structure, could serve as active sites for the chemisorption of N2 and facilitate the electron transfer from unsaturated sites to activated N2. Moreover, based on the analysis of banding energy, the oxygen vacancies not only boosted the ability of visible light harvesting but also elevated the defect energy level to the Fermi level, further inhibiting the defect relaxation effect. The findings offer an insight into the design of the efficient photocatalysts via structure engineering and defect engineering for photocatalytic N2 fixation.

miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2.

Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3' untranslated region (3'-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.

Integrated Bioinformatics Analysis for Identificating the Therapeutic Targets of Aspirin in Small Cell Lung Cancer.

PURPOSE: We explored the mechanism of aspirin in SCLC by dissecting many publicly available databases. METHODS AND RESULTS: Firstly, 11 direct protein targets (DPTs) of aspirin were identified by DrugBank 5.0. Then protein-protein interaction (PPI) network and signaling pathways of aspirin DPTs were analyzed. We found that aspirin was linked with many kinds of cancer, and the most significant one is SCLC. Next, we classified the mutation of 4 aspirin DPTs in SCLC (IKBKB, NFKBIA, PTGS2 and TP53) using cBio Portal. Further, we identified top 50 overexpressed genes of SCLC by Oncomine, and the interconnected genes with the 4 aspirin DPTs in SCLC (IKBKB, NFKBIA, PTGS2 and TP53) by STRING. Lastly, we figured out 5 consistently genes as potential therapeutic targets of aspirin in SCLC. CONCLUSION: The integrated bioinformatical analysis could improve our understanding of the underlying molecular mechanism about how aspirin working in SCLC. Integrated bioinformatical analysis may be considered as a new paradigm for guiding future studies about interaction in drugs and diseases.

Pin1 modulates chemo-resistance by up-regulating FoxM1 and the involvements of Wnt/ß-catenin signaling pathway in cervical cancer.

The prolyl isomerase Pin1, which is frequently highly expressed in many different cancers, can directly regulate cell proliferation and the cell cycle. However, the role of Pin1 in chemo-resistance remains to be elucidated in cervical cancer. The purpose of the present study was to investigate the role of Pin1 in the chemo-resistance of cervical cancer. The cisplatin resistance was assessed using the MTT assay. Pin1, FoxM1, ß-catenin, Cyclin D1, and c-myc expression levels were detected by RT-qPCR or Western blot. The results showed that Pin1 expression displayed a similar expression pattern with the resistance to cisplatin in five cervical cell lines. Knockdown of Pin1 significantly increased the sensitivity to cisplatin in HeLa cells, while Pin1 overexpression decreased the sensitivity to cisplatin in Me180 cells. Knockdown of Pin1 significantly down-regulated FoxM1 expression in HeLa cells, while Pin1 overexpression showed a contrary effect in Me180 cells. Besides, overexpression of Pin1 markedly increased the protein expression of ß-catenin and its target genes cyclin D1 and c-myc. FoxM1 siRNA remarkably reversed the promotory effect of pcDNA-Pin1(+) on ß-catenin and its target genes cyclin D1 and c-myc in Me180 cells. Furthermore, we also found that FoxM1 siRNA and IWP-2 markedly decreased cell viability, and IWP-2 decreased cell viability to the maximum extent in the Me180 cells co-transfected with pcDNA-Pin1(+) and FoxM1 siRNA. Taken together, these data suggest that Pin1 contributes to cisplatin resistance, partly by up-regulating FoxM1 and Wnt/ß-catenin signaling pathway involved in cervical cancer.

Randomized phase III trial of radiotherapy or chemoradiotherapy with topotecan and cisplatin in intermediate-risk cervical cancer patients after radical hysterectomy.

BACKGROUND: In cervical cancer patients with intermediate-risk factors, the optimal adjuvant therapy is still controversial. We undertook a randomized trial (ClinicalTrials.gov Identifier: NCT01418859) to compare the efficacy and toxicity of concurrent chemoradiotherapy with topotecan and cisplatin with radiotherapy alone in intermediate-risk cervical cancer patients. METHODS: Eligible patients were randomly assigned to one of three treatment arms including arm A (radiotherapy only,RT), arm B(concurrent chemoradiotherapy only, CCRT), and arm C (concurrent chemoradiotherapy with following consolidation chemotherapy, CCRT + CT). All eligible patients completed external RT (IMRT or 3D-CRT), receiving 45-50 Gy /25 f uniformly to the pelvis. Concurrent chemotherapy regimen was topotecan 0.75 mg/m(2) for days 1, 2 and 3, followed by cisplatin 25 mg/m(2) for days 1, 2 and 3. Three cycles of consolidation chemotherapy regimen was topotecan 1.5 mg/m(2) for days 1 and 2, and 0.75 mg/m(2) for day 3; followed by cisplatin 25 mg/m(2) for days 1, 2 and 3, repeated every 21 days. Adverse events of each group were investigated and compared. RESULTS: Thirty-nine patients enrolled onto the remaining regimens: 14 to RT, 15 to CCRT and 10 to CCRT + CT. Six patients (15.4%) did not complete the protocol treatment. Hematologic toxicity was more frequent and more severe in the CCRT and CCRT + CT arms compared with the RT arm. The incidence of grade 3-4 neutropenia was significantly different statistically between the RT, CCRT and CCRT + RT groups (15.4%, 46.7% and 100%, respectively; P = 0.002). Specially, three patients in CCRT + CT arm of all six patients who did not complete the protocol treatment discontinued planned therapy because of persistent grade 4 neutropenia. However, there were no significant differences in grade 3-4 non-hematologic toxicities between the three groups(all P > 0.05). Recurrence-free survival and overall survival of each group were not analyzed on account of a median follow-up of only 16 months. CONCLUSIONS: Concurrent chemoradiotherapy with topotecan and cisplatin showed severe hematologic toxicity in intermediate-risk cervical cancer patients after radical hysterectomy. Thus, the study was closed ahead of schedule. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01418859 .

Association between bone marrow dosimetric parameters and acute hematologic toxicity in cervical cancer patients undergoing concurrent chemoradiotherapy: comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy.

OBJECTIVE: We compare different dosimetric parameters in cervical cancer patients receiving concurrent chemotherapy and three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiation therapy (IMRT) and explore the incidence of hematological toxicity (HT) in these patients. METHODS: Twenty patients receiving 3DCRT or IMRT and 4 weekly doses of cisplatin (25 mg/m/w) were studied. The volumes of bone marrow receiving 10, 20, 30, 40 and 50 Gy or greater (V10, V20, V30, V40, and V50, respectively) were calculated. The HT was graded according to the guidelines of the Radiation Therapy Oncology Group system. The associations between dosimetric parameters and HT and chemotherapy delivery were analyzed. RESULTS: The bone marrows V30, V40, and V50 were lower in the IMRT group than in the 3DCRT group (62.93% vs 76.91%, 31.36% vs 39.60%, and 9.79% vs 15.44%, respectively). No statistical difference was observed for both V10 and V20. Acute hematologic toxicity occurred in both groups but was more frequent in the 3DCRT group. The percentage of patients with grade 2 and worse leukopenia and neutropenia was 90% and 80% in the 3DCRT group, whereas it was 80% and 40% in the IMRT group. The median nadir of white blood cells and the absolute neutrophil count were significantly lower in the 3DCRT group than in the IMRT group (1.96 × 10(9) vs 2.72 × 10(9) and 1.09 × 10(9) vs 1.86 × 10(9), respectively). CONCLUSION: The IMRT reduced the volume of bone marrow irradiated at the higher doses and the incidence and severity of acute hematologic toxicity in cervical cancer patients undergoing concurrent chemoradiotherapy.

Simplifying Multimodal With Single EOG Modality for Automatic Sleep Staging.

Polysomnography (PSG) recordings have been widely used for sleep staging in clinics, containing multiple modality signals (i.e., EEG and EOG). Recently, many studies have combined EEG and EOG modalities for sleep staging, since they are the most and the second most powerful modality for sleep staging among PSG recordings, respectively. However, EEG is complex to collect and sensitive to environment noise or other body activities, imbedding its use in clinical practice. Comparatively, EOG is much more easily to be obtained. In order to make full use of the powerful ability of EEG and the easy collection of EOG, we propose a novel framework to simplify multimodal sleep staging with a single EOG modality. It still performs well with only EOG modality in the absence of the EEG. Specifically, we first model the correlation between EEG and EOG, and then based on the correlation we generate multimodal features with time and frequency guided generators by adopting the idea of generative adversarial learning. We collected a real-world sleep dataset containing 67 recordings and used other four public datasets for evaluation. Compared with other existing sleep staging methods, our framework performs the best when solely using the EOG modality. Moreover, under our framework, EOG provides a comparable performance to EEG.

CareSleepNet: A Hybrid Deep Learning Network for Automatic Sleep Staging.

Sleep staging is essential for sleep assessment and plays an important role in disease diagnosis, which refers to the classification of sleep epochs into different sleep stages. Polysomnography (PSG), consisting of many different physiological signals, e.g. electroencephalogram (EEG) and electrooculogram (EOG), is a gold standard for sleep staging. Although existing studies have achieved high performance on automatic sleep staging from PSG, there are still some limitations: 1) they focus on local features but ignore global features within each sleep epoch, and 2) they ignore cross-modality context relationship between EEG and EOG. In this paper, we propose CareSleepNet, a novel hybrid deep learning network for automatic sleep staging from PSG recordings. Specifically, we first design a multi-scale Convolutional-Transformer Epoch Encoder to encode both local salient wave features and global features within each sleep epoch. Then, we devise a Cross-Modality Context Encoder based on co-attention mechanism to model cross-modality context relationship between different modalities. Next, we use a Transformer-based Sequence Encoder to capture the sequential relationship among sleep epochs. Finally, the learned feature representations are fed into an epoch-level classifier to determine the sleep stages. We collected a private sleep dataset, SSND, and use two public datasets, Sleep-EDF-153 and ISRUC to evaluate the performance of CareSleepNet. The experiment results show that our CareSleepNet achieves the state-of-the-art performance on the three datasets. Moreover, we conduct ablation studies and attention visualizations to prove the effectiveness of each module and to analyze the influence of each modality.

Navitoclax safety, tolerability, and effect on biomarkers of senescence and neurodegeneration in aged nonhuman primates.

Alzheimer's disease (AD) is the most common global dementia and is universally fatal. Most late-stage AD disease-modifying therapies are intravenous and target amyloid beta (Aß), with only modest effects on disease progression: there remains a high unmet need for convenient, safe, and effective therapeutics. Senescent cells (SC) and the senescence-associated secretory phenotype (SASP) drive AD pathology and increase with AD severity. Preclinical senolytic studies have shown improvements in neuroinflammation, tau, Aß, and CNS damage; most were conducted in transgenic rodent models with uncertain human translational relevance. In this study, aged cynomolgus monkeys had significant elevation of biomarkers of senescence, SASP, and neurological damage. Intermittent treatment with the senolytic navitoclax induced modest reversible thrombocytopenia; no serious drug-related toxicity was noted. Navitoclax reduced several senescence and SASP biomarkers, with CSF concentrations sufficient for senolysis. Finally, navitoclax reduced TSPO-PET frontal cortex binding and showed trends of improvement in CSF biomarkers of neuroinflammation, neuronal damage, and synaptic dysfunction. Overall, navitoclax administration was safe and well tolerated in aged monkeys, inducing trends of biomarker changes relevant to human neurodegenerative disease.

Narcolepsy Diagnosis With Sleep Stage Features Using PSG Recordings.

Narcolepsy is a sleep disorder affecting millions of people worldwide and causes serious public health problems. It is hard for doctors to correctly and objectively diagnose narcolepsy. Polysomnography (PSG) recordings, a gold standard for sleep monitoring and quality measurement, can provide abundant and objective cues for the narcolepsy diagnosis. There have been some studies on automatic narcolepsy diagnosis using PSG recordings. However, the sleep stage information, an important cue for narcolepsy diagnosis, has not been fully utilized. For example, some studies have not considered the sleep stage information to diagnose narcolepsy. Although some studies consider the sleep stage information, the stages are manually scored by experts, which is time-consuming and subjective. And the framework using sleep stages scored automatically for narcolepsy diagnosis is designed in a two-phase learning manner, where sleep staging in the first phase and diagnosis in the second phase, causing cumulative error and degrading the performance. To address these challenges, we propose a novel end-to-end framework for automatic narcolepsy diagnosis using PSG recordings. In particular, adopting the idea of multi-task learning, we take the sleep staging as our auxiliary task, and then combine the sleep stage related features with narcolepsy related features for our primary task of narcolepsy diagnosis. We collected a dataset of PSG recordings from 77 participants and evaluated our framework on it. Both of the sleep stage features and the end-to-end fashion contribute to diagnosis performance. Moreover, we do a comprehensive analysis on the relationship between sleep stages and narcolepsy, correlation of different channels, predictive ability of different sensing data, and diagnosis results in subject level.

Radiosynthesis of PET radiotracer as a prodrug for imaging group II metabotropic glutamate receptors in vivo.

Group II metabotropic glutamate receptors (mGluRs) have been implicated in a variety of neurological and psychiatric disorders in recent studies. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers the possibility to visualize and study group II mGluRs in vivo under physiologic and pathologic conditions. We synthesized a PET tracer, (S,S,S)-2-(2-carboxycyclopropyl)-2-(3-[(11)C]methoxyphenethyl) glycine dimethyl ester ([(11)C]CMGDE), as a prodrug for group II mGluRs, and studied its preliminary biological properties in Sprague-Dawley rats to visualize group II mGluRs. The microPET studies demonstrated that [(11)C]CMGDE readily penetrated into the brain and the radiotracer generated from [(11)C]CMGDE had fast reversible binding in the group II mGluRs rich regions including striatum, hippocampus and different cortical areas. Blocking studies with LY341495 showed 20-30% decrease of binding of the radiotracer generated from [(11)C]CMGDE in all brain areas with the highest decrease in the striatum 31.5±3.2%. The results show [(11)C]CMGDE is the first PET tracer that is brain penetrating and can be used to image group II mGluRs in vivo.

Outcomes for Hyperthermia Combined with Concurrent Radiochemotherapy for Patients with Cervical Cancer.

PURPOSE: To evaluate the effect of hyperthermia combined with concurrent radiochemotherapy (RCT) and treatment-related toxicity in patients with cervical cancer (CC) stage IB-IV. METHODS AND MATERIALS: This study was conducted between 2009 and 2013 in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IV CC. The patients were randomly assigned into 2 treatment groups: RCT and RCT plus hyperthermia (RCHT). Five-year survival, treatment-related toxicity, and other prognostic factors were evaluated. RESULTS: Three hundred seventy-three patients completed treatment and were analyzed by per-protocol (PP) analysis. The 5-year overall survival (OS) in the RCHT group (81.9%) was better than that in RCT group (72.3%), and the log-rank test showed a statistically significant difference between the 2 groups (P = .040). Univariate and multivariate Cox regression analysis for 5-year OS showed a statistically significant difference (P = .043, P = .045, respectively). The 5-year local relapse-free survival in RCHT (86.8%) was also better than that in RCT (82.7%), but the difference was not significant. Acute or late toxicity was not significantly different between the 2 groups. Advanced clinical stage (FIGO) and larger tumor size showed higher risk of death and a relatively poor prognosis in univariate and multivariate analysis. CONCLUSIONS: The study confirmed that hyperthermia combined with RCT yielded a better 5-year OS in CC. Acute and late toxicity was similar between the RCT and RCHT groups. Clinical stage (FIGO) and tumor size were independent prognostic factors in CC.

An Improved Real-Coded Genetic Algorithm Using the Heuristical Normal Distribution and Direction-Based Crossover.

A multi-offspring improved real-coded genetic algorithm (MOIRCGA) using the heuristical normal distribution and direction-based crossover (HNDDBX) is proposed to solve constrained optimization problems. Firstly, a HNDDBX operator is proposed. It guarantees the cross-generated offsprings are located near the better individuals in the population. In this way, the HNDDBX operator ensures that there is a great chance of generating better offsprings. Secondly, as iterations increase, the same individuals are likely to appear in the population. Therefore, it is possible that the two parents of participation crossover are the same. Under these circumstances, the crossover operation does not generate new individuals, and therefore does not work. To avoid this problem, the substitution operation is added after the crossover so that there is no duplication of the same individuals in the population. This improves the computational efficiency of MOIRCGA by leading it to quickly converge to the global optimal solution. Finally, aiming at the shortcoming of a single mutation operator which cannot simultaneously take into account local search and global search, a Combinational Mutation method is proposed with both local search and global search. The experimental results with sixteen examples show that the multi-offspring improved real-coded genetic algorithm (MOIRCGA) has fast convergence speed. As an example, the optimization model of the cantilevered beam structure is formulated, and the proposed MOIRCGA is compared to the RCGA in optimizing the parameters of the cantilevered beam structure. The optimization results show that the function value obtained with the proposed MOIRCGA is superior to that of RCGA.

Alantolactone enhances gemcitabine sensitivity of lung cancer cells through the reactive oxygen species-mediated endoplasmic reticulum stress and Akt/GSK3ß pathway.

Lung cancer is one of the leading causes of cancer­associated mortality in China and globally. Gemcitabine (GEM), as a first­line therapeutic drug, has been used to treat lung cancer, but GEM resistance poses a major limitation on the efficacy of GEM chemotherapy. Alantolactone (ALT), a sesquiterpene lactone compound isolated from Inula helenium, has been identified to exert anticancer activity in various types of cancer, including breast, pancreatic, lung squamous and colorectal cancer. However, the underlying mechanisms of the anticancer activity of ALT in lung cancer remain to be fully elucidated. The present study aimed to determine whether ALT enhances the anticancer efficacy of GEM in lung cancer cells and investigated the underlying mechanisms. The cell viability was assessed with a Cell Counting Kit­8 assay. The cell cycle, apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression of cell cycle­associated and apoptosis­associated proteins were determined by western blot analysis. The results demonstrated that ALT inhibited cell growth and induced S­phase arrest and cell apoptosis in A549 and NCI­H520 cells. Furthermore, ALT increased the level of ROS, inhibited the Akt/glycogen synthase kinase (GSK)3ß pathway and induced endoplasmic reticulum (ER) stress in A549 and NCI­H520 cells. Additionally, ALT treatment sensitized lung cancer cells to GEM. Analysis of the molecular mechanisms further revealed that ALT enhanced the anticancer effects of GEM via ROS­mediated activation of the Akt/GSK3ß and ER stress pathways. In conclusion, combined treatment with ALT and GEM may have potential as a clinical strategy for lung cancer treatment.

Pristimerin enhances the effect of cisplatin by inhibiting the miR­23a/Akt/GSK3ß signaling pathway and suppressing autophagy in lung cancer cells.

Lung cancer is a common type of cancer with a high mortality rate in China. Cisplatin (Cis) is one of the most effective broad­spectrum chemotherapeutic drugs for the treatment of advanced lung cancer. However, Cis resistance remains an obstacle in the treatment of advanced lung cancer. Pristimerin (Pris), a naturally occurring triterpenoid quinone compound, not only possesses anticancer properties, but also enhances chemosensitivity. Therefore, the present study aimed to investigate whether Pris can enhance the chemosensitivity of lung cancer cells to Cis and identify the underlying mechanism. A Cell Counting kit­8 and flow cytometry were used to determine cell viability, cell cycle progression and apoptosis in A549 and NCI­H446 cells. Western blotting was used to determine cell apoptosis­related, cell cycle­related and autophagy­related proteins. The results showed that Pris inhibited cell proliferation, and induced G0/G1 arrest and cell apoptosis in A549 and NCI­H446 cells. The western blotting revealed that Pris effectively synergized with Cis to induce cell apoptosis by inhibiting the microRNA­23a/Akt/glycogen synthase kinase 3ß signaling pathway and suppressing autophagy. In vivo xenograft experiments confirmed that Pris effectively synergized with Cis to suppress tumor growth. Collectively, these results indicate that Pris synergized with Cis and that this may be a potential therapeutic strategy to overcome lung cancer.

Facile synthesis of new carbon-11 labeled conformationally restricted rivastigmine analogues as potential PET agents for imaging AChE and BChE enzymes.

Rivastigmine is a newer-generation inhibitor with a dual inhibitory action on both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, and is used for the treatment of AChE- and BChE-related diseases such as brain Alzheimer's disease and cardiovascular disease. New carbon-11 labeled conformationally restricted rivastigmine analogues radiolabeled quaternary ammonium triflate salts, (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(methylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]8) and (3aR,9bS)-1-[(11)C]methyl-1-methyl-6-(heptylcarbamoyloxy)-2,3,3a,4,5,9b-hexahydro-1H-benzo[g]indolium triflate ([(11)C]9), were designed and synthesized as potential positron emission tomography (PET) agents for imaging AChE and BChE enzymes. The appropriate precursors were labeled with [(11)C]CH(3)OTf through N-[(11)C]methylation, and the target tracers were isolated by solid-phase extraction (SPE) using a cation-exchange CM Sep-Pak cartridge in 40-50% radiochemical yields decay corrected to end of bombardment (EOB), 15-20 min overall synthesis time, and 148-222 GBq/micromol specific activity at EOB.

Evaluation of four pyridine analogs to characterize 6-OHDA-induced modulation of mGluR5 function in rat brain using microPET studies.

Micro-positron emission tomography imaging studies were conducted to characterize modulation of metabotropic glutamate subtype-5 receptor (mGluR5) function in a 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease using four analogical PET ligands: 2-[(11)C]methyl-6-(2-phenylethynyl) pyridine ([(11)C]MPEP), 2-(2-(3-[(11)C]methoxyphenyl)ethynyl)pyridine ([(11)C]M-MPEP), 2-(2-(5-[(11)C]methoxypyridin-3-yl)ethynyl)pyridine ([(11)C]M-PEPy), and 3-[(2-[(18)F]methyl-1,3-thiazol-4-yl)ethynyl]pyridine ([(18)F]M-TEP). A total of 45 positron emission tomography (PET) imaging studies were conducted on nine male Sprague-Dawley rats within 4 to 6 weeks after unilateral 6-OHDA lesioning into the right medial forebrain bundle. The severity of the lesion was determined with [(11)C]CFT ([(11)C]2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane), a specific and sensitive ligand for imaging dopamine transporter function. The binding potential (BP) images were processed on pixel-by-pixel basis by using a method of the distribution volume ratio with cerebellum as a reference tissue. The values for BP were determined on striatum, hippocampus, and cortex. [(11)C]CFT binding was decreased on the lesioned (right) striatum by 35.4%+/-13.4% compared with the intact left striatum, indicating corresponding loss of presynaptic dopamine terminals. On the same areas of the lesioned striatum, three of the four tested mGluR5 ligands showed enhanced binding characteristics. The average differences between the right and left striatum were 4.4%+/-6.5% (P<0.05) with [(11)C]MPEP, -0.1%+/-1.7% (P>0.05) with [(11)C]M-MPEP, 3.9%+/-4.6% (P<0.05) with [(11)C]M-PEPy, and 6.6%+/-2.7% (P>0.05) with [(18)F]M-TEP. The enhanced binding was also observed in the right hippocampus and cortex. These studies showed that glutamatergic neurotransmission might have a complementary role in dopaminergic degeneration, which can be evaluated by in vivo PET imaging.

Evaluation of oasis ecosystem risk by reliability theory in an arid area: a case study in the Shiyang River Basin, China.

Ecosystem risk is a new concept in understanding environmental problems. It is important to study and develop quantitative methods for regional ecosystem risk analysis. In this study, some new indicators and methods for measuring oasis ecosystem risk were established using reliability theory. These indicators are linked to water resource, which is the key restricting factor in arid area oasis ecosystems. They have clear meanings and can also be compared in different arid area oases. A case study in the Liangzhou oasis of the Shiyang River Basin in China shows how to calculate these ecosystem risk indicators. The results of the case study are as follows: the reliability indicator, risk indicator, stability indicator, and integrated loss indicator of the Liangzhou oasis are 0.686, 0.314, 0.743, and 0.301, respectively. This means that the reliability degree of the oasis's ecosystem safety is 68.6%; the degree of risk that it is unsafe is 31.4%; the stability degree is 74.3%; and 30.1% of the oasis's area is supported by over-exploiting underground water and damaging the lower reaches of the ecosystem. This result can be used as a guide in controlling and managing ecosystem risk in the research area.

Kallistatin Suppresses Cell Proliferation and Invasion and Promotes Apoptosis in Cervical Cancer Through Blocking NF-κB Signaling.

Kallistatin has been recognized as an endogenous angiogenesis inhibitor and exerts pleiotropic effects in inhibiting tumor growth, migration, apoptosis, and inflammation. The purpose of the present study was to investigate the potential role and mechanisms of kallistatin in cervical cancer. We demonstrated that kallistatin effectively inhibited cell proliferation and enhanced apoptosis in a dose-dependent manner. Additionally, kallistatin suppressed migration and invasion activities and markedly reduced the expression of matrix-degrading metalloproteinases, progelatinase (MMP-2), MMP-9, and urokinase-type PA (uPA). Kallistatin reversed the epithelial-mesenchymal transition (EMT) and caused the upregulation of epithelial markers such as E-cadherin and inhibited mesenchymal markers such as N-cadherin and vimentin. Moreover, kallistatin led to a marked decrease in the expression of vascular endothelial growth factor (VEGF) and HIF-1α. In a xenograft mouse model, kallistatin treatment reduced tumor growth. Importantly, kallistatin strikingly impeded NF-κB activation by suppressing IκBα degradation and the level of phosphorylation of p65. Interestingly, similar to kallistatin, treatment with PDTC (an inhibitor of NF-κB) also attenuated cell invasion and migration. Taken together, these findings suggest that kallistatin suppresses cervical cancer cell proliferation, migration, and EMT and promotes cell apoptosis by blocking the NF-κB signaling pathway, suggesting that kallistatin may be a novel therapeutic target for cervical cancer treatment.