Wei Chen
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Pubmed
Journal: MedChemComm
February/19/2017
Abstract

Hydrogen sulfide (H2S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H2S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H2S while minimizing its toxicity, we synthesized a series of H2S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effect of H2S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H2S, levels. These studies suggest that H2S-donor compounds that increase intracellular sulfane sulfur are potentially useful neuroprotective agents against neurodegenerative diseases.

Pubmed
Journal: IEEE/ACM transactions on computational biology and bioinformatics
February/9/2017
Abstract

Promoters are DNA regulatory elements located directly upstream or at the 5' end of the transcription initiation site (TSS), which are in charge of gene transcription initiation. With the completion of a large number of microorganism genomics, it is urgent to predict promoters accurately in bacteria by using computational method. In this work, a sequence-based predictor named "iPro70-PseZNC" was designed for identifying sigma70 promoters in prokaryote. In the predictor, the samples of DNA sequences are formulated by a novel pseudo nucleotide composition, called PseZNC, into which the multi-window Z-curve composition and six local DNA structural properties are incorporated. In the 5-fold cross-validation, the area under the curve of receiver operating characteristic of 0.909 was obtained on our benchmark dataset, indicating that the proposed predictor is promising and will provide important guide in this area. Further studies showed that the performance of PseZNC is better than it of multi-window Z-curve composition. For the sake of convenience for researchers, a user-friendly online service was established and can be freely accessible at http://lin.uestc.edu.cn/server/iPro70-PseZNC. The PseZNC approach can be also extended to other DNA-related problems.

Pubmed
Journal: Angewandte Chemie (International ed. in English)
August/15/2017
Abstract

Hydrogen sulfide (H2 S) and hydrogen polysulfides (H2 Sn , n>1) are endogenous regulators of many physiological processes. In order to better understand the symbiotic relationship and cellular cross-talk between H2 S and H2 Sn , it is highly desirable to develop single fluorescent probes which enable dual-channel discrimination between H2 S and H2 Sn . Herein, we report the rational design, synthesis, and evaluation of the first dual-detection fluorescent probe DDP-1 that can visualize H2 S and H2 Sn with different fluorescence signals. The probe showed high selectivity and sensitivity to H2 S and H2 Sn in aqueous media and in cells.

Pubmed
Journal: Bioelectrochemistry (Amsterdam, Netherlands)
October/7/2004
Abstract

The effects of a supra-physiological membrane potential shock on the conducting system of the delayed rectifier K(+) channels in the skeletal muscle fibers of frogs were studied. An improved double Vaseline gap voltage clamp technique was used to deliver stimulation pulses and to measure changes in the channel currents. Our results showed that a single 4 ms, -400 mV pulsed shock can cause a reduction in the K(+) channel conductance and a negative-shift of the channel open-threshold. Following the Boltzmann theory of channel voltage-dependence, we analyzed the shock-induced changes in the channel open-probability by employing both two-state and multi-state models. The results indicate a reduction in the number of channel gating particles after the electric shock, which imply possible conformational changes at domains that gate the channels proteins. This study provides further evidence supporting our hypothesis that high intensity electric fields can cause conformational changes in membrane proteins, most likely in the channel gating system. These structural changes in membrane proteins, and therefore their dysfunctions, may be involved in the mechanisms underlying electrical injury.

Authors
Pubmed
Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
September/27/2015
Abstract

BACKGROUND

Multidrug resistance (MDR) directly contributes to the clinical failure of chemotherapy in breast cancer (BCA). β-elemene is a natural antitumor drug from plants. We previously confirmed that MDR could be reversed by β-elemene. In this study, we intended to investigate the reversal effect of β-elemene on MDR in human BCA adriacin (Adr) -resistant MCF-7 cells (MCF-7/Adr) and docetaxel (Doc) - resistant MCF-7 cells (MCF-7/Doc) through the gene regulatory network.

METHODS

MTT-cytotoxic, miRNA microarray, Real-time quantitative PCR, Dual Luciferase Activity Assay, Western blot analysis were performed to investigate the impact of β-elemene on chemo-resistant BCA cell suvival, and its impact on the expression of chemo-resistance specific miRNA and the downstream target genes PTEN and Pgp.

RESULTS

Compared with the miRNAs expression profiles of MCF-7/Adr and MCF-7/Doc cell lines from our previous studies, there were 322 differentially expressed miRNAs in MCF-7/Adr and MCF-7/Doc breast cancer cells with β-elemene intervention (50μM/L) for 30h, and 6 miRNAs were significantly up-regulated and 12 miRNAs were significantly down-regulated in both MCF-7/Adr and MCF-7/Doc. We have testified that 5 miRNA is related to MDR before, in this study, the expression of miR-34a, miR-222, miR-452 and miR-29a can lead to changes of the characteristics of chemo-resistant MCF-7/Adr and MCF-7/Doc. The PTEN expression under intervention of β-elemene was significantly increased and Pgp expression under β-elemene intervention was significantly decreased in both cell lines.

CONCLUSIONS

β-elemene could influence MDR related miRNA expression and subsequently regulate the expression of the target genes PTEN and Pgp, which may lead to reduction of the viability of the chemo-resistant breast cancer cells.

Pubmed
Journal: PloS one
March/29/2016
Abstract

OBJECTIVE

Lifestyle factors are well-known important modifiable risk factors for obesity; the association between tobacco smoking and central obesity, however, is largely unknown in the Chinese population. This study examined the relationship between smoking and central obesity in 0.5 million Chinese adults, a population with a low prevalence of general obesity, but a high prevalence of central obesity.

METHODS

A total of 487,527 adults (200,564 males and 286,963 females), aged 30-79 years, were enrolled in the baseline survey of the China Kadoorie Biobank (CKB) Study conducted during 2004-2008. Waist circumference (WC) and WC/height ratio (WHtR) were used as measures of central obesity.

RESULTS

The prevalence of regular smokers was significantly higher among males (60.6%) than among females (2.2%). The prevalence of central obesity increased with age and BMI levels, with a significant gender difference (females>males). Of note, almost all obese adults (99.4%) were centrally obese regardless of gender. In multivariable regression analyses, adjusting for age, education, physical activity, alcohol use and survey site, regular smoking was inversely associated with BMI in males (standardized regression coefficients, β= -0.093, p<0.001) and females (β= -0.025, p<0.001). Of interest, in the BMI stratification analyses in 18 groups, all βs of regular smoking for WHtR were positive in both genders; the βs showed a significantly greater increasing trend with increasing BMI in males than in females. In the analyses with model adjustment for BMI, the positive associations between regular smoking and WHtR were stronger in males (β= 0.021, p<0.001) than in females (β= 0.008, p<0.001) (p<0.001 for gender difference). WC showed considerably consistent results.

CONCLUSIONS

The data indicate that tobacco smoking is an important risk factor for central obesity, but the association is gender-specific and depends on the adjustment for general obesity.

Pubmed
Journal: International journal of molecular medicine
November/25/2014
Abstract

The inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene not only results in tumor initiation, but also mediates tumor metastasis. However, the mechanisms by which VHL inactivation leads to metastasis have not yet been well defined. In this study, the silencing of VHL in 3AO and SKOV3 ovarian cancer cells was found to promote cell motility and to increase the expression of matrix metalloproteinase (MMP)2, MMP9, hypoxia-inducible factor 1-α (HIF-1α) and microRNA (miR)-210. The suppression of HIF-1α with its inhibitor 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) in VHL-silenced 3AO cells antagonized the pro-migratory activity induced by the VHL deficiency and reversed the upregulation of MMP2, MMP9, HIF-1α and miR-210; however, it had no obvious effect on the VHL protein level. The introduction of miR-210 inhibitor into VHL-silenced 3AO cells resulted in similar changes as those induced by YC-1. Furthermore, vacuole membrane protein 1 (VMP1) was found to be diminished by VHL silencing in a HIF-1α/miR-210-dependent manner. Taken together, our data demonstrate that the loss of VHL stimulates ovarian cancer cell migration by stabilizing HIF-1α, upregulating miR-210 and decreasing VMP1 expression. These results indicate that the aberrant signaling of the VHL/HIF-1α/miR-210/VMP1 pathway may be involved in ovarian cancer aggressiveness.

Pubmed
Journal: Biochemical and biophysical research communications
March/20/2016
Abstract

NADPH oxidase 1 (NOX1) plays a key role in tumorigenesis and metastasis through generating reactive oxygen species (ROS), an important intracellular signaling molecule. However, how it is expressed in gallbladder cancer (GBC) tissue sample and whether it associates with GBC chemoresistance have never been investigated. Our study analyzed the relationship between NOX1 expression and cisplatin-sensitivity both in vivo and in vitro. We found that reduced NOX1 expression promoted cisplatin efficiency in GBC-SD cells, whereas overexpression of which potentially inhibited the sensitivity of cisplatin in SGC-996 cells. Further study into the mechanism we found that increased NOX1 expression elevated intracellular ROS levels, which then activated HIF-1α/MDR1 pathway. These findings established NOX1 a novel accelerant of chemoresistance in GBC, and NOX1-targeted therapeutics might be exploited as a strategy for increasing the efficacy of cisplatin treatment.

Pubmed
Journal: Journal of hypertension
April/6/2009
Abstract

OBJECTIVE

The aim of this study was to examine the association of prehypertension with measures of cardiovascular disease risk in a biracial (black-white) population of young adults.

METHODS

As part of the Bogalusa Heart Study, echocardiography and carotid ultrasonography were performed along with cardiovascular risk factor measurements in 1379 young adult participants (age range 20-44 years, average 36 years; 43% men, 70% white). Participants were categorized as normotensives (60%), prehypertensives (27%) and hypertensives (13%).

RESULTS

The prevalence of prehypertension was significantly higher among men than women (35 vs. 22%) and among blacks than whites (29 vs. 27%). Compared with normotensives, prehypertensives had a greater adverse cardiovascular risk factor profile. Male sex and BMI equally and significantly contributed to the prehypertension status in both whites [odds ratio (OR) and 95% confidence interval 2.66 (1.88-3.74) and 1.10 (1.07-1.14)] and blacks [OR: 2.56 (1.51-4.33) and 1.05 (1.01-1.09)]. Additionally, prehypertensives compared with normotensives had significantly higher left ventricular (LV) mass index, LV internal diameter, and carotid artery intima-media thickness.

CONCLUSIONS

The condition of prehypertension in young adults shows men>women and black women>white women, and participants with prehypertension already have adverse profiles of risk factors and indices of subclinical cardiovascular disease. A greater percentage of blacks at a relatively young age fall into the hypertensive category. These findings underscore the need for aggressive management of cardiovascular risk in youth at levels below those considered as hypertension.

Pubmed
Journal: International journal of surgery (London, England)
September/6/2018
Abstract

OBJECTIVE

Although many studies have reported risk factors of mortality following hip fracture surgery, the preventable risk factors of mortality following hip fracture surgery have not been well-identified. The aim of this study was to identify the preventable risk factors of mortality following hip fracture surgery.

METHODS

We searched PubMed, Web of Science, Google scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases from January 1997 to March 2017 for studies reporting risk factors of mortality following hip fracture surgery. The primary outcomes assessed in this meta-analysis were time to surgery, residential status, smoking, cardiovascular disease, pulmonary disease, diabetes, and malignancy. All analyses were conducted using Stata/SE version 11.0 software.

RESULTS

Sixteen studies involving 25 349 patients meeting the inclusion criteria were included. Statistically significant associations between the mortality after hip fracture surgery and the risk factors, including the time to surgery (>2days/<2days) (odds ratio[OR] = 1.91; 95%CI, 1.14-3.18; P = 0.013), residential status (nursing home/home) (OR = 1.97; 95%CI, 1.02-3.78; P = 0.043), cardiovascular disease (OR = 1.14; 95%CI, 1.03-1.26; P = 0.012), pulmonary disease (OR = 1.52; 95%CI, 1.37-1.69; P < 0.001), diabetes (OR = 1.41; 95%CI, 1.19-1.67; P < 0.001), and malignancy (OR = 2.99, 95%CI, 1.14-7.83; P = 0.013) were established. However, the available data failed to demonstrate an association between the mortality, and time to surgery (>1day/<1day) (OR = 1.25; 95%CI, 0.93-1.66; P = 0.136) and smoking (OR = 0.89; 95%CI, 0.69-1.14; P = 0.340).

CONCLUSIONS

This meta-analysis explicitly indicated that malignancy, nursing home residence, time to surgery (>2days/<2days), pulmonary disease, diabetes, and cardiovascular disease significantly increased the risk of mortality after hip fracture surgery. These preventable risk factors may be used to create algorithms that are more effective and pertinent to reduce the mortality following hip fracture surgery.

Pubmed
Journal: PloS one
June/2/2016
Abstract

The genome of a high lipid-producing fungus Mucor circinelloides WJ11 (36% w/w lipid, cell dry weight, CDW) was sequenced and compared with that of the low lipid-producing strain, CBS 277.49 (15% w/w lipid, CDW), which had been sequenced by Joint Genome Institute. The WJ11 genome assembly size was 35.4 Mb with a G+C content of 39.7%. The general features of WJ11 and CBS 277.49 indicated that they have close similarity at the level of gene order and gene identity. Whole genome alignments with MAUVE revealed the presence of numerous blocks of homologous regions and MUMmer analysis showed that the genomes of these two strains were mostly co-linear. The central carbon and lipid metabolism pathways of these two strains were reconstructed and the numbers of genes encoding the enzymes related to lipid accumulation were compared. Many unique genes coding for proteins involved in cell growth, carbohydrate metabolism and lipid metabolism were identified for each strain. In conclusion, our study on the genome sequence of WJ11 and the comparative genomic analysis between WJ11 and CBS 277.49 elucidated the general features of the genome and the potential mechanism of high lipid accumulation in strain WJ11 at the genomic level. The different numbers of genes and unique genes involved in lipid accumulation may play a role in the high oleaginicity of strain WJ11.

Pubmed
Journal: The Science of the total environment
June/14/2018
Abstract

The preparation of a landslide susceptibility map is considered to be the first step for landslide hazard mitigation and risk assessment. However, these maps are accepted as end products that can be used for land use planning. The main goal of this study is to assess and compare four advanced machine learning techniques, namely the Bayes' net (BN), radical basis function (RBF) classifier, logistic model tree (LMT), and random forest (RF) models, for landslide susceptibility modelling in Chongren County, China. A total of 222 landslide locations were identified in the study area using historical reports, interpretation of aerial photographs, and extensive field surveys. The landslide inventory data was randomly split into two groups with a ratio of 70/30 for training and validation purposes. Fifteen landslide conditioning factors were prepared for landslide susceptibility modelling. The spatial correlation between landslides and conditioning factors was analyzed using the information gain (IG) method. The BN, RBF classifier, LMT, and RF models were constructed using the training dataset. Finally, the receiver operating characteristic (ROC) and statistical measures, including sensitivity, specificity, and accuracy, were employed to validate and compare the predictive capabilities of the models. Out of the tested models, the RF model had the highest sensitivity, specificity, and accuracy values of 0.787, 0.716, and 0.752, respectively, for the training dataset. Overall, the RF model produced an optimized balance for the training and validation datasets in terms of AUC values and statistical measures. The results of this study also demonstrate the benefit of selecting optimal machine learning techniques with proper conditioning selection methods for landslide susceptibility modelling.

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Pubmed
Journal: Journal of general internal medicine
November/13/2018
Abstract

BACKGROUND

The transition to later-life caregiving roles, especially for couples caring for each other, can be rife with ambiguity. The incident discordance in spousal perceptions of one another's role and its relationship to mental health outcomes have not been well-described.

OBJECTIVE

(1) To describe the range of daily agreement between older adult spouses' perceptions of care given and care received; (2) to explore associations between caregiving agreement and daily caregiver depression, anxiety, and marital satisfaction; and (3) to evaluate differential effects for male and female caregivers.

METHODS

Cross-sectional, ecological assessment (daily diary).

METHODS

Sample of 191 couples aged 60-64 (total 5196 daily surveys) drawn from the longitudinal Life and Family Legacies study.

METHODS

During 2011-2012, spouses independently completed 14 consecutive daily surveys about their mood, marital interactions, and support exchanges. Caregiving agreement was defined as the daily ratio of spouse-reported care received to self-reported care given. Using generalized linear mixed effect modeling, we examined associations between spousal care agreement and outcomes of depression, anxiety, and marital satisfaction.

RESULTS

Sample data demonstrated broad variability in spousal agreement, with couples exhibiting substantial disagreement on nearly one-third of couple days (780/2598 days). On days where care was exchanged, higher caregiving agreement was associated with lower caregiver depression (p < 0.01) and anxiety (p < 0.01) in male caregivers, and higher marital satisfaction (p = 0.03) in female caregivers. When care recipients reported receiving more support than their spouse reported giving, these associations did not persist.

CONCLUSIONS

Findings suggest that spousal agreement about the amount of care given and received varies broadly and is an important consideration for primary care providers who counsel these patients day-to-day. Furthermore, agreement appears to predict mental health and relationship outcomes and should be further evaluated in this growing population of mid-to-late life adults emerging into caregiving.

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Pubmed
Journal: Journal of neurosurgery
May/31/2018
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Pubmed
Journal: ACS applied materials & interfaces
July/25/2018
Abstract

The development of simple yet powerful methods for monitoring enzyme activity is of great significance. Herein, a facile, convenient, cost-effective, and continuous fluorescent method for the detection of arginase and its inhibitor has been reported based on a host-guest interaction-controlled and enzymatic hydrolysis-controlled luminescent nanoswitch. The fluorescence intensity of 6-aza-2-thiothymine-stabilized gold nanoparticle (ATT-AuNP) is enhanced by l-arginine, owing to the formation of a supramolecular host-guest assembly between the guanidine group of l-arginine and ATT molecules capped on the AuNP surface. However, hydrolysis of l-arginine, catalyzed by arginase, leads to a decrease in the fluorescence intensity of l-arginine/ATT-AuNPs hybrids. Upon incorporation of the arginase inhibitor l-norvaline, the fluorescence of the ATT-AuNP-based detecting system is restored. The linear range of arginase activity determination is from 0.0625 to 1.15 U/mL and the limit of detection is 0.056 U/mL. The half-maximal inhibition value IC50 of l-norvaline is determined to be 5.6 mM. The practicability of this luminescent nanoswitch is validated by assaying the arginase activity in rat liver and monitoring the response of rat liver arginase to pharmacological agent. Compared to the existing fluorescent method of arginase activity assay, the approach demonstrated here does not involve any complicated technical manipulation, thereby greatly simplifying the detection steps. We propose that this AuNP-based luminescent nanoswitch would find wide applications in the field of life sciences and medicine.

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Pubmed
Journal: Annals of biomedical engineering
January/4/2017
Abstract

Pulmonary granulomas--the hallmark of Mycobacterium tuberculosis (MTB) infection--are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis-Menten kinetics. An approximate analytical solution--using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis--was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.

Pubmed
Journal: Cerebral cortex (New York, N.Y. : 1991)
March/22/2017
Abstract

Our perception of the world builds upon dynamic inputs from multiple senses with different temporal resolutions, and is threaded with the passing of subjective time. How time is extracted from multisensory inputs is scantly known. Utilizing psychophysical testing and electroencephalography, we show in healthy human adults that odors modulate object visibility around critical flicker-fusion frequency (CFF)-the limit at which chromatic flickers become perceived as a stable color-and effectively alter CFF in a congruency-based manner, despite that they afford no clear environmental temporal information. The behavioral gain produced by a congruent relative to an incongruent odor is accompanied by elevated neural oscillatory power around the object's flicker frequency in the right temporal region ~150-300 ms after object onset, and is not mediated by visual awareness. In parallel, odors bias the subjective duration of visual objects without affecting one's temporal sensitivity. These findings point to a neuronal network in the right temporal cortex that executes flexible temporal filtering of upstream visual inputs based on olfactory information. Moreover, they collectively indicate that the very process of sensory integration at the stage of object processing twists time perception, hence casting new insights into the neural timing of multisensory events.

Pubmed
Journal: Biochimica et biophysica acta
May/24/2010
Abstract

Due to prevalence of negative charges on the protein surface, opposite to the active site pocket of human carbonic anhydrase XII (hCA XII), both positively charged CdTe quantum dots (Qds(+)) and polylysine electrostatically interact with the enzyme, and such interaction does not influence the catalytic activity of the enzyme. However, both these cationic macromolecules differently modulate the active site environment of the enzyme. The steady-state kinetic data revealed that whereas polylysine exhibited no influence on dansylamide (DNSA) dependent inhibition of the enzyme, Qds(+) overcame such an inhibitory effect, leading to almost 70% restoration of the catalytic activity of the enzyme. We provide evidence that DNSA remains bound to the enzyme upon interaction with both polylysine and Qds(+). Arguments are presented that the above differential feature of polylysine and Qds(+) on hCA XII is encoded in the "rigidity" versus "flexibility" of these cationic macromolecules.

Pubmed
Journal: The Journal of chemical physics
August/9/2015
Abstract

Self-assembled two-dimensional molecular arrays and photoinduced polymerization of 4-bromo-4'-hydroxybiphenyl on Ag(111) were studied using low-temperature scanning tunneling microscopy combined with density functional theory calculations. Square-like self-assembled structures of 4-bromo-4'-hydroxybiphenyl stabilized by intermolecular hydrogen and halogen bonds were transformed into hexagonal nanopores of biphenyl biradicals by 266 nm UV laser irradiation at 80 K. The biradicals further coupled to each other and formed covalently linked polyphenylene polymer chains at room temperature.

Pubmed
Journal: The journal of physical chemistry. B
August/9/2015
Abstract

The molecular dynamics of Poly(L-lactic Acid) (PLLA) chains in the α phase was investigated by Solid-State NMR spectroscopy. (13)C high-resolution NMR clearly indicates that the crystalline signals split into 2, 3, and 4 signals for the CH3, CH and CO groups, respectively at 25 °C, while the amorphous signals give a broad component at the bottom of the crystalline signals. (13)C NMR spectra show that the crystalline line shape changes with increasing temperatures well above the glass transition temperature (Tg) and imply the presence of the molecular dynamics in the crystalline region. Comparisons of the evolution-time dependence of CODEX data and simulation results based on reorientation of chemical shift anisotropy (CSA) indicate that the chains in the α phase perform helical jump motions in the slow dynamic range at temperatures above 115 °C. The mixing-time dependence of the CODEX data yields an activation energy of Ea of (95 ± 8) kJ/mol for the helical jump motions. Moreover, two-dimensional exchange NMR with highly resolved signals for the CO group provides cross peaks among four well resolved signals due to the helical jumps. Comparison of 2D buildup curves of the cross peaks and calculated data determines that helical jump motions prefer largely uncorrelated random back-and-forth motions between the neighboring sites, possibly enabling large-scale chain diffusion in the crystalline regions.

Pubmed
Journal: European journal of pharmacology
November/23/2017
Abstract

Hydrogen sulfide (H2S) can exert different effects on the gastrointestinal tract by modulating ion channels. Previously, we found that H2S donor sodium hydrosulfide (NaHS) regulates colonic motility through L-type calcium channels, but the molecular mechanism remains unknown. The present study was designed to investigate possible mechanisms underlying the modulation of L-type calcium channels by NaHS in rat colonic smooth muscle cells. L-type calcium currents in colonic smooth muscle cells were recorded using the whole-cell patch-clamp technique. Spontaneous contractions of mid-colonic smooth muscle strips were measured in an organ bath system and a biological signal acquisition system. NaHS evoked a significant rightward shift in the steady-state activation curve of L-type calcium channels, changed the shape of the current-voltage (I-V) curve, and decreased the peak current density at 0mV, although it significantly increased with higher stimulatory voltage. The sulfhydryl-modifying reagent DL-dithiothreitol (DTT) enhanced the effects of NaHS on L-type calcium channels, while diamide (DM) and reduced L-glutathione (GSH) alleviated the effects of NaHS. Additionally, NaHS inhibited the spontaneous high-amplitude contractions of both longitudinal and circular smooth muscle strips in a dose-dependent manner. The inhibitory effects were reversible. DTT and GSH enhanced the effects of NaHS, while DM attenuated the effects of NaHS. In conclusion, NaHS modulates L-type calcium channels in rat colonic smooth muscle cells and regulates the contractile activity of colonic smooth muscle, potentially by modifying the free sulfhydryl groups of L-type calcium channels.

Pubmed
Journal: Microbiology (Reading, England)
March/12/2012
Abstract

We characterized the de novo biosynthetic pathway of tetrahydrobiopterin (BH₄) in the lipid-producing fungus Mortierella alpina. The BH₄ cofactor is essential for various cell processes, and is probably present in every cell or tissue of higher organisms. Genes encoding two copies of GTP cyclohydrolase I (GTPCH-1 and GTPCH-2) for the conversion of GTP to dihydroneopterin triphosphate (H₂-NTP), 6-pyruvoyltetrahydropterin synthase (PTPS) for the conversion of H₂-NTP to 6-pyruvoyltetrahydropterin (PPH₄), and sepiapterin reductase (SR) for the conversion of PPH₄ to BH₄, were expressed heterologously in Escherichia coli. The recombinant enzymes were produced as His-tagged fusion proteins and were purified to homogeneity to investigate their enzymic activities. Enzyme products were analysed by HPLC and electrospray ionization-MS. Kinetic parameters and other properties of GTPCH, PTPS and SR were investigated. Physiological roles of BH₄ in M. alpina are discussed, and comparative analyses between GTPCH, PTPS and SR proteins and other homologous proteins were performed. The presence of two functional GTPCH enzymes has, as far as we are aware, not been reported previously, reflecting the unique ability of this fungus to synthesize both BH₄ and folate, using the GTPCH product as a common substrate. To our knowledge, this study is the first to report the comprehensive characterization of a BH₄ biosynthesis pathway in a fungus.

Pubmed
Journal: ACS nano
September/26/2017
Abstract

This work developed an ionic sensor for human motion monitoring by employing durable H-reduced graphene oxide (RGO)/carbon nanotubes (CNTs)/Ag electrodes and an ionic polymer interlayer. The sensor functions as a result of unbalanced ion transport and accumulation between two electrodes stimulated by applied deformation. The networking structure and stable electrodes provide convenient ion-transport channels and a large ion accumulation space, resulting in a sensitivity of 2.6 mV in the strain range below 1% and high stability over 6000 bending cycles. Ionic sensors are of intense interest motivated by detecting human activities, which usually associate with a large strain or deformation change. More importantly, direction identification and spatial deformation recognition are feasible in this research, which is beneficial for the detection of complex multidimensional activities. Here, an integrated smart glove with several sensors mounted on the hand joints displays a distinguished ability in the complex geometry of hand configurations. Based on its superior performance, the potential applications of this passive ionic sensor in sign language recognition and human-computer interaction are demonstrated.

Pubmed
Journal: ACS nano
September/26/2017
Abstract

Two-dimensional (2D) semiconductors offer a convenient platform to study 2D physics, for example, to understand doping in an atomically thin semiconductor. Here, we demonstrate the fabrication and unravel the electronic properties of a lateral doped/intrinsic heterojunction in a single-layer (SL) tungsten diselenide (WSe2), a prototype semiconducting transition metal dichalcogenide (TMD), partially covered with a molecular acceptor layer, on a graphite substrate. With combined experiments and theoretical modeling, we reveal the fundamental acceptor-induced p-doping mechanism for SL-WSe2. At the 1D border between the doped and undoped SL-WSe2 regions, we observe band bending and explain it by Thomas-Fermi screening. Using atomically resolved scanning tunneling microscopy and spectroscopy, the screening length is determined to be in the few nanometer range, and we assess the carrier density of intrinsic SL-WSe2. These findings are of fundamental and technological importance for understanding and employing surface doping, for example, in designing lateral organic TMD heterostructures for future devices.

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