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Chen Chen - Top 30 Publications

A sustained activation of pancreatic NMDARs is a novel factor of β-cell apoptosis and dysfunction.

Type 2 diabetes, which features β-cell failure, is caused by the decrease of β-cell mass and insulin secretory function. Current treatments fail to halt the decrease of functional β-cell mass. Strategies to prevent β-cell apoptosis and dysfunction are highly desirable. Recently, our group and others have reported that blockade of N-methyl-D-aspartate receptors (NMDARs) in the islets has been proposed to prevent the progress of type 2 diabetes through improving β-cell function. It suggests that a sustained activation of the NMDARs may exhibit deleterious effect on β-cells. However, the exact functional impact and mechanism of the sustained NMDAR stimulation on islet β-cells remains unclear. Here, we identify a sustained activation of pancreatic NMDARs as a novel factor of apoptotic β-cell death and function. The sustained treatment with NMDA results in an increase of intracellular [Ca2+] and reactive oxygen species (ROS), subsequently induces mitochondrial membrane potential depolarization and a decrease of oxidative phosphorylation expression, and then impairs the mitochondrial function of β-cells. NMDA specifically induces the mitochondrial-dependent pathway of apoptosis in β-cells through up-regulation of the pro-apoptotic Bim and Bax, and down-regulation of anti-apoptotic Bcl-2. Furthermore, a sustained stimulation of NMDARs impairs β-cell insulin secretion through decrease of Pdx-1 and ATP synthesis. The activation of NF-κB partly contributes to the reduction of Pdx-1 expression induced by overstimulation of NMDARs. In conclusion, we show that the sustained stimulation of NMDARs is a novel mediator of apoptotic signaling and β-cell dysfunction, providing a mechanistic insight into the pathological role of NMDARs activation in diabetes.

Pulse pressure is associated with plasma amyloid-β transport dysfunction.

Increased pulse pressure (PP) has been implicated in the development and progression of Alzheimer's disease in middle-aged and elderly adults. Considering the close relationship between peripheral amyloid-β clearance and brain amyloid-β deposition, we investigated the potential association between PP and plasma amyloid-β transport function.

Drought stress modulates diurnal oscillations of circadian clock and drought-responsive genes in Oryza sativa L.

Endogenous circadian rhythms play a key role in regulating plant growth and development, and in allowing plants to respond and adapt to changing environments. To understand how drought regulates upland rice(Oryza sativa L.) IRAT109, we examined the expression levels of circadian clock and drought-responsive genes through real-time PCR. The results revealed that, first, drought reduced the relative expression level and amplitude of peak expression of several morning circadian clock components (such as OsPRRs, OsLHY and OsZTL1), increased the relative expression level and amplitude of some evening circadian clock components (such as OsTOC1, OsGI and OsELF3), but did not influence OsFKF1. Secondly, the relative expression level of most drought-responsive genes was generally increased, except for OsDST, a negative regulator. Lastly, expression rhythms of most drought-responsive genes were disturbed, but not that of OsCIPK12, OsCDPK7 and OsDREB1A. The results indicate that drought stress modulates the expression of circadian clock components and the interplay regulates diurnal oscillations of relative genes.

Short-channel field-effect transistors with 9-atom and 13-atom wide graphene nanoribbons.

Bottom-up synthesized graphene nanoribbons and graphene nanoribbon heterostructures have promising electronic properties for high-performance field-effect transistors and ultra-low power devices such as tunneling field-effect transistors. However, the short length and wide band gap of these graphene nanoribbons have prevented the fabrication of devices with the desired performance and switching behavior. Here, by fabricating short channel (L ch ~ 20 nm) devices with a thin, high-κ gate dielectric and a 9-atom wide (0.95 nm) armchair graphene nanoribbon as the channel material, we demonstrate field-effect transistors with high on-current (I on > 1 μA at V d = -1 V) and high I on /I off ~ 10(5) at room temperature. We find that the performance of these devices is limited by tunneling through the Schottky barrier at the contacts and we observe an increase in the transparency of the barrier by increasing the gate field near the contacts. Our results thus demonstrate successful fabrication of high-performance short-channel field-effect transistors with bottom-up synthesized armchair graphene nanoribbons.Graphene nanoribbons show promise for high-performance field-effect transistors, however they often suffer from short lengths and wide band gaps. Here, the authors use a bottom-up synthesis approach to fabricate 9- and 13-atom wide ribbons, enabling short-channel transistors with 10(5) on-off current ratio.

Concentration Effect on Quenching of Chlorophyll a Fluorescence by All-Trans-β-Carotene in Photosynthesis.

Absorption, fluorescence spectra of chlorophyll a (Chl-a) and all-trans-β-carotene (β-Car) mixing solution are investigated in different polarity and polarizability solvents. The carotenoids regulate the energy flow in photosynthesis by interaction with chlorophyll, leading to an observable reduction of Chl-a fluorescence. The fluorescence red shifts with the increasing solvent polarizability. The energy transfer in the Chl-a and β-Car system is proposed. The electron transfer should be dominant in quenching Chl-a fluorescence rather than the energy transfer in this system. Polar solvent with large polarizability shows high quenching efficiency. When dissolved in carbon tetrachloride, Chl-a presents red shift of absorption and blue shift of fluorescence spectra with increasing β-Car concentration, which implies a Chl-a conformational change.

Yinchen Linggui Zhugan Decoction Ameliorates Nonalcoholic Fatty Liver Disease in Rats by Regulating the Nrf2/ARE Signaling Pathway.

Yinchen Linggui Zhugan Decoction (YCLGZGD) is the combination of Linggui Zhugan (LGZGD) and Yinchenhao (YCHD) decoctions, two famous traditional Chinese medicine prescriptions. In previous studies, we found that Yinchen Linggui Zhugan Decoction (YCLGZGD) could regulate lipid metabolism disorder and attenuate inflammation in pathological process of nonalcoholic fatty liver disease (NAFLD). However, the exact underlying mechanism remains unknown. The aim of this study was to explore the effect of Yinchen Linggui Zhugan Decoction on experimental NAFLD and its mechanism in rats with high-fat diet (HFD) which was established by 8-week administration of HFD. YCLGZGD, LGZGD, and YCHD were administered daily for 4 weeks, after which the rats were euthanized. The level of blood lipid, liver enzymes, H&E, and Oil Red O staining were determined to evaluate NAFLD severity. Western blotting and real-time polymerase chain reaction were, respectively, used to determine hepatic protein and gene expression of Keap1, Nrf2, NQO1, and HO-1. Oral YCLGZGD ameliorated HFD-induced NAFLD. Furthermore, YCLGZGD increased the protein and gene expression of Nrf2, NQO1, and HO-1 without changing Keap1. Overall, these results suggest that YCLGZGD ameliorates HFD-induced NAFLD in rats by upregulating the Nrf2/ARE signaling pathway.

Inhibition of Lymphatic Drainage With a Self-Designed Surgical Approach Prolongs the Vascularized Skin Allograft Survival in Rats.

Vascularized composite allotransplantation (VCA) is an emerging treatment for significant tissue defects. However, VCAs usually consist of multiple highly antigenic skin tissues. Previous studies have shown that the lymphatic system in skin plays important roles in the initiation of immune responses during acute rejection, by transporting T cells and antigen-presenting dendritic cells to regional lymph nodes. Therefore, we designed a new surgical treatment to inhibit lymphatic drainage of skin allografts and investigated whether this approach could promote the survival of allografts and suppress immunological events after transplantation. This procedure was achieved by connecting the vascularized allografts to recipient tissues with only an annular plastic holder, allowing the minimum of allograft contact with recipients. Our results showed that the self-designed treatment for inhibiting lymphatic drainage promoted the survival of allografts, reduced the serum concentration of IL-2, and decreased the percentage of CD4CD25 and CD8CD25 from the lymphatic nodes draining the transplantation region. In conclusion, these data suggest that self-designed surgical approach is effective in inhibiting lymphatic drainage of skin allografts, and the lymphatic system may be new therapeutic targets for developing techniques or drugs against acute rejection after VCAs.

Ambient air pollution and daily hospital admissions for mental disorders in Shanghai, China.

Few studies have investigated the associations between ambient air pollution and mental disorders (MDs), especially in developing countries. We conducted a time-series study to explore the associations between six criteria air pollutants and daily hospital admissions for MDs in Shanghai, China, from 2013 to 2015. The MDs data were derived from the Shanghai Health Insurance System. We used over-dispersed, generalized additive models to estimate the associations after controlling for time trend, weather conditions, day of the week, and holidays. In addition, we evaluated the effect of modification by age, sex, and season. A total of 39,143 cases of hospital admissions for MDs were identified during the study period. A 10-μg/m(3) increase in 2-day, moving-average concentration of inhalable particulate matter, sulfur dioxide (SO2), and carbon monoxide was significantly associated with increments of 1.27% [95% confidence interval (CI): 0.28%, 2.26%], 6.88% (95% CI, 2.75%, 11.00%), and 0.16% (95% CI: 0.02%, 0.30%) in daily hospital admissions for MDs, respectively. We observed positive but insignificant associations of fine particulate matter, nitrogen dioxide and ozone. The estimated association of SO2 was relatively robust to the adjustment of simultaneous exposure to other pollutants. We found generally stronger associations of air pollutants with MDs in warm seasons than in cool seasons. There were no significant differences in the associations between different sex and age groups. This study suggested that short-term exposure to air pollution, especially to sulfur dioxide, was associated with increased risk of hospital admissions for MDs in Shanghai, China.

How bicycle level of traffic stress correlate with reported cyclist accidents injury severities: A geospatial and mixed logit analysis.

Transportation agencies need efficient methods to determine how to reduce bicycle accidents while promoting cycling activities and prioritizing safety improvement investments. Many studies have used standalone methods, such as level of traffic stress (LTS) and bicycle level of service (BLOS), to better understand bicycle mode share and network connectivity for a region. However, in most cases, other studies rely on crash severity models to explain what variables contribute to the severity of bicycle related crashes. This research uniquely correlates bicycle LTS with reported bicycle crash locations for four cities in New Hampshire through geospatial mapping. LTS measurements and crash locations are compared visually using a GIS framework. Next, a bicycle injury severity model, that incorporates LTS measurements, is created through a mixed logit modeling framework. Results of the visual analysis show some geospatial correlation between higher LTS roads and "Injury" type bicycle crashes. It was determined, statistically, that LTS has an effect on the severity level of bicycle crashes and high LTS can have varying effects on severity outcome. However, it is recommended that further analyses be conducted to better understand the statistical significance and effect of LTS on injury severity. As such, this research will validate the use of LTS as a proxy for safety risk regardless of the recorded bicycle crash history. This research will help identify the clustering patterns of bicycle crashes on high-risk corridors and, therefore, assist with bicycle route planning and policy making. This paper also suggests low-cost countermeasures or treatments that can be implemented to address high-risk areas. Specifically, with the goal of providing safer routes for cyclists, such countermeasures or treatments have the potential to substantially reduce the number of fatalities and severe injuries.

Symptoms-Based Phenotypes Among Women With Dysmenorrhea: A Latent Class Analysis.

Dysmenorrhea is highly prevalent and may increase women's risk for developing other chronic pain conditions. Although it is highly variable, symptom-based dysmenorrhea phenotypes have not been identified. The aims of the study were to identify symptom-based dysmenorrhea phenotypes and examine their relationships with demographic and clinical characteristics. In a cross-sectional study, 762 women with dysmenorrhea rated severity of 14 dysmenorrhea-related symptoms. Using latent class analysis, we identified three distinctive phenotypes. Women in the "mild localized pain" phenotype ( n = 202, 26.51%) had mild abdominal cramps and dull abdominal pain/discomfort. Women in the "severe localized pain" phenotype ( n = 412, 54.07%) had severe abdominal cramps. Women in the "multiple severe symptoms" phenotype ( n = 148, 19.42%) had severe pain at multiple locations and multiple gastrointestinal symptoms. Race, ethnicity, age, and comorbid chronic pain conditions were significantly associated with phenotypes. Identification of these symptom-based phenotypes provides a foundation for research examining genotype-phenotype associations, etiologic mechanisms, and/or variability in treatment responses.

A resequencing pathogen microarray method for high-throughput molecular diagnosis of multiple etiologies associated with central nervous system infection.

Central nervous system infection (CNSI) results in significant health and economic burdens worldwide, but the diversity of causative pathogens makes differential diagnosis very difficult. Although PCR and real-time fluorescent quantitative PCR (q-PCR) assays are widely applied for pathogen detection, they are generally optimized for the detection of a single or limited number of targets and are not suitable for the diagnosis of numerous CNSI agents. In this study, we describe the development of a resequencing pathogen microarray (RPM-IVDC4) method for the simultaneous detection of viruses, bacteria, fungi and parasites that cause CNSI. The test panel of this assay included more than 100 microorganism species across 45 genera and 30 families. The analytical specificity and sensitivity were examined using a panel of positive reference strains, and the clinical performance was evaluated using 432 clinical samples by comparing the results with q-PCR assays. Our results demonstrated good performance of the RPM-IVDC4 assay in terms of sensitivity, specificity and detection range, suggesting that the platform can be further developed for high-throughput CNSI diagnosis.

Long-term treatment with the ghrelin receptor antagonist, D-Lys3-GHRP-6 does not improve glucose homeostasis in non-obese diabetic MKR mice.

Ghrelin secretion has been associated with increased caloric intake and adiposity. The expressions of ghrelin and its receptor (GHS-R1a) in pancreas have raised the interest about the role of ghrelin in glucose homeostasis. Most of the studies showed that ghrelin promoted hyperglycaemia and inhibited insulin secretion. This raised the interest in using GHS-R1a antagonists as therapeutic targets for type 2 diabetes. Available data of GHS-R antagonists are on a short-term basis. Moreover, the complexity of GHS-R1a signalling makes it difficult to understand the mechanism of action of GHS-R1a antagonists. This study examined the possible effects of long-term treatment with a GHS-R1a antagonist, [D-Lys3]-GHRP-6 on glucose homeostasis, food intake and indirect calorimetric parameters in non-obese diabetic MKR mice. Our results showed that [D-Lys3]-GHRP-6 (200nmol/mouse), reduced pulsatile growth hormone secretion and body fat mass as expected, but worsened glucose and insulin intolerances and increased cumulative food intake unexpectedly. In addition, a significant increase in blood glucose and decreases in plasma insulin and c-peptide levels were observed in MKR mice following long-term [D-Lys3]-GHRP-6 treatment, suggested a direct inhibition of insulin secretion. Immunofluorescence staining of pancreatic islets showed a proportional increase in somatostatin positive cells and a decrease in insulin positive cells in [D-Lys3]-GHRP-6 treated mice. Furthermore, [D-Lys3]-GHRP-6 stimulated food intake on long-term treatment via reduction of POMC gene expression and antagonized GH secretion via reduced GHRH gene expression in hypothalamus. These results demonstrate that [D-Lys3]-GHRP-6 is not completely opposite to ghrelin and may not be a treatment option for type 2 diabetes.

Inositol hexaphosphate hydrolysate competitively binds to AKT to inhibit the proliferation of colon carcinoma.

Phytate, myto-inositol 1,2,3,4,5,6 hexaphosphate (IP6), is recognized as an anti-nutrition phytochemical for decades. Recently, numerous studies have indicated that IP6 and its hydrolysates could suppress colon oncogenesis. However, very little is known concerning the mechanism of IP6 hydrolysates in regulating colon oncogenesis. The aim of the present study was to identify the underlying relationship between IP6 hydrolysates and colon cancer. Three types of human colorectal cancer cells were utilized in the present study. The proliferation inhibition and migration assays were employed to reveal that IP6 hydrolysates inhibited the proliferation of SW620 cells. Real-time PCR, cell-based ELISA and the AKT inhibitor assay were utilized to reveal that 20 and 30% degree of hydrolysis hydrolysates of IP6 inhibited SW620 cell growth by inhibiting the activation of AKT protein. The docking simulation study revealed that IP4 and IP5 could inhibit the activation of AKT by binding to PIP3 receptor. Collectively, our results indicated that the IP6 hydrolysates inhibit SW620 cell proliferation; IP4 and IP5, the probable primary constituents of the 20-30% degree of hydrolysis hydrolysates of IP6, inhibited the proliferation of SW620 cells by competitively inhibiting the AKT protein.

A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug.

Adenoid cystic carcinomas (ACC) are rare salivary gland cancers with a high incidence of metastases. In order to study this tumor type, a reliable model system exhibiting the molecular features of this tumor is critical, but none exists, thereby inhibiting in-vitro studies and the analysis of metastatic behavior. To address this deficiency, we have coupled an efficient method to establish tumor cell cultures, conditional reprogramming (CR), with a rapid, reproducible and robust in-vivo zebrafish model. We have established cell cultures from two individual ACC PDX tumors that maintain the characteristic MYB translocation. Additional mutations found in one ACC culture also seen in the PDX tumor. Finally, the CR/zebrafish model mirrors the PDX mouse model and identifies regorafenib as a potential therapeutic drug to treat this cancer type that mimic the drug sensitivity profile in PDX model, further confirming the unique advantages of multiplex system.

Ring 14 chromosome syndrome in a boy mainly manifesting as drug-resistant epilepsy.

Seasonal Variation in Water-Soluble Ions in Airborne Particulate Deposition in the Suburban Nanjing Area, Yangtze River Delta, China, During Haze Days and Normal Days.

To investigate the seasonal variation and characterization of water-soluble ions (WSIs) present in airborne particle deposition (APD) during Haze Days (visibility ≤7.5 km) and Normal Days (visibility >7.5 km) in suburban Nanjing area, 151 filter samples were collected from 18 May 2013 to 26 May 2014. Ten different WSIs from the samples were determined by Ion Chromatography. The results indicated that secondary WSIs (NH4(+), NO3(-), and SO4(2-)) were the main ions in the WSIs, averaging 17.2, 18.5, and 17.1 μg/m(3), respectively, and accounting respectively 20.9, 22.5, and 20.8% of the total WSIs. On Haze Days, the concentration of WSIs increased dramatically in fine size (particle size <2.1 μm), especially for NH4(+), NO3(-), and SO4(2-) (increased by 52.6, 71.3, and 73.1%, respectively), whereas the concentrations of WSIs increased slowly in coarse size (2.1 μm < particle size < 10 μm), in which NH4(+), NO3(-), and SO4(2-) increased by 14.7, 27.2, and 54.5%, respectively. According to the backward trajectories and the principal component analysis analysis, Nanjing APD were mainly derived from the soil dust in northern China (35%) in the spring, from ocean air masses (61 and 55%) in the summer and the autumn, and from local air masses (73%) in the winter. On summer Haze Days, secondary components in PM2.1 consisted mainly of (NH4)2SO4 and NH4NO3, whereas secondary components in PM2.1-10 consisted mainly of (NH4)2SO4, NH4Cl, and NH4NO3. The increasing concentrations of secondary components increase the light extinction coefficients of aerosol on winter and autumn Haze Days. The concentrations of WSIs in fine size rose sharply on Haze Days, leading the visibility to exponential decline. Differently, the concentrations of WSIs in coarse size were not the main cause in the change of the visibility.

Profiling dendritic cell subsets in the patients with active pulmonary tuberculosis.

Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT. Meanwhile, the number of DCs was associated with the prolonged/complicated TB, ATD treatment effect and lymphocyte immune reactions, as manifested that relapsed APT patients with a higher number of tDC and lower number of pDC compared to newly diagnosed patients. Interestingly, mDC from APT patients displayed high expressions of CD83 and CCR7, but pDC displayed low expressions of CD83 and CCR7. Moreover, DCs from APT patients expressed lower levels of HLA-DR and CD80, but expressed a higher level of CD86 than those from HCs. However, the antigen uptake capacity of DC subsets was not different between APT and HCs, despite the antigen uptake capacity of pDC was much lower than that of mDC in both APT patients and HCs. Our data represent a systematic profile of DC subsets in the blood of APT patients, and would represent a useful biomarker for APT.

When Escherichia coli doesn't fit the mold: A pertussis-like toxin with altered specificity.

Bacterial toxins introduce protein modifications such as ADP-ribosylation to manipulate host cell signaling and physiology. Several general mechanisms for toxin function have been established, but the extent to which previously uncharacterized toxins utilize these mechanisms is unknown. A study of an Escherichia coli pertussis-like toxin demonstrates that this protein acts on a known toxin substrate but displays distinct and dual chemoselectivity, suggesting this E. coli pertussis-like toxin may serve as a unique tool to study G-protein signaling in eukaryotic cells.

Refractive index engineering through swift heavy ion irradiation of LiNbO3 crystal towards improved light guidance.

Swift heavy ion irradiation has been widely used to modify refractive indices of optical materials for waveguide fabrication. In this work, we propose refractive index engineering by swift heavy ion (Ar) irradiation via electronic energy deposition to construct waveguides of diverse geometries in LiNbO3 crystal. The feasibility to modulate the refractive index of LiNbO3 crystal at variable depths through electronic energy depositions of argon ions at different energies has been experimentally explored. The surface and cladding-like optical waveguides with thicknesses of ~13, ~36 and ~23 μm have been produced by using swift Ar ion irradiation at single energy of ~120, ~240, and double energy of (120 + 240) MeV, respectively. The fabricated waveguides are capable of effective waveguiding in single and multiple modes at 1064 nm, which enables efficient guided-wave second harmonic generation at room temperature. This work paves the way to produce waveguides with diverse geometries in dielectric crystals through electronic damage of multiple swift heavy ion irradiation.

Enhanced efficacy of the engineered antimicrobial peptide WLBU2 via direct airway delivery in a murine model of P. aeruginosa pneumonia.

P. aeruginosa is a common cause of pneumonia in cystic fibrosis patients with the property to generate multidrug resistance against clinically used antibiotics. Antimicrobial peptides (AMPs) are a diverse group of effector molecules of the innate immunity that protect the host against pathogens. However, the lack of activity in common biological matrices has hampered efforts towards clinical development. In this study, we evaluated the therapeutic potential of engineered antimicrobial peptide WLBU2 via direct airway delivery in a murine model of P. aeruginosa infection.

Net1, a therapeutic potential target for cancer.

Dental Composite Formulation Design with Bioactivity on Protein Adsorption Combined with Crack-Healing Capability.

Fracture and secondary caries are the primary reasons for the failure of dental restorations. To face this omnipresent problem, we report the formulation design and synthesis of a protein-resistant dental composite composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) that also can self-repair damage and recover the load-bearing capability via microencapsulated triethylene glycol dimethacrylate (TEGDMA) and N,N-dihydroxy ethyl-p-toluidine (DHEPT). The bioactivity of the resulting MPC-microencapsulated TEGDMA-DHEPT was evaluated on protein adsorption through early bacterial attachment. Its mechanical properties were also investigated, including self-healing assessment. Microcapsules of poly (urea-formaldehyde) (PUF) were synthesized by incorporating a TEGDMA-DHEPT healing liquid. A set of composites that contained 7.5% of MPC, 10% of microcapsules, and without MPC/microcapsules were also prepared as controls. The two distinct characteristics of strong protein repellency and load-bearing recovery were achieved by the combined strategies. The novel dual composite with a combination of protein-repellent MPC and PUF microcapsules for restoring microcracks is a promising strategy for dental restorations to address the two main challenges of fracture and secondary caries. The new dual composite formulation design has the potential to improve the longevity of dental restorations significantly.

Hierarchical Sparse Representation for Robust Image Registration.

Similarity measure is an essential component in image registration. In this article, we propose a novel similarity measure for registration of two or more images. The proposed method is motivated by the fact that optimally registered images can be sparsified hierarchically in the gradient domain and frequency domain with the separation of sparse errors. One of the key advantages of the proposed similarity measure is its robustness in dealing with severe intensity distortions, which widely exist on medical images, remotely sensed images and natural photos due to differences of acquisition modalities or illumination conditions. Two efficient algorithms are proposed to solve the batch image registration and pair registration problems in a unified framework. We have validated our method on extensive and challenging data sets. The experimental results demonstrate the robustness, accuracy and efficiency of our method over nine traditional and state-of-the-art algorithms on synthetic images and a wide range of real-world applications.

Proteomic analysis on roots of Oenothera glazioviana under copper-stress conditions.

Proteomic studies were performed to identify proteins involved in the response of Oenothera glazioviana seedlings under Cu stress. Exposure of 28-d-old seedlings to 50 μM CuSO4 for 3 d led to inhibition of shoot and root growth as well as a considerable increase in the level of lipid peroxidation in the roots. Cu absorbed by O. glazioviana accumulated more easily in the root than in the shoot. Label-free proteomic analysis indicated 58 differentially abundant proteins (DAPs) of the total 3,149 proteins in the roots of O. glazioviana seedlings, of which 36 were upregulated and 22 were downregulated under Cu stress conditions. Gene Ontology analysis showed that most of the identified proteins could be annotated to signal transduction, detoxification, stress defence, carbohydrate, energy, and protein metabolism, development, and oxidoreduction. We also retrieved 13 proteins from the enriched Kyoto Encyclopaedia of Genes and Genomes and the protein-protein interaction databases related to various pathways, including the citric acid (CA) cycle. Application of exogenous CA to O. glazioviana seedlings exposed to Cu alleviated the stress symptoms. Overall, this study provided new insights into the molecular mechanisms of plant response to Cu at the protein level in relation to soil properties.

Decision of surgical approach for advanced gallbladder adenocarcinoma based on a Bayesian network.

To determine whether radical resection can benefit patients with advanced gallbladder adenocarcinoma using a Bayesian network (BN) with clinical data.

Intrinsic renal cells induce lymphocytosis of Th22 cells from IgA nephropathy patients through B7-CTLA-4 and CCL-CCR pathways.

IgA nephropathy (IgAN), the most common glomerulonephritis, has an unclear pathogenesis. The role of Th22 cells, which are intimately related to proteinuria and progression in IgAN, in mediating infection-related IgAN is unclear. This study aimed to characterize the association between intrinsic renal cells (tubular epithelial cells and mesangial cells) and Th22 cells in immune regulation of infection-related IgAN and to elucidate the impact of Th22 lymphocytosis; the proinflammatory cytokines IL-1, IL-6, and TNF-α; and CCL chemokines on kidney fibrosis. Hemolytic streptococcus infection induced an increase in IL-1, IL-6, and TNF-α, resulting in Th22 cell differentiation from T lymphocytes obtained from patients with IgAN, and the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes facilitated Th22 cell chemotaxis. The increased amount of Th22 cells caused an increase in TGF-β1 levels, and anti-CD80, anti-CD86, and CTLA-4Ig treatment reduced TGF-β1 levels by inhibiting Th22 lymphocytosis and secretion of cytokines and chemokines, thus potentially relieving kidney fibrosis. Our data suggest that Th22 cells might be recruited into the kidneys via the CCL20-CCR6, CCL22-CCR4, and/or CCL27-CCR10 axes by mesangial cells and tubular epithelial cells in infection-related IgAN. Th22 cell overrepresentation was attributed to stimulation of the B7-CTLA-4Ig antigen-presenting pathway and IL-1, IL-6, and TNF-α.

Molecular mechanism of water reorientational slowing down in concentrated ionic solutions.

Water dynamics in concentrated ionic solutions plays an important role in a number of material and energy conversion processes such as the charge transfer at the electrolyte-electrode interface in aqueous rechargeable ion batteries. One long-standing puzzle is that all electrolytes, regardless of their "structure-making/breaking" nature, make water rotate slower at high concentrations. To understand this effect, we present a theoretical simulation study of the reorientational motion of water molecules in different ionic solutions. Using an extended Ivanov model, water rotation is decomposed into contributions from large-amplitude angular jumps and a slower frame motion which was studied in a coarse-grained manner. Bearing a certain resemblance to water rotation near large biological molecules, the general deceleration is found to be largely due to the coupling of the slow, collective component of water rotation with the motion of large hydrated ion clusters ubiquitously existing in the concentrated ionic solutions. This finding is at variance with the intuitive expectation that the slowing down is caused by the change in fast, single-molecular water hydrogen bond switching adjacent to the ions.

Added Value of Computer-aided CT Image Features for Early Lung Cancer Diagnosis with Small Pulmonary Nodules: A Matched Case-Control Study.

Purpose To test whether computer-aided diagnosis (CAD) approaches can increase the positive predictive value (PPV) and reduce the false-positive rate in lung cancer screening for small nodules compared with human reading by thoracic radiologists. Materials and Methods A matched case-control sample of low-dose computed tomography (CT) studies in 186 participants with 4-20-mm noncalcified lung nodules who underwent biopsy in the National Lung Screening Trial (NLST) was selected. Variables used for matching were age, sex, smoking status, chronic obstructive pulmonary disease status, body mass index, study year of the positive screening test, and screening results. Studies before lung biopsy were randomly split into a training set (70 cancers plus 70 benign controls) and a validation set (20 cancers plus 26 benign controls). Image features from within and outside dominant nodules were extracted. A CAD algorithm developed from the training set and a random forest classifier were applied to the validation set to predict biopsy outcomes. Receiver operating characteristic analysis was used to compare the prediction accuracy of CAD with the NLST investigator's diagnosis and readings from three experienced and board-certified thoracic radiologists who used contemporary clinical practice guidelines. Results In the validation cohort, the area under the receiver operating characteristic curve for CAD was 0.9154. By default, the sensitivity, specificity, and PPV of the NLST investigators were 1.00, 0.00, and 0.43, respectively. The sensitivity, specificity, PPV, and negative predictive value of CAD and the three radiologists' combined reading were 0.95, 0.88, 0.86, and 0.96 and 0.70, 0.69, 0.64, and 0.75, respectively. Conclusion CAD could increase PPV and reduce the false-positive rate in the early diagnosis of lung cancer. (©) RSNA, 2017 Online supplemental material is available for this article.

Microdissection testicular extraction for a patient with transverse testicular ectopia and testicular fusion.

Attitudes of Chinese community members and psychiatrists towards forensic psychiatric assessments.

The aim of this study was to investigate the attitudes of Chinese community members and psychiatrists towards forensic psychiatric assessments. A questionnaire designed to record attitudes toward the current forensic psychiatric assessment procedures and the disposal of mentally ill offenders was developed and distributed via a mobile App. A total of 134 community members and 132 psychiatrists voluntarily completed the questionnaire. Most of responders agreed that the department of public-security has the right to apply for a forensic psychiatric assessment but should not be held solely by that department. Community members were less significantly confident in the validation of forensic psychiatric opinions than were the psychiatrists. A significantly higher proportion of community members than psychiatrists considered that offenders judged Not Criminally Responsible on Account of Mental Disorder (NCRMD) should be punished as would be sane people. In addition, only a minority of responders supported that NCRMD should not be held criminally responsible. Our results indicate that both groups have comments on the current distribution of right of startup of forensic psychiatric assessments. Compared to psychiatrists, community members have lower confidence in the validation of forensic psychiatric assessment and have stricter attitudes toward the disposal of offenders with psychiatric disorders.