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Liver injury is a core pathological process in the majority of liver diseases, yet the genetic factors predisposing individuals to its initiation and progression remain poorly understood. Here we show that asialoglycoprotein receptor 1 (ASGR1), a lectin specifically expressed in the liver, is downregulated in patients with liver fibrosis or cirrhosis and male mice with liver injury. ASGR1 deficiency exacerbates while its overexpression mitigates acetaminophen-induced acute and CCl4-induced chronic liver injuries in male mice. Mechanistically, ASGR1 binds to an endoplasmic reticulum stress mediator GP73 and facilitates its lysosomal degradation. ASGR1 depletion increases circulating GP73 levels and promotes the interaction between GP73 and BIP to activate endoplasmic reticulum stress, leading to liver injury. Neutralization of GP73 not only attenuates ASGR1 deficiency-induced liver injuries but also improves survival in mice received a lethal dose of acetaminophen. Collectively, these findings identify ASGR1 as a potential genetic determinant of susceptibility to liver injury and propose it as a therapeutic target for the treatment of liver injury. [ABSTRACT FROM AUTHOR]

Background: The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to the progression of hepatocellular carcinoma (HCC). However, the clinical significance of lncRNAs associated with cuproptosis remains unclear. Methods: Based on The Cancer Genome Atlas (TCGA) liver hepatocellular carcinoma (LIHC) dataset, we identified characteristic prognostic lncRNAs by univariate, LASSO, and multifactorial regression analysis, and constructed a prognostic signature of cuproptosis-related lncRNAs in HCC. The role of lncRNAs were identified through CCK-8, clone formation in Huh-7 cells with high expression of FDX1. Prognostic potential of the characteristic lncRNAs was evaluated in each of the two cohorts created by randomly dividing the TCGA cohort into a training cohort and a test cohort in a 1:1 ratio. Immune profiles in defined subgroups of cuproptosis-related lncRNA features as well as drug sensitivity were analyzed. Results: We constructed a multigene signature based on four characteristic prognostic lncRNAs (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These four lncRNAs participated in the development of cuproptosis. HCC patients were classified into high-risk and low-risk groups based on the median value of the risk score. The receiver operating characteristic curve area under the curve values for 1-, 3-, and 5-year survival were 0.773, 0.728, and 0.647, respectively, for the training cohort, and 0.764, 0.671, and 0.662, respectively, for the test cohort. Univariate and multifactorial regression analyses indicated that this prognostic feature was an independent prognostic factor for HCC. Principal component analysis plots clearly distinguished between low- and high-risk patients in terms of their probability of survival. Furthermore, gene set enrichment analysis showed that a variety of processes associated with tumor proliferation and progression were enriched in the high-risk group compared with the low-risk group. Moreover, there were significant differences in the expression of immune cell subpopulations, immune checkpoint genes, and potential drug screening, which provided distinct therapeutic recommendations for individuals with various risks. Conclusions: We constructed a novel cuproptosis-associated lncRNA signature with a significant predictive value for the prognosis of patients with HCC. Cuproptosis-associated lncRNAs are associated with the tumor immune microenvironment of HCC and even the efficacy of tumor immunotherapy. [ABSTRACT FROM AUTHOR]

A photoredox-catalysed chlorination of quinoxalin-2(1H)-ones was developed by using CHCl3 as a chlorine source, thus affording various 3-chloroquinoxalin-2(1H)-ones in moderate to high yields. This protocol is characterized by mild reaction conditions, excellent regioselectivity, and readily available chlorination agent. Considering the operational simplicity and low cost of this chlorination approach, this developed method offers an innovative pathway for rapid incorporation of chlorine functionality into heteroarenes, and will inspire broader exploitation of new chlorination strategies. [ABSTRACT FROM AUTHOR]

Red mud as the main byproduct generated during alumina extraction from bauxite. Owing to the high iron content in the red mud and the high correlation between iron and scandium during the leaching process, it is necessary to extract the iron from the red mud and to further enrich the scandium in advance for the acid leaching extraction of scandium. In this research, the theory of red mud segregation roasting ore phase reconstruction is proposed, so that the iron and scandium in the red mud undergo a corresponding transformation, thereby achieving iron recovery in magnetic separation concentrate by magnetic separation, and enrichment of scandium in magnetic separation tailings. On this basis, the effects of temperature, leaching time, solid to liquid ratio and hydrochloric acid concentration on the leaching of scandium in magnetic separation tailings were studied optimal leaching process conditions and determine the leaching kinetics. A maximum Sc leaching efficiency of 83.94% was obtained at optimum leaching conditions of 200 rpm agitation speed, hydrochloric acid solution 20%, 80°C for 3 h, and solid/liquid ratios 1:10 (g/mL), −74 µm sample particle size. The process of leaching scandium with magnetic separation tailings conforms to the kinetic characteristics of multiphase liquid-solid region reaction, the apparent activation energy of scandium is 26.77 kJ/mol, and the leaching efficiency of scandium is controlled by the chemical reaction step. [ABSTRACT FROM AUTHOR]

Red mud is the main solid waste generated by the aluminum industry for the extraction of alumina. Considering the environmental problems associated with red mud, the recovery of iron from bauxite slag is still a promising field. The effect of sodium sulfate on the red mud separation roasting-magnetic separation process was studied. The results show that at the roasting temperature of 1100°C for 65 min, the segregation roasting–magnetic separation is carried out with 8 wt.% sodium sulfate. The total iron grade of the magnetic separation iron concentrate is 79.32 wt.% and iron recovery rate of 85.43%. X-ray diffraction analysis (XRD), optical microscopy analysis and scanning electron microscopy-X-ray energy spectroscopy (SEM-EDS) were used to study the addition of sodium sulfate segregation roasting products to red mud. The results show that adding the proper amount of sodium sulfate during the red mud segregation roasting process can enhance the separation and recovery of iron. During the red mud segregation roasting process, sodium sulfate reacts with alumina, silica, etc. to form sodium silicate and sodium aluminosilicate, which inhibits the formation of fayalite and promotes the chlorination of iron oxide. Element migration and chemical reaction can destroy the original ore structure, promote the formation of molten phase and accelerate the aggregation and growth of metallic iron particles. Thus, a metallic iron concentrate with high quality is obtained. [ABSTRACT FROM AUTHOR]

We experimentally study the dependences of high-order Stokes lines on the erbium-doped fiber (EDF) pump power PEDF, the Brillouin pump (BP) power PBP, and its working wavelength in a multiwavelength Brillouin erbium-doped fiber laser (MBEFL). By using the rate and propagation equations, and the coupled wave equations of stimulated Brillouin scattering, we establish a lumped model to describe the MBEFL. Numerical simulations show that the number of Stokes lines can be increased by decreasing the spacing between the BP wavelength and the EDF peak gain or PBP as long as it is larger than a critical value PBP(cr) = 1.7 mW, or by increasing PEDF without reaching a saturation value PEDF(cr) = 250 mW. However, when PBP and PEDF are varied beyond PBP(cr) and PEDF(cr), respectively, the number of Stokes lines is reduced, accompanied by some self-lasing cavity modes. These results by numerical simulation are consistent with experimental observations from the MBEFL. [ABSTRACT FROM AUTHOR]

A multiwavelength erbium-doped fiber laser with linear cavity configuration is proposed and demonstrated. A power-symmetric nonlinear optical loop mirror (NOLM) serves as the laser's output coupler and has an intensity-induced increase in transmission (IIT) that leads to higher cavity loss for oscillating wavelengths with higher power. The IIT feature of the NOLM suppresses the mode competition in the erbium-doped fiber and ensures stable multiwavelength operation at room temperature. Both the wavelength number and the output power of the laser can be flexibly controlled by adjusting the work state of the NOLM via a quarter wave plate and/or a polarization controller. [ABSTRACT FROM AUTHOR]

A novel synthetic protocol for the assembly of pyrrolo[1,2- a]indolenine has been developed through a highly diastereoselective [3+2] annulation of 1,1-cyclopropanediesters with indolenines in the presence of catalytic Yb(OTf)3. This new strategy allows a facile construction of the multicyclic system with the flexible variation on the substituents in high yields (up to 86%) with excellent diastereoselectivities (>20:1 dr) in most cases. [ABSTRACT FROM AUTHOR]

The potential of reduced-pressure radio-frequency air plasma (RFAP) in the modification of konjac glucomannan (KGM) was investigated. KGM film was exposed to 100 W RFAP for 50 s, 100 s, 150 s, 200 s, and 250 s, ground, and then subjected to various characterizations. Fourier Transform Infrared Spectroscopy (FTIR) revealed that RFAP treatment increased the content of -OH groups in KGM, with the lowest and highest rise occurring at the exposure durations 150 s and 250 s, respectively. RFAP radiation decreased the solubility of KGM at certain exposure durations, but slightly increased its thermal stability. Exposure to RFAP for 150 s and 250 s increased the hardness of the resultant KGM gel, but decreased the viscosity and elasticity of the KGM solution in a duration-dependent manner. Scanning Electron Microscope (SEM) observation revealed that RFAP treatment led to rougher surfaces and XRD (X-Ray Diffraction) analysis indicated the destroyed crystallinity of KGM. Hence, RFAP has potential application in the modification of KGM. [ABSTRACT FROM AUTHOR]

Chronic myeloid leukemia is characterized by the presence of the reciprocal translocation t(9;22) and the BCR/ABL oncogene. The BCR/ABL oncogene activates multiple signaling pathways and involves the dysregulation of oncogenes during the progression of chronic myeloid leukemia. The cell division cycle protein 6, an essential regulator of DNA replication, is elevated in some human cancer cells. However, the expression of cell division cycle protein 6 in chronic myeloid leukemia and the underlying regulatory mechanism remain to be elucidated. In this study, our data showed that cell division cycle protein 6 expression was significantly upregulated in primary chronic myeloid leukemia cells and the chronic myeloid leukemia cell line K562 cells, as compared to the normal bone marrow mononuclear cells. BCR/ABL kinase inhibitor STI571 or BCR/ABL small interfering RNA could significantly downregulate cell division cycle protein 6 messenger RNA expression in K562 cells. Moreover, phosphoinositide 3-kinase/AKT pathway inhibitor LY294002 and Janus kinase/signal transducer and activator of transcription pathway inhibitor AG490 could downregulate cell division cycle protein 6 expression in K562 cells, but not RAS/mitogen-activated protein kinase pathway inhibitor PD98059 had such effect. Cell division cycle protein 6 gene silencing by small interfering RNA effectively resulted in decrease of proliferation, increase of apoptosis, and arrest of cell cycle in K562 cells. These findings have demonstrated that cell division cycle protein 6 overexpression may contribute to the high proliferation and low apoptosis in chronic myeloid leukemia cells and can be regulated by BCR/ABL signal transduction through downstream phosphoinositide 3-kinase/Akt and Janus kinase/signal transducer and activator of transcription pathways, suggesting cell division cycle protein 6 as a potential therapeutic target in chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

The present study aimed to investigate the effects of blocking nuclear factor (NF)-κB and/or extracellular signal regulated kinase (ERK) signaling pathways on proliferation and apoptosis of melanoma cells in vitro. A375 Human melanoma cells were treated with U0126 (ERK signaling pathway inhibitor) and BMS 345541 (NF κB inhibitor), alone or in combination. At 12, 24 and 48 h after treatment, cell viability was assessed using the 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide assay, cell cycle progression and apoptosis were evaluated by flow cytometry, and Bcl 2 protein content was determined by western blot analysis. BMS 345541 and U0126 significantly inhibited A375 cell proliferation in a dose and time dependent manner (P<0.01). The rate of proliferation inhibition at 24 h was 35.41±1.38% for BMS 345541 alone, 30.64±2.86% for U0126 alone, and 77.27±2.70% for BMS 345541 and U0126 in combination. The difference between combination and single treatment was significantly different (P<0.01). The proportion of cells in S phase was 14.20, 18.40 and 22.64% following treatment with BMS 345541, U0126, and BMS 345541 and U0126 in combination, respectively; these values were all significantly reduced compared with the untreated control group (P<0.01). The apoptosis rate was 24.98±1.03% in the BMS 345541 group, 13.96±0.96% in the U0126 group and 38.91±1.46% in the combination group; all significantly increased compared with the control group (P<0.01). Bcl 2 protein content in A375 cells was significantly increased following treatment with BMS 345541 and U0126, alone or in combination, when compared with the untreated control group (P<0.01). Therefore, NF-κB and ERK signaling pathway inhibitors may serve as potential therapeutic targets for melanoma. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress is closely associated with cardiac fibrosis. However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction. This study was aimed to investigate the effect of PEP-1-SOD1 fusion protein on angiotensin II (ANG II)-induced collagen metabolism in rat cardiac myofibroblasts (MCFs). Methods: MCFs were pretreated with SOD1 or PEP-1-SOD1 fusion protein for 2 h followed by incubation with ANG II for 24 h. Cell proliferation was measured by Cell Counting Kit-8. Superoxide anion productions were detected by both fluorescent microscopy and Flow Cytometry. MMP-1 and TIMP-1 were determined by ELISA. Intracellular MDA content and SOD activity were examined by commercial assay kits. Protein expression was analyzed by western blotting. Results: PEP-1-SOD1 fusion protein efficiently transduced into MCF, scavenged intracellular O2 (-), decreased intracellular MDA content, increased SOD activity, suppressed ANG II-induced proliferation, reduced expression of TGF-β1, α-SMA, collagen type I and III, restored MMP-1 secretion, and attenuated TIMP-1 secretion. Conclusion: PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III. Therefore, PEP-1-SOD1 fusion protein may be a potential novel therapeutic agent for cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Competing endogenous RNAs (ceRNAs) are transcripts that can regulate each other at post-transcription level by competing for shared miRNAs. CeRNA networks link the function of protein-coding mRNAs with that of non-coding RNAs such as microRNA, long non-coding RNA, pseudogenic RNA and circular RNA. Given that any transcripts harbouring miRNA response element can theoretically function as ceRNAs, they may represent a widespread form of post-transcriptional regulation of gene expression in both physiology and pathology. CeRNA activity is influenced by multiple factors such as the abundance and subcellular localisation of ceRNA components, binding affinity of miRNAs to their sponges, RNA editing, RNA secondary structures and RNA-binding proteins. Aberrations in these factors may deregulate ceRNA networks and thus lead to human diseases including cancer. In this review, we introduce the mechanisms and molecular bases of ceRNA networks, discuss their roles in the pathogenesis of cancer as well as methods of predicting and validating ceRNA interplay. At last, we discuss the limitations of current ceRNA theory, propose possible directions and envision the possibilities of ceRNAs as diagnostic biomarkers or therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: SKF83959 stimulates the phospholipase Cp/inositol phosphate 3 pathway, resulting in the activation of Ca2+/ calmodulin-dependent kinase lia, which affects the synthesis of brain-derived neurotrophic factor, a neurotrophic factor critical for the pathophysiology of depression. Previous reports showed that SKF83959 elicited antidepressant activity in the forced swim test and tail suspension test as a novel triple reuptake inhibitor. However, there are no studies showing the effects of SKF83959 in a chronic stress model of depression and the role of phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway in SKF83959-mediated antidepressant effects. Methods: In this study, SKF83959 was firstly investigated in the chronic social defeat stress model of depression. The changes in hippocampal neurogenesis, dendrite spine density, and brain-derived neurotrophic factor signaling pathway after chronic social defeat stress and SKF83959 treatment were then investigated. Pharmacological inhibitors and small interfering RNA/ short hairpin RNA methods were further used to explore the antidepressive mechanisms of SKF83959. Results: We found that SKF83959 produced antidepressant effects in the chronic social defeat stress model and also restored the chronic social defeat stress-induced decrease in hippocampal brain-derived neurotrophic factor signaling pathway, dendritic spine density, and neurogenesis. By using various inhibitors and siRNA/shRNA methods, we further demonstrated that the hippocampal dopamine Ds receptor, phospholipase C/inositol phosphate 3/ calmodulin-dependent kinase lia pathway, and brain-derived neurotrophic factor system are all necessary for the SKF83959 effects. Conclusion: These results suggest that SKF83959 can be developed as a novel antidepressant and produces antidepressant effects via the hippocampal Ds/ phospholipase C/inositol phosphate 3/calmodulin-dependent kinase IIα/brain-derived neurotrophic factor pathway. [ABSTRACT FROM AUTHOR]

The mechanism of stray grain formation at the platform of turbine blade simulator and the effect of withdrawal rate (V) on the stray grain phenomenon have been investigated using a macro-scale ProCAST coupled with a 3D Cellular Automaton Finite Element (CAFE) model. The results indicate that the stray grains nucleate at the edges of platform at V =150 μm·s-1 and 200 μm·s-1. Using ProCAST computer simulation software, it was proven that the stray grain formation is significantly dependent on the undercooling and the temperature field distribution in the platform. The macroscopic curvature of the liquidus isotherm becomes markedly concave with an increase in the withdrawal rate. The probability of stray grain formation at the edges of platform can be increased by increasing the withdrawal rate in the range of 70 μm·s-1 to 200 μm·s-1. [ABSTRACT FROM AUTHOR]

Objective. The interaction between advanced glycation end products and their cellular receptor (RAGE) has an important role in the pathogenesis of diabetic microvascular complications. The aim of this study was to investigate the relationship between the 2184A/G polymorphism in the RAGE gene and diabetic nephropathy in Chinese Han patients with type 2 diabetes mellitus. Methods. A total of 868 patients with type 2 diabetes mellitus (486 without and 382 with diabetic nephropathy) were enrolled in this study. The genotype and allele frequencies of the 2184A/G polymorphism were detected using the polymerase chain reactionrestriction fragment-length polymorphism method. Results. The G allele and AG + GG genotype frequencies in patients with diabetic nephropathy were significantly lower than those in patients without diabetic nephropathy (𝑃 = 0.001 and 𝑃 = 0.005, resp.). After adjustments for possible confounders, multivariate logistic regression analyses showed that the 2184A/G polymorphism was independently associated with diabetic nephropathy (OR = 0.46, 95% CI: 0.22–0.92, 𝑃 = 0.028). Conclusions. Our study indicated that the 2184A/G polymorphism in the RAGE gene was significantly associated with diabetic nephropathy in Chinese Han patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

We present a versatile add-drop integrated photonic filter (ADF) consisting of nonreciprocal waveguides in which the propagation of light is restricted in one predetermined direction. With the bus and add/drop waveguides symmetrically coupled through a cavity, the four-port device allows each individual port to add and/or drop a signal of the same frequency. The scheme is general and we demonstrate the nonreciprocal ADF with magneto-optical photonic crystals. The filter is immune to waveguide defects, allowing straightforward implementation of multi-channel ADFs by cascading the four-port designs. The results should find applications in wavelength-division multiplexing and related integrated photonic techniques. [ABSTRACT FROM AUTHOR]

Plasmonic nanocubes are ideal candidates in realizing controllable reflectance surfaces, unidirectional nanoantennas and other plasmon-associated applications. In this work, we perform full-wave calculations of the optical forces in three-dimensional gold nanocube dimers. For a fixed center-to-center separation, the rotation of the plasmonic nanocube leads to a slight shift of the plasmonic resonance wavelength and a strong change in the optical binding forces. The effective gap and the near field distribution between the two nanocubes are shown to be crucial to this force variation. We further find that the optical binding force is dominated by the scattering process while the optical forces in the wavevector direction are affected by both scattering and absorption, making the former relatively more sensitive to the rotation of (an effective gap between) the nanocubes. Our results would be useful for building all-optically controllable meta-surfaces. [ABSTRACT FROM AUTHOR]

In the quantum metrology, applications of quantum techniques based on entanglement bring in some better performances than conventional approaches. We experimentally investigate an application of entanglement in accurate ranging based on the second-order coherence in the time domain. By a fitting algorithm in the data processing, the optimization results show a precision of ±200 μm at a distance of 1043.3m. In addition, the influence of jamming noise on the ranging scheme is studied. With some different fitting parameters, the result shows that the proposed scheme has a powerful anti-jamming capability for white noise. [ABSTRACT FROM AUTHOR]

This study was designed to test a hypothesis that the functional activity of big-conductance, Ca2+-activated K+ (BK) channels is different in cerebral and pulmonary artery smooth muscle cells (CASMCs and PASMCs). Using patch-clamp recordings, we found that the activity of whole cell and single BK channels were significantly higher in CASMCs than in PASMCs. The voltage and Ca2+ sensitivity of BK channels were greater in CASMCs than in PASMCs. Targeted gene knockout of β1-subunits significantly reduced BK currents in CASMCs but had no effect in PASMCs. Western blotting experiments revealed that BK channel α-subunit protein expression level was comparable in CASMCs and PASMCs; however, β1-subunit protein expression level was higher in CASMCs than in PASMCs. Inhibition of BK channels by the specific blocker iberiotoxin enhanced norepinephrine- induced increase in intracellular calcium concentration in CASMCs but not in PASMCs. Systemic artery blood pressure was elevated in β1-/- mice. In contrast, pulmonary artery blood pressure was normal in β1-/- mice. These findings provide the first evidence that the activity of BK channels is higher in cerebral than in PASMCs. This heterogeneity is primarily determined by the differential β1- subunit function and contributes to diverse cellular responses in these two distinct types of cells. [ABSTRACT FROM AUTHOR]

Oxidative stress has recently been considered as a pivotal player in the pathogenesis of diabetic gastrointestinal dysfunction. We therefore investigated the role of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) that has a strong anti-oxidant property, in diabetic gastrointestinal dysmotility as well as the underlying protective mechanisms. THSG restored the delayed gastric emptying and the increased intestinal transit in streptozotocin (STZ)-induced diabetic mice. Loss of neuronal nitric oxide synthase (nNOS) expression and impaired nonadrenergic, noncholinergic (NANC) relaxations in diabetic mice were relieved by long-term preventive treatment with THSG. Meanwhile, THSG (10-7,10-4 mol/L) enhanced concentration-dependently NANC relaxations of isolated colons in diabetic mice. Diabetic mice displayed a significant increase in Malondialdehyde (MDA) level and decrease in the activity of glutathione peroxidase (GSH-Px), which were ameliorated by THSG. Inhibition of caspase-3 and activation of ERK phosphorylation related MAPK pathway were involved in prevention of enhanced apoptosis in diabetes afforded by THSG. Moreover, THSG prevented the significant decrease in PPAR-γ and SIRT1 expression in diabetic ileum. Our study indicates that THSG improves diabetic gastrointestinal disorders through activation of MAPK pathway and upregulation of PPAR-γ and SIRT1. [ABSTRACT FROM AUTHOR]

Binding details of roscovitine, ATP and HHASPRK peptide in complex with both unphosphorylated and phosphorylated cyclin-dependent kinase 5 (CDK5) from molecular dynamics simulations using a crystal structure of CDK2/cyclinA/ATP/HHASPRK and three CDK5/p25/roscovitine systems as references are presented. The influence of phosphorylation on well-conserved amino acids (Thr14 and Tyr15) on the conformation of the inhibition loop (G-loop) is investigated. The simulations suggest that the long ATP phosphate group affects the conformation of the loop differently in different complexes. Binding patterns of ATP in CDK5 are then studied and compared with those in CDK2. The residues on the G-loop affect the conformation of the ATP phosphate group and thus influence the hydrogen bonding network around the ligand. In addition, bindings of the peptide in CDK5 are investigated and compared with that in the crystal structure. Also, the possible conformation of the terminal lysine side chain of the peptide is analysed and suggested. [ABSTRACT FROM PUBLISHER]

The polyphenolic compound 2,3,5,4′-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) has been shown to possess anti-inflammatory effects. Here, we examined the effects of THSG on experimental mice with colitis induced by acetic acid and whether the underlying mechanisms were associated with the PPAR-γ and NF-κB pathways. Mice were randomized into six equal groups: normal, colitis model, THSG (10, 30, 60 mg·kg−1) and mesalazine. The mice were administered 10, 30, 60 mg·kg-1 THSG or 100 mg·kg-1 mesalazine or saline once daily by intragastric administration for 7 days after induction of colitis by acetic acid irrigation. THSG dramatically attenuated acetic acid-induced colon lesions, including reversing the body weight loss and improving histopathological changes. THSG apparently decreased the increase of malondialdehyde (MDA) which is a marker of lipid peroxidation. THSG appears to exert its beneficial effects on acetic acid-induced experimental colitis through upregulation of PPAR-γ mRNA and protein levels and inhibition of the NF-κB pathway, which in turn decreases the protein overexpression of the downstream inflammatory mediators TNF-α, IL-6 and COX-2. The effect of THSG 60 mg·kg-1 on PPAR-γ mRNA expression was higher than that of mesalazine. THSG may thus be a promising new candidate or lead compound for the treatment of IBD. [ABSTRACT FROM AUTHOR]

Isoflavones are among the major bioactive compounds found in a wide variety of plant-derived foods, especially in soybeans and soy-based foods. In this study, the effect of a soy-derived isoflavone mixture (designated as SI-I, containing 71% daidzein, 14.3% genistein and 14.7% glycitein) on HeLa cells and its mechanism were investigated. SI-I in concentration range 5-80 μg/ml significantly reduced the survival rate of HeLa cells by MTT assay, whereas showed no side effect on that of L929 cells. After HeLa cells were exposed to 10, 20 and 40 μg/ml SI-I for 4 days, typical apoptotic morphological changes, including nuclear fragmentation, cytoplasm shrinkage and decrease of cell volume, were observed by fluorescence microscope and CLSM, respectively. FCM analysis revealed that the percentages of early apoptotic cells with lost Δψm increased by 2.27, 2.74 and 4.05 folds respectively, compared with control. The results showed that SI-I inhibited HeLa cell growth through inducing apoptosis via the mitochondrial pathway and comparisons with reported data indicated that synergistic effect existed between the isoflavone species contained in SI-I. It is proposed that natural soy-derived isoflavones are potential candidates as chemoterapeutic agents against human cervical cancer. [ABSTRACT FROM AUTHOR]

The Godson project with an R&D history of 10 years is an independent national program of China that aims at developing advanced microprocessor technologies based on fundamental research and commercialization of the chip technology. We will give a comprehensive presentation of the Godson project, including its history, technical roadmaps, and several unique technical merits. [ABSTRACT FROM AUTHOR]

The application of konjac glucomannan (KGM) in flavor encapsulation in the spray-dry method was investigated in this paper using sweet orange oil as the model. KGM provided the highest encapsulation yield when the apparent viscosity of the KGM solution was reduced to 200 mPa S by cellulase hydrolysis. In the presence of emulsifier Tween 80, the hydrolyzed KGM offered comparable encapsulation yield with Arabic gum and starch sodium octenyl succinate (SSOS), but provided significantly higher encapsulation yield than maltodextrin. Besides, the combination of KGM with Arabic gum, SSOS, and maltodextrin, were also studied. The combination could significantly ( P < 0.05) increase the encapsulation yield in the KGM content up to 80% compared with pure KGM; when the KGM content was reduced to 20%, the combination with maltodextrin resulted in a significant ( P < 0.05) decrease in encapsulation yield, possibly due to the poor emulsifying capability of both KGM and maltodextrin. The effect of encapsulation on flavor composition was investigated by using the fingerprint technique and the vectorial angle method was adopted to assess the similarity between the chromatographs. The comparison showed that KGM had similar flavor retention with SSOS and Arabic gum, but provided a significant ( P < 0.05) higher retention than maltodextrin. The encapsulated flavors exhibited few pores and smooth surface under TEM with the size ranging from 5 to 15 μm. It was concluded that KGM provided comparable flavor retention capability as the most widely used Arabic gum and SSOS and had great potential as a flavor encapsulant. [ABSTRACT FROM AUTHOR]

To investigate the effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside (THSG), a compound extracted from the root of Polygonum multiflorum Thunb, on lipoprotein (LDL and VLDL) oxidation, proliferation and nitric oxide (NO) content of coronary arterial smooth cells (CASMCs) induced by LDL, VLDL, ox-LDL and ox-VLDL. The oxidation level of lipoprotein was determined by thiobabituric acid (TBA) method and agarose gel electrophoresis. The proliferative degree was determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) method. The NO content was assayed by nitrate reductase method. (1)THSG (0.1 ∼ 100 μmol·L- 1) could dose-dependently prevent lipoprotein from oxidation induced by Cu2+ and CASMCs. (2)THSG (0.1 ∼ 100 μmol·L- 1) inhibited porcine CASMCs proliferation elicited by LDL, VLDL, ox-LDL and ox-VLDL. (3)THSG (0.1 ∼ 100 μmol·L- 1) counterpoised the decrease of NO content in CASMCs evoked by LDL, VLDL, ox-LDL and ox-VLDL. As compared with control, it was found that the threshold concentration of THSG, which significantly exerted the actions mentioned above, were at the concentration of 1μmol·L- 1 (P < 0.01). In conclusion, THSG possesses the antagonistic effects on oxidation of lipoprotein, proliferation and decrease of NO content of CASMCs, which partially explain the mechanism of anti-atherosclerosis of Polygonum multiflorum Thunb. [ABSTRACT FROM AUTHOR]

Abstract  It can be observed from looking backward that processor architecture is improved through spirally shifting from simple to complex and from complex to simple. Nowadays we are facing another shifting from complex to simple, and new innovative architecture will emerge to utilize the continuously increasing transistor budgets. The growing importance of wire delays, changing workloads, power consumption, and design/verification complexity will drive the forthcoming era of Chip Multiprocessors (CMPs). Furthermore, typical CMP projects both from industries and from academics are investigated. Through going into depths for some primary theoretical and implementation problems of CMPs, the great challenges and opportunities to future CMPs are presented and discussed. Finally, the Godson series microprocessors designed in China are introduced. [ABSTRACT FROM AUTHOR]

Abstract The role of homocysteine for store-operated calcium influx was investigated in human umbilical cord endothelial cell line. Homocysteine significantly decreased thapsigargin-evoked Ca 2+ entry, membrane hyperpolarization and actin polymerization. GSH and DTT prevented homocysteine-induced inhibition of thapsigargin-evoked Ca 2+ entry, membrane hyperpolarization and actin polymerization; while GSSG had the opposite effect. Homocysteine blocked large conductance Ca 2+ -activated K + (BK C a ) channels in a concentration-dependent manner and related to the redox status of the endothelial cells. BK C a channels opener NS1619 reversed thapsigargin-evoked Ca 2+ entry, membrane hyperpolarization and actin polymerization; BK C a channels inhibitor iberiotoxin had the opposite effect. The findings suggest that homocysteine is involved in store-regulated Ca 2+ entry through membrane potential-dependent and actin cytoskeleton-dependent mechanisms, redox status of homocysteine and BK C a channels may play a regulatory role in it. (Mol Cell Biochem 269 : 37–47, 2005) [ABSTRACT FROM AUTHOR]

A novel compound, biotinylated 18 β-glycyrrhetinic acid (BGA), was synthesized. It is a compound of 18 β-glycyrrhetinic acid linked with biotin. [ABSTRACT FROM AUTHOR]

We propose a multiscale spoof–insulator–spoof (SIS) waveguide by introducing periodic geometry modulation in the wavelength scale to a SIS waveguide made of a perfect electric conductor. The MSIS consists of multiple SIS subcells. The dispersion relationship of the fundamental guided mode of the spoof surface plasmon polaritons (SSPPs) is studied analytically within the small gap approximation. It is shown that the multiscale SIS possesses microwave band gap (MBG) due to the Bragg scattering. The ‘gap maps’ in the design parameter space are provided. We demonstrate that the geometry of the subcells can efficiently adjust the effective refraction index of the elementary SIS and therefore further control the width and the position of the MBG. The results are in good agreement with numerical calculations by the finite element method (FEM). For finite-sized MSIS of given geometry in the millimeter scale, FEM calculations show that the first-order symmetric SSPP mode has zero transmission in the MBG within frequency range from 4.29 to 5.1 GHz. A cavity mode is observed inside the gap at 4.58 GHz, which comes from a designer ‘point defect’ in the multiscale SIS waveguide. Furthermore, ultrathin MSIS waveguides are shown to have both symmetric and antisymmetric modes with their own MBGs, respectively. The deep-subwavelength confinement and the great degree of control of the propagation of SSPPs in such structures promise potential applications in miniaturized microwave device. [ABSTRACT FROM AUTHOR]