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Defensive behaviors induced by innate fear or Pavlovian fear conditioning are crucial for animals to avoid threats and ensure survival. The zona incerta (ZI) has been demonstrated to play important roles in fear learning and fear memory, as well as modulating auditory-induced innate defensive behavior. However, whether the neuronal subtypes in the ZI and specific circuits can mediate the innate fear response is largely unknown. Here, we found that somatostatin (SST)-positive neurons in the rostral ZI of mice were activated by a visual innate fear stimulus. Optogenetic inhibition of SST-positive neurons in the rostral ZI resulted in reduced flight responses to an overhead looming stimulus. Optogenetic activation of SST-positive neurons in the rostral ZI induced fear-like defensive behavior including increased immobility and bradycardia. In addition, we demonstrated that manipulation of the GABAergic projections from SST-positive neurons in the rostral ZI to the downstream nucleus reuniens (Re) mediated fear-like defensive behavior. Retrograde trans-synaptic tracing also revealed looming stimulus-activated neurons in the superior colliculus (SC) that projected to the Re-projecting SST-positive neurons in the rostral ZI (SC-ZIrSST-Re pathway). Together, our study elucidates the function of SST-positive neurons in the rostral ZI and the SC-ZIrSST-Re tri-synaptic circuit in mediating the innate fear response.

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2(+)) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST(+)), but not protein kinase C-δ-expressing (PKC-δ(+)), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2(+) neurons. The SST(+) neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST(+) GABAergic neurons, but not PKC-δ(+) GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeA(SST)–DpMe(VGLUT2) circuit that regulates licking behavior and promotes water intake. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12264-021-00817-2.

Although it is known that inflammation is involved in Parkinson's disease (PD) pathogenesis and vitamin K2 (VK2) has anti-inflammatory effects, to date few studies have been reported on the relationship between VK2 and PD development. Herein we presented a case-control study involving 93 PD patients and 95 healthy controls. Overall, the serum VK2 level of PD patients (3.49 ± 1.68 ng/ml) was significantly lower than that of healthy controls (5.77 ± 2.71 ng/ml). When the PD patients were stratified by disease progression, we observed that the serum VK2 level of late stage patients was further decreased to 3.15 ± 1.18 ng/ml while the serum VK2 level of early stage patients was 3.92 ± 2.09 ng/ml. Furthermore, the curve analysis showed that the serum VK2 level decreased gradually with the increment of PD Hoehn-Yahr (H-Y) stage. We also confirmed the dysregulated inflammatory responses and coagulation cascades in PD patients by public dataset, which are associated to the decreased VK2 level. In summary, we found the serum VK2 level in PD patients is lower than that in healthy controls. The decrease of VK2 level may be related to the occurrence and progression of PD by loosening the regulation of inflammatory responses and coagulation cascades signal.

Corylin is a naturally occurring flavonoid isolated from the fruit of Psoralea corylifolia L. (Fabaceae), which is a Chinese medicinal herb in treating osteoporosis. Although a variety of pharmacological activities of corylin have been reported, its osteogenic action and the underlying mechanism in bone development remain unclear. In the present study, the involvement of bone-specific genes in corylininduced differentiated osteoblasts was analyzed by RT-PCR, promoter-reporter assay, and Western blotting. In cultured osteoblasts, corylin-induced cell differentiation and mineralization, as well as increased the expressions of vital biological markers for osteogenesis, such as Runx2, Osterix, Col1, and ALP. Corylin was proposed to have dual pathways in triggering the osteoblastic differentiation. First, the osteogenic function of corylin acted through the activation of Wnt/β-catenin signaling. The nuclear translocation of β-catenin of cultured osteoblasts, as determined by flow cytometry and confocal microscopy, was triggered by applied corylin, and which was blocked by DKK-1, an inhibitor of Wnt/β-catenin signaling. Second, the application of corylin-induced estrogenic response in a dose-dependent manner, and which was blocked by ICI 182 780, an antagonist of estrogen receptor. Furthermore, the activation of Runx2 promoter by corylin was abolished by both DKK-1 and ICI 182,780, indicating that the corylin exhibited its osteogenic effect via estrogen and Wnt/β-catenin signaling pathways. In addition, corylin regulated the metabolic profiles, as well as the membrane potential of mitochondria, in cultured osteoblasts. Corylin also stimulated the osteogenesis in bone micromass derived from mesenchymal progenitor cells. This study demonstrated the osteogenic activities of corylin in osteoblasts and micromass, suggesting that corylin has the potential to be developed as a novel pro-osteogenic agent in targeting for the treatment of osteoblast-mediated osteoporosis.

Lactobacillus plantarum FZU3013, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorders of lipid metabolism. This study aimed to investigate the role of L. plantarum FZU3013 in improving non-alcoholic fatty liver (NAFL) associated with hyperlipidemia in mice fed a high-fat diet. The results indicated that L. plantarum FZU3013 intervention significantly reduced the HFD-induced body weight gain and the abnormal levels of serum total triglycerides (TG), total cholesterol (TC) and low-density lipoprotein (LDL-C), and inhibited the excessive accumulation of liver lipids. In addition, L. plantarum FZU3013 also promoted the excretion of bile acids through feces. Metagenomic and multivariate statistical analysis revealed that L. plantarum FZU3013 made significant structural changes in the intestinal microbiome of the mice fed with HFD, in particular by modulating the relative abundance of some function related microbial phylotypes. Furthermore, ultra-performance liquid chromatography with quadruple-time of flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. plantarum FZU3013 had a significant regulatory effect on the composition of liver metabolites in hyperlipidemic mice, especially on the levels of some important biomarkers involved in the pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Moreover, L. plantarum FZU3013 regulated the mRNA expression levels of the genes responsible for liver lipid and cholesterol metabolism. L. plantarum FZU3013 intervention increased the hepatic mRNA levels of cholesterol 7α-hydroxylase (CYP7A1) and the bile salt export pump (BSEP), suggesting enhanced bile acid synthesis and excretion from the liver. These findings present new evidence supporting that L. plantarum FZU3013 has the potential to improve lipid metabolism disorders through modulating specific intestinal microbial phylotypes and regulating hepatic lipid metabolism related genes, therefore it could be used as a potential functional food for the prevention of NAFL and hyperlipidemia.

Coprinus comatus, widely known as “Jituigu”, is an important commodity and food in China. The yield of C. comatus, however, is substantially reduced by the autolysis of the fruiting bodies after harvest. To gain insight into the molecular mechanism underlying this autolysis, we divided the growth of C. comatus fruiting bodies into four stages: infant stage (I), mature stage (M), discolored stage (D), and autolysis stage (A). We then subjected these stages to de novo transcriptomic analysis using high-throughput Illumina sequencing. A total of 12,946 unigenes were annotated and analyzed with the Gene Ontology (GO), Clusters of Orthologous Groups of proteins (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG). We analyzed the differentially expressed genes (DEGs) between stages I and M, M and D, and D and A. Because the changes from M to D are thought to be related to autolysis, we focused on the DEGs between these two stages. We found that the pathways related to metabolic activity began to decline in the transition from M to D. In contrast, expression levels of chitinases, β-1,3-glucanases, and the ubiquitin-conjugating enzyme E2 related to degradation of cell walls were higher in D than in M. In addition, 20 genes of interest were analyzed by quantitative real-time PCR to verify their expression profiles at the four developmental stages. This study, which is the first to describe the transcriptome of C. comatus, provides a foundation for future studies concerning the molecular basis of the autolysis of its fruiting bodies.

Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Here, in mice, we identified that BLA cholecystokinin (CCK) glutamatergic neurons mediated negative reinforcement via D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and that chronic social defeat selectively potentiated excitatory transmission of the CCKBLA-D2NAc circuit in susceptible mice via reduction of presynaptic cannabinoid type-1 receptor (CB1R). Knockdown of CB1R in the CCKBLA-D2NAc circuit elevated synaptic activity and promoted stress susceptibility. Notably, selective inhibition of the CCKBLA-D2NAc circuit or administration of synthetic cannabinoids in the NAc was sufficient to produce antidepressant-like effects. Overall, our studies reveal the circuit and molecular mechanisms of depression.

Anxiety-like behaviors in mice include social avoidance and avoidance of bright spaces. Whether these features are distinctly regulated is unclear. We demonstrate that in mice, social and anxiogenic stimuli, respectively, increase and decrease serotonin (5-HT) levels in basal amygdala (BA). In dorsal raphe nucleus (DRN), 5-HT∩vGluT3 neurons projecting to BA parvalbumin (DRN

Background Recent studies in cancer biology suggest that metabolic glucose reprogramming is a potential target for cancer treatment. However, little is known about drug intervention in the glucose metabolism of cancer stem cells (CSCs) and its related underlying mechanisms. Methods The crude realgar powder was Nano-grinded to meets the requirements of Nano-pharmaceutical preparations, and Nano-realgar solution (NRS) was prepared for subsequent experiments. Isolation and characterization of lung cancer stem cells (LCSCs) was performed by magnetic cell sorting (MACS) and immunocytochemistry, respectively. Cell viability and intracellular glucose concentration were detected by MTT assay and glucose oxidase (GOD) kit. Protein expressions related to metabolic reprogramming was detected by ELISA assay. Determination of the expression of HIF-1α and PI3K/Akt/mTOR pathways was carried out by RT-PCR and western blotting analysis. A subcutaneous tumor model in BALB/c-nu mice was successfully established to evaluate the effects of Nano-realgar on tumor growth and histological structure, and the expression of HIF-1α in tumor tissues was measured by immunofluorescence. Results Nano-realgar inhibits cell viability and induces glucose metabolism in LCSCs, and inhibits protein expression related to metabolic reprogramming in a time- and dose-dependent manner. Nano-realgar downregulated the expression of HIF-1α and PI3K/Akt/mTOR pathways in vitro and in vivo. Nano-realgar inhibits tumor growth and changes the histological structure of tumors through in vivo experiments and consequently inhibits the constitutive activation of HIF-1α signaling. Conclusions These results reveal that Nano-realgar inhibits tumor growth in vitro and in vivo by repressing metabolic reprogramming. This inhibitory effect potentially related to the downregulation HIF-1α expression via PI3K/Akt/mTOR pathway.

Methyl-CpG-binding protein 2 (MeCP2) encoded by the MECP2 gene is a transcriptional regulator whose mutations cause Rett syndrome (RTT). Mecp2-deficient mice show fear regulation impairment; however, the cellular and molecular mechanisms underlying this abnormal behavior are largely uncharacterized. Here, we showed that Mecp2 gene deficiency in cholinergic interneurons of the nucleus accumbens (NAc) dramatically impaired fear learning. We further found that spontaneous activity of cholinergic interneurons in Mecp2-deficient mice decreased, mediated by enhanced inhibitory transmission via α2-containing GABAA receptors. With MeCP2 restoration, opto- and chemo-genetic activation, and RNA interference in ChAT-expressing interneurons of the NAc, impaired fear retrieval was rescued. Taken together, these results reveal a previously unknown role of MeCP2 in NAc cholinergic interneurons in fear regulation, suggesting that modulation of neurons in the NAc may ameliorate fear-related disorders.

Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.

The amygdala, which is involved in various behaviors and emotions, is reported to connect with the whole brain. However, the long-range inputs of distinct cell types have not yet been defined. Here, we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse amygdala. We identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2, 78 regions to parvalbumin-expressing neurons, 104 regions to neurons expressing protein kinase C-δ, and 89 regions to somatostatin-expressing neurons. The amygdala received massive projections from the isocortex and striatum. Several nuclei, such as the caudate-putamen and the CA1 field of the hippocampus, exhibited input preferences to different cell types in the amygdala. Notably, we identified several novel input areas, including the substantia innominata and zona incerta. These findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala. Electronic supplementary material The online version of this article (10.1007/s12264-020-00545-z) contains supplementary material, which is available to authorized users.

Three new species, Calocybe aurantiaca, C. convexa, and C. decolorata, are described based on collections made in Shenyang City, Liaoning Province, China. The main characters of C. aurantiaca are its orange-yellow sporocarps and small and smooth basidiospores. Calocybe convexa is characterized by its orange-buff pileus, very small basidiospores, and tortuous stipe, whereas C. decolorata is mainly characterized by its gills that turn blue when bruised. The sequences of nuc rDNA ITS1-5.8S-ITS2 (ITS) and the 28S D1-D5 region of the Calocybe species were analyzed, and the results indicated that the three new species belonged to the genus Calocybe and differed from other species of Calocybe. The morphological similarities of the new species to other Calocybe species and the classification system within the genus Calocybe based on molecular data are also discussed. A key is provided for the Calocybe species as reported from China in order to facilitate future studies of the genus.

Major depressive disorder is a devastating psychiatric disease that afflicts up to 17% of the world's population. Postmortem brain analyses and imaging studies of patients with depression have implicated basal lateral amygdala (BLA) dysfunction in the pathophysiology of depression. However, the circuit and molecular mechanisms through which BLA neurons modulate depressive behavior are largely uncharacterized. Here, in mice, we identified that BLA cholecystokinin (CCK) glutamatergic neurons mediated negative reinforcement via D2 medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and that chronic social defeat selectively potentiated excitatory transmission of the CCK

Lepista nuda is a popular wild edible mushroom that grows in China. In this study, we used ISSR and SRAP molecular markers to analyze the genetic diversity of 72 samples of L. nuda from eight populations in Northeast China. In total, six ISSR primers and five pairs of SRAP primers that produced clear and polymorphic banding profiles were selected for assessing L. nuda genetic diversity. The results revealed a high level of genetic variation among the 72 samples (94.4% polymorphism) but a low degree of gene flow among the populations. Among L. nuda populations, genetic distance was not correlated significantly with geographic distance. The antioxidant activity of the samples from each population was also tested and the result showed that all the selected samples had more than 60% DPPH scavenging activities. Nonetheless, the antioxidant activity diversity is not coincident with both the genetic diversity and the geographic distribution. The results indicate that ISSR and SRAP molecular markers are useful for studying the genetic diversity of L. nuda. The results also suggest that L. nuda populations in Northeast China require protection.

The authors describe ten new taxa for science using mostly both morphological and molecular data. In Ascomycota, descriptions are provided for Bambusistroma didymosporum gen. et spec. nov. (Pleosporales), Neodeightonia licuriensis sp. nov. (Botryosphaeriales) and Camposporium himalayanum sp. nov. (Fungi imperfecti). In Zygomycota, Gongronella guangdongensis sp. nov. (Mucorales) is described. Finally, in Basidiomycota descriptions are provided for Boidinia parva sp. nov. and Russula katarinae sp. nov. (Russsulales), Gloiocephala parvinelumbonifolia sp. nov. (Agaricales), Hypochnicium austrosinensis sp. nov. (Polyporales), Phallus ultraduplicatus sp. nov. (Phallales) and Suillus lariciphilus sp. nov. (Boletales).

Pogostemonis Herba is an important Chinese medicine widely used in the treatment of gastrointestinal dysfunction. Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major active constituent of Pogostemonis Herba. This study aimed to investigate the possible anti-ulcerogenic potential of PA and the underlying mechanism against ethanol, indomethacin and water immersion restraint-induced gastric ulcers in rats. Gross and histological gastric lesions, biochemical and immunological parameters were taken into consideration. The gastric mucus content and the antisecretory activity were analyzed through pylorus ligature model in rats. Results indicated that oral administration with PA significantly reduced the ulcer areas induced by ethanol, indomethacin and water immersion restraint. PA pretreatment significantly promoted gastric prostaglandin E2 (PGE2) and non-protein sulfhydryl group (NP-SH) levels, upregulated the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) mRNA expression, and considerably boosted the gastric blood flow (GBF) and gastric mucus production in comparison with vehicle. In addition, PA modulated the levels of interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). The levels of glutathione (GSH), catalase (CAT) and malonaldehyde (MDA) were also restored by PA. However, the gastric secretion parameters (pH, volume of gastric juice and pepsin) did not show any significant alteration. These findings suggest that PA exhibited significant gastroprotective effects against gastric ulceration. The underlying mechanisms might involve the stimulation of COX-mediated PGE2, improvement of antioxidant and anti-inflammatory status, preservation of GBF and NP-SH, as well as boost of gastric mucus production.

The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H. pylori and jack bean in concentration-dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver-Burk plots indicated that the type of inhibition was non-competitive against H. pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA-inactivated urease assay showed DL-dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H. pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H. pylori infection. Copyright © 2014 John Wiley & Sons, Ltd.

To improve the design and performance of anoxic phosphorus uptake process, the biomass fractions of PAOs grown in anoxic environment and denitrification rate, with PHAs as carbon source, was investigated in a pilot scale study of EBPR system which was based on stoichiometry and mass balance. The system, containing Modified University of Cape Town (MUCT) reactor, was maintained at steady state with COD loading of 0.25 kg COD/(kg MLVSS d), and solid retention time (SRT) of 12 d. Based on mass balance calculation, 46.74% of organic matter, 50.95% of nitrogen, and 42.03% of phosphorus in the influent were converted to carbon dioxide, nitrogen gas, and poly-phosphate, respectively. In the second anoxic stage, the biomass yield of PAOs with nitrate as electron acceptor was 4.90 gC5H7O2N/d, and its yield fraction was 20.63%. For the reaction to proceed properly, 10.48 g PHA/d of PHAs was oxidized, and 3.68 g -N/d of nitrate was reduced. The denitrification rate with PHAs as carbon source was 0.058 kg -N/...

Applying ecological footprint model to calculate the ecological footprint and ecological carrying capacity of Dongying ,a typical oil city between the year 2005-2009,the results showed that ecological footprint was deficit in recent years, and the trend had been exacerbated. The economic development of Dongying was in an ecologically unsustainable condition. Measures are put forward to facilitate the sustainable development in two aspects: the reduction of the ecological footprint demand such as industrial structure adjustment, low carbon industry system construction and green life pattern formation; the increase of ecological carrying capacity supply, such as rationally utilizing land and making full use of marine resources.

In the version of this article originally published, there were several errors in Fig. 4. In Fig. 4a, the title read ‘3D repeated optical inhibition after CSDS.’ It should have read ‘3-day repeated optical inhibition after CSDS.’ In Fig. 4c, two labels that should have been aligned with the time axis appeared in the wrong place in the figure. The ticks labeled ‘SI’ and ‘Fiber implant’ should have also been labeled with ‘10’ and ‘14,’ respectively. Additionally, in Fig. 4j, a label that should have been aligned with the time axis appeared in the wrong place in the figure. The tick labeled ‘Fiber implant’ should have also been labeled with ‘14.’ The errors have been corrected in the print, PDF and HTML versions of the manuscript.

In the present study, the inactivation effect of scutellarin (SL) on jack bean urease was investigated to elucidate the inhibitory potency, kinetics and mechanism of inhibition. It was revealed that SL acted as a concentration- and time-dependent inactivator of urease characteristic of slow-binding inhibition with an IC50 of 1.35±0.15 mM. The rapid formation of the initial SL-urease complex with an inhibition constant of Ki=5.37×10(-2) mM was followed by a slow isomerization into the final complex with the overall inhibition constant of Ki*=3.49×10(-3) mM. High effectiveness of thiol protectors, such as L-cysteine (L-cys), 2-mercaptoethanol (2-ME) and dithiothreitol (DTT) significantly slowed down the rate of inactivation, indicating the strategic role of the active site sulfhydryl group in the blocking process. While the insignificant protection by boric acid and fluoride from the inactivation further confirmed that the active site cysteine should be obligatory for urease inhibition, which was also rationalized by the molecular docking study. The inhibition of SL on urease proved to be reversible since SL-blocked urease could be reactivated by DTT application and multidilution. The results obtained indicated that urease inactivation resulted from the reaction between SL and the sulfhydryl group.

We propose an iterative detection scheme for Turbo-BLAST system with optimal power allocation in the presence of channel state information imperfection. The proposed scheme uses the channel estimation matrix for detection and treats the interference caused by channel estimation errors and additive white Gaussian noise as equivalent noise where the channel estimation matrix and the statistical characteristic of channel estimation errors are necessitated. Simulation results show the proposed algorithm is effective to improve bit error rate (BER) performance through iterative detection for modified Turbo-BLAST system with optimal power allocation in the presence of imperfect channel state information.

The uplink performance of multi-user space–time-coded code-division multiple access (STC-CDMA) system in Rician fading channel is presented. A simple and effective multi-user receiver scheme is developed for STC-CDMA system. The scheme has linear decoding complexity when compared to the existing scheme with exponential decoding complexity, and thus implements low-complexity decoding. Based on the bit error rate (BER) analysis and moment generation function, theoretical BER expressions are derived for STC-CDMA with orthogonal and quasi-orthogonal spreading code, respectively. It is shown that these expressions have more accuracy. Using these expressions and the approximation of error function, closed-form approximate BER expressions are obtained, which can simplify the calculation of the derived theoretical BER. Simulation results show that the developed low-complexity decoding scheme can achieve almost the same performance as the existing scheme. The theoretical BER are in good agreement with the corresponding simulated values. Moreover, the presented approximate expressions are also close to the simulated values due to the better approximation. Under the same system throughput and concatenation of channel code, the presented full-rate STC-CDMA system has lower BER than the corresponding full-diversity STC-CDMA systems.

Lespedeza bicolor has developed root system and the ability of carbon sequestration, which can effectively improve the soil nutrient. We measured the correlation of net photosynthetic rate and physiological and environmental factors using space mutated Lespedeza bicolor of SP1 generation, the change of soil carbon and nitrogen content and microbial biomass was also discussed. The conclusion showed that the diurnal variation of photosynthesis was registered as double－peak curve and had "noon break" phenomenon. It showed strong ability of photosynthesis and its mean diurnal photosynthetic rates was 8.77 umolCO2·m-2s-1. Highly correlation was existed between net photosynthetic rate and atmospheric CO2 concentration ,the content of soil organic carbon and total nitrogen and soil microbial biomass displayed negatively relationship to the depth of the soil. Base on the study , we can conclude that the photosynthetic organic matter was effectively accumulated by Lespedeza bicolor of SP1 generation which made use of atmospheric CO2 and the root system located in the superficial soil has better potential of carbon sequestration.

Estrogen receptor alpha (ERalpha) plays an important role in the development and progression of breast cancer, and recent studies showed that ERalpha expression is associated with resistance to hormonal therapy. Therefore, a number of studies have explored ways to deplete ERalpha from breast cancer cells as a new therapy especially for hormone-refractory breast cancer. We reported here that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, effectively depletes ERalpha in breast cancer MCF-7 cells. However, the intrinsic mechanisms by which SAHA decreases ERalpha levels are not clear. Our present data demonstrated that both inhibition of ERalpha mRNA level and promotion of ERalpha degradation by the proteasome contribute to SAHA-induced ERalpha depletion, indicating that SAHA may exert its effects through transcriptional and posttranslational mechanisms. Furthermore, the decrease of ERalpha protein level in MCF-7 cells after SAHA treatment is mainly the result of its rapid degradation by the ubiquitin-proteasome pathway rather than transcriptional inhibition. In addition, we showed that inactivation of the heat shock protein-90 (Hsp90) is involved in SAHA-induced ERalpha degradation, and ubiquitin ligase CHIP (C-terminal Hsc70 interacting protein) enhances SAHA-induced ERalpha degradation. SAHA-induced ERalpha depletion is paralleled with reduction of transcriptional activity of ERalpha and SAHA is able to effectively inhibit cell proliferation and induce apoptosis of MCF-7 cells. Taken together, our results revealed a mechanism for SAHA-induced ERalpha degradation and indicated that SAHA is a suitable pharmacological agent for depletion of ERalpha and a potential choice for breast cancer expressing high ERalpha.

As a transcription factor family dependent of oxygen, hypoxia-inducible factors (HIFs) play important roles in organic and cellular homeostasis, which are master regulators of tumorigenesis, angiogenesis and embryogenesis. Up to date, some known posttranslational modifications, such as hydroxylation, acetylation, phosphorylation and S-nitrosylation, have been proved to influence protein stability and transcriptional activity of HIFs. On the other hand, HIFs can be physiologically degraded through ubiquitin-dependent or -independent proteasome pathway. Two biochemical processes involve in many modulators, which are correlated and compose an intricate mechanism to control the biological function of HIFs systemically. Herein, we review and discuss the diverse roles of involved modulators in both HIFs stability and degradation, describe the potential link between the two molecular scenarios.

This review provides a brief overview of the basic principles of epigenetic gene regulation and then focuses on recent development of epigenetic drugs for cancer treatment and prevention with an emphasis on the molecular mechanisms of action. The approved epigenetic drugs are either inhibitors of DNA methyltransferases or histone deacetylases (HDACs). Future epigenetic drugs could include inhibitors for histone methyltransferases and histone demethylases and other epigenetic enzymes. Epigenetic drugs often function in two separate yet interrelated ways. First, as epigenetic drugs per se, they modulate the epigenomes of premalignant and malignant cells to reverse deregulated epigenetic mechanisms, leading to an effective therapeutic strategy (epigenetic therapy). Second, HDACs and other epigenetic enzymes also target non-histone proteins that have regulatory roles in cell proliferation, migration and cell death. Through these processes, these drugs induce cancer cell growth arrest, cell differentiation, inhibition of tumor angiogenesis, or cell death via apoptosis, necrosis, autophagy or mitotic catastrophe (chemotherapy). As they modulate genes which lead to enhanced chemosensitivity, immunogenicity or dampened innate antiviral response of cancer cells, epigenetic drugs often show better efficacy when combined with chemotherapy, immunotherapy or oncolytic virotherapy. In chemoprevention, dietary phytochemicals such as epigallocatechin-3-gallate and sulforaphane act as epigenetic agents and show efficacy by targeting both cancer cells and the tumor microenvironment. Further understanding of how epigenetic mechanisms function in carcinogenesis and cancer progression as well as in normal physiology will enable us to establish a new paradigm for intelligent drug design in the treatment and prevention of cancer.

Objective The effect of nucleoside analogue,2-chlorodeoxyadenosine(2-CDA) on human malignant melanoma has not been fully studied heretofore.The aim of present study was to investigate the mechanisms of apoptosis of human melanoma A375 cells induced by 2-chlorodeoxyadenosine(2-CDA).Methods A375 cells were treated with different doses(0,0.5,1,2,5μmol/L) of 2-CDA for different duration.The inhibitory effect on cell proliferation was measured by MTT assay.The cell apoptosis was detected by flow cytometry after annexin V-FITC/PI double staining.The expressions of p-Stat3,t-Stat3,Caspase-3,PARP and β-actin proteins were determined by Western blot.Results 2-CDA inhibited the proliferation of A375 cells in a time-and dose-dependent manner.After treatment for 48h,the IC50 of 2-CDA was 3.04μmol/L.Results of annexin V-FITC/PI double staining and flow cytometry indicated that 2-CDA effectively induced A375 apoptosis in a dose-dependent manner.The apoptotic rate of A375 cells was increased from 1.01% to 32.0% after treatment with 5μmol/L 2-CDA for 48h.The results of Western blotting showed that 2-CDA decreased the phosphorylation level of Stat3 kinase in time-and dose-dependent manner.When the cells treated with 5μmol/L 2-CDA for 36h,there was a prominent inhibitory effect on Stat3 kinase,indicated by a sharp decline of its phosphorylation level.At the same time,both the Caspase-3 and its client PARP,a hallmark of apoptosis,were all cleaved,implying that the cell apoptosis was induced in a caspase-dependent pathway.Conclusion 2-CDA may inhibit proliferation and induce apoptosis in human melanoma A375 cells by blocking the activity of Stat3 kinase and activating the Caspase-3/PARP apoptosis pathway.

The aim of this study is to evaluate the antibacterial activity and urease inhibitory effects of patchouli alcohol (PA), the bioactive ingredient isolated from Pogostemonis Herba, which has been widely used for the treatment of gastrointestinal disorders. The activities of PA against selected bacteria and fungi were determined by agar dilution method. It was demonstrated that PA exhibited selective antibacterial activity against Helicobacter pylori, without influencing the major normal gastrointestinal bacteria. Noticeably, the antibacterial activity of PA was superior to that of amoxicillin, with minimal inhibition concentration value of 78 µg/mL. On the other hand, PA inhibited ureases from H.pylori and jack bean in concentration-dependent fashion with IC50 values of 2.67 ± 0.79 mM and 2.99 ± 0.41 mM, respectively. Lineweaver-Burk plots indicated that the type of inhibition was non-competitive against H.pylori urease whereas uncompetitive against jack bean urease. Reactivation of PA-inactivated urease assay showed DL-dithiothreitol, the thiol reagent, synergistically inactivated urease with PA instead of enzymatic activity recovery. In conclusion, the selective H.pylori antibacterial activity along with urease inhibitory potential of PA could make it a possible drug candidate for the treatment of H.pylori infection.