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A bidirectional relationship between insomnia and depression has been observed. However, few studies have used network analysis to explore the interaction patterns in that association at the symptom level. This study aimed to estimate network structures of insomnia and depressive symptoms among shift workers, as well as to compare the differences in network properties between individuals without and with insomnia symptoms and/or at risk of depression. A total of 1883 shift workers were included in our study. Insomnia symptoms were evaluated by three items based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, and depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale. Network analyses were used for the statistical analysis. "Difficulty initiating sleep", "Hard to get started", and "Depressed mood" with higher expected influence (EI) values were identified as the most central symptoms within the insomnia-depressive networks among shift workers. The significant differences between individuals without and with insomnia symptoms and/or at risk of depression were observed in symptoms of "Difficulty initiating sleep" and "Hard to get started". "Depressed mood", "Difficulty initiating sleep", or "Hard to get started" were the most key symptoms that trigger and sustain the structure of insomnia and depressive symptom among shift workers. Hence, timely intervention for the above three symptoms in future research or clinical practice (e.g., cognitive behavioral therapy for insomnia) may be crucial in alleviating insomnia and depressive symptoms among shift workers.

Purple-fleshed sweetpotato (Ipomoea batatas（L.）Lam.) is rich in anthocyanins. R2R3-type MYB transcription factors（TFs）with EAR motifs inhibiting anthocyanin biosynthesis have been reported, and there is still a lack of information on how mutations in the EAR motifs of MYBs affect anthocyanin accumulation. In this study, we obtained three IbMYB44 TFs by bioinformatics. Among these TFs, IbMYB44.1, IbMYB44.3 with a complete EAR motif and IbMYB44.2 with a single amino acid mutant in the EAR motif caused an amino acid substitution from leucine to valine. RT-qPCR analysis showed that IbMYB44s was expressed at lower levels in the purple-fleshed sweetpotato than in nonpurple-fleshed sweetpotato (P 0.01). Transient expression assays showed that the inhibitory effect of IbMYB44.1/3 was stronger than IbMYB44.2 in tobacco leaves and red-skinned pears. RT-qPCR analysis further proved that IbMYB44.1/3 significantly inhibited the expression of anthocyanin biosynthesis-related genes compared with IbMYB44.2 in tobacco leaves and red-skinned pears. A dual luciferase reporter assay showed that IbMYB44s cannot directly activate the IbANS promoter, and the result was also verified by yeast one-hybrid (Y1H) experiments. Moreover, we identified the interaction of IbMYB340 with IbMYB44.1, IbMYB44.2 and IbMYB44.3 via yeast two-hybrid (Y2H) assays. Thus, IbMYB44.1/3 could interact with IbMYB340 to negatively regulate anthocyanin biosynthesis. This study enriched the regulatory network of anthocyanins and also provided a theoretical basis for a single amino acid mutant from leucine to valine in the EAR motif of IbMYB44.2 affecting anthocyanin biosynthesis in the purple-fleshed sweetpotato.

Through searching the literature on the mechanism of acupuncture for primary dysmenorrhea in the last 15 years, this paper summarizes systematically the current study progress on the analgesic mechanism of acupuncture for primary dysmenorrhea, from the perspectives of animal experiment and human trials. In terms of research methods, the behavioral observation, evaluation of central and peripheral biochemical indexes, and molecular biological techniques were mainly used in the animal experiments; whilst the clinical symptoms and evaluation of peripheral serum biochemical indexes were focused on in human trials. As for the research results, the animal experiments showed that acupuncture may play an analgesic role by regulating endocrine, promoting the release of central and peripheral neurotransmitters, regulating immune function, and relieving uterine smooth muscle spasm. However, the human trials have found that acupuncture can produce analgesic effects by regulating serum prostaglandin and ovarian hormone levels, promoting the release of peripheral β-endorphin, improving the uterine artery flow status, and relieving uterine smooth muscle spasm. Although different research methods were used in animal and human studies, the similar results were obtained in acupuncture regulating endocrine levels, promoting release of peripheral neurotransmitters, and alleviating uterine smooth muscle spasms. In addition, at present stage, animal experiments are more than human trials in numbers, and there are relatively few studies on the central mechanism of acupuncture analgesia in human trials. Therefore, in view of this phenomenon, this paper proposes to use functional magnetic resonance imaging (fMRI) technology to explore the central mechanism of acupuncture analgesia in human body, so as to provide a new idea for further exploring the mechanism of acupuncture analgesia in treating primary dysmenorrhea.

We in this paper study the current-state estimation problem of probabilistic Boolean networks with output observations. First, we propose the concepts of three fundamental categories of detectability in the context of PBNs based on the different purposes, which are periodic detectability, (periodic) k-detectability, and (periodic) d-detectability. Second, utilizing the semi-tensor product technique, we create a uniform methodology for the verification of all the aforementioned categories of detectability. Accordingly, several necessary and sufficient verification criteria are derived. All results obtained in this paper are numerically tractable since they avoid the graph-based symbolic manipulations. Finally, several examples modeled by the same PBN are provided to instantiate the correctness and effeteness of the obtained results.

Background Sleep disturbance can be an important predictor associated with suicide behaviors. However, to date, few studies have examined the prospective relationships between different types of sleep disturbance and suicidal behaviors. The current study examined which sleep disturbance types were independent risk factors for subsequent suicidal behaviors in a large sample of Chinese college students. Methods Data came from a large-scale health-related cohort study in Guangdong, China. Participants were 11,740 college students initially assessed in March and April in 2019 and reassessed six month later. Self-administered structured questionnaires were used to assess suicidal behaviors, insomnia, nightmares, sleep disordered breathing (SDB) symptoms, restless legs syndrome (RLS) symptoms, depression, substance abuse and demographic characteristics. A series of logistic regression analyses were conducted to examine the associations between different types of sleep disturbance and suicidal behaviors. Results Overall, 12.2% and 1.2% of college students reported suicidal ideation and attempts at baseline, and 8.6% and 2.4% reported similar behavior at follow-up. After adjustment for key covariates and prior suicidal behaviors, frequent nightmares (AORs = 1.35–1.69) and RLS symptoms (AOR = 1.37) at baseline predicted subsequent suicidal ideation, and only frequent nightmares (AOR = 2.40) at baseline predicted subsequent suicidal attempts. Limitations All measures were based on self-report instead of objective assessments or clinical diagnostic evaluations. Conclusions Frequent nightmares and RLS symptoms were independently associated subsequent suicidal ideation or attempts. Screening and managing sleep disturbance may be helpful for reducing the risk of suicidal behaviors among college students.

Background : Maternal psychopathology can be an important factor associated with psychological adjustment of children. However, there is limited research on long-term impacts of maternal posttraumatic stress disorder (PTSD) on children's mental health. This study examined how PTSD trajectories of women exposed to the 2008 Wenchuan earthquake in China predicted their children's mental health symptoms 10 years after the earthquake. Methods : 410 dyads of mothers and their adolescent children who exposed to the Wenchuan earthquake were investigated at 12 and 18 months post-earthquake. While the mothers completed measures of earthquake exposure and PTSD symptoms, the children completed measures of earthquake exposure, PTSD, depression and anxiety symptoms. In the 10-year follow up, 257 out of the 410 children completed measures of PTSD, depression and anxiety symptoms. Data were analyzed using linear regression. Results : Four trajectories of maternal PTSD symptoms were identified: (a) chronic (9.5%); (b) resilient (66.3%); (c) delayed (7.6%); and (d) recovery (16.6%); More importantly, the findings demonstrated that children whose mothers experienced chronic PTSD reported higher level of PTSD and anxiety symptoms 10 years after the earthquake. Limitations : Only two waves of maternal PTSD were collected, self-reported tools other than clinical reviews were used to collect data, and a significant proportion of participants did not respond at the 10-year follow-up. Conclusions : This study identified maternal PTSD trajectories following the Wenchuan earthquake. Chronic PTSD symptoms in mothers were associated with increased risk of children's PTSD and anxiety 10 years after the earthquake.

Vascular dysfunction is a common pathological basis for complications in individuals affected by diabetes. Previous studies have established that endothelial dysfunction is the primary contributor to vascular complications in type 2 diabetes (T2DM). However, the role of vascular smooth muscle cells (VSMCs) in vascular complications associated with T2DM is still not completely understood. The aim of this study is to explore the potential mechanisms associated with Ca2+ handling dysfunction and how this dysfunction contributes to diabetic vascular smooth muscle impairment. The results indicated that endothelium-dependent vasodilation was impaired in diabetic aortae, but endothelium-independent vasodilation was not altered. Various vasoconstrictors such as phenylephrine, U46619 and 5-HT could induce vasoconstriction in a concentration-dependent manner, such that the dose-response curve was parallel shifted to the right in diabetic aortae, compared to the control. Vasoconstrictions mediated by L-type calcium (Cav1.2) channels were attenuated in diabetic aortae, but effects mediated by store-operated calcium (SOC) channels were enhanced. Intracellular Ca2+ concentration ([Ca2+]i) in VSMCs was detected by Fluo-4 calcium fluorescent probes, and demonstrated that SOC-mediated Ca2+ entry was increased in diabetic VSMCs. VSMC-specific knockout of STIM1 genes decreased SOC-mediated and phenylephrine-induced vasoconstrictive response in mice aortae. Additionally, Orai1 expression was up-regulated, Cav1.2 expression was downregulated, and the phenotypic transformation of diabetic VSMCs was determined in diabetic aortae. The overexpression of Orai1 markedly promoted the OPN expression of VSMCs, whereas SKF96365 (SOC channel blocker) reversed the phenotypic transformation of diabetic VSMCs. Our results demonstrated that the vasoconstriction response of aortic smooth muscle was weakened in type 2 diabetic rats, which was related to the downregulation of the Cav1.2 channel and the up-regulation of the SOC channel signaling pathway.

Metal-organic frameworks (MOFs) have high surface area, tunable pore size, and high loading capacity, making them promising for drug delivery. However, their synthesis requires organic solvents, high temperature and high pressure that are incompatible with biomacromolecules. Zeolitic imidazole frameworks (ZIF-8) which forms through coordination between zinc ions and 2-methylimidazole (MeIM) have emerged as an advanced functional material for drug delivery due to its unique features such as high loading and pH-sensitive degradation. In this study, we took advantage of a natural biomineralization process to create aluminum-containing nanoZIF-8 particles for antigen delivery. Without organic solvents or stabilizing agent, nanoparticles (ZANPs) were synthesized by a mild and facile method with aluminum, model antigen ovalbumin (OVA) and ZIF-8 integrated. A high antigen loading capacity (%) of 30.6% and a pH dependent antigen release were achieved. A Toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides (CpG) was adsorbed on the surface of ZANPs (hereafter CpG/ZANPs) to boost the immune response. After subcutaneous injection in vivo, CpG/ZANPs targeted lymph nodes (LNs), where their cargo was efficiently internalized by LN-resident antigen-presenting cells (APCs). ZANPs decomposition in lysosomes released antigen into the cytoplasm and enhanced cross-presentation. Moreover, CpG/ZANPs induced strong antigen-specific humoral and cytotoxic T lymphocyte responses that significantly inhibited the growth of EG7-OVA tumors while showing minimal cytotoxicity. We demonstrate that ZANPs may be a safe and effective vehicle for the development of cancer vaccines.

Previous studies have found a negative effect of depression and insomnia on the psychological health domain of quality of life (QOL) among earthquake survivors. However, little is known about the symptom-to-symptom interactions among the above psychological outcomes. This study thus aimed to assess the interplay among the above three variables in survivors 10 years after the Wenchuan earthquake at the symptom level.A total of 744 survivors completed the questionnaire at 10 years post-earthquake, reporting depressive symptoms, insomnia symptoms, and the psychological health domain of QOL. All network structures were estimated and compared using the network analysis approach in R version 4.1.1.Among the 744 survivors, 593 individuals did not have significant depressive and insomnia symptoms, while 151 individuals reported depressive and/or insomnia symptoms. "Little energy", "Suicidal ideation", and "Spirituality" were the key highest bridge symptoms in the three networks, respectively. Additionally, there were significant differences in network global strength, network structure, and individual edge weights between individuals with and without depression and/or insomnia.Intervention programs aimed at treating symptoms, such as exercise therapy, cognitive behavioural therapy, and spirituality education, may improve the QOL of survivors following an earthquake.

Rainfall or snow-melted water recharge easily saturates loose top soils with a less permeable underlayer, such as cultivated soil slope and partially thawed top soil layer, and thus, may influence the velocity of water flow. This study suggested a methodology and device system to supply water from the bottom soil layer at the different locations of slopes. Water seeps into and saturates the soil, when the water level is controlled at the same height of the soil surface. The structures and functions of the device, the components, and the operational principles are described in detail. A series of laboratory experiments were conducted under slope gradients of 5°, 10°, 15°, and 20° and flow rates of 2, 4, and 8 L min−1 to measure the water flow velocities over eroding and non-eroded loess soil slopes, under saturated conditions by using electrolyte tracing. Results showed that flow velocities on saturated slopes were 17% to 88% greater than those on non-saturated slopes. Flow velocity increased rapidly under high flow rates and slope gradients. Saturation conditions were suitable in maintaining smooth rill geomorphology and causing fast water flow. The saturated soil slope had a lubricant effect on the soil surface to reduce the frictional force, resulting in high flow velocity. The flow velocities of eroding rills under different slope gradients and flow rates were approximately 14% to 33% lower than those of non-eroded rills on saturated loess slopes. Compared with that on a saturated loess slope, the eroding rill on a non-saturated loess slope can produce headcuts to reduce the flow velocity. This study helps understand the hydrodynamics of soil erosion and sediment transportation of saturated soil slopes.

Loess and purple soils are two very important cultivated soils, with the former in the loess region and the latter in southern sub-tropical region of China, featured with high-risks of erosion, considerable differences of soil structures due to differences in mineral and nutrient compositions. Study on soil erodibility (Kr) and critical shear stress (τc) of these two soils is beneficial to predict soil erosion with such models as WEPP. In this study, rill erosion experimental data sets of the two soils are used for estimating their Kr and τc before they are compared to understand their differences of rill erosion behaviors. The maximum detachment rates of the loess and purple soils are calculated under different hydrodynamic conditions (flow rates: 2, 4, 8 L/min; slope gradients: 5°, 10°, 15°, 20°, 25°) through analytical and numerical methods respectively. Analytical method used the derivative of the function between sediment concentration and rill length to estimate potential detachment rates, at the rill beginning. Numerical method estimated potential detachment rates with the experimental data, at the rill beginning and 0.5 m location. The Kr and τc of these two soils are determined by the linear equation based on experimental data. Results show that the methods could well estimate the Kr and τc of these two soils as they remain basically unchanged under different hydrodynamic conditions. The Kr value of loess soil is about twice of the purple soil, whereas the τc is about half of that. The numerical results have good correlations with the analytical values. These results can be useful in modeling rill erosion processes of loess and purple soils.

A dual-functional copper porphyrin-catalyzed cross dehydrogenative coupling (CDC) of carboxylic acids with alkanes was reported firstly. The reaction gives allylic esters or alkylalkenes depending on the carboxylic acid substrates. Copper porphyrin catalyzed CDC method has the superiority of short reaction time, good functional group tolerance, base and solvent free, producing target products in an atom-economic manner.

The digestibility of isomalto-oligosaccharides (IMO) as well as their metabolism by gut microbiota depends on the degree of polymerization and the ratio of α-(1→4) to α-(1→6) linkages. Both parameters are influenced by the method of production. Commercial IMO are produced by transglycosylation of starch hydrolysates, or by transglycosylation with dextransucrase and sucrose as glucosyl-donor and maltose as glucosyl-acceptor. This study aimed to quantitatively and qualitatively assess the acceptor reaction with dextransucrase. α-Glucans were selected by systematic variation of degree of polymerization and linkage type; the dextransucrase DsrM from Weissella cibaria 10M was used as biocatalyst. The efficiency of α-glucans as acceptor carbohydrates decreased in the order DP2>DP3>DP1; among disaccharides, the efficiency decreased in the order α-(1→6)>α-(1→4)>α-(1→3); the α-(1→2) linked kojibiose did not support oligosaccharide formation. Equimolar addition of efficient acceptor molecules and sucrose shifted the dextransucrase reaction to oligosaccharides as virtually exclusive product. DsrM readily extended a commercial IMO preparation by adding α-(1→6)-linked glucose moieties. Conversion of commercial IMO by dextransucrase reduced their in vitro digestibility as analyzed by two different protocols. This study facilitates the synthesis of oligosaccharides produced in the acceptor reaction with dextransucrase with controlled yields and degree of polymerization, and hence with optimal functional properties in food applications.

Rill detachment is an important process in rill erosion. The rill detachment rate is the fundamental basis for determination of the parameters of a rill erosion model. In this paper, an analytical method was proposed to estimate the rill detachment rate. The method is based on the exact analytical solution of rill erosion to the differential equation of rill detachment. The rill sediment concentration distribution as a function of rill length was identified through laboratory experiments under different slope gradients and flow rates. The sediment concentration processes from experiments on loess and purple rills were considered to estimate the rill detachment rates of both soils analytically. They were respectively used as a function of rill length and sediment concentration. The analytical detachment rates were compared with the numerically determined values to verify the analytical methods. The rill detachment rates of the two soils under different flow rates and slope gradients estimated by the analytical method were further compared on the basis of detachment-sediment function and detachment-rill length function. Results indicated that the analytically estimated values were very close to the numerically estimated values. Numerical and analytical methods were equally useful for rill detachment rate estimation. Therefore, the analytical method was verified to be rational and applicable for the rapid determination of the rill detachment rates based on either sediment concentration or rill length. The analytical detachment values of purple and loess soils suggested that the detachment rates of loess soil were significantly and considerably higher than those of purple soil. The erosion potentials of loess soil were also significant higher than those of purple soil. The differences in the erosion of the two soils decreased as the slope gradient and flow rate increased. These observations implied that the degree of loess soil erosion was greater than that of purple soil erosion at low slope gradients and flow rates. The factors causing these differences may be determined in terms of the properties of the two soils. Therefore, the proposed analytical method, in addition to the concepts and direct relationship to erosion process, could be applied to obtain the rill detachment rate for the determination of rill erosion model parameters.

Thromboxane A2 (TXA2) has been implicated in the pathogenesis of diabetic vascular complications, although the underlying mechanism remains unclear. The present study investigated the alterations in TXA2 receptor signal transduction in type 2 diabetic renal arteries. The contraction of renal arterial rings in control (db/m+) mice and type 2 diabetic (db/db) mice was measured by a Multi Myograph System. Intracellular calcium concentration ([Ca2+]i) in vascular smooth muscle cells was measured by Fluo-4/AM dye and confocal laser scanning microscopy. Quantitative real-time PCR and Western blot analysis were used to determine gene and protein expression levels, respectively. A stable TXA2 mimic U46619 caused markedly stronger dose-dependent contractions in the renal arteries of db/db mice than in those of db/m+ mice. This response was completely blocked by a TXA2 receptor antagonist GR32191 and significantly inhibited by U73122. U46619-induced vasoconstriction was increased in the presence of nifedipine in db/db mice compared with that in db/m+ mice, whereas the response to U46619 did not differ between the two groups in the presence of SKF96365. Sarcoplasmic reticulum Ca2+ release-mediated and CaCl2-induced contractions did not differ between the two groups. In db/db mice, store-operated Ca2+(SOC) entry-mediated contraction in the renal arteries and SOC entry-mediated Ca2+ influx in smooth muscle cells were significantly increased. And the gene and protein expressions of TXA2 receptors, Orai1 and Stim1 were upregulated in the diabetic renal arteries. Therefore the enhancement of U46619-induced contraction was mediated by the upregulation of TXA2 receptors and downstream signaling in the diabetic renal arteries.

The main object of this paper is to construct a new generalization of the Bernstein operator, depending on a non-negative real parameter. We investigate some elementary properties of this operator, such as end point interpolation, linearity and positivity, etc. By using these generating operators, we provide another proof of the Weierstrass Approximation Theorem. We give the detailed proofs to the rate of convergence and Voronovskaja type asymptotic estimate formula for the operators. Moreover, an upper bound for the error is obtained in terms of the usual modulus of continuity. Shape preserving properties of the generalized Bernstein operators are also studied. It is proved that monotonic or convex functions produce monotonic or convex generalized Bernstein polynomials.

Valorization of lactose is achieved by enzymatic conversion to lactose derivatives with nutraceutical properties. This review summarizes recent developments on composition and functional properties of lactose-derived oligosaccharides. Lactose conversion by β-galactosidase yields galacto-oligosaccharides (GOS); hetero-oligosaccharides with structural and/or functional similarity to human milk oligosaccharides are synthesized by transglycosylation with β-galactosidase, sialidase, glucansucrase, fructansucrase or α-fucosidase using lactose as donor or acceptor sugar. Application development for GOS was based on their prebiotic properties; intestinal fermentation of GOS to short-chain fatty acids confers health benefits. Several novel oligosaccharides exhibit additional potent biological activities that are based on direct interaction of oligosaccharides with glycan-binding domains of bacterial adhesins and toxins, and are highly specific to the oligosaccharide structure. Particularly the use of lactose-derived oligosaccharides to prevent binding of bacterial toxins or adhesins is supported by in vivo studies.

Poly(ADP-ribose)polymerase (PARP)1/2 inhibitors have been proved to be clinically effective anticancer drugs. Here we report a new PARP1/2 inhibitor, simmiparib, displaying apparently improved preclinical anticancer activities relative to the first approved inhibitor olaparib. Simmiparib inhibited PARP1/2 approximately 2-fold more potently than olaparib, with more than 90-fold selectivity over the other tested PARP family members. Simmiparib and olaparib caused similar cellular PARP1-DNA trapping. Simmiparib selectively induced the accumulation of DNA double-strand breaks, G2/M arrest and apoptosis in homologous recombination repair (HR)-deficient cells. Consistently, simmiparib showed 26- to 235-fold selectivity in its antiproliferative activity against HR-deficient cells over the corresponding isogenic HR-proficient cells. Notably, its antiproliferative activity was 43.8-fold more potent than that of olaparib in 11 HR-deficient cancer cell lines. Simmiparib also potentiated the proliferative inhibition of several conventional anticancer drugs. Simmiparib reduced the poly(ADP-ribose) formation in HR-deficient cancer cells and xenografts. When orally administered to nude mice bearing xenografts, simmiparib revealed excellent pharmacokinetic properties. Simmiparib caused approximately 10-fold greater growth inhibition than olaparib against HR-deficient human cancer cell- or tissue-derived xenografts in nude mice. Collectively, these findings support the undergoing clinical trials of simmiparib.

Exopolysaccharides from lactic acid bacteria may improve texture and shelf life of bread. The effect of exopolysaccharides on bread quality, however, depends on properties of the EPS and the EPS producing strain. This study investigated structure-function relationships of EPS in baking application. The dextransucrase DsrM and the reuteransucrase GtfA were cloned from Weissella cibaria 10M and Lactobacillus reuteri TMW1.656, respectively, and heterologously expressed in Escherichia coli. Site-directed mutagenesis of GtfA was generates reuterans with different glycosidic bonds. NMR spectrum indicated reuteranPI, reuteranNS and reuteranPINS produced by GtfA-V1024P:V1027I, GtfA-S1135N:A1137S and GtfA-V1024P:V1027I:S1135N:A1137S, respectively, had a higher proportion of α-(1→4) linkages when compared to reuteran. ReuteranNS has the lowest molecular weight as measured by asymmetric flow-field-flow fractionation. The reuteransucrase negative mutant L. reuteri TMW1.656ΔgtfA was generated as EPS-negative derivative of L. reuteri TMW1.656. Cell counts, pH, and organic acid levels of sourdough fermented with L. reuteri TMW1.656 and TMW1.656ΔgtfA were comparable. Reuteran produced by L. reuteri TMW1.656 during growth in sourdough and reuteran produced ex situ by GtfA-ΔN had comparable effects on bread volume and crumb hardness. Enzymatically produced dextran improved volume and texture of wheat bread, and of bread containing 20% rye flour. ReuteranNS but not reuteranPI or reuteran was as efficient as dextran in enhancing wheat bread volume and texture. Overall, reuteran linkage type and molecular weight are determinants of EPS effects on bread quality. This study established a valuable method to elucidate structure-function relationships of glucans in baking applications.

Bacillus spp. cause ropy bread spoilage of bread, which is characterized by a rotten fruity odor, followed by discoloration and degradation of the crumb. Bacillus spp. are wheat grain endophytes and form heat resistant endospores, therefore, process hygiene and heating during baking do not prevent ropy spoilage. This study used 8 strains of Bacillus subtilis and Bacillus amyloliquefaciens to determine whether the presence and the copy number of spoVA2mob operon influences survival after baking; in addition, the spoilage phenotype was correlated with the presence of amylolytic enzymes in genomes of Bacillus spp.. The presence and copy number of the spoVA2mob operon had only a minor effect on survival of Bacillus endospores. Strains of B. amyloliquefaciens caused ropy spoilage faster than strains of B. subtilis, this difference correlated to the number and type of extracellular amylases encoded in the genomes of the strains of B. amyloliquefaciens and B. subtilis. The inhibitory effect of sourdough on ropy spoilage was determined by addition of 3–24% sourdough fermented with L. reuteri TMW1.656. Addition of 12% and 24% sourdough, corresponding to a bread pH of 5.93 ± 0.041 and 5.53 ± 0.040, respectively, delayed ropy spoilage for 2 and more than 5 d, respectively. The comparison of addition of 12% sourdough fermented with the reutericyclin producing L. reuteri TMW1.656 and the isogenic reutericyclin-negative strain L. reuteri TMW1.656ΔgtfAΔrtcN demonstrated that reutericyclin produced in sourdough inhibits growth of Bacillus in bread. In conclusion, sourdough inhibits germination of Bacillus spores in bread and the effect of sourdough is enhanced by reutericyclin.

Cobalt(III) corrole was firstly applied to the hydration of terminal alkynes. The alkyne hydration proceeded in good to excellent yield with 0.03 to 0.3 mol% cobalt corrole catalyst loading. A wide range of substrates were tolerated. Particularly, the reaction can give 90% yield in a gram scale experiment.

Water temperature is an important environmental factor in aquaculture farming that affects the survival and growth of organisms. The change in culture water temperature may not only modify various chemical and biological processes but also affect the status of fish populations. In previous studies, high temperature induced apoptosis and oxidative stress. However, the precise mechanism and the pathways that are activated in fish are still unclear. In the present study, we investigated the effects of high temperature (34°C) on the induction of apoptosis and oxidative stress in pufferfish (Takifugu obscurus) blood cells. The data showed that high temperature exposure increased oxygen species (ROS), cytoplasmic free-Ca(2+) concentration and cell apoptosis. To test the apoptotic pathway, the expression pattern of some key apoptotic related genes including P53, Bax, caspase 9 and caspase 3 were examined. The results showed that acute high temperature stress induced up-regulation of these genes, suggesting that the p53-Bax pathway and the caspase-dependent apoptotic pathway could be involved in apoptosis induced by high temperature stress. Furthermore, the gene expression of antioxidant enzymes (Cu/Zn-SOD, Mn-SOD, CAT, GPx, and GR) and heat shock proteins (HSP90 and HSP70) in the blood cells were induced by high temperature stress. Taken together, our results showed that high temperature-induced oxidative stress may cause pufferfish blood cells apoptosis, and cooperatively activated p53-Bax and caspase-dependent apoptotic pathway.

Depression is a frequent mood disorder that affects around a third of stroke patients and has been associated with poorer outcome. Our aim was to determine whether there is a relationship between serum Brain-derived neurotrophic factor (BDNF) levels and post-stroke depression (PSD).Two hundred and sixteen ischemic stroke patients admitted to the hospital within the first 24h after stroke onset were consecutively recruited and followed up for 3 months. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for post-stroke depression at day 90. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of BDNF at admission. Multivariate analyses were performed using logistic regression models.In our study, 59 patients (27.3%) were diagnosed as having major depression at 3 months. Patients with major depression showed lower levels of serum BDNF [8.1 (5.6-9.4) vs. 13.7 (10.4-16.5)ng/ml, P0.0001] at admission. In multivariate analyses, serum BDNF was an independent predictor of PSD at 3 months [odds ratio (OR): 0.79(0.72-0.87), P=0.003]. Serum levels of BDNF≤10.2ng/ml were independently associated with post-stroke (OR, 11.5; 95% CI, 5.6-23.4, P0.0001), after adjustment for possible variables.The present study demonstrates a strong relationship between serum BDNF levels at admission and the development of PSD within 3 months. Further studies are necessary to confirm this association, which may open the way to the proposal of new therapeutic options.

In this study, Fe3O4/carbon nanocomposites as anode materials of Li-ion batteries were synthesized through heating hierarchically porous Fe-based xerogels under N2 atmosphere. The pyrolysis of amorphous Fe-xerogel base materials resulted in the simultaneous formation of Fe3O4/C composites, in which Fe3O4 particles of less than 50 nm were uniformly dispersed and embedded in a porous carbon matrix. Due to the favorable nanostructure, the synthesized Fe3O4/C composites with a proper carbon content of 18.8 wt.% exhibited good electrochemical performance including high capacity and rate capability as well as much enhanced cyclic stability.

As a continuation of our previous studies of light lanthanides (La, Ce, Pr, and Nd) with (Pyrazol-1-yl)acetic acid (L), we reacted L with the heavier lanthanides in aqueous solution at pH 5 and synthesized lanthanide complexes of the general formula [Ln(L)3(H2O)2]·H2O (Ln = Eu, 1; Gd, 2; Dy, 3; Ho, 4; Er, 5; Yb, 6; Lu, 7) and [HoL(NO3)2(H2O)3] (8). All complexes were characterized by single crystal X-ray diffraction analysis revealing one-dimensional chain formations. Three distinct crystallographic structures are governed by the different coordination modes of the carboxylate groups in L: terminal bidentate, bridging bidentate and tridentate coordination in 1–3, terminal and bridging bidentate coordination in 4–7, and bridging bidentate coordination in 8. The solid state UV–Vis–NIR diffuse reflectance spectra and the solution UV–Vis–NIR absorption spectra differ, suggesting different coordination environments in solution and solid state. The coordination-induced shifts of the 13C NMR signals for [Lu(L)3(H2O)2]·H2O (7) in D2O show that the carboxylate groups of the ligand are coordinated with the Lu(III) ion in solution.

Crocin is a pharmacologically active component of Crocus sativus L. (saffron) and has been reported to be useful in the treatment of neuronal damage. In the present study, we investigated the neuroprotective effect of crocin on retinal ganglion cells (RGCs) after retinal ischaemia/reperfusion (IR) injury, and our results show that crocin acts through the PI3K/AKT signalling pathway. Retinal IR injury was induced by raising the intraocular pressure of Sprague-Dawley rats to 110 mmHg for 60 min. The neuroprotective effect of crocin was determined by quantifying the surviving RGCs and apoptotic RGCs following IR injury by means of retrograde labelling and TUNEL staining, respectively. The phosphorylated AKT protein level was determined by western blot and immunohistochemical analysis. To determine the extent to which the PI3K/AKT pathway contributes to the neuroprotective effect of crocin, experiments were also performed using the PI3K inhibitor LY294002. Compared with the IR + vehicle group, crocin (50 mg/kg) treatment enhanced RGC survival by approximately 36% and decreased RGC apoptosis by 44% after retinal IR injury. Western blot and immunohistochemical analysis demonstrated that the PI3K/AKT pathway was activated by crocin in the ganglion cell layer after retinal IR injury. Intravitreal injection of LY294002 blocked the neuroprotective effect of crocin on IR-induced RGC death. In conclusion, crocin prevents retinal IR-induced apoptosis of RGCs by activating the PI3K/AKT signalling pathway.

The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -31 C/T polymorphism and duodenal ulcer (DU). Systematic searches of electronic databases Embase, PubMed and Web of Science were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were conducted using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were applied. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 12 studies including 1151 cases and 2642 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -31 C/T polymorphism and DU (allelic model: OR=0.96, 95%CI=0.86-1.07; additive model: OR=0.85, 95%CI=0.67-1.07; dominant model: OR=0.95, 95%CI=0.81-1.13; and recessive model: OR=0.95, 95%CI=0.79-1.15). Significant association was found in additive model for PB subgroup (OR=0.65, 95%CI=0.44-0.96) and recessive model for non-Asian subgroup (OR=0.72, 95%CI=0.52-0.99). In conclusion, our meta-analysis suggested that there was no evidence of significant association between IL-1β -31 C/T polymorphism and DU with or without Helicobacter pylori infection in overall population, whereas significant association was found by subgroup analyses which showed protective effect of C/C genotype against DU risk.

Modern CAD/CAM systems are not able to dispose the circles represented by the implicit equations or the parametric equations with trigonometric function. Parametric (rational) polynomials are used to approximate the circular arcs. A new approximation method by means of quartic Bezier curves is presented to effectively approximate the circular arcs. It is shown that our method provides the approximation of order eight and yields a smaller error than previous methods. By equally spaced subdivision of circular arcs, the curvature continuous spline approximation algorithm of the circular arcs is given.

Summary Excessive nutrient loading and changing hydrological regimes can significantly impact the ecological function of wetland ecosystems. Three wetland sediment samples collected from West Lake, Xiazhuhu Wetland and Baoyang River in the Taihu Lake Watershed, China, were compared to understand the P retention properties responding to hydrological regimes by using static column and steady-flow flume laboratory-scale experiments. Sediment in Xiazhuhu Wetland currently function as a P sink with equilibrium P concentration (EPC 0 ) values of 0.010 mg L −1 , while sediments from West Lake and Baoyang River, have EPC 0 values of 0.050 mg L −1 and 0.023 mg L −1 , respectively, and serve as an internal P source. The P retention by sediments ranged from 17.20 to 22.61 mg m −2 d −1 under 35-d static conditions, while sediment beds continuously fed by the simulated inflow water containing 2 mg L −1 P ranged from 59.20 to 171.93 mg m −2 d −1 . The P removal capacities by sediments were higher during the rainy season than the dry season when wetlands were subjected to excessive P input. Since the majority of external P stored in sediment is in the form of Al-P (e.g., for Xiazhuhu wetland), the application of alum to water column could potentially increase the P retention capacity of sediment.

The influence of some additives on bulk density, phase composition, mechanical strength and thermal shock resistance of aluminium titanate (AT) ceramics was investigated. AT ceramics with different additives of MgO, SiO(2) and Fe(2)O(3) were prepared by reaction sintering. Properties of AT ceramics were tested by using Archimedes, three-point bending and thermal cycling tests. It was found that additives of MgO, SiO(2) and Fe(2)O(3) or their compound additives are favorable to reduce the porosities of AT, enhance mechanical strength and thermal shock resistance. The role of additives can be rationalized in terms of promotion of sintering process, formation of new phases and influence on lattice constant c of AT ceramics.

Cancer preventive reagent trans-resveratrol is intracellularly biotransformed to different metabolites. However, it is still unclear whether trans-resveratrol exerts its biological effects directly or through its metabolite(s). This issue was addressed here by identifying the metabolic pattern and the bioactive form of resveratrol in a resveratrol-sensitive human medulloblastoma cell line, UW228-3. The cell lysates and condition media of UW228-3 cells with or without 100 microM resveratrol treatment were analyzed by HPLC and LC/MS which revealed (1) that resveratrol was chemically unstable and the spontaneous generation of cis-resveratrol reduced resveratrol's anti-medulloblastoma efficacy and (2) that resveratrol monosulfate was the major metabolite of the cells. To identify the bioactive form of resveratrol, a mixture-containing approximately half fraction of resveratrol monosulfate was prepared by incubating trans-resveratrol with freshly prepared rat brain lysates. Medulloblastoma cells treated by 100 microM of this mixture showed attenuated cell crisis. The overall levels of the three brain-associated sulfotransferases (SULT1A1, 1C2 and 4A1) were low in medulloblastoma cells in vivo and in vitro in comparison with that in human noncancerous and rat normal cerebella; resveratrol could more or less up-regulate the production of these enzymes in UW228-3 cells but their overall level was still lower than that in normal cerebellum tissue. Our study thus demonstrated for the first time that trans-resveratrol is the bioactive form in medulloblastoma cells in which the expression of brain-associated SULTs was down-regulated, resulting in the increased intracellular bioavailability and anti-medulloblastoma efficacy of trans-resveratrol.

The objectives of this study were to characterize polymorphisms within the coding region of estrogen receptor beta (ERbeta) gene in a population of 57 female Japanese flounder (Paralichthys olivaceus) and to analyze the association of ERbeta polymorphisms with reproductive indices by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP). Two single nucleotide polymorphisms (SNPs), SNP1 (c.577delC) and SNP2 [c.A891T (p.Gln114Leu)], were identified in the ERbeta gene. A one-way ANOVA revealed that SNP1 was significantly associated with the gonadosomatic index (GSI) in female Japanese flounder (P < 0.05). And SNP2 was significantly associated with the serum 17beta-estradiol (E2) level and GSI (P < 0.05). Individuals with genotype AB of SNP2 had significantly higher serum E2 level and GSI than those of genotype AA (P < 0.05). Moreover, the hepatosomatic index (HSI), a marker for genetic effects, was significantly higher for diplotype D2 compared with the other three diplotypes (P < 0.05). These results obtained in this study suggested that SNP2 could influence reproductive endocrinology of female Japanese flounder and be useful as a potential candidate genetic marker for the selection of reproductive indices in female Japanese flounder.

S100A4 promotes cancer metastasis, but its overall status and splicing manner during gastrocarcinogenesis remains less known. We therefore examined S100A4 frequencies, splicing pattern(s) and the underlying reason(s) for S100A4 expression in gastric cancers. Immunohistochemistry revealed frequent S100A4 expression in intestinal gastric cancers (37/45; 82%) and diffuse gastric cancers (12/20; 60%), but uncommon in noncancerous epithelia (0/12), chronic gastritis (2/24; 8%), and intestinal metaplasia (3/15; 20%). Of 65 primary tumors, 18 were found with focal S100A4 expression, while their LN metastases showed homogenous distribution. S100A4-oriented reverse transcription-polymerase chain reaction yielded a transcript containing exons 1, 3, and 4 (AS1) in 20% of noncancerous, 84% premalignant, and 92% tumor tissues and a transcript harboring exons 1 to 4 (AS2) in 65% of gastric cancers (GCs), 26% premalignant but none in noncancerous tissues. Further analyses found AS1 expression in stromal but not epithelial cells of premalignant tissues, absence of AS2 in endoscopic inflammatory mucosa, and the coexistence of AS1/AS2 in the cultured fibroblasts. Methylation DNA sequencing revealed hypermethylation of four critical CpG sites within S100A4 intron first among S100A4-negative gastric tissues and hypomethylation in S100A4-expressing GC tissues/cell lines. E-cadherin reduction and Wnt activation were common in gastric cancers, which were closely correlated but unnecessarily overlapped with S100A4 expression. Our findings suggest that S100A4 expression is closely related with GC formation, which, as a hypomethylation event, is accompanied with E-cadherin reduction and Wnt activation. The preferential S100A4 AS2 expression in GC cells would have potential values in GC surveillance and prognostic assessment.

In this study, the potential influence of resveratrol (3,5,4′-trihydroxy-trans-stilbene) in signal transducer and activator of transcription 3 (STAT3) signaling of medulloblastoma cells was evaluated by checking the status of STAT3 signaling and its downstream gene expression in two medulloblastoma cell lines (UW228-2 and UW228-3) with and without resveratrol treatment. The results revealed that resveratrol induced neuronal differentiation of medulloblastoma cells. Signal transducer and activator of transcription 3 expression and phosphorylation were detected in normally cultured UW228-2 and UW228-3 cells that were apparently attenuated after resveratrol treatment. The expression of STAT3 downstream genes, survivin, cyclin D1, Cox-2, and c-Myc, was suppressed but Bcl-2 was enhanced by resveratrol. Meanwhile, the production and secretion of leukemia inhibitory factor, a STAT3 activator, became active in resveratrol-treated cells. To further ascertain the significance of STAT3 signaling for medulloblastoma cells, AG490, a selective inhibitor of STAT3 phosphorylation, was used to treat UW228-3 cells. Phosphorylation of STAT3 was inhibited by AG490 accompanied with growth suppression, differentiation-like changes, and down-regulation of survivin, cyclin D1, Cox-2, and c-Myc. Our data thus suggest the importance of STAT3 signaling in maintenance and survival of medulloblastoma cells. This signaling may be the major target of resveratrol. Enhanced leukemia inhibitory factor and Bcl-2 expressions in resveratrol-treated cells might reflect a compensatory response to the loss of STAT3 function.

Two copper(II)–poly(pyrazolyl)methane complexes [Cu2(bpm)4(ta)](ClO4) 2 · 2H2O 1 and {[Cu2(tpm)2(ta)2] · H2O}n 2 (bpm = bis(3,5-dimethylpyrazolyl)methane, tpm = tris(pyrazolyl)methane, H2ta = terephthalic acid) were synthesized and characterized by elemental analysis, FT-IR and UV–vis spectra. 1 is a binuclear complex, while 2 exhibits as a 1D zigzag coordination polymer.

According to the conserved sequences flanking the 3' end of the 16S and the 5' end of the 23S rDNAs, PCR primers were designed, and the 16S-23S rDNA intergenic spacers (IGSs) of two strains of Vibrio vulnificus were amplified by PCR and cloned into pGEM-T vector. Different clones were selected to be sequenced and the sequences were analyzed with BLAST and the software DNAstar. Analyses of the IGS sequences suggested that the strain ZSU006 contains five types of polymorphic 16S-23S rDNA intergenic spacers, namely, IGSGLAV, IGSGLV, IGSIA, IGSG and IGSA; while the strain CG021 has the same types of IGSs except lacking IGSA. Among these five IGS types, IGSGLAV is the biggest type, including the gene cluster of tRNAGlu-tRNALys-tRNAAla-tRNAVal; IGSGLV includes that of tRNAGlu-tRNALys-tRNAVal; IGSAG, tRNAAla-tRNAGlu; IGSIA, tRNAIle-tRNAAla; IGSG, tRNAGlu and IGSA, tRNAAla. Intraspecies multiple alignment of all the IGS sequences of these two strains with those of V. vulnificus ATCC27562 available at GenBank revealed several highly conserved sequence blocks in the non- coding regions flanking the tRNA genes within all of strains, most notably the first 40 and last 200 nucleotides, which can be targeted to design species-specific PCR primers or detection probes. The structural variations of the 16S-23S rDNA intergenic spacers lay a foundation for developing diagnostic methods for V. vulnificus.

The coordination polymer {K[Mn(C6H5O7)(H2O)]}n (1) (C6H5O73− = citrate trianion) was synthesized by solvothermal reaction and characterized analytically, spectroscopically (IR, EPR, XPS), thermally and magnetically. In compound 1, each citrate served as the unique pentadentate ligand coordinating to three Mn(II) ions. The carboxylate-bridged di-manganese cores were interlocked by α- and β-carboxylates of the citrate chains into 2D layers, which are then woven in [1 0 0] direction into a novel 3D network by the K+ linkers.

A novel 4d–4f coordination polymer {[GdAg 2 (dtpa)(H 2 O)] · 3H 2 O} n ( 1 ) (dtpa = diethylenetriamine pentaacetate) was synthesized and characterized by magnetic and EPR studies. Its one-dimensional Gd–Ag ladder-like chains built upon tetranuclear rings are further connected by Ag–O bonds and Ag–Ag interactions to form a lamellar 2D packing.

A tetranuclear copper(II) complex [Cu4(NSI)4] · 2C2H5OH · 2H2O (NSI=hydroxethylsalicydeneimine) has been synthesized and characterized by X-ray diffraction analysis. The compound crystallizes in the monoclinic system, space group P2(1), a=9.494(3) A, b=18.687(5) A, c=13.149(4) A, β=110.162(5)°, Z=2, R1=0.0482 and wR2=0.0978. The crystal structure contains a tetranuclear pseudo-cubane core based on an approximately cubane array of alternating copper and oxygen atoms. Each copper atom resides in a distorted square planar coordination environment with one nitrogen and three oxygen atoms from two NSI ligands. The tetranuclear units are linked in the crystal by O–H⋯O hydrogen bonds and weak Cu⋯O co-ordination bonds into one-dimensional structure. Variable temperature (5–300 K) magnetic measurements indicate the existence of ferromagnetic interactions among copper atoms. The IR and ESR spectra have also been investigated.

Resveratrol induces differentiation and Fas-independent apoptosis of medulloblastoma cells by a largely unknown mechanism. CYP1A1 and 1B1 are involved in resveratrol-mediated tumor suppression but their expression in medulloblastoma cells and their relevance to anti-medulloblastoma activity of resveratrol have not been described. The statuses of CYP1A1 and 1B1 in UW228-3 medulloblastoma cells without and with resveratrol treatments were elucidated in this study with ethoxyresorufin O-deethylation assay, followed by RT-PCR, immunocytochemical staining and Western blot hybridization. CYP1A1/1B1 enzymatic activity was low in UW228-3 cells but became several folds higher upon resveratrol treatments. CYP1A1 was undetectable and CYP1B1 was expressed in normally cultured cells. Accompanied by the increased fraction of apoptosis, enhanced CYP1A1 and downregulated CYP1B1 were observed in resveratrol-treated cells in time- and dose-related fashions. Our results demonstrate for the first time that in the medulloblastoma cell system, CYP1A1 upregulation is paralleled with resveratrol-induced differentiation and apoptosis, while CYP1B1 may not be an essential element in metabolic activation of resveratrol in those cells. CYP1A1 and 1B1 are resveratrol response genes and potential chemosensitive markers of medulloblastoma cells.

A marked difference in the dissolution rate between two brands of nimodipine tablets was observed using a newly developed dissolution medium of pH 4.5 acetate buffer containing 0.05% sodium dodecyl sulfate (SDS). However, when pH 4.5 acetate buffer containing 0.3% SDS was used as dissolution medium, which was specified in the edition, the dissolution results of the both brands conformed to the BP requirements and no significant difference in dissolution was observed. The dissolution data obtained for two commercial brands of nimodipine tablets indicate the superiority of the proposed system as a discriminatory dissolution medium for nimodipine tablets. The relative bioavailability of the two brands of nimodipine tablets was determined in healthy adult volunteers after a single dose in a randomized crossover study. Plasma concentrations were determined by a liquid chromatography-tandem mass spectrometry method. Statistical comparison of the AUC(0-T), AUC(0- infinity), C(max), and T(max) indicated a significant difference in the two brands of nimodipine tablets.

Resveratrol has tumor-suppressive activities in some in vitro and in vivo experimental systems but its effect on medulloblastoma cells is still unknown. In this study, resveratrol was used to treat four human medulloblastoma cell lines (Med-3, UW228-1, -2 and -3) and its effects on cell growth, differentiation and death were examined by multiple approaches. Expression of Fas, FasL and caspase-3 in the cells without and with resveratrol treatments was examined by immunocytochemical staining and mRNA in situ hybridization and the influence of anti-Fas antibody (200 ng/ml) in cell growth and survival was determined as well. The results demonstrated that resveratrol could suppress growth, promote differentiation and commit its target cells to apoptosis in time- and dose-related fashions. Fas was constitutively expressed but FasL was undetectable in the four lines in spite of resveratrol treatment. Anti-Fas antibody (200 ng/ml) neither inhibited growth nor induced apoptosis of those cell lines. Up-regulated caspase-3 was found in resveratrol-treated populations and appearance of its cleaved form was closely associated with the apoptotic event. These findings suggest for the first time that resveratrol is an effective anti-medulloblastoma agent that kills medulloblastoma cells through a Fas-independent pathway.

A novel dicyanamide (dca) complex, [Cu(pn)(dca)2]n (pn=1,2-diaminopropane), was synthesized and characterized. X-ray diffraction analysis reveals that the title complex crystallizes in the monoclinic space group C2/c with a=12.436(5) A , b=8.395(3) A , c=20.747(8) A , β=96.662(6)°, Z=8, and R1=0.0476, wR2=0.1094. The complex exhibits one-dimensional zigzag chain structure constructed by μ1,5-dca bridges. The coordination geometry around the copper atom was a distorted square-pyramid. The spectroscopic and magnetic properties have also been discussed.

Quantum size effect was strongly supported by the experiment on correlation between size of gold nanoparticles (below 10 nm) and activity of glucose oxidase attached to them. The attractive enhancement effect of gold nanoparticles on the activity of glucose oxidase was then satisfactorily explained. In this experiment, 2 nm and 6 nm (average diameter) particles were obtained on monolayer matrix. The 2 nm particles proved to be much more able to increase the activity of glucose oxidase.

With money liquidity, transaction liquidity, funding liquidity and their interactions, this article analyzes the innovation of the sub-prime mortgage crisis and its transformation into the financial crisis. The findings show that as in other historical financial crises the overall liquidity meltdown is the direct cause. The default in sub-prime mortgage is just the fuse. Typically, as the money policy is getting tightened, money liquidity deteriorates, which will have great impact on transactions liquidity and then on funding liquidity. And the exacerbation of funding liquidity will lead transactions liquidity (and then money liquidity) to decline even further. Then the financial market appears less money liquidity, which again feeds back on transaction liquidity and funding liquidity. Such two positive feedback loops will eventually result in an overall liquidity meltdown.