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Acute renal failure (ARF) is a huge threat to the lives of most patients in intensive care units, and there is currently no satisfactory treatment strategy. SRY-box transcription factor 4 (SOX4) plays a key role in the development of various diseases, but its effect on ARF is unknown. Therefore, this study aimed to explore the relationship between SOX4 and ARF. Blood samples were collected from 20 ARF patients and 20 healthy volunteers. We also established an ARF rat model by excising the right kidney and ligating the left renal artery, and SOX4 knockdown in ARF rats was achieved down by means of lentiviral infection. Subsequently, we used quantitative polymerase chain reaction and western bolt assays to detect the expression levels of SOX4 and nuclear factor-κB (NF-κB) signaling pathway-related proteins in human blood or rat renal tissue and hematoxylin and eosin and terminal deoxynucleotidyl transferase (TdT) 2'- deoxyuridine 5'-triphosphate (dUTP) nick-end labeling staining to observe the pathological changes and apoptosis of renal tissue. Enzyme-linked immunosorbent assay and biochemical kits were used to measure the levels of renal function-related indicators (blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin) and inflammatory factors (interleukin [IL]-1β, IL-6, and tumor necrosis factor-alpha), as well as changes in oxidative stress-related indicators (malondialdehyde [MDA], superoxide dismutase [SOD], and reactive oxygen species [ROS]) in rat serum. SOX4 expression levels in blood samples from ARF patients and renal tissue from ARF rats were significantly higher compared with those in healthy volunteers and control rats, respectively. ARF model rats displayed the typical ARF phenotype, while SOX4 silencing significantly improved pathological injury and apoptosis of renal tissue in ARF rats. Moreover, SOX4 silencing significantly inhibited increased levels of renal functionrelated indicators and inflammatory factors and reduced the level of excessive oxidative stress (MDA and ROS were upregulated, and SOD was downregulated) in ARF rats. SOX4 also reduced the activity of the NF-κB signaling pathway in ARF samples. Thus, SOX4 knockdown may reduce oxidative stress, the inflammatory response, and apoptosis by reducing the activity of the NF-κB signaling pathway, thereby improving renal injury in ARF rats. [ABSTRACT FROM AUTHOR]

Introduction: Regulatory T cells (Tregs) play an important role in inflammatory bowel diseases (IBDs) through modulating intestinal inflammation. However, the factors affecting Treg function and plasticity during IBD progression are not thoroughly disclosed. The current study aims to reveal new molecular mechanisms affecting Treg plasticity. Methods: A mouse strain, in which tdTomato and enhanced green fluorescent protein were under the control of the Foxp3 promoter and Il17a promoter, was established and subjected to colitis induction with dextran sulfate sodium. The existence of Tregs and IL-17-expressing Tregs (i.e., Treg/T helper 17 [Th17] cells) were observed and sorted from the spleen, mesenteric lymph nodes, and lamina propria by flow cytometry, followed by measuring Sirtuin2 (Sirt2) expression using quantitative reverse transcription polymerase chain reaction and Immunoblotting. Lentivirus-induced Sirt2 silencing was applied to determine the impact of Sirt2 on Treg polarization to Treg/Th17 cells and even Th17 cells. The effect of Sirt2 on Stat3 was analyzed by flow cytometry and immunoblotting. Results: Sirt2 was highly expressed in lamina propria Tregs and it moderately suppressed Foxp3 expression as well as the immunosuppressive function of Tregs. Surprisingly, lentivirus-mediated Sirt2 silencing promoted the generation of Treg/Th17 cells out of Tregs. Sirt2 silencing also enhanced the generation of Th17 cells out of Tregs under the Th17 induction condition. Furthermore, Sirt2 inhibited Th17 induction by suppressing the protein level of the signal transducer and activator of transcription 3. Conclusion: Sirt2 suppresses Treg function but also inhibits Treg polarization toward Treg/Th17 cells and Th17 cells. The ultimate effect of Sirt2 on colitis might depend on the balance among Tregs, Treg/Th17 cells, and Th17 cells. [ABSTRACT FROM AUTHOR]

Transient receptor potential ankyrin 1 (TRPA1) is expressed in gastrointestinal tract and plays important roles in intestinal motility and visceral hypersensitivity. However, the potential role of TRPA1 in host defense, particularly against intestinal pathogens, is unknown. Here, we show that Trpa1 knockout mice exhibited increased susceptibility to Citrobacter rodentium infection, associated with the increased severity of diarrhea and intestinal permeability associated with the disrupted tight junctions (TJs) in colonic epithelia. We further demonstrated the expression of TRPA1 in murine colonic epithelial cells (CECs) and human epithelial Caco-2 cells both at protein level and transcription level. Using calcium imaging, TRPA1 agonists allyl isothiocyanates (AITC) and hydrogen peroxide were observed to induce a transient Ca2+ response in Caco-2 cells, respectively. Moreover, TRPA1 knockdown in Caco-2 cells resulted in the decreased expression of TJ proteins, ZO-1 and Occludin, and in the increased paracellular permeabilities and the reduced TEER values of Caco-2 monolayers in vitro. Furthermore, inhibition of TRPA1 by HC-030031 in the confluent Caco-2 cells caused the altered distribution and expression of TJ proteins, ZO-1, Occludin, and Claudin-3, and exacerbated the bacterial endotoxin lipopolysaccharide (LPS)-induced damage to these TJ proteins and actin cytoskeleton. By contrast, AITC pretreatment restored the distribution and expression of these TJ proteins in the confluent Caco-2 cells upon LPS challenge. Our results identify an unrecognized protective role of TRPA1 in host defense against an enteric bacterial pathogen by maintaining colonic epithelium barrier function, at least in part, via preserving the distribution and expression of TJ proteins in CECs. [ABSTRACT FROM AUTHOR]

Background: This study examined and compared the attitudes and willingness of guardians of children with cancer and adult cancer patients toward donating biospecimens and clinical data for cancer research. Methods: We conducted a cross-sectional study among guardians of children with cancer (Guardian group) from Shanghai Children's Medical Center and adult cancer patients (Adult group) from Shanghai Ninth People's Hospital between February 1, 2019, and January 31, 2020. Participants' demographic data, willingness, and motivations for biospecimen donation were collected and analyzed. Results: Of 670 participants, 90.8% (318/350) in the Guardian group and 88.1% (282/320) in the Adult group completed the questionnaire. Most participants were willing to donate residual tissue samples (92.8% in the Guardian group vs. 79.4% in the Adult group, pψ = 0.032) and clinical data (94.0% vs. 72.3%, pψ < 0.001) for medical research. Logistic regression analysis indicated that only child status (odds ratio [OR] = 0.140, p = 0.02), history of blood donation (OR = 4.467, p = 0.019) in the Guardian group, education (OR = 0.387, p = 0.037), and history of blood donation (OR = 2.556, p = 0.016) in the Adult group were significantly associated with participants' willingness to donate biospecimens. The primary motivation for donation was helping other patients with cancer (65.4% vs. 24.5%, pψ < 0.001). The major barriers to donation were the potential to cause physical discomfort (61.0% vs. 64.9%, pψ = 0.032). Conclusions: Guardians of children with cancer were more willing to donate biospecimens than adult cancer patients in China. It is essential to promote awareness of biospecimens donation, especially in adult cancer patients. [ABSTRACT FROM AUTHOR]

In view of the adulteration of Lycium barbarum with chemicals and dyes in the market, hyperspectral imaging technology is proposed to identify fumigated and dyed specimens. The hyperspectral data were preprocessed by visual molecular dynamics (VMD) to reduce the influence of noise. Furthermore, competitive adaptive reweighted sampling (CARS) was used to select the characteristic bands from the preprocessed spectral data. Since the classification effect of the traditional support vector machine (SVM) model was influenced by the kernel parameters c and g, the slime mold algorithm was adopted to optimize SVM. The optimal c and g were set to 93.3603 and 4.5652, respectively. The results showed that the VMD–CARS–SVM had higher prediction accuracy, and the accuracy of training and testing sets were 98.2 and 96.7% separately. Practical applications: The aim of this article is to identify fumigated and dyed L. barbarum by hyperspectral imaging technology. After fumigation and dyeing, the type and contents of active ingredients in the surface and interior of L. barbarum changes, seriously affecting the health of consumers. The results of this article provide a valuable reference to develop a portable inspection device to identify the fumigated and dyed L. barbarum rapidly, precisely, and non‐destructively. [ABSTRACT FROM AUTHOR]

Aiming at the common problems of weak controllability of damping temperature range and poor mechanical properties in damping elastomer materials. Herein, we design a polyurethane‐containing dynamic disulfide bonds and dangling chains to address this dilemma. The as‐prepared polyurethane exhibits an unprecedented damping range of 182°C (−62 to 120°C), and the tensile strength reaches 6.8 MPa, which is at the forefront of the same type of research. We innovatively introduce aromatic disulfides to the system, in which disulfide bonds can be spontaneously exchanged dynamically at room temperature, making the damping performance of the elastomer above room temperature improved, and a small amount of hydroxyl‐terminated polydimethylsiloxane (OH‐PDMS) is used as a dangling chain to promote the damping property of the elastomer between the glass transition temperature and room temperature. The synergistic effect of disulfide bonds and dangling chains makes the controllability of polyurethane damping temperature range realized. Furthermore, polyurethane elastomer is equipped with good thermal stability duo to the introduction of OH‐PDMS. And, the high‐performance polyurethane elastomer has great potential in practical application. [ABSTRACT FROM AUTHOR]

Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no therapeutic drugs approved for this pathology. Insulin resistance (IR) is implicated both in pathogenesis of nonalcoholic fatty liver disease (NAFLD) and in disease progression from steatosis to nonalcoholic steatohepatitis. In this study, we have characterized effects of an α2-adrenoceptor agonist, dexmedetomidine (DEX), which can alleviate IR in hepatocytes in high-fat diet (HFD)-induced NAFLD mice. The NAFLD mice received a daily intraperitoneal administration of DEX (100 µg⋅kg-1) after 16 days exhibited lower body weight, fewer and smaller fat droplets in the liver, markedly reduced the plasma triglyceride levels, accompanied by improvement of liver damage. This inhibition of lipid accumulation activity in obese mice was associated with a robust reduction in the mRNA and protein expression of the lipogenic enzyme stearyl-coenzyme A desaturase 1 (SCD1), which was probably mediated by the inhibition of C/EBP β, PPAR γ and C/EBP α through suppressing α2A-adrenoceptor (α2A-AR) via negative feedback. Additionally, DEX can also improve IR and inflammation by inhibiting the mitogen-activated protein kinases (MAPK) and nuclear factor kappa beta (NFκB) signaling pathway in vivo. Our findings implicate that DEX may act as a potential anti-steatotic drug which ameliorates obesity-associated fatty liver and improves IR and inflammation, probably by suppressing the expression of SCD1 and the inhibition of MAPK/NFκB pathway and suggest the potential adjuvant use for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

The objectives of this study were to determine the influence of waterlogging alone, drought alone, and alternating drought and waterlogging on cotton (Gossypium hirsutum L.) yield and yield components. Water deficit and waterlogging experiments were conducted at the flowering and boll-setting stages of cotton. The lint and cottonseed yields were reduced after waterlogging alone, drought alone, and alternating drought and waterlogging. The lint and cottonseed yields under alternating drought and waterlogging were greater than those under drought alone. When alternating drought and waterlogging, the drought stage decreased the lint and cottonseed yields, whereas the waterlogging stage had a compensatory effect. The decrease in the number of opening bolls might be the major reason for the observed decrease in lint and cottonseed yields. Waterlogging alone, drought alone, and alternating drought and waterlogging all led to an increase in the proportion of the boll wall biomass and a decrease in the proportion of the fiber biomass of cotton bolls. The proportion of the seed biomass of cotton bolls always decreased, except under alternating drought and heavy waterlogging in 2015. The seed/seed biomass ratio decreased, except under drought alone in 2015. These findings might provide data to support the prevention of cotton yield loss under drought and waterlogging. [ABSTRACT FROM AUTHOR]

It is essential for electric vehicle to equalise the voltages of battery or supercapacitor (SC) cells in series connection. Comparing with other equalisation methods based on energy transfer, Cockcroft-Walton (CW) voltage multiplier brings great benefits to the simplification of equalisation structure. Voltage equaliser formed by voltage multiplier can realise voltage balance automatically without voltage detection and control unit. However, the traditional (CW) voltage multiplier structure has two demerits. One is incapable of realising the voltage balancing for all the cells in series; the other one is the large inrush current of parallel capacitors that reduces the lifetime of the equaliser. To solve these problems, a modified voltage equalisation circuit is proposed. The new equaliser is constituted by a half-bridge frontend and a multiplier backend. The half-bridge generates the alternating voltage, and the multiplier accomplishes the voltage balancing. The operation principles, circuit analysis and parameters calculation are examined in detail. The performance is evaluated by simulation and experimental with three SCs in series. The accordance between simulation and experiment further proves that the voltage balancing is achieved for all the series cells and the inrush current of capacitors is declined at the turning on of power switches. [ABSTRACT FROM AUTHOR]

In order to obtain novel hollow latexes with both opaque and self film-forming properties, the four-layer core/shell latex particles-sequentially consisting of a high carboxyl-containing soft core, a transition layer, a rigid supporting layer, and an outermost film-forming layer-are first designed and prepared by emulsion polymerization, and then treated with alkali tofabricate self filmforming hollow latexes. On the basis of the previous research on the three-layer core/shell latex, influences of the composition and thickness of the film-forming layer on the properties and morphologies of the four-layer core/shell and the final hollow latexes are investigated. Results show that under optimized conditions with butyl acrylate/styrene (BA/St) mass ratio of 2/1, divinyl benzene (DVB) content of 1 wt %, and core/film-forming layer mass ratio of 1/6 in the film-forming layer preparation, the final hollow latex particles exhibit best morphology considering both light scattering efficiency and film-forming capability at room temperature. [ABSTRACT FROM AUTHOR]

The IL-6/signal transducer and activator of transcription 3 (STAT3) pathway is a critical signaling pathway for colitis-associated colorectal cancer (CAC). Peroxisome proliferator-activated receptor (PPAR)-δ, a lipid nuclear receptor, up-regulates IL-6. 15-Lipoxygenase-1 (15-LOX-1), which is crucial to production of lipid signaling mediators to terminate inflammation, down-regulates PPAR-δ. 15-LOX-1 effects on IL-6/STAT3 signaling and CAC tumorigenesis have not been determined. We report that intestinally targeted transgenic 15-LOX-1 expression in mice inhibited azoxymethane- and dextran sodium sulfate--induced CAC, IL-6 expression, STAT3 phosphorylation, and IL-6/STAT3 downstream target (Notch3 and MUC1) expression. 15-LOX-1 down-regulation was associated with IL-6 up-regulation in human colon cancer mucosa. Reexpression of 15-LOX-1 in human colon cancer cells suppressed IL-6 mRNA expression, STAT3 phosphorylation, IL-6 promoter activity, and PPAR-δ mRNA and protein expression. PPAR-δ overexpression in colonic epithelial cells promoted CAC tumorigenesis in mice and increased IL-6 expression and STAT3 phosphorylation, whereas concomitant 15-LOX-1 expression in colonic epithelial cells (15-LOX-1-PPAR-δ-Gut mice) suppressed these effects: the number of tumors per mouse (mean ± SEM) was 4.22 ± 0.68 in wild-type littermates, 6.67 ± 0.83 in PPAR-δ-Gut mice (P = 0.026), and 2.25 ± 0.25 in 15-LOX-1-PPAR-δ-Gut mice (P = 0.0006). Identification of 15-LOX-1 suppression of PPAR-δ to inhibit IL-6/STAT3 signaling-driven CAC tumorigenesis provides mechanistic insights that can be used to molecularly target CAC. [ABSTRACT FROM AUTHOR]

VgrG proteins form the spike of the type VI secretion system (T6SS) syringe-like complex. VgrG3 of Vibrio cholerae degrades the peptidoglycan cell wall of rival bacteria via its C-terminal region (VgrG3C) through its muramidase activity. VgrG3C consists of a peptidoglycan-binding domain (VgrG3CPGB) and a putative catalytic domain (VgrG3CCD), and its activity can be inhibited by its immunity protein partner TsiV3. Here, the crystal structure of V. cholerae VgrG3CCD in complex with TsiV3 is presented at 2.3 Å resolution. VgrG3CCD adopts a chitosanase fold. A dimer of TsiV3 is bound in the deep active-site groove of VgrG3CCD, occluding substrate binding and distorting the conformation of the catalytic dyad. Gln91 and Arg92 of TsiV3 are located in the centre of the interface and are important for recognition of VgrG3C. Mutation of these residues destabilized the complex and abolished the inhibitory activity of TsiV3 against VgrG3C toxicity in cells. Disruption of TsiV3 dimerization also weakened the complex and impaired the inhibitory activity. These structural, biochemical and functional data define the molecular mechanism underlying the self-protection of V. cholerae and expand the understanding of the role of T6SS in bacterial competition. [ABSTRACT FROM AUTHOR]

Prediction of cotton (Gossypium hirsutum L.) production under a changing climate requires a coupled modeling system that represents climate-cotton interactions. The existing Cotton growth model GOSSYM has drawbacks that prohibit its effective coupling with climate models. We developed a geographically distributed cotton growth model from the original GOSSYM and optimized it for coupling with the regional Climate-Weather Research Forecasting model (CWRF). This included software redesign, physics improvement, and parameter specification for consistent coupling of CWRF and GOSSYM. Through incorporation of the best available physical representations and observational estimates, the long list of inputs in the original GOSSYM was reduced to two parameters, the initial NO3 amount in the top 2 m of soil and the ratio of irrigated water amount to potential evapotranspiration. The geographic distributions of these two parameters are determined by optimization that minimizes model errors in simulating cotton yields. The result shows that the redeveloped GOSSYM realistically reproduces the geographic distribution of mean cotton yields in 30-km grids, within ±10% of observations across most of the U.S. Cotton Belt, whereas the original GOSSYM overestimated yields by 27 to 135% at the state level and 92% overall. Both models produced interannual yield variability with comparable magnitude; however, the temporal correspondence between modeled and observed interannual anomalies was much more realistic in the redeveloped than the original GOSSYM because significant (P = 0.05) correlations were identified in 87 and 40% of harvest grids, respectively. The redeveloped GOSSYM provides a starting point for additional improvements and applications of the coupled CWRF-GOSSYM system to study climate-cotton interactions. [ABSTRACT FROM AUTHOR]

Climate variability and changes affect crop yields by causing climatic stresses during various stages of the plant life cycle. A crop growth model must be able to capture the observed relationships between crop yields and climate stresses before its credible use as a prediction tool. This study evaluated the ability of the geographically distributed cotton growth model redeveloped from GOSSYM in simulating U.S. cotton (Gossypium hirsutum L.) yields and their responses to climate stresses during 1979 to 2005. Driven by realistic climate conditions, the model reproduced long-term mean Cotton yields within ±10% of observations at the 30-km model resolution across virtually the entire U.S. Cotton Belt and correctly captured the critical dependence of their geographic distributions on regional climate characteristics. Significant correlations between simulated and observed interannual variations were found across 87% of the total harvest grids. The model also faithfully represented the predictive role of July to August air temperature and August to September soil temperature anomalies on interannual Cotton yield changes on unirrigated lands, with a similar but weaker predictive signal for irrigated lands as observed. The modeled cotton yields exhibited large, positive correlations with July to August leaf area index. These results indicate the model's ability to depict the regional impact of climate stresses on cotton yields and suggest the potential predictive value of satellite retrievals. They also provide a baseline reference for further model improvements and applications in the future study of climate-cotton interactions. [ABSTRACT FROM AUTHOR]

Background: To investigate the association between serum concentrations of total bilirubin (TBil) in the physiological range and metabolic syndrome (MS) in middle-aged and elderly Chinese, as well as any associations between serum TBil concentrations and insulin resistance, hyperinsulinemia, and systemic inflammation. Methods: A cross-sectional study was conducted on 1423 individuals recruited from an urban community of Shanghai (average age 62.3 years) to investigate the relationship between bilirubin and cardiovascular diseases. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Results: Total bilirubin concentrations were significantly lower in individuals with MS compared with those without (0.65 ± 0.21 vs 0.69 ± 0.22 mg/dL, respectively; P = 0.002). The adjusted mean concentration of TBil decreased gradually with an increase in the number of components of MS ( Ptrend < 0.0001). After adjustment for a range of potential confounders (e.g. age, sex, body mass index, smoking, alcohol intake, homeostasis model assessment of insulin resistance etc.), each 1 SD increase in TBil was found to be associated with a 17% reduction in the risk of MS (odds ratio 0.83; 95% confidence interval 0.73-0.95; P = 0.006). Furthermore, after adjustment for all covariables, each 1 SD increase in TBil was found to be associated with lower odds of central obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, and hyperglycemia. Serum TBil concentrations were inversely associated with hyperinsulinemia, insulin resistance, and systemic inflammation. Conclusions: Serum TBil concentrations within the physiological range were inversely associated with MS and insulin resistance, hyperinsulinemia, and systemic inflammation in middle-aged and elderly Chinese. [ABSTRACT FROM AUTHOR]

Study Type - Therapy (case series) Level of Evidence 4 Lingual mucosal graft harvesting for urethroplasty is feasible, safe, provides long grafts and is easy to carry out. Most patients have minimal immediate or short-term donor site complications. The oral complications appeared to be related to the graft length and patient age. Most complications resolved within 1 year. Oral complications after LMGs harvesting were related to the patient's age at surgery. The children did not experience any persistent complications. Cases of bilateral or longer LMGs were associated with higher complication rates. However, most of these oral complications subsided gradually within 1 year. • This study was to evaluate donor-site complications of lingual mucosal graft harvesting for substitution urethroplasty. • 110 patients with anterior urethral strictures or hypospadias underwent lingual mucosal grafts (LMGs) urethroplasty. Dual LMGs were harvested from both sites separately or a long mucosal graft was harvested from one side to other side of tongue in 29 patients (group one); a shorter mucosal graft was harvested from one side of tongue in 81 patients (group two). A standard proforma (Appendix) was used for all patients. • The mean follow up time was 22 months (range 6∼41). At six months follow-up, numbness of tongue was reported in 19 patients (17.27%), parageusias in six (5.45%) and slurring of speech in 9 (8.18%). • Ninety-six patients were followed up for more than 12 mo. Numbness in operative area of tongue was documented in seven patients (7.29%), parageusias in three (3.13%) and slurred speech in three (3.13%). • None of these complications occurred in the six pediatric cases (<14 year) with a history of failed hypospadias repair. • LMGs urethroplasty, as most patients, were satisfied, but there were certain complications that have not been previously described in the literature. • Most oral complications subsided gradually within the first year. [ABSTRACT FROM AUTHOR]

Although associations of the liver enzymes alanine aminotransaminase (ALT) and -glutamyltransferase (GGT) with metabolic syndrome (MetS) are well recognized, whether they are independent of insulin resistance and which enzyme is more effective are yet to be clarified. A total of 5404 subjects aged ≥40 years were recruited from two urban communities in Shanghai for cross-sectional analyses. A subgroup of 681 participants without MetS at baseline was included in the longitudinal analyses. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR), and the modified National Cholesterol Education Program Adult Treatment Panel III criteria were adopted to diagnose MetS. Both GGT and ALT were strongly and positively associated with MetS risks in simple and multivariate analyses. Further adjustment for HOMA-IR and ALT did not change the association of GGT and MetS materially, whereas adjustment for HOMA-IR and GGT substantially attenuated the ALT-MetS association. In longitudinal analyses, risks of developing MetS were increased across GGT quartiles in a dose-dependent manner after extensive adjustments (odds ratios were 1.00, 1.38, 1.62, and 2.29 for GGT, quartile 1 through quartile 4; P for trend = 0.01). In contrast, ALT was no longer associated with MetS development after final adjustment for GGT ( P for trend = 0.09). Our study confirmed significant and independent associations of GGT and ALT with MetS in adult Chinese people. Moreover, GGT might be more effective for indicating the future development of MetS. [ABSTRACT FROM AUTHOR]

Four new patchoulol derivatives, 8 α,9 α-dihydroxypatchoulol (), 3 α,8 α-dihydroxypatchoulol (), 6 α-hydroxypatchoulol (), and 2 β,12-dihydroxypatchoulol (), were isolated from the aerial part of Pogostemon cablin (Labiatae), together with nine known compounds, sesquiterpenoids - and flavonoids -. Their structures were elucidated by detailed spectroscopic analysis, using 1D- and 2D-NMR techniques. [ABSTRACT FROM AUTHOR]

Background: Prehypertension is a risk factor for hypertension, diabetes, and cardiovascular diseases. However, the association between prehypertension and atherosclerosis in Type 2 diabetes mellitus (T2DM) has not been evaluated. In the present study, we investigated the impact of prehypertension on atherosclerosis in T2DM. Methods: Patients ( n = 930) with T2DM were recruited for the present study from the outpatient clinic of Shanghai Ruijin Hospital. The intima–media thickness (IMT) of the common carotid artery (CCA) was determined using ultrasound and brachial–ankle pulse wave velocity (baPWV) was determined by volume plethysmography to assess atherosclerosis. Results: Of the 930 patients with T2DM (mean age of 59 years), 167 were categorized as normotensive, 213 were prehypertensive, and 550 were hypertensive. Diabetic subjects with prehypertension had significantly higher CCA-IMT and baPWV than those with normal blood pressure after adjustment for age and gender. Multiple logistic regression analysis revealed that, compared with normotension, prehypertension was a significant independent determinant of atherosclerosis (for maximum IMT ≥1.1 mm, odds ratio (OR) 2.10 and 95% confidence interval (CI) 1.28–3.44; for baPWV ≥1400 cm/s, OR 3.09 and 95% CI 1.78–5.36). Conclusion: Prehypertension is associated with atherosclerosis independent of conventional cardiovascular risk factors in T2DM patients. We speculate that maintenance of systolic blood pressure <120 mmHg and diastolic blood pressure <80 mmHg may reduce the risk of atherosclerosis in T2DM. [ABSTRACT FROM AUTHOR]

Male concave-eared torrent frogs ( Odorrana tormota) have an unusually large call repertoire and have been shown to communicate ultrasonically. We investigated the individual specificity of male advertisement calls in order to explore the acoustic bases of individual recognition, which was demonstrated in an accompanying study. Vocalizations of 15 marked males were recorded in the field. A quantitative analysis of the signals revealed eight basic call-types. Two of them (the single- and multi-note long-calls) were investigated in more detail. Long-calls were characterized by pronounced and varying frequency modulation patterns, and abundant occurrence of nonlinear phenomena (NLP), i.e., frequency jumps, subharmonics, biphonations and deterministic chaos. The occurrence of NLP was predictable from the contour of the fundamental frequency in the harmonic segment preceding the onset of the NLP, and this prediction showed individual-specific patterns. Fifteen acoustic variables of the long calls were measured, all of which were significantly different among individuals, except biphonic segment duration. Discriminant function analysis (DFA) showed that 54.6% of the calls could be correctly assigned to individual frogs. The correct classification was above chance level, suggesting that individual specificity of calls underlie the ability of males to behaviorally discriminate the vocal signals of their neighbors from those of strangers, a remarkable feat for a frog species with a diverse vocal repertoire. The DFA classification results were lower than those for other anurans, however. We hypothesize that there is a tradeoff between an increase in the fundamental frequency of vocalizations to avoid masking by low-frequency ambient background noise, and a decrease in individual-specific vocal tract information extractable from the signal. [ABSTRACT FROM AUTHOR]

We critically reviewed recent reports of lingual mucosal grafts (LMGs) for substitution urethroplasty, to determine the efficacy and complications of this approach. Only a few centres have published the short or interim outcome of LMG urethroplasty. These studies dealt mainly with surgical techniques and harvesting LMGs, emphasizing the comparison of different intra-oral donor sites. The preliminary results seem to be encouraging for the safety and efficacy of LMG urethroplasty. When compared with other substitute materials, LMG give equally good results with much easier harvesting and minimal donor site morbidity. Thus, lingual mucosa is most likely to become an alternative to oral mucosa for substitution urethroplasty and longer term results of its use are awaited with interest. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the feasibility of tissue engineering of corpus cavernosal smooth muscle. Acellular corporal collagen matrices (ACCMs) were obtained from the penis of adult rabbits by a cell removal procedure. ACCMs were implanted into the back muscles of allogenic rabbits to investigate the resulting immunological reaction. Human umbilical artery smooth muscle cells (HUASMCs) were isolated from human umbilical arteries through explant techniques and expanded in vitro. Subsequently, third and fifth passage HUASMCs were seeded to ACCMs at a concentration of 30 × 106 cells/mL. Then, seeded ACCMs were implanted subcutaneously in athymic mice. The implants were retrieved at 10, 20 and 40 days after implantation. Histochemistry, immunohistochemistry and scanning electron microscopy were performed to analyse the morphological characteristics of the engineered tissues. Additionally, organ bath studies were performed to address the contractility of the engineered tissues. The decellularization process successfully extracted all cellular components while preserving the original collagen fibers. The immunological reaction to ACCMs consisted of only a transient nonspecific inflammatory response. Light and scanning electron microscopy demonstrated that HUASMCs extended onto the three-dimensional ACCMs scaffolds in vitro. Histological analyses of the explants from all time points demonstrated a progressive regeneration of smooth muscle, with structures very similar to native corpus cavernosum smooth muscle. The maximum contraction force induced by phenylephrine and electrical stimulation were 3.64 ± 0.18 g/100 mg and 2.50 ± 0.21 g/100 mg, respectively. Our study demonstrates that HUASMCs can be seeded on three-dimensional ACCM scaffolds and will develop tissues similar to that of the native corpus cavernosum smooth muscle. [ABSTRACT FROM AUTHOR]

The dear enemy phenomenon in which animals discriminate familiar neighbors from unknown strangers, and respond more aggressively to strangers is well established in various social animals, especially in songbirds and mammals. So far, very few studies of neighbor–stranger discrimination have been carried out in amphibians and the results have been mixed. Thus, it is unclear whether this phenomenon exists commonly in frogs and toads, and whether it is exhibited by species with large vocal repertoires. We conducted acoustic playback experiments with male concave-eared torrent frogs ( Odorrana tormota, a species with an unusually large vocal repertoire) kept in a tank in a quiet room to investigate whether or not they can discriminate strangers from neighbors acoustically. Nine of the 14 males tested showed evoked vocal responses to the calls from strangers, but none to calls from neighbors; vocal response to the calls from strangers was accompanied by aggressive motor activity. These results demonstrate that male O. tormota possess the ability to discriminate neighbors from strangers acoustically. Odorrana tormota therefore joins three ranid species ( Rana catesbiana, Rana clamitans, Rana dalmatina, all known to have a comparatively small and stereotyped vocal repertoires) as the only anurans demonstrated to have this ability. Given the difference in signaling complexity between these frog species, the salient acoustic features used for discriminating neighbors and strangers are likely to be quite distinct. [ABSTRACT FROM AUTHOR]

Objective Serum C-reactive protein (CRP) and microalbuminuria are predictors of cardiovascular disease. The association of these factors of cardiovascular risk with fasting and 2-h postload plasma glucose in a group of Chinese subjects was investigated. Design This was a cross-sectional cohort study. Subjects and methods In 1776 subjects randomly selected from the permanent residents of a community in the city of Shanghai, China, a simplified 75-g oral glucose tolerance test (fasting and 2-h postload blood sampling only) was performed, and serum CRP concentrations and urinary albumin : creatinine ratio were measured. Results Serum CRP concentration significantly increased from 1·62 mg/l in normoglycaemic subjects to 2·63 mg/l in subjects with impaired glucose regulation, and to 3·09 mg/l in newly diagnosed diabetic patients ( P < 0·0001). The corresponding prevalence of microalbuminuria also increased from 4·3% to 6·6% and to 11·4% ( P < 0·0001). Both before and after adjustment for confounders, fasting and 2-h postload plasma glucose levels were significantly associated with serum CRP concentration and the risk of microalbuminuria ( P < 0·003). However, the association for CRP tended to be more prominent with 2-h postload plasma glucose than with fasting plasma glucose. Indeed, with adjustments applied, for 1 SD change in fasting and 2-h postload plasma glucose concentration, serum CRP concentration increased by 14% and 18% (between the two regression coefficients, P = 0·01), respectively. With similar adjustments, for 1 SD change in fasting and 2-h postload plasma glucose concentration, the odds of microalbuminuria increased by 28% and 32% ( P = 0·28 for the difference between 28% and 32%), respectively. Conclusions Our finding suggests that in Chinese plasma glucose, especially 2-h postload, is associated with biological markers of cardiovascular disease, such as serum CRP concentration and microalbuminuria. [ABSTRACT FROM AUTHOR]

Two new acylated secoiridoid glucosides, 4′acetyl6′2hydroxy31βDglucopyranosyloxybenzoyloxysweroside and 3′,4′diacetyl6′2hydroxy31βDglucopyranosyloxybenzoyloxyswertiamarin, named gentistraminosides A 1 and B 2, were isolated from the MeOH extract of Gentiana stramineaMaximGentianaceae, together with twelve known ones, including eight iridoid and secoiridoid glucosides, macrophylloside A 3, loganic acid 4, secologanic acid 5, swertiamarin 6, gentiopicroside 7, loganic acid methyl ester 8, 6′OβDglucopyranosyl gentiopicroside 9, and loganic acid 11OβDglucopyranosyl ester 10, one flavone Cglucoside, isovitexin 11, one chromenecarboxylic acid glycosyl ester, macrophylloside D 12, and two triterpenoids, 1α,2α,3β,24tetrahydroxyolean12en28oic acid 13, and 3β,6α,24trihydroxyolean12en28oic acid 14. Their structures were determined by means of detailed spectroscopic NMR and MS analysis. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the feasibility of urethral substitution using free lingual mucosa grafts (LMGs) in a dog model. MATERIALS AND METHODS The study included 10 female mongrel dogs in which a 4 × 1 cm2 section of urethral mucosa was excised. The defect was immediately repaired with a size-matched free LMG harvested from the inferior lateral surface of the tongue. A 12 F urethral catheter was kept inside the urethra for a mean of 7 days. At 3 months after the procedure, the patency of the urethra was assessed by both insertion of a 12 F catheter and by retrograde urethrography. Dogs were killed, the grafted areas excised, and evaluated by gross and histopathological examination. RESULTS All dogs survived the procedure and there were no tongue complications. One of the 10 dogs developed a slight urethral stricture near the proximal anastomosis. The remaining nine dogs voided spontaneously with no difficulty. Retrograde urethrography showed that no strictures or fistulas had formed. The LMGs shortened by 9.5% after surgery, from a mean (sd) of 4 (0.13) to 3.62 (0.11) cm (statistically significant, P < 0.05). Histological examination showed that the LMGs were well-incorporated into the urethral walls and covered by a keratinized squamous epithelium. Neovascularization was evident beneath the grafts. CONCLUSION We successfully developed an dog model for free LMGs and showed the feasibility of this approach for urethral substitution. [ABSTRACT FROM AUTHOR]

Aim: Metallothionein (MT) protein is related to different stages of development and progression of various tumors in humans. The aim of the present study was to investigate expression and localization of MT and their association with clinicopathological characteristics in hepatocellular carcinoma (HCC). Methods: Histological specimens of 400 HCC with corresponding non-cancerous liver tissues were stained for MT (E9), P53 and Ki-67 by immunohistochemical staining using tissue microarrays. RNA expression of MT-1X and MT-2A isoforms was determined by real-time reverse transcription–polymerase chain reaction in a set of independent samples of 161 HCC. Results: Downregulated expression of MT at both mRNA and protein levels was detected in HCC, compared with non-cancerous liver tissues. The frequencies of MT positivity were significantly lower in cases with positive hepatitis B surface antigen than in those with negative hepatitis B surfaceantigen ( P = 0.042). The positive rate of MT expression was more frequent in tumors ≤2 cm than in tumors >2 cm in diameter ( P = 0.007). There was a tendency for MT expression to decrease with the progression of histological grade. Mainly nuclear expression of MT correlated with poorly differentiated HCC. No statistical correlation was found between P53, Ki-67 and MT expression. Conclusions: Downregulated expression of MT in HCC may play a role in hepatocarcinogenesis and be a marker of hepatocellular differentiation. Hepatitis B virus infection may be correlated to downregulated expression of MT. The mainly nuclear MT immunostaining may reflect an aggressive behavior in poorly differentiated HCC. [ABSTRACT FROM AUTHOR]

The bacterial pathogen Xanthomonas campestris pv. campestris co-ordinates virulence factor production and biofilm dispersal through a diffusible signal factor (DSF)-mediated cell–cell communication mechanism. The RpfC/RpfG two-component system plays a key role in DSF signal transduction and appears to modulate downstream DSF regulon by changing intracellular content of cyclic dimeric GMP (c-di-GMP), an unusual nucleotide second messenger. Here we show that Clp, a conserved global regulator showing a strong homology to the cAMP nucleotide receptor protein Crp of Escherichia coli, is essential for DSF regulation of virulence factor production but not for biofilm dispersal. Deletion of clp in Xcc changed the transcriptional expression of 299 genes including a few encoding transcription factors. Further genetic and microarray analysis led to identification of a homologue of the transcriptional regulator Zur, and a novel TetR-type transcription factor FhrR. These two regulatory factors regulated different sets of genes within Clp regulon. These results outline a hierarchical signalling network by which DSF modulates different biological functions, and may also provide a clue on how the novel nucleotide signal can be coupled to its downstream regulatory networks. [ABSTRACT FROM AUTHOR]

Aims Traditional Chinese medicine (TCM) has been used to treat drug addiction for more than 160 years and valuable experiences have been accumulated with regard to patients' detoxification and rehabilitation. The aims of this project were (1) to establish a computerized, bilingual (Chinese–English) database on TCM for drug addiction; (2) to analyse the literature published in this field; and (3) to identify those Chinese herbs commonly used for drug addiction treatment. Design (1) Paper collection: related papers were collected through electronic databases and hand-searched materials; (2) data computerization: the Microsoft Access program and Delphi language were used as the major data management systems; (3) paper analysis: annual publications from 1989 to 2003 were classified and calculated; and (4) herbal analysis: the frequency of herbs used and herbal function categories were analysed. Findings (1) A special bilingual database that contained 340 works of professional literature, including 85 patent files on TCM for drug addiction, was established, in which more than 90% of the publications originated from mainland China; (2) the literature classification showed a significant increase in the number of publications on clinical and laboratory researches in this field over the past decade; (3) five functional categorizations of Chinese herbs and the 10 most frequently used Chinese herbs as well as three toxic herbs were identified from more than 200 herbs reported in 150 original research articles and 85 patent files. Conclusions For the first time, the published data on TCM in the treatment of drug addiction were analysed systematically by using a new database. The results are invaluable for further laboratory and clinical studies to obtain more direct evidence. [ABSTRACT FROM AUTHOR]

The serine protease Omi/HtrA2 is released from mitochondria into the cytosol after apoptotic stimuli, inducing apoptosis in a caspase-independent manner through its protease activity and in a caspase-dependent manner by neutralizing the inhibition of inhibitor of apoptosis proteins (IAPs) on caspases. Alteration of apoptosis is essential for cancer development, and cancer cell death by radiation and chemotherapy is largely dependent upon apoptosis. Thus, analysis of the expression status of Omi/HtrA2, a regulator of apoptosis, in cancer tissues is needed for an understanding of cancer development. In the current study we analyzed the expression of Omi/HtrA2 in 65 prostate cancer, 40 benign prostatic hyperplasia and 10 normal prostate specimens by immunohistochemistry. Omi/HtrA2 mRNA levels of in vivo prostate cancer and benign prostatic hyperplasia samples were also assayed by semiquantitative reverse transcription-polymerase chain reaction. Immunopositivity (defined as ≥30%) was observed for Omi/HtrA2 in most of the prostate cancers, and the positive rate of Omi/HtrA2 was lower in the well-differentiated group than in the poorly and moderately differentiated groups (p<0.005). By contrast, the cells in the normal prostate and benign prostatic hyperplasia groups showed no or only weak expression of Omi/HtrA2. Meanwhile, the Omi/HtrA2 mRNA level of prostate cancer is much higher than that of benign prostatic hyperplasia (p<0.001). Taken together, these results suggest that prostate cancer cells in vivo may need Omi/HtrA2 expression for apoptosis, and that Omi/HtrA2 expression might be involved in prostate cancer development. [ABSTRACT FROM AUTHOR]

Objective Carotid intima–media thickness (IMT) has proved to be an independent marker of preclinical atherosclerosis. The aim of this study was to determine whether carotid IMT is associated with the plasma glucose concentration in the fasting state, after loading with oral glucose, or with the insulin sensitivity index (ISI) in nondiabetic subjects with different levels of glucose intolerance and insulin resistance. Design Cross-sectional study. Patients A total of 160 nondiabetic subjects (147 from our obesity-overweight clinic and 13 healthy normal subjects) were included in the present study , among them 33 had normal glucose tolerance (NGT), 13 had impaired fasting glucose (IFG), 80 had impaired glucose tolerance (IGT) and 34 had both IFG and IGT. Measurements Carotid IMT was assessed in the common carotid artery by a high-resolution B-mode ultrasound system. Plasma glucose was measured after fasting and at 30 min, 1, 2 and 3 h after a standard 75-g load of glucose. The ISI was calculated from the frequent sampling intravenous glucose tolerance test (FSIGT). Results The IMT values in the NGT group were lower than those in the IFG, IGT and IFG + IGT groups ( P < 0·03). No statistical difference in IMT values was found among the latter three groups. Univariate correlation analyses showed that the IMT was positively associated with age, plasma glucose concentrations 1 and 2 h after glucose loading, and serum concentration of low density lipoprotein (LDL) cholesterol ( r = 0·39, 0·22, 0·25 and 0·18, respectively, P < 0·05). Multiple regression analysis showed that only age, plasma glucose concentration 2 h after glucose loading, and LDL cholesterol appeared to be significant correlates of the IMT ( P < 0·0001), whereas the ISI was not. Conclusions In nondiabetic subjects with various degrees of glucose intolerance, there was a significant increase in IMT in those with IFG and IGT. Significant determinants of IMT, an indicator of preclinical atherosclerosis, include hyperglycaemia 2 h after a glucose load, age and LDL cholesterol, whereas fasting glucose concentration and the ISI were not significantly associated with IMT. [ABSTRACT FROM AUTHOR]

Notch signals are important for lymphocyte development but downstream events that follow Notch signaling are not well understood. Here, we report that signaling through Notch modulates the turnover of E2A proteins including E12 and E47, which are basic helix-loop-helix proteins crucial for B and T lymphocyte development. Notch-induced degradation requires phosphorylation of E47 by p42/p44 MAP kinases. Expression of the intracellular domain of Notch1 (N1-IC) enhances the association of E47 with the SCFSkp2 E3 ubiquitin ligase and ubiquitination of E47, followed by proteasome-mediated degradation. Furthermore, N1-IC induces E2A degradation in B and T cells in the presence of activated MAP kinases. Activation of endogenous Notch receptors by treatment of splenocytes with anti-IgM or anti-CD3 plus anti-CD28 also leads to E2A degradation, which is blocked by the inhibitors of Notch activation or proteasome function. Notch-induced E2A degradation depends on the function of its downstream effector, RBP-Jκ, probably to activate target genes involved in the ubiquitination of E2A proteins. Thus we propose that Notch regulates lymphocyte differentiation by controlling E2A protein turnover. [ABSTRACT FROM AUTHOR]

Transcriptional activation is associated commonly with recruitment of histone acetylases, while repression involves histone deacetylases (HDACs). Here, we provide evidence to suggest that STAT5 activates gene expression by recruiting HDAC. The interleukin-3 (IL-3)-dependent expression of the Id-1 gene, encoding a helix-loop-helix (HLH) transcriptional inhibitor, is activated by both C/EBPβ and STAT5 transcription factors bound to its pro-B-cell enhancer (PBE), but is inhibited by HDAC inhibitors in Ba/F3 cells. STAT5 interacts with HDAC1 in the PBE region, resulting in deacetylation of histones, as well as C/EBPβ, whose acetylation diminishes its DNA-binding activity. Consistently, expression of an acetylation-resistant mutant of C/EBPβ results in IL-3-independent expression of the Id-1 gene. Thus, we propose a novel mechanism by which STAT5 mediates the deacetylation of C/EBPβ, allowing transcriptional activation. [ABSTRACT FROM AUTHOR]

A novel method combining the conjugate-gradient and nonuniform fast Fourier transform (CG–NUFFT) algorithms for solving integral equations in electromagnetics is presented. The CG–NUFFT method has been applied to one- and two-dimensional inhomogeneous media. Numerical results show the advantages of the CG–NUFFT method over the CG–FFT method for problems with both electrically large and small regions. © 2000 John Wiley & Sons, Inc. Microwave Opt Technol Lett 24: 385–389, 2000. [ABSTRACT FROM AUTHOR]

Histone modifications play critical roles in DNA damage repair to safeguard genome integrity. However, how different histone modifiers coordinate to build appropriate chromatin context for DNA damage repair is largely unknown. Here, we report a novel interplay between the histone methyltransferase KMT5A and two E3 ligases RNF8 and RNF168 in establishing the histone modification status for DNA damage repair. KMT5A is a newly identified substrate of RNF8 in vitro and in vivo. In response to DNA double-strand breaks (DSBs), RNF8 promotes KMT5A recruitment onto damaged chromatin in a ubiquitination-dependent manner. RNF8-induced KMT5A ubiquitination increases the binding capacity of KMT5A to RNF168. Interestingly, KMT5A not only drives a local increase in H4K20 monomethylation at DSBs, but also promotes RNF168's activity in catalyzing H2A ubiquitination. We proved that the interaction between the H2A acidic patch and KMT5A R188/R189 residues is critical for KMT5A-mediated regulation of H2A ubiquitination. Taken together, our results highlight a new role for KMT5A in linking H4K20 methylation and H2A ubiquitination and provide insight into the histone modification network during DNA damage repair. [ABSTRACT FROM AUTHOR]

The article presents a reprint of the article "Single novel mutation in transmembrane region of glycoprotein (GP) IX affects GP Ib- IX complex expression and causes Bernard-Soulier syndrome," which appeared online on May 20, 2010. It discusses the impact of glycoprotein (GP) IX mutation in GP lb-IX complex and development of Bernard-Soulier syndrome (BSS) on a 6-year-old girl. It also mentions the implication of GP IX's transmembrane (TM) domain in GP Ib- IX-V expression on blood platelets.

In the title compound, [CuCl2(C9H12N2O)], the CuII atom is coordinated by two Cl− anions and two N atoms of one O-ethyl 3-methyl­pyridine-2-carboximidic acid mol­ecule in a slightly distorted square-planar geometry, with Cu—N distances of 2.0483 (17) and 1.9404 (18) Å, and Cu—Cl distances of 2.2805 (10) and 2.2275 (14) Å. In addition, each CuII atom is connected by one Cl− anion and the CuII atom from a neighbouring mol­ecule, with Cu⋯Cl and Cu⋯Cu distances of 2.9098 (13) and 3.4022 (12) Å, respectively, and, therefore, a centrosymmetric dimer is formed. Adjacent mol­ecular dimers are connected by π–π stacking inter­actions between pyridine rings to form a zigzag mol­ecular chain. The mol­ecular chains are also enforced by N—H⋯Cl and C—H⋯Cl inter­actions. [ABSTRACT FROM AUTHOR]

Bioluminescence tomography (BLT) is employed to reconstruct internal bioluminescent source to reveal the molecular and cellular information. However, BLT faces many challenges such as quantitative reconstruction. In this paper, a reconstruction–oriented multigrid finite element algorithm is proposed to fully reconstruct the source density. A source permissible region is utilized to raise the numerical stability. The proposed algorithm transfers diffuse equation into liner relationship between the inner source and boundary information on a mesh. A tolerant algorithm for linearly constrained optimization algorithm can solve the box-constrained quadratic optimization problem. By setting a threshold as the average reconstruction densities, we can refine every possible source element and form next mesh until the reconstructed densities are accepted. Numerical simulation of homogeneous and heterogeneous phantom demonstrates the feasibility and potential of the proposed algorithm. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]