Small-for-size syndrome (SFSS) may occur when graft volume is less than 45% of the standard liver volume, and it manifests as retarded growth and failure of the grafts and an increased mortality. However, its pathogenesis is poorly understood, and few effective interventions have been attempted.
The present study aims to delineate the critical role of oxidant stress in SFSS and protective effects of a superoxide dismutase (SOD) mimetic, MnTBAP, on graft function, growth and survival in the recipient rats.
Small size graft liver transplantation (SSGLT) was performed to determine the survival, graft injury and growth. MnTBAP was administered in SSGLT recipients (SSGLT+MnTBAP).
Serum ALT levels were sustained higher in SSGLT recipients, which were correlated with an increased apoptotic cell count and hepatocellular necrosis in liver sections. Malondialdehyde content, gene expression of TNF-α and IL-1β and DNA binding activity of NF-κB in the grafts were increased significantly in SSGLT recipients compared to sham-operated controls. Both phosphorylated p38 MAPK and nuclear c-jun were increased in SSGLT. All these changes were strikingly reversed by the administration of MnTBAP, with an increase in serum SOD activity. Moreover, in situ bromo-deoxyuridine incorporation demonstrated that graft regeneration in SSGLT+MnTBAP group was much profound than in the SSGLT group. Finally, the survival of recipients with MnTBAP treatments was significantly improved.
Enhanced oxidant stress with activation of the p38-c-Jun-NF-κB signaling pathway contributes to SFS-associated graft failure, retarded graft growth and poor survival. MnTBAP effectively reversed the pathologic changes in SFS-associated graft failure.
Living donor liver transplantation; Small-for-size syndrome; Oxidant stress; SOD mimetics
Rice stripe virus (RSV) is the type member of the genus Tenuivirus. RSV is known to have four segmented, single-stranded RNA molecules and causes rice stripe disease in the rice fields of China, Japan, and Korea. Based on the complete genomic sequences of the determined 6 RSV isolates (from Yunnan, Jiangsu, Zhejiang, and Liaoning Provinces, China) and 27 other RSV isolates (from Yunnan, Jiangsu, Anhui, Henan, and Shandong Provinces of China, also Japan and Korea) downloaded from GenBank, we provided a genotyping profile of RSV field isolates and described the population structure of RSV. All RSV isolates, except isolate CX, could be divided into two subtypes, one including 6 isolates from Yunnan Province, and the other including 26 isolates from different parts of China, Japan, and Korea, which were referred to as subtype II and subtype I, respectively. The amino acid distances between subtypes range from 0.053 to 0.085. RSV isolates in Yunnan Province were genetically differentiated from other parts of China, Japan, and Korea and showed infrequent gene flow. The RSV populations collected from other parts of China, Japan, and Korea were only composed of subtype I and showed very low genetic diversity. We speculated that isolate CX may be the result of recombination of isolates from two subtypes. Two potential recombination events were detected in RNA4 of isolate CX.
Rice stripe virus; Genetic variability; Genetic evolution
The catalytic (C) subunit of cAMP-dependent protein kinase (PKA) is a serine/threonine kinase responsible for most of the effects of cAMP signaling, and PKA serves as a prototype for the entire kinase family. Despite multiple studies of PKA, the steps involved in phosphoryl transfer, the roles of the catalytically essential magnesium ions, and the processes that govern the rate-limiting step of ADP release are unresolved. Here we identified conditions that yielded slow phosphoryl transfer of the γ-phosphate from the generally non-hydrolyzable analog of ATP, adenosine-5'-(β,γ-imido)triphosphate (AMP-PNP), onto a substrate peptide within protein crystals. By trapping both products in the crystal lattice, we now have a complete resolution profile of all the catalytic steps. One crystal structure refined to 1.55 Å resolution shows two states of the protein with 55% displaying intact AMP-PNP and unphosphorylated substrate and 45% displaying transfer of the γ-phosphate of AMP-PNP onto the substrate peptide yielding AMP-PN and phosphorylated substrate. Another structure refined to 2.15 Å resolution displays complete phosphoryl transfer to the substrate. These structures, in addition to trapping both products in the crystal lattice, implicate one magnesium ion, previously termed Mg2, as the more stably bound ion. Following phosphoryl transfer, Mg2 recruits a water molecule to retain an octahedral coordination geometry suggesting strong binding character of this magnesium ion, and Mg2 remains in the active site following complete phosphoryl transfer while Mg1 is expelled. Loss of Mg1 may thus be an important part of the rate-limiting step of ADP release.
Role of metal ions on kinase activity; protein kinase mechanism; crystal structure reaction intermediates; divalent metals; cAMP-dependent protein kinase
Epidemiologic evidence suggests that a diet rich in fruits and vegetables is associated with a reduced risk of prostate cancer (PCa) development. Although several dietary compounds have been tested in preclinical PCa prevention models, no agents have been identified that either prevent the progression of premalignant lesions or treat advanced disease. Momordica charantia, known as bitter melon in English, is a plant that grows in tropical areas worldwide and is both eaten as a vegetable and used for medicinal purposes. We have isolated a protein, designated as MCP30, from bitter melon seeds. The purified fraction was verified by SDS-PAGE and mass spectrometry to contain only 2 highly related single chain Type I ribosome-inactivating proteins (RIPs), α-momorcharin and β-momorcharin. MCP30 induces apoptosis in PIN and PCa cell lines in vitro and suppresses PC-3 growth in vivo with no effect on normal prostate cells. Mechanistically, MCP30 inhibits histone deacetylase-1 (HDAC-1) activity and promotes histone-3 and -4 protein acetylation. Treatment with MCP30 induces PTEN expression in a prostatic intraepithelial neoplasia (PIN) and PCa cell lines resulting in inhibition of Akt phosphorylation. In addition, MCP30 inhibits Wnt signaling activity through reduction of nuclear accumulation of β-catenin and decreased levels of c-Myc and Cyclin-D1. Our data indicate that MCP30 selectively induces PIN and PCa apoptosis and inhibits HDAC-1 activity. These results suggest that Type I RIPs derived from plants are HDAC inhibitors that can be utilized in the prevention and treatment of prostate cancer.
ribosome inactivating protein; HDAC inhibitor; prostate cancer; tumor suppresive gene; dietary factors
Annotating protein functions and linking proteins with similar functions are important in systems biology. The rapid growth rate of newly sequenced genomes calls for the development of computational methods to help experimental techniques. Phylogenetic profiling (PP) is a method that exploits the evolutionary co-occurrence pattern to identify functional related proteins. However, PP-based methods delivered satisfactory performance only on prokaryotes but not on eukaryotes. This study proposed a two-stage framework to predict protein functional linkages, which successfully enhances a PP-based method with machine learning. The experimental results show that the proposed two-stage framework achieved the best overall performance in comparison with three PP-based methods.
Hopping provides efficient and energy saving locomotion for kangaroos, but it results in great forces in the knee joints. A previous study has suggested that a unique fibrous cartilage in the central region of the tibial cartilage could serve to decrease the peak stresses generated within kangaroo tibiofemoral joints. However, the influences of the microstructure, composition and mechanical properties of the central fibrous and peripheral hyaline cartilage on the function of the knee joints are still to be defined. The present study showed that the fibrous cartilage was thicker and had a lower chondrocyte density than the hyaline cartilage. Despite having a higher PG content in the middle and deep zones, the fibrous cartilage had an inferior compressive strength compared to the peripheral hyaline cartilage. The fibrous cartilage had a complex three dimensional collagen meshwork with collagen bundles parallel to the surface in the superficial zone, and with collagen bundles both parallel and perpendicular to the surface in the middle and deep zones. The collagen in the hyaline cartilage displayed a typical Benninghoff structure, with collagen fibres parallel to the surface in the superficial zone and collagen fibres perpendicular to the surface in the deep zone. Elastin fibres were found throughout the entire tissue depth of the fibrous cartilage and displayed a similar alignment to the adjacent collagen bundles. In comparison, the elastin fibres in the hyaline cartilage were confined within the superficial zone. This study examined for the first time the fibrillary structure, PG content and compressive properties of the central fibrous cartilage pad and peripheral hyaline cartilage within the kangaroo medial tibial plateau. It provided insights into the microstructure and composition of the fibrous and peripheral hyaline cartilage in relation to the unique mechanical properties of the tissues to provide for the normal activities of kangaroos.
Papanicolaou (Pap) smears have revolutionized the management of patients with cervical cancers by permitting the detection of early, surgically curable tumors and their precursors. In recent years, the traditional Pap smear has been replaced by a liquid-based method, which allows not only cytologic evaluation but also collection of DNA for detection of human papillomavirus, the causative agent of cervical cancer. We reasoned that this routinely collected DNA could be exploited to detect somatic mutations present in rare tumor cells that accumulate in the cervix once shed from endometrial or ovarian cancers. A panel of genes that are commonly mutated in endometrial and ovarian cancers was assembled with new whole-exome sequencing data from 22 endometrial cancers and previously published data on other tumor types. We used this panel to search for mutations in 24 endometrial and 22 ovarian cancers and identified mutations in all 46 samples. With a sensitive massively parallel sequencing method, we were able to identify the same mutations in the DNA from liquid Pap smear specimens in 100% of endometrial cancers (24 of 24) and in 41% of ovarian cancers (9 of 22). Prompted by these findings, we developed a sequence-based method to query mutations in 12 genes in a single liquid Pap smear specimen without previous knowledge of the tumor’s genotype. When applied to 14 samples selected from the positive cases described above, the expected tumor-specific mutations were identified. These results demonstrate that DNA from most endometrial and a fraction of ovarian cancers can be detected in a standard liquid-based Pap smear specimen obtained during routine pelvic examination. Although improvements need to be made before applying this test in a routine clinical manner, it represents a promising step toward a broadly applicable screening methodology for the early detection of gynecologic malignancies.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms. However, duodenal GISTs compromise a small and rare subset and few studies have focused on them. We evaluated the surgical management of patients with duodenal GISTs treated by pancreaticoduodenectomy (PD) versus local resection (LR) in our institution and analyzed the postoperative outcomes.
This was a retrospective review of patients with duodenal GISTs managed in our institution from January 2006 to January 2012. Clinicopathologic findings and disease-free survival (DFS) of duodenal GIST patients were analyzed.
A total of 48 patients were selected. The most common presentation was bleeding (60.4%), and the second portion of the duodenum (35.4%) was the most common dominant site. Of the patients, 34 (70.8%) underwent LR while 14 (29.2%) underwent PD. The surgical margins for all studied patients were free. Patients who ultimately underwent PD were more likely to present with a larger tumor (median size: PD, 6.3 cm vs LR, 4.0 cm; P = 0.02) and more commonly presented with a tumor in the second portion of the duodenum (second portion: PD, 64.3% vs LR, 23.5%; P = 0.007). The tumors treated by PD had a higher grade of risk compared with LR as defined by National Institutes of Health (NIH) criteria (P = 0.019). PD was significantly associated with a longer operation time and a longer hospital stay compared to LR (P < 0.001 and P = 0.001, respectively). In our study, the median follow-up period was 36 months (range: 0 to 81 months). The 1- and 3-year DFS was 100% and 88%, respectively. From multivariable analysis, the only significant factor associated with a worse DFS was an NIH high risk classification (hazard ratio = 4.24).
The recurrence of duodenal GIST was correlated to tumor biology rather than type of operation. PD was associated with a longer hospital stay and longer operation time. Therefore, LR with clear surgical margins should be considered a reliable and curative option for duodenal GIST and PD should be reserved for lesions not amenable to LR.
Gastrointestinal stromal tumor (GIST); Duodenum; Local resection; Pancreaticoduodenectomy; Surgery
The luminescence characteristics of six osmium carbonyl complexes with phenanthroline (phen) or bipyridine (bpy) and pyridine (py), 4-phenylpyridine (4-phpy), or triphenylphosphine (PPh3) complexes in the presence of polyanion heparin were studied in both ethanol and aqueous solutions. The influence of heparin on the luminescence of the complexes is heavily dependent on the type of ligands in the complexes and the solvent used. In the ethanol solutions, the heparin solution enhanced the luminescence of the five osmium complexes, with the strongest enhancement to the 4-phenylpyridine complexes; linear curves were obtained in the luminescence enhancement ratio (F/F0) versus the heparin concentration range of 1–40 μg/mL. In aqueous solutions, heparin quenching of the complexes was more significant; a linear quenching curve was obtained with [Os(phen)2CO(PPh3)](PF6)2 in the lower concentration range of 1–12 μg/mL. The interaction of these complexes with heparin in the solutions is discussed. The complexes are shown to be successful in the fast and sensitive detection of heparin in commercial injectable samples.
AIM: To assess the value of plasma melatonin in predicting acute pancreatitis when combined with the acute physiology and chronic health evaluation II (APACHEII) and bedside index for severity in acute pancreatitis (BISAP) scoring systems.
METHODS: APACHEII and BISAP scores were calculated for 55 patients with acute physiology (AP) in the first 24 h of admission to the hospital. Additionally, morning (6:00 AM) serum melatonin concentrations were measured on the first day after admission. According to the diagnosis and treatment guidelines for acute pancreatitis in China, 42 patients suffered mild AP (MAP). The other 13 patients developed severe AP (SAP). A total of 45 healthy volunteers were used in this study as controls. The ability of melatonin and the APACHEII and BISAP scoring systems to predict SAP was evaluated using a receiver operating characteristic (ROC) curve. The optimal melatonin cutoff concentration for SAP patients, based on the ROC curve, was used to classify the patients into either a high concentration group (34 cases) or a low concentration group (21 cases). Differences in the incidence of high scores, according to the APACHEII and BISAP scoring systems, were compared between the two groups.
RESULTS: The MAP patients had increased melatonin levels compared to the SAP (38.34 ng/L vs 26.77 ng/L) (P = 0.021) and control patients (38.34 ng/L vs 30.73 ng/L) (P = 0.003). There was no significant difference inmelatoninconcentrations between the SAP group and the control group. The accuracy of determining SAP based on the melatonin level, the APACHEII score and the BISAP score was 0.758, 0.872, and 0.906, respectively, according to the ROC curve. A melatonin concentration ≤ 28.74 ng/L was associated with an increased risk of developing SAP. The incidence of high scores (≥ 3) using the BISAP system was significantly higher in patients with low melatonin concentration (≤ 28.74 ng/L) compared to patients with high melatonin concentration (> 28.74 ng/L) (42.9% vs 14.7%, P = 0.02). The incidence of high APACHEII scores (≥ 10) between the two groups was not significantly different.
CONCLUSION: The melatonin concentration is closely related to the severity of AP and the BISAP score. Therefore, we can evaluate the severity of disease by measuring the levels of serum melatonin.
Pancreatitis; Melatonin concentrations; Predict; Cutoff; Bedside index for severity in acute pancreatitis; Acute physiology and chronic health evaluation II
Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus), is one of the most devastating fungal diseases and imposes huge yield loss each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL) for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR) at the mature plant stage and three QTLs for leaf resistance (LR) at the seedling stage in multiple environments were mapped on nine linkage groups (LGs) of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54–15.86% and 29.01%–32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790) was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.
Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average each tumor had 19 somatic alterations in coding genes (range, 3–70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients.
Maize chlorotic mottle virus (MCMV) infects maize plants and causes significant losses in corn production worldwide. In this study, purified MCMV particles were used as the immunogen to produce monoclonal antibodies (MAbs) and polyclonal antibodies (PAbs). Four murine MAbs (4B8, 8C11, 6F4, and 9G1) against MCMV were obtained through the hybridoma technology. The triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA), dot-immunobinding assay (DIBA), and immunocapture reverse transcription-polymerase chain reaction (IC-RT-PCR) using the MAb 4B8 were then developed for sensitive, specific, and rapid detection of MCMV in fields. MCMV could be detected in infected leaf crude extracts at dilutions of 1:327 680, 1:64 000, and 1:3 276 800 (w/v, g/ml) by TAS-ELISA, DIBA, and IC-RT-PCR, respectively. One hundred and sixty-one maize field samples showing virus-like symptoms and sixty-nine symptomless maize field samples from ten different provinces of China were collected and screened for the presence of MCMV using the established serological methods. A phylogenetic tree was constructed based on the full length CP genes and Chinese MCMV isolates formed one branch with Thailand isolates. The detection results demonstrated that MCMV is one of most prevalent viruses infecting maize in the Yunnan and Sichuan provinces of China.
Maize chlorotic mottle virus (MCMV); Immunocapture reverse transcription-polymerase chain reaction (IC-RT-PCR); Triple antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA); Monoclonal antibody (MAb); Dot-immunobinding assay (DIBA)
The increased accumulation of intracellular lipid droplets within hepatocytes is a pathologic hallmark of liver injury of various etiologies, especially non-alcoholic steatohepatitis (NASH). The dynamics, subcellular origin, and chemical composition of lipid droplets under various pathophysiologic conditions, however, remain poorly understood. We used coherent Raman microscopy and spontaneous Raman spectroscopy to monitor and analyze the formation of lipid droplets in living primary rat hepatocytes exposed to VLDL lipolysis products. After exposure to lipolysis products for 30 minutes, new lipid droplets rapidly appeared within hepatocytes and increased in size and number over the observation period of 205 minutes. Intracellular lipid droplet transport appears to be greatly reduced after lipolysis product treatment. Spontaneous Raman spectroscopy of individual intracellular lipid droplets before and after exposure to VLDL lipolysis products reveals that the major components of these droplets are esterified unsaturated fatty acids. The fatty acid unsaturation ratio increases with droplet size. In response to simultaneous exposure to an oxidized form of linoleic acid, 13-hydroxy-9,11-octadecadienoic acid (13-HODE) and palmitic acid, a marked increase in saturated fat content was found when compared to treatment with palmitic acid alone. Lipid aggregation in hepatocytes induced by VLDL lipolysis products may be the initial event leading to non-alcoholic fatty liver disease (NAFLD).
NASH; NAFLD; CARS; Non-linear microscopy; Raman spectroscopy; lipolysis; VLDL
Protosappanin A (PrA), an immunosuppressive ingredient of the medicinal herb Caesalpinia sappan L, prolongs heart allograft survival in rats, possibly by impairing the function of antigen-presenting cells (APCs). We examined the effects of PrA on the maturation and function of dendritic cells (DCs), a potent class of APCs, and the downstream cell–cell and intracellular signaling pathways mediating the immunosuppressive activity of PrA. PrA inhibited LPS-stimulated maturation of Wistar rat DCs in vitro as reflected by reduced expression of costimulatory molecules (CD80 and CD86) and reduced expression of TLR4 and NF-κB, two critical signaling components for antigen recognition. PrA also enhanced the release of IL-10 and decreased the release of IL-12 from DCs, but had no effect on the production of TGF-ß. In mixed cultures, Wistar DCs pretreated with PrA impaired the proliferation of Sprague Dawley (SD) rat T cells while promoting the expansion of SD rat CD4+CD25+ regulatory T cells (Tregs). Both oral PrA treatment and infusion of PrA-pretreated Wistar DCs prolonged cardiac allograft survival (Wistar donor, SD recipient) and expanded recipient CD4+CD25+Foxp3+ Tregs. Donor spleen cells, but not spleen cells from a third rat strain (DA), supported the expansion of recipient CD4+CD25+Foxp3+ Tregs and suppressed recipient T cell proliferation. We conclude that PrA triggers a tolerogenic state in DCs that allows for the induction of alloantigen-specific Tregs and the suppression of allograft rejection in vivo.
We report a case of pancreatic hemolymphangioma. Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels. The incidence of this disease in the pancreas is extremely rare. To the best of our knowledge, only seven cases have been reported worldwide (PubMed). A 39-year-old woman with a one-day history of abdominal pain was admitted to our hospital. There was no obvious precipitating factor. The preoperative examination, including ultrasonography and computed tomography, showed a cystic-solid tumor in the pancreas, and it was considered to be a mucinous cystadenoma or cystadenocarcinoma. Pancreatic body-tail resection combined with splenectomy was performed. After the operation, the tumor was pathologically demonstrated to be a pancreatic hemolymphangioma. Although pancreatic hemolymphangioma is rare, we believe that it should be considered in the differential diagnosis of cystic-solid tumors of the pancreas, particularly when there is no sufficient evidence for diagnosing cystadenoma, cystadenocarcinoma or some other relatively common disease of the pancreas.
Pancreatic neoplasm; Hemolymphangioma; Differential diagnosis; Computed tomography; Ultrasonography
Apigenin (4’,5,7-trihydroxyflavone) was recently shown effective in inhibiting several cancers. The aim of this study was to investigate the effect and mechanism of apigenin in the human bladder cancer cell line T24 for the first time.
T24 cells were treated with varying concentrations and time of apigenin. Cell viability was evaluated by MTT assay. Cell motility and invasiveness were assayed by Matrigel migration and invasion assay. Flow cytometry and western blot analysis were used to detect cell apoptosis, cell cycle and signaling pathway.
The results demonstrated that apigenin suppressed proliferation and inhibited the migration and invasion potential of T24 bladder cancer cells in a dose- and time-dependent manner, which was associated with induced G2/M Phase cell cycle arrest and apoptosis. The mechanism of action is like to involve PI3K/Akt pathway and Bcl-2 family proteins. Apigenin increased caspase-3 activity and PARP cleavage, indicating that apigenin induced apoptosis in a caspase-dependent way.
These findings suggest that apigenin may be an effective way for treating human bladder cancer.
Apigenin; Bladder cancer; Cell cycle arrest; Apoptosis; Invasion
A simple two-step method was employed for preparing nano-sized gold nanoparticles-graphene composite to construct a GNPs-GR-SDS modified electrode. Hemoglobin (Hb) was successfully immobilized on the surface of a basal plane graphite (BPG) electrode through a simple dropping technique. Direct electrochemistry and electrocatalysis of the hemoglobin-modified electrode was investigated. The as-prepared composites showed an obvious promotion of the direct electro-transfer between hemoglobin and the electrode. A couple of well-defined and quasi-reversible Hb CV peaks can be observed in a phosphate buffer solution (pH 7.0). The separation of anodic and cathodic peak potentials is 81 mV, indicating a fast electron transfer reaction. The experimental results also clarified that the immobilized Hb retained its biological activity for the catalysis toward NO. The biosensor showed high sensitivity and fast response upon the addition of NO, under the conditions of pH 7.0, potential -0.82 V. The time to reach the stable-state current was less than 3 s, and the linear response range of NO was 0.72-7.92 μM, with a correlation coefficient of 0.9991.
hemoglobin; graphene; gold nanoparticles; nitric oxide; biosensor
Epidemiological and clinico-pathological studies indicate a causal relationship between heart disease and Alzheimer’s disease (AD). To learn whether heart disease causes an onset of AD, mice with myocardial infarction (MI) and congestive heart failure (HF) were used to test neuropsychiatric and cognitive behaviors as well as for measurements of AD related protein markers. To this end, adult mice were subjected to ligation of left anterior descending artery (LAD) and about two weeks later high-frequency echocardiography was performed to exam the resulting cardiac structure and function. Three months after successful induction of chronic heart failure (CHF) these mice showed an impairment of learning in the Morris Water Maze task. In addition, the expression of selected molecules, which are involved in β-amyloid metabolism, apoptosis and inflammation on the level of gene transcription and translation, was altered in CHF mice. Our findings provide a plausible explanation that CHF increases the risk of cognitive impairments and alters cerebral β-amyloid metabolism. In addition, our data indicate that the cerebral compensatory mechanisms in response to CHF are brain area and gender specific.
As Doppler ultrasound has been proven to be an effective tool to predict and compress the optimal pulsing windows, we evaluated the effective dose and diagnostic accuracy of coronary CT angiography (CTA) incorporating Doppler-guided prospective electrocardiograph (ECG) gating, which presets pulsing windows according to Doppler analysis, in patients with a heart rate >65 bpm.
Materials and Methods
119 patients with a heart rate >65 bpm who were scheduled for invasive coronary angiography were prospectively studied, and patients were randomly divided into traditional prospective (n = 61) and Doppler-guided prospective (n = 58) ECG gating groups. The exposure window of traditional prospective ECG gating was set at 30%–80% of the cardiac cycle. For the Doppler group, the length of diastasis was analyzed by Doppler. For lengths greater than 90 ms, the pulsing window was preset during diastole (during 60%–80%); otherwise, the optimal pulsing intervals were moved from diastole to systole (during 30%–50%).
The mean heart rates of the traditional ECG and the Doppler-guided group during CT scanning were 75.0±7.7 bpm (range, 66–96 bpm) and 76.5±5.4 bpm (range: 66–105 bpm), respectively. The results indicated that whereas the image quality showed no significant difference between the traditional and Doppler groups (P = 0.42), the radiation dose of the Doppler group was significantly lower than that of the traditional group (5.2±3.4mSv vs. 9.3±4.5mSv, P<0.001). The sensitivities of CTA applying traditional and Doppler-guided prospective ECG gating to diagnose stenosis on a segment level were 95.5% and 94.3%, respectively; specificities 98.0% and 97.1%, respectively; positive predictive values 90.7% and 88.2%, respectively; negative predictive values 99.0% and 98.7%, respectively. There was no statistical difference in concordance between the traditional and Doppler groups (P = 0.22).
Doppler-guided prospective ECG gating represents an improved method in patients with a high heart rate to reduce effective radiation doses, while maintaining high diagnostic accuracy.
Dufulin is a novel, highly effective antiviral agent that activatives systemic acquired resistance of plants. This compound is widely used in China to prevent and control viral diseases in tobacco, vegetable and rice. Dufulin can treat plants infected by the tobacco mosaic virus and the cucumber mosaic virus. However, the achiral analysis and residue determination of dufulin remain underdeveloped because of its high enantioselectivity rates and high control costs. The enantioselectivity of an antiviral compound is an important factor that should be considered when studying the effect of chiral pesticides on the environment. The enantioselective degradation of dufulin in water remains an important objective in pesticide science.
The configuration of dufulin enantiomers was determined in this study based on its circular dichroism spectra. The S-(+)-dufulin and R-(−)-dufulin enantiomers were separated and identified using an amylose tris-(3,5-dimethylphenylcarbamate) chiral column by normal phase high-performance liquid chromatography. The degradation of the rac-dufulin racemate and its separate enantiomers complied with first-order reaction kinetics and demonstrated acceptable linearity. The enantioselective photolysis of rac-dufulin allowed for the faster degradation of R-(−)-dufulin, as compared with S-(+)-dufulin. However, S-(+)-dufulin was hydrolyzed faster than its antipode.
The photolysation and hydrolyzation of dufulin in water samples normally complied with the first-order kinetics and demonstrated acceptable linearity (R2>0.66). A preferential photolysation of the R-(−)-enantiomer was observed in water samples. Moreover, the S-(+)-enantiomer was hydrolyzed faster than its antipode.
We report a case of hidroacanthoma simplex with giant lesion that was found on the left lumbar part which was treated with surgical excision.
Hidroacanthoma simplex; lumbar part; skin
Nilaparvata lugens, a major pest in rice-growing areas, is extremely difficult to manage. Neonicotinoids have increasingly been used in crop protection and animal health care against N. lugens. To discover new bioactive molecules and pesticides, we combined the active structure of cyanoacrylates, aromatic aldehydes, and substituted pyridyl (thiazolyl) methyl-2-substituted-methylidene-imidazolidine derivatives for the design and synthesis of a series of novel neonicotinoid analogs with dihydropyridine.
A series of neonicotinoid analogs with dihydropyridine were synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR, and elemental analysis and their insecticidal and antibacterial activities were assessed. Preliminary biological activity tests showed that all of the title compounds feature insecticidal activities against N. lugens at 500 mg/L. Moreover, some compounds showed promising antibacterial activities against Pseudomonas solanacearum (e.g., Tobacco bacterial wilt and Tomato bacterial wilt) at a dose of 200 mg/L.
A synthetic route to obtain neonicotinoid analogs with dihydropyridine by the reaction of intermediates 2 (pyridyl (thiazolyl) methyl-2-substituted-methyl-ideneimidazolidine) and intermediates 1 (cyanoacrylates) and different aromatic aldehydes in acetonitrile under reflux conditions is presented. The effects of different solvents, bases, and reaction time on the reaction of 3a were investigated. The results of this study suggest that neonicotinoid analogs with dihydropyridine could cause N. lugens death and restrain P. solanacearum growth.