沉之深,意之著,思无涯 林华《司空图二十四诗品曲解集注》第四首《沉着》音乐诗品解读

作曲家林华创作的《司空图二十四诗品曲解集注》,由二十四首前奏曲与赋格组成,相间搭配,各自独立。第四首《沉着》表现了“沉之深,意之著,思无涯”的诗品意境。作曲家从当代视角观照《沉着》诗品,音乐与唐代诗品实现古今对话,中西交融的创作技法诠释诗品的音韵。本文从诗歌解读到音乐解读,借助作曲技法分析,深入挖掘音乐作品内涵,进一步解读《沉着》的音乐创作特征。

Liver iron transport

The liver plays a central role in iron metabolism. It is the major storage site for iron and also expresses a complex range of molecules which are involved in iron transport and regulation of iron homeostasis. An increasing number of genes associated with hepatic iron transport or regulation have been identified. These include transferrin receptors （TFRI and 2）, a ferrireductase （STEAP3）, the transporters divalent metal transporter-1 （DMT1） and ferroportin （FPN） as well as the haemochromatosis protein, HFE and haemojuvelin （HJV）, which are signalling molecules. Many of these genes also participate in iron regulatory pathways which focus on the hepatic peptide hepcidin. However, we are still only beginning to understand the complex interactions between liver iron transport and iron homeostasis. This review outlines our current knowledge of molecules of iron metabolism and their roles in iron transport and regulation of iron homeostasis.

Role of iron in hepatic fibrosis: One piece in the puzzle

Iron is an essential element involved in various biological pathways. When present in excess within the cell, iron can be toxic due to its ability to catalyse the formation of damaging radicals, which promote cellular injury and cell death. Within the liver, iron related oxidative stress can lead to fibrosis and ultimately to cirrhosis. Here we review the role of excessive iron in the pathologies associated with various chronic diseases of the liver. We also describe the molecular mechanism by which iron contributes to the development of hepatic fibrosis.

Hepcidin modulation in human diseases: From research to clinic

By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.

Pathology of hepatic iron overload

Although progress in imaging and genetics allow for a noninvasive diagnosis of most cases of genetic iron overload, liver pathology remains often useful （1） to assess prognosis by grading fibrosis and seeking for associated lesions and （2） to guide the etiological diagnosis, especially when no molecular marker is available. Then, the type of liver siderosis （parenchymal, mesenchymal or mixed） and its distribution throughout the Iobule and the liver are useful means for suggesting its etiology： HLA-linked hemochromatosis gene （HFE） hemochromatosis or other rare genetic hemochromatosis, nonhemochromatotic genetic iron overload （ferroportin disease, aceruloplasminemia）, or iron overload secondary to excessive iron supply, inflammatory syndrome, noncirrhotic chronic liver diseases including dysmetabolic iron overload syndrome, cirrhosis, and blood disorders.

Combined effects of light intensity and NH_4^+-enrichment on growth, pigmentation, and photosynthetic performance of Ulva prolifera(Chlorophyta)

The aim of this study was to investigate the effects of light intensity and enhanced nitrogen supply on the growth and photosynthesis of the green-tide macroalga, Ulvaprolifera. Thalli of U. prolifera were grown in natural or NH^-enriched seawater under two different light intensities for 7 days, and then the growth rate, pigmentation, and photosynthetic performance of the thalli were evaluated. The results show that the relative growth rate （RGR） was markedly higher under the high light level than under the low light level. Enrichment with NH~ enhanced the RGR under high light intensity, but did not affect RGR under low light intensity. In low light conditions, NH;-enrichment resulted in a marked decrease in the maximal photosynthetic rate （Pro） and the maximum carbon fixation rate （Vmax）, but it did not affect the half saturation constant for carbon （K0.5） or the ratio of Vmax to K0.5, which reflects the carbon acquisition efficiency. In high light conditions, Pm, K05, and the dark respiration rate （Rd） increased under NHI enrichment, but Vmax and the Vmax/Ko5 ratio decreased. Regardless of the light intensity, NH^＋4-enrichment did not affect the apparent photosynthetic efficiency （a）, which reflects the ability of the alga to use light energy at low light levels. Under both low and high light intensities, the chlorophyll a （Chl a）, chlorophyll b （Chl b）, and carotenoids （Car） contents in thalli were higher in NH1-enriched than in natural seawater, except that there was a decrease in the Chl b content of thalli in NH1-enriched seawater under low light intensity. Therefore, NH^＋4 enrichment improved the growth and photosynthetic performance of U. prolifera under high light intensity, but not under low light intensity. We discuss the possible mechanisms underlying these physiological responses.

Cronkhite-Canada syndrome associated with myelodysplastic syndrome

We report a case of Cronkhite-Canada syndrome(CCS)associated with myelodysplastic syndrome(MDS).A 54-year-old woman,diagnosed as MDS the prior year after evaluation of anemia,visited our hospital with the chief complaint of epigastric discomfort.She also had dysgeusia,alopecia,atrophic nail change,and pigmentation of the palm,all of which began several months ago.Blood tests revealed severe hypoalbuminemia.Colonoscopy(CS)showed numerous,dense,red polyps throughout the colon and rectum.Biopsy specimens showed stromal edema,infi ltration of lymphocytes,and cystic dilatation of the crypt.Her clinical manifestations and histology were consistent with CCS.We prescribed corticosteroids,which dramatically improved her physical findings,laboratory data,and endoscopic fi ndings.This is the first report of CCS in a patient with MDS.

Non-HFE haemochromatosis

Non-HFE hereditary haemochromatosis （HH） refers to a genetically heterogeneous group of iron overload disorders that are unlinked to mutations in the HFE gene. The four main types of non-HFE HH are caused by mutations in the hemojuvelin, hepcidin, transferrin receptor 2 and ferroportin genes. Juvenile haemochromatosis is an autosomal recessive disorder and can be caused by mutations in either hemojuvelin or hepcidin. Ar~ adult onset form of HH similar to HFE-HH is caused by homozygosity for mutations in transferrin receptor 2. The autosomal dominant iron overload disorder ferroportin disease is caused by mutations in the iron exporter ferroportin. The clinical characteristics and molecular basis of the various types of non-HFE haemochromatosis are reviewed. The study of these disorders and the molecules involved has been invaluable in improving our understanding of the mechanisms involved in the regulation of iron metabolism.

Hyperferritinemia is a risk factor for steatosis in chronic liver disease

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in 57 (45.9%), and cryptogenic liver damage in 14 (11.3%). None was diagnosed as hereditary hemochromatosis (HH). Hepatic siderosis on liver biopsy was present in 17 of 54 (32%) patients; grade 1 in eight and grade 2 in nine. Overall, 92 patients (74.2%) had steatosis. By logistic regression, ferritin and γ-glutamyltransferase were independent predictors of steatosis. Ferritin levels were signifi cantly related to low platelet count, steatosis and hepatitis C virus infection. CONCLUSION: In a non-obese cohort of non-alcoholic patients with chronically abnormal LFTs without HH, high serum ferritin level is a risk factor for steatosis.

Function of the hemochromatosis protein HFE:Lessons from animal models

Hereditary hemochromatosis （HH） is caused by chronic hyperabsorption of dietary iron. Progressive accumulation of excess iron within tissue parenchymal cells may lead to severe organ damage. The most prevalent type of HH is linked to mutations in the HFE gene, encoding an atypical major histocompatibility complex class I molecule. Shortly after its discovery in 1996, the hemochromatosis protein HFE was shown to physically interact with transferrin receptor 1 （TfR1） and impair the uptake of transferrin-bound iron in cells. However, these findings provided no clue why HFE mutations associate with systemic iron overload. It was later established that all forms of HH result from misregulation of hepcidin expression. This liverderived circulating peptide hormone controls iron efflux from duodenal enterocytes and reticuloendothelial macrophages by promoting the degradation of the iron exporter ferroportin. Recent studies with animal models of HH uncover a crucial role of HFE as a hepatocyte iron sensor and upstream regulator of hepcidin. Thus, hepatocyte HFE is indispensable for signaling to hepcidin, presumably as a constituent of a larger ironsensing complex. A working model postulates that the signaling activity of HFE is silenced when the protein is bound to TfR1. An increase in the iron saturation of plasma transferrin leads to displacement of TfR1 from HFE and assembly of the putative iron-sensing complex. In this way, iron uptake by the hepatocyte is translated into upregulation of hepcidin, reinforcing the concept that the liver is the major regulatory site for systemic iron homeostasis, and not merely an iron storage depot.

Porphyria cutanea tarda as a complication of therapy for chronic hepatitis C

There is a strong association between porphyria cutanea tarda (PCT) and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo development of PCT during therapy for chronic viral hepatitis C. We describe the development of PCT in a 56-year-old patient with chronic viral hepatitis C after 12 wk of peginterferon/ribavirin therapy. In addition, the patient was homozygous for the H63D hereditary hemochromatosis gene (HFE ) mutation. The association of PCT with chronic viral hepatitis C and the possible role of hepatic iron overload and ribavirin-induced hemolytic anemia in the development of PCT during therapy for chronic viral hepatitis C are discussed.

The First Isolation of a Cyanophage-Synechococcus System from the East China Sea

A cyanophage strain and its host Synechococcus were isolated from the East China Sea. The host Synechococcus sp. S J01 was characterized by its 16S rRNA, ITS, andpsbA gene sequences as well as by its morphological appearance and pigmentation. The cyanophage, strain S-SJ2, was able to cause a lytic infection of the coastal Synechococcus. TEM of negative-stained specimens showed that the phage isolate has an isometric head with a diameter of 68 nm and a long tail with a length of 280 nm. The cyanophage-Synechococcus system from the East China Sea shares many properties with other marine cyanophage-Synechocoecus systems worldwide.

The Effects of Trehalose on the Bioluminescence and Pigmentation of the Phase I Variant of Photorhabdus luminescens

Photorhabdus luminescens is a Gram-negative, bioluminescent, pigment producing enteric bacterium, which is pathogenic to insects and has the capability to undergo phase variation. The phase I variant of P. luminescens exists as a mutualistic symbiont where it plays a critical role in the life-cycle of the soil-dwelling nematode, Heterorhabditis bacteriophora. Both the bacterium and the nematode receive their nutritional requirements from the bioconversion of the insect host which is rich in many macromolecules such as the disaccharide, trehalose. Trehalose is a non-reducing disaccharide of glucose that is formed by an a-1,1-glycosidic bond and is associated with the physiology of many bacteria, insects and nematodes. Trehalose has been shown to be the most abundant storage sugar found within insect hemolymph （1%-2%）. The physicochemical properties of trehalose allow this carbohydrate to act as a stress protectant where it has been implicated with thermal stress, dehydration, and osmotic protection of many microorganisms. Due to these properties, trehalose may allow culture stability of the phase I variant in vitro and in vivo. Traits of the phase I variant that were studied in this work include bioluminescence and the production of the red anthroquinone-derived pigment. The carbohydrates that were utilized in this study were glucose and trehalose; where shake flask cultures of the phase I variant were cultured at room temperature for up to six days in carbohydrate supplemented basal media with increasing carbohydrate concentrations of 0. 1%, 0.5% and 1.0% （v/v）. Relative luminosity, pigmentation and pH were graphed as a function of time, carbohydrate used, and carbohydrate concentration. Data obtained from this study suggests that the supplementation of 1.0% trehalose, when culturing the phase I variant ofP. luminescens, can maintain bioluminosity and pigmentation over extended periods of time （five days） as compared to basal media and basal media supplemented with 1.0% glucose.

Turbot Scophthalmus maximus: stocking density on growth, pigmentation and feed conversion

Juvenile turbot （Scophthalmus maximus） the initial stock densities at 0.28, 0.87, 1.12, 1.16, 2.75 were reared in five different experiment groups in kg/m^2 respectively for the study of the density effect on growth, pigmentation and feed coefficient rate. The experiment lasted for 60 days with final stock densities at 1.91, 6.31, 8.86, 11.97, 17.67 kg/m^2 respectively. Result showed that, in the same experiment condition, the stocking density has a positive effect on growth in low density and negative in high density. The SGR （special growth rate） was 3.189, 3.304, 3.447, 3.341, and 3.087 respectively. The uniformity of weight distributing among experiment groups decreased with increasing density. The stocking density had positive effect on feed coefficient rate. Group 1 had the least feed coefficient rate 0.96, and highest at 1.25 in Group 5, the highest density group. High stocking density inhibited the growth and increased the feed coefficient rate. The stocking density had negative relationship to pigmentation improvement for whitened fish.

Occult celiac disease prevents penetrance of hemochromatosis

AIM:To report a patient with C282Y homozygocity,depleted body iron and intestinal atrophy caused by celiac disease (CD) who experienced resolution of the enteropathy with subsequent normalization of iron metabolism upon gluten free diet. METHODS:To obtain information on the tissue distribution and quantitative expression of proteins involved in duodenal iron trafficking,we determined the expression of divalent-metal transporter 1 (DMT1),ferroportin 1 (FP1) and transferrin receptor (TfR1) by means of immunohist-ochemistry and real-time PCR in duodenal biopsies of this patient. RESULTS:Whereas in hereditary hemochromatosis patients without CD, DMT1 expression was up-regulated leading to excessive uptake of iron, we identified a significant reduction in protein ana mRNA expression of DMT1 as a compensatory mechanism in this patient with HH and CD. CONCLUSION:Occult CD may compensate for increased DMT1 expression in a specific subset of individuals with homozygous C282Y mutations in the hemochromatosis (HFE) gene,thus contributing to the low penetrance of HH.

Hepatic adenomatosis associated with hormone replacement therapy and hemosiderosis:A case report

We have reported a case of hepatic adenomatosis associated with hormone replacement therapy （estrogen and progesterone） and hemosiderosis caused by excessive blood transfusion for the treatment of chronic myeloid leukemia. A 34-year-old woman was found to have several hepatic tumors on a routine medical examination. The general condition was good. Laboratory studies showed iron overload. Abdominal computed tomography and selective hepatic angiography showed several hypervascular tumors in the right lobe of the liver （up to 20 mm in diameter）. Since hepatocellular carcinoma could not be ruled out, subsegmental hepatectomy was performed. Histopathological examination of the surgical specimen showed hepatic adenomatosis with hemosiderosis. Both hormone replacement therapy and iron overload could be the cause of hepatic adenomatosis.

An unhappy triad:Hemochromatosis, porphyria cutanea tarda and hepatocellular carcinoma-A case report

Liver fibrosis and cirrhosis are predisposing factors for the development of hepatocellular carcinoma （HCC）. Hemosiderosis has also been described to trigger carcinogenesis. A significant iron overload, as found in hereditary hemochromatosis （HHC）, is a risk factor for HCC and may also promote the symptoms of porphyria cutanea tarda （PCT）. A 68-year old male patient presented to our clinic with a suspected HCC, elevated alpha-fetoprotein but normal liver function tests. He reported a 25 year-old history of vitiligo upon exposure to sunlight. The patient underwent an extended left hemihepatectomy, and the recovery was uneventful, with the exception of a persistent hyperbilirubinemia. Perfusion problems and extrahepatic cholestasis were ruled out by CT-scan with angiography and MR-cholangiopancreatography. However, MR1 showed an iron overload. Histology confirmed the HCC （pT3, pN0, G3, R0） and revealed a portal fibrosis and hemosiderosis. Based on the skin lesions we suspected a PCT that was confirmed by laboratory tests showing elevated porphyrin, uroporphyrin, coproporphyrin and porphobilinogen. Concurrently, molecular diagnostics revealed homozygosity for the C282Y mutation within the hemochromatosis HFE gene. After phlebotomy and normalization of liver function tests the patient was discharged. This is the first case ever showing the unusual combination of HCC in a fibrotic liver with HHC and PCT. This diagnosis not only warrants oncological follow-up but also symptomatic therapy to normalize iron metabolism and thereby improve liver function and alleviate the symptoms of HHC and PCT. Thus progression of fibrosis may be prevented and liver regeneration supported.

Sporadic somatic mutation of c-kit gene in a family with gastrointestinal stromal tumors without cutaneous hyperpigmentation

We described two members in a family with gastrointestinal stromal tumors （GISTs） without cutaneous hyperpigmentation. The patients were father and son who did not have cutaneous hyperpigmentation. Histological examination showed that these tumors were GISTs expressing CD34 and CD117. Tumor DNA extracted from paraffin-embedded specimens revealed somatic mutation with a deletion mutation at different codons in exon 11 of c-kit gene after direct sequencing analysis. No germline mutation was detected in DNA extracted from peripheral leukocytes obtained from the father and son. We propose that GISTs could be caused by sporadic somatic mutation in a family without germline mutation and hyperpigmentation.

Marine Green Algae as a Supplement for Chlorophyll and Other Nutrients in Vigna Radiata under UV-C Radiation-Induced Stress

The potential protective effect of marine green algae （Codium iyengerii） was examined in UV-C treated seedlings of Vigna radiata. The study comprises of three treatments of UV-C radiation （100-290 nm） dose for one min in alternative days. This results in deformed morphological parameters, including： decrease in plant height, fresh mass of leaves, shoots and roots, as well as leaf areas, which may be attributed with decreased in the relative growth rate, carbohydrate, amino acids, and protein contents of plant. A drastic effect of UV-C radiation was found on the photosynthetic apparatus where increase in red pigmentations on the leaves surface indicates the presence of UV-C absorbing pigments instead of chloroplast pigments. Visible spectrum of leaves chlorophyll showed reduced concentration of visible absorbing pigments which showed the deleterious effect of these radiations on physiological processes of seedlings. These negative effects of UV-C radiation on plant growth were found to be decreased by the application of green seaweed （Codium iyengerii）, and absorption spectrums of chloroplast contents showed that UV-C radiation inducing damages were appropriately managed by enhanced concentration of seaweeds which significantly increased morphological and physiological parameters like leaf, stem, root biomass, and plant height under UV-C radiation were observed.

Study on Development of Formulated Feed for Improving Growth and Pigmentation of Koi Carp （Cyprinus carpio L,, 1758） Juveniles

The aim of the present study was to develop a formulated feed for improving skin pigmentation and growth performance of koi carp juveniles. Two experiments were conducted for determination of an optimal dietary astaxanthin and FM （fish meal） ration for koi carp juveniles. In the first experiment, three isonitrogenous and isoenergetic dietary treatments were designed with three different levels of astaxanthin consisted of 60, 80 and 100 mg/kg and a commercial feed served as a control. For the second experiment, four isonitrogenous and isoenergetic dietary treatments were formulated with graded inclusions of dietary FM replaced from 0% to 60% at 20% increments by SM （soybean meal）, PBM （poultry by-product meal）, and a CD （control diet）. Obtained results demonstrated that skin pigmentation of koi carp juveniles fed the diet containing 80 mg/kg astaxanthin, 36.02% protein, 7.78% lipid, 4.20 Kcal/g GE （gross energy） were more better than those at the diet with lower estaxanthin content and commercial diet. Moreover, the highest growth and feed utilization of fish were observed at this diet with WG （weight gain）, SGR （specific growth rate） and FCR （feed conversion ratio） were 121.80%, 0.95 （%/day） and 1.6, respectively.