Type-II/type-II band alignment to boost spatial charge separation: a case study of g-C3N4 quantum dots/a-TiO2/r-TiO2 for highly efficient photocatalytic hydrogen and oxygen evolution.

Efficient spatial charge separation and transfer that are critical factors for solar energy conversion primarily depend on the energetic alignment of the band edges at interfaces in heterojunctions. Herein, we first report that constructing a 0D/0D type-II(T-II)/T-II heterojunction is an effective strategy to ingeniously achieve long-range charge separation by taking a ternary heterojunction of TiO2 and graphitic carbon nitride (g-C3N4) as a proof-of-concept. Incorporating g-C3N4 quantum dots (QCN), as the third component, into the commercial P25 composed of anatase (a-TiO2) and rutile (r-TiO2) can be realized via simply mixing the commercially available Degussa P25 and QCN solution followed by heat treatment. The strong coupling and matching band structures among a-TiO2, r-TiO2 and QCN result in the construction of novel T-II/T-II heterojunctions, which would promote the spatial separation and transfer of photogenerated electrons and holes. Moreover, QCN plays a key role in reinforcing light absorption. Particularly, the unique 0D/0D architecture possesses the advantages of abundant active sites for the photocatalytic reaction. As a result, the optimized QCN/a-TiO2/r-TiO2 heterojunctions exhibit enhanced photocatalytic H2 and O2 evolution, especially the hydrogen evolution rate (49.3 µmol h-1) is 11.7 times that of bare P25 under visible light irradiation, and sufficient catalytic stability as evidenced by the recycling experiments. The remarkably enhanced photocatalytic activity can be attributed to the synergistic effects of the energy level alignment at interfaces, the dimensionality and component of the heterojunctions. This work provides a stepping stone towards the design of novel heterojunctions for photocatalytic water splitting.

Bioactive Azaphilone Derivatives from the Fungus Talaromyces aculeatus.

Six new azaphilone derivatives, talaraculones A-F (1-6), together with five known analogues (7-11), were obtained from the saline soil-derived fungus Talaromyces aculeatus. The absolute configurations of 1 and 6 were assigned by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. Compounds 1 and 5 represent the first reported azaphilone derivatives with a C4 aliphatic side chain and a methylal group at C-3, respectively. Talaraculones A and B (1 and 2) exhibited stronger inhibitory activity against α-glucosidase than the positive control acarbose (IC50 = 101.5 µM), with IC50 values of 78.6 and 22.9 µM, respectively.

A new quinolinone from freshwater lake-derived fungus Myrothecium verrucaria.

One new quinolinone, 7-hydroxy-3-methoxyviridicatin (1), along with eight known compounds (2-9) was isolated from the fungus Myrothecium verrucaria, which was collected from lake water of Chenghai, Yunnan Province, China. Their structures were elucidated by detailed analysis of spectroscopic data and comparison with related known compounds. Compounds 1 and 2 exhibited weak antibacterial activity. To the best of our knowledge, this is the first report on quinolinones (1-4) as the secondary metabolites of M. verrucaria.

A PCR-based Rapid Neutralization Assay for GII.4 Norovirus Infection in HIEC6 Cell Culture.

Because of limited viral replication and lack of cytopathic effect in cell culture, a new PCR-based rapid seroneutralization assay for detection of GII.4 norovirus neutralized antibodies was developed with serum samples from acute-phase patients, convalescent-phase patients and healthy controls. According to this study, neutralizing antibodies were detected in 100% of convalescent-phase sera, and in 2.5% of healthy controls sera. However, all of the acute-phase serum samples could not neutralize virus efficiently. Compared to the results from ELISA (96.2% at sensitivity and 80% at specificity), the present in vitro neutralization assay is more specific and more sensitive.

[Clinical and laboratory investigation of pericentric inv(9)(p22q34) with the der(9)t(9;22)(q34;q11) in Ph-positive leukemia].

OBJECTIVE: To investigate clinical and molecule genetics features of four Ph-positive leukemia patients characterized by pericentric inv(9)(p22q34) with the der(9)t(9;22)(q34;q11). METHODS: Cytogenetic analysis was carried out on bone marrow directly or after short-period culture. R banding was used for karyotype analysis. BCR/ABL fusion gene was detected with interphase fluorescence in situ hybridization (FISH), and chromosome painting was carried out using specific probes. RT-PCR was used to detect BCR/ABL chimeric transcripts. RESULTS: One patient with acute myeloid leukemia (AML) presented three clones, which included one with a normal karyotype, one with t(9;22)(q34;q11), and one with inv(9)(p22q34) involving the der(9)t(9;22) and additional t(8;12)(q12;p11). The inv(9)(p22q34) has always co-occurred with der(9)t(9;22)(q34;q11) accompanied by der(22)t(9;22)(q34;q11) in all metaphases from the three patients with chronic myeloid leukemia (CML). B3a2 transcript was detected in all patients by RT-PCR. Inv(9)(p22q34) was found in both CML and AML, and was associated with poor prognosis. CONCLUSION: Inv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Leukemia with der(9)t(9;22) and inv(9)(p22q34) has unique clinical and laboratory characteristics.

The urotensin-II receptor antagonist palosuran improves pancreatic and renal function in diabetic rats.

Urotensin-II (U-II) is a cyclic peptide that acts through a specific G-protein-coupled receptor, UT receptor. Urotensin-II and UT receptors have been described in pancreas and kidney, but their function is not well understood. We studied the effects of chronic treatment of diabetic rats with the orally active selective U-II receptor antagonist palosuran. Streptozotocin treatment causes pancreatic beta-cell destruction and leads to the development of hyperglycemia, dyslipidemia, and renal dysfunction. Long-term treatment of streptozotocin-induced diabetic rats with palosuran improved survival, increased insulin, and slowed the increase in glycemia, glycosylated hemoglobin, and serum lipids. Furthermore, palosuran increased renal blood flow and delayed the development of proteinuria and renal damage. The U-II system is unique in that it plays a role both in insulin secretion and in the renal complications of diabetes. Urotensin receptor antagonism might be a new therapeutic approach for the treatment of diabetes.

Pharmacology of the urotensin-II receptor antagonist palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt): first demonstration of a pathophysiological role of the urotensin System.

Urotensin-II (U-II) is a cyclic peptide now described as the most potent vasoconstrictor known. U-II binds to a specific G protein-coupled receptor, formerly the orphan receptor GPR14, now renamed urotensin receptor (UT receptor), and present in mammalian species. Palosuran (ACT-058362; 1-[2-(4-benzyl-4-hydroxy-piperidin-1-yl)-ethyl]-3-(2-methyl-quinolin-4-yl)-urea sulfate salt) is a new potent and specific antagonist of the human UT receptor. ACT-058362 antagonizes the specific binding of (125)I-labeled U-II on natural and recombinant cells carrying the human UT receptor with a high affinity in the low nanomolar range and a competitive mode of antagonism, revealed only with prolonged incubation times. ACT-058362 also inhibits U-II-induced calcium mobilization and mitogen-activated protein kinase phosphorylation. The binding inhibitory potency of ACT-058362 is more than 100-fold less on the rat than on the human UT receptor, which is reflected in a pD'(2) value of 5.2 for inhibiting contraction of isolated rat aortic rings induced by U-II. In functional assays of short incubation times, ACT-058362 behaves as an apparent noncompetitive inhibitor. In vivo, intravenous ACT-058362 prevents the no-reflow phenomenon, which follows renal artery clamping in rats, without decreasing blood pressure and prevents the subsequent development of acute renal failure and the histological consequences of ischemia. In conclusion, the in vivo efficacy of the specific UT receptor antagonist ACT-058362 reveals a role of endogenous U-II in renal ischemia. As a selective renal vasodilator, ACT-058362 may be effective in other renal diseases.

[The preliminary studies on the cross action between endothelin-1 and angiotensin II in kidney tissue of rats with diabetic nephropathy].

OBJECTIVE: To investigate the interrelation between endothelin-1 (ET-1) and angiotensin II (AngII) in kidney tissue of rats with diabetic nephropathy. METHODS: Wistar rats were performed a removal operation of right kidney. Two weeks later the uninephrectomized rats were given intravenous injection of streptozotocin (STZ, 35 mg/kg). The diabetic rats were randomly divided into the following four groups: DM + bos group (bosentan 100 mg/kg/d by gavage); DM + ena group (enalapril 10 mg/kg/d by gavage); DM + bos + ena group (the same doses of both bosentan and enalapril by gavage); DM + veh group (only buffer by gavage). Besides, uninephrectomized rats without STZ injection were assigned as control group. Each group consisted of 6 rats. Twenty weeks later, they were sacrificed and left kidney of each rat was harvested respectively. The mRNA expression of angiotensinogen (Ao), angiotensin type 1 receptor (AT1R), preproendothelin-1 and endothelin A receptor (ETaR), and the protein expression of AngII, AT1R, ET-1 and ETaR in kidney tissue were semi-quantitatively detected with reverse transcription- polymerase chain reaction and immunohistochemical staining respectively. RESULTS: In the diabetic group without treatment (DM + veh group), the expression of Ao (AII), AT1R and ET-AR was significantly up-regulated (1.25, 1.94 and 2.56-folds in mRNA respectively, 2.52, 3.84 and 3.30-folds in protein respectively, P < 0.01 or P < 0.05) compared with control group. In three treatment groups, i.e. DM + bos group, DM + ena group and DM + bos + ena group, the up-regulated expression of Ao (AII), AT1R and ET-AR was significantly attenuated (-38.2% to -54.8% in mRNA and -55.3% to -69.7% in protein, P < 0.05 or P < 0.01) compared with DM group. The inhibitory rates among these three treatment groups had no significant difference (P > 0.05). In this study, the expression of preproendothelin-1 mRNA and ET-1 protein was not significantly changed among all groups (P > 0.05). CONCLUSION: Either endothelin receptor antagonist or ACE inhibitor can significantly inhibit the expression of AngII, AT1R and ETaR in kidney tissue of diabetic rats, which suggest that there are close relationship and cross action between ET-1 and AngII.

Chronic endothelin receptor blockade prevents both early hyperfiltration and late overt diabetic nephropathy in the rat.

Diabetic nephropathy is associated with enhanced renal synthesis of endothelin (ET)-1. The goal of this study was to investigate the effects of dual ET receptor antagonism in the early phase (2 months) and in the late phase (5 months) of diabetic nephropathy in rats, and to compare this approach to angiotensin-converting enzyme inhibition. Four groups of uninephrectomized streptozotocin-induced diabetic rats were assigned to receive orally vehicle, bosentan, enalapril, or their combination. A fifth group consisted of nondiabetic, uninephrectomized rats. At 2 weeks, untreated diabetic rats exhibited increased glomerular filtration rate and renal plasma flow. Bosentan, enalapril, and the combination all prevented hyperfiltration and hyperperfusion. By 5 months, diabetic rats developed marked increases in mean arterial pressure and renal vascular resistance, progressive proteinuria, and renal structural damage with glomerular sclerosis and hypertrophy. Bosentan completely prevented the development of hypertension and renal vasoconstriction, and largely prevented the development of proteinuria and renal structural injury. The renal protective effect of bosentan was comparable to that of enalapril or the combination, although its anti-proteinuric effect was less. Clinical studies are warranted to assess whether ET receptor antagonism can have additive effects on top of ACE inhibition, the current treatment of choice in diabetic nephropathy.

Chronic endothelin receptor blockade prevents renal vasoconstriction and sodium retention in rats with chronic heart failure.

OBJECTIVE: Importance of endothelin in mediating the chronic renal alterations of chronic heart failure was studied in rats chronically treated with bosentan after myocardial infarction. METHODS: Rats were subjected to coronary artery ligation and were treated for 8 weeks with placebo or bosentan, a dual ET(A) and ET(B) receptor antagonist, (approximately 100 mg/kg/day) as food admix. Sham-operated rats served as normal controls. Cardiac and renal functions were measured at the end of 8-week treatment. RESULTS: Bosentan significantly reduced the elevated left ventricular end-diastolic pressure (from 26.6+/-3.3 to 11.4+/-2.2 mmHg, P<0.001) and the increased heart-to-body-weight ratio seen in untreated rats with myocardial infarction. Bosentan prevented the marked increase in renal vascular resistance (bosentan, 7.7+/-0.6; untreated, 15.6+/-2.5 mmHg/ml/min; P<0.001). This led to a significant increase in renal plasma flow resulting in a decrease in filtration fraction. Bosentan furthermore increased urinary sodium excretion. CONCLUSIONS: Prolonged ET receptor blockade in rats with myocardial infarction has chronic renal vasodilatory effect and improves renal sodium excretory function. Thus, dual ET antagonists such as bosentan might be useful in the treatment of the progressive renal failure associated with human chronic heart failure.