Amplification of a terahertz wave via stimulated Raman scattering.

Extremely strong terahertz (THz) waves are desperately demanded for investigating nonlinear physics, spectroscopy, and imaging in the THz range. However, traditional crystal-/semiconductor-based THz sources have limitations of reaching extremely high amplitude due to the damage threshold of devices. Here, by introducing Raman amplification to the THz range, we propose a novel, to the best of our knowledge, scheme to amplify THz waves in plasma. A long-pulse CO2 pump laser transfers its energy to a multicycle, 10-THz seed in a two-step plasma. By one-dimensional simulations, a 0.87-GV/m, 1.2-ps-duration THz seed is amplified to 10 GV/m in a 5.7-mm-long plasma with an amplification efficiency approaching 1%. The method provides a new technology to manipulate the intensity of THz waves.

The incidence of acute kidney injury in hospitalized patients receiving aminoglycoside antibiotics: a retrospective study.

OBJECTIVE: Our aim is to investigate the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients who received aminoglycoside antibiotics. MATERIALS AND METHODS: A retrospective analysis was performed on the electronic medical record information of inpatients who received aminoglycoside (AG) antibiotics in our center from January 2018 to December 2020. The diagnosis of AKI was based on serum creatinine changes. Several statistical methods, including chi square test and two sample Wilcoxon rank sum test, were used to evaluate the epidemiological characteristics of aminoglycosides associated AKI. The multivariate logistic regression analysis was used to screen the risk factors. RESULTS: Finally, 8,040 patients who received AGs were included in the study. Among them, 494 patients (6.14%) were judged as incidence with AKI, while only 29 patients were diagnosed with AKI in the medical record. The multiple logistic regression analysis suggested that admission to ICU, complicated with diabetes mellitus, heart failure, anemia, shock, combined use of diuretics, ß-lactam antibiotics, proton pump inhibitors were independent risk factors for AKI related to aminoglycosides. CONCLUSIONS: It is urgent to improve the understanding and attention of AKI for medical workers, and the assessment of risk factors before the use of aminoglycosides should be contributed to the early prevention, diagnosis, and treatment of AKI.

Glucagon-like peptide-1 regulates mitochondrial biogenesis and tau phosphorylation against advanced glycation end product-induced neuronal insult: Studies in vivo and in vitro.

Our previous study has proved that glucagon-like peptide-1 (GLP-1), which is developed to treat type 2 diabetes, has a significant effect on neuroprotection against advanced glycation end product (AGE)-induced neuronal insult in vitro models of diabetes-related Alzheimer's disease (AD). However, the molecular mechanisms remain to be elucidated and it is not clear whether GLP-1 receptor mediates the down-regulation effects on AGE-induced AD-like changes in vivo. This study aims to explore the effect and mechanisms of GLP-1 receptor agonists (GLP-1RA) against the AGE-dependent signaling pathway both in vitro and in vivo. In this study, we demonstrated that GLP-1RA could inhibit oxidative stress and repair mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with AGEs. Importantly, we first observed AGEs in the circulatory system could induce tau hyperphosphorylation after we injected AGEs (1µg/kg bodyweight) into the mice tail vein. We found GLP-1RA could promote mitochondrial biogenesis and antioxidant system via regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling pathway in vivo besides down-regulating the activity of glycogen synthase kinase 3ß (GSK-3ß) to reverse tau hyperphosphorylation directly. Collectively, our results suggest that GLP-1RA protects neurons against AGE-induced tau hyperphosphorylation via regulating GSK-3ß and PGC-1α two cooperative signaling pathways.

Glucagon-like peptide-1 protects hippocampal neurons against advanced glycation end product-induced tau hyperphosphorylation.

We have previously demonstrated that glucagon-like peptide-1 (GLP-1) receptor agonist ameliorated neurodegenerative changes in rat models of diabetes-related Alzheimer's disease (AD), and protected neurons from glucose toxicity in vitro. Herein, we investigated the effects of GLP-1 receptor mediates on cell toxicity and tau hyperphosphorylation induced by advanced glycation end products (AGEs), which are associated with glucose toxicity, and the molecular mechanism in PC12 cells and the primary hippocampal neurons. Our study demonstrated that the similar protection effects of GLP-1 existed in PC12 cells treated with glucose-bovine serum albumin (BSA) in hyperglycemic conditions or with glycoaldehyde-BSA alone. Additionally, glucose-BSA alone did not induce significant cytotoxicity in PC12 cells, but resulted in tau hyperphosphorylation in primary hippocampal neurons in 24h. And we found that GLP-1 could reduce cell tau phosphorylation induced by high glucose or glucose-BSA. Furthermore, our data in the present study suggested that GLP-1 regulated tau phosphorylation induced by AGEs through a signaling pathway involving glycogen synthase kinase 3ß (GSK-3ß), similarly to the GSK-3ß inhibitor, lithium chloride. Our findings suggest that GLP-1 can protect neurons from diabetes-associated AGE insults in vitro, and provide new evidence for a potential therapeutic value of GLP-1 receptor agonist in the treatment of AD especially diabetes-related AD.

Optimization of auto-induction medium for G-CSF production by Escherichia coli using artificial neural networks coupled with genetic algorithm.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine widely used in cancer patients receiving high doses of chemotherapeutic drugs to prevent the chemotherapy-induced suppression of white blood cells. The production of recombinant G-CSF should be increased to meet the increasing market demand. This study aims to model and optimize the carbon source of auto-induction medium to enhance G-CSF production using artificial neural networks coupled with genetic algorithm. In this approach, artificial neural networks served as bioprocess modeling tools, and genetic algorithm (GA) was applied to optimize the established artificial neural network models. Two artificial neural network models were constructed: the back-propagation (BP) network and the radial basis function (RBF) network. The root mean square error, coefficient of determination, and standard error of prediction of the BP model were 0.0375, 0.959, and 8.49 %, respectively, whereas those of the RBF model were 0.0257, 0.980, and 5.82 %, respectively. These values indicated that the RBF model possessed higher fitness and prediction accuracy than the BP model. Under the optimized auto-induction medium, the predicted maximum G-CSF yield by the BP-GA approach was 71.66 %, whereas that by the RBF-GA approach was 75.17 %. These predicted values are in agreement with the experimental results, with 72.4 and 76.014 % for the BP-GA and RBF-GA models, respectively. These results suggest that RBF-GA is superior to BP-GA. The developed approach in this study may be helpful in modeling and optimizing other multivariable, non-linear, and time-variant bioprocesses.

Effects of thyroxine on L-cysteine desulfuration in mouse liver.

The effect of exogenous thyroxine (T4) administration on the activity of rhodanese, cystathionase, and 3-mercaptopyruvate sulfurtransferase (MPST) in the mitochondrial and cytosolic fractions of mouse liver was investigated. Three groups of mice were treated for 6 consecutive days with subcutaneous injections of T4 (50 micrograms, 100 micrograms, and 250 micrograms per 100 g of body wt, respectively). The other 3 groups were given 100 micrograms of T4 per 100 g of body wt for 1, 2, or 3 days. The dose of 100 micrograms T4 per 100 g of body wt given for 6 days exerted the strongest effect on the activity of all of the investigated enzymes. In comparison to the control, rhodanese activity diminished in the mitochondrial fraction by 40% (P < 0.05), cystathionase activity diminished in the cytosolic fraction by 15% (P < 0.05), and MPST activity in the mitochondrial fraction was reduced by 34% (P < 0.05), whereas cytosolic MPST activity was unaltered. Simultaneously, in the liver homogenate, elevated levels of ATP and sulfate were observed after 6 days of T4 administration. Thus, the present results seem to suggest that in the mouse liver, after 6 days of administration of 100 micrograms T4 per 100 g of body wt, the desulfuration metabolism of L-cysteine is diminished, which is probably accompanied by an increase in oxidative L-cysteine metabolism. The dose of 100 micrograms per 100 g of body wt administered for a shorter period, and the use of a lower dosage (50 micrograms T4 per 100 g of body wt) for 6 days had a stimulatory effect upon MPST activity level, and an increased level of sulfane sulfur was observed.

Experimental beta-alaninuria induced by (aminooxy)acetate.

Experimental beta-alaninuria was induced in rats by injection of (aminooxy)acetate (AOA), a potent inhibitor of aminotransferases, in order to elucidate the pathogenesis of hyper-beta-alaninemia. A 27-fold increase of beta-alanine (BALA) excretion was induced by subcutaneous injection of 1 5 mg of AOA per kg of body weight. A 13-fold and a 9-fold increase of beta-aminoisobutyric acid (BAIBA) and gamma-aminobutyric acid (GABA), respectively, were also induced simultaneously by the AOA injection. Identification of BALA and BAIBA isolated from the rat urine was performed by chromatographic and mass spectrometric analyses. The effects of AOA injection on the tissue levels of these amino acids were also studied. Contents of BALA in the liver and kidney and GABA in the brain increased significantly in response to AOA injection. The present study indicates that BALA transaminase is involved in hyper-beta-alaninemia.

High-performance liquid chromatographic determination of beta-alanine, beta-aminoisobutyric acid and gamma-aminobutyric acid in tissue extracts and urine of normal and (aminooxy)acetate-treated rats.

A method is described for the simultaneous determination of beta-alanine, beta-aminoisobutyric acid and gamma-aminobutyric acid in biological materials. Amino acids including these beta- and gamma-amino acids were derivatized with 4-dimethylaminoazobenzene-4'-sulfonyl (dabsyl) chloride and dabsyl amino acids formed were separated by reversed-phase high-performance liquid chromatography. Dabsyl derivatives of these beta- and gamma-amino acids were well separated from other dabsyl-amino acids. The method was applied to the determination of these beta- and gamma-amino acids in trichloroacetic acid extracts of various tissues and to the urine of normal rats and those injected with (aminooxy)acetate (AOA). AOA injection (15 mg per kg of body mass) produced remarkable increase in beta-alanine contents in liver, kidney and urine (10.2, 4.6 and 25.7 times, respectively).

Excretion of sulfate and taurine in rats fed with a high protein diet.

Sulfate and taurine are the main metabolites of L-cysteine in mammals and are excreted in the urine. The effect of a high protein diet on the ratio of sulfate to taurine excretion was studied in rats using synthetic 25% (standard protein diet group, group A) and 40% (high protein diet group, group B) casein diets. Average taurine and sulfate excretions (mumol/kg of body weight per day) were 280.4 +/- 93.8 and 943.2 +/- 144.8 in group A and 553.4 +/- 124.5 and 2675.0 +/- 390.9 in group B, respectively. Thus, the average taurine/sulfate ratio in group A was 0.30 +/- 0.08. By a single administration of 5 mmol of L-cysteine/kg of body weight in group A, the average taurine and sulfate excretions increased to 1127.5 +/- 120.2 and 4043.0 +/- 305.6, respectively, but the taurine/sulfate ratio changed only slightly (0.28). The average taurine/sulfate ratio in group B was 0.22 +/- 0.07, a significantly lower ratio than that in group A, which means that daily intake of a high protein diet resulted in more sulfate excretion. The taurine/sulfate ratio in group B was affected only slightly (0.19) by the cysteine administration as well. These results suggest that the ratio of taurine and sulfate production was determined by dietary protein content and that the increase in sulfate production is larger than that of taurine production when the intake of dietary protein is increased.

Excretion of taurine and sulfate in rats fed with a low protein diet.

The effects of a low protein diet on the excretion of sulfate and taurine, major metabolites of L-cysteine in mammals, were studied in rats fed with synthetic 10% (group A) and 25% (group B) casein diets. The average excretions of total taurine (taurine plus hypotaurine) and total sulfate (free plus ester sulfate) (mumol/kg of body weight per day after the adaptation to the synthetic diet) in group A were 14.2 +/- 13.4 and 122.3 +/- 39.6, respectively, which were very low compared with 280.4 +/- 93.8 and 943.2 +/- 144.8, respectively, in group B. The taurine/sulfate ratio in group A was 0.12 +/- 0.11, which was significantly lower than that (0.30 +/- 0.08) in group B. A single intraperitoneal injection of 5 mmol of L-cysteine per kg of body weight in group A resulted in an increase in average taurine and sulfate excretion to 693.4 +/- 195.6 and 2440.6 +/- 270.0, respectively, and thus the average taurine/sulfate ratio increased to 0.29. These increases were transient and low taurine excretion resumed again 24 h after the L-cysteine administration. L-Cysteine injection in group B resulted in a similar increase in taurine and sulfate excretion, but the ratio changed only slightly (0.28). The present results suggest that in vivo production of taurine is reduced preferentially over sulfate production when sulfur amino acid supply is limited.

L-cysteine metabolism in guinea pig and rat tissues.

Rhodanese, gamma-cystathionase and 3-mercaptopyruvate sulfurtransferase activities were examined in guinea pig and rat liver, kidney and brain. In the liver of both species rhodanese showed the same high range of activity but in guinea pig kidney and brain a slightly lower level was determined than that in corresponding rat tissues. The 3-mercaptopyruvate sulfurtransferase and gamma-cystathionase activities in all the investigated tissues of guinea pig were significantly lower than those in rat. The sulfane sulfur pool, a source of sulfur transferred by rhodanese, can be augmented in vitro in guinea pig liver, but not in rat liver when 3-mercaptolactate-cysteine disulfide is used as a substrate of gamma-cystathionase.

Effect of glucose-cysteine adduct on cysteine desulfuration in guinea pig tissues.

Effect of intraperitoneal administration (12 mmol/kg of body weight) of glucose-cysteine adduct 2-(D-gluco-pentahydroxypentyl)-thiazolidine-4-carboxylate, (glc-cys) on the rhodanese, gamma-cystathionase and 3-mercaptopyruvate sulfurtransferase (MPST) activity levels in guinea pig tissues was studied. The rhodanese activity value in liver increased by 41%, 3-mercaptopyruvate sulfurtransferase by 24%, and gamma-cystathionase by 12% after three successive days of the administration. In the kidney, on the contrary, glc-cys administration resulted in about 18% decrease in the gamma-cystathionase activity value, whereas no changes in MPST and rhodanese activity values were observed. In the case of the brain, rhodanese and gamma-cystathionase did not change their activity but the activity of MPST decreased by 21%. MPST level did not change substantially in whole blood after glc-cys treatment. The results seem to indicate that in guinea pig liver but not in kidney and brain, glc-cys has a potential to activate the desulfuration pathway of L-cysteine metabolism.

A method for determination of total glutathione and total cysteine as S-carboxymethyl derivatives by using an amino acid analyzer, and its application to samples from rat liver, kidney and blood after intraperitoneal administration of 2-(4-carboxy-D-gluco-tetrahydroxybutyl)thiazolidine-4-carboxylic acid.

The effects of intraperitoneal administration of 2-(4-carboxy-D-gluco-tetrahydroxybutyl)thiazolidine-4-carboxylic acid (CGUA), a cysteine derivative conjugated with glucuronic acid, on total glutathione and total cysteine contents in rat tissues were investigated. Total glutathione (GSH and GSSG) and total cysteine (cysteine and cystine) were determined by a new method consisting of preparation of S-carboxymethylglutathione (CMSG) and S-carboxymethylcysteine (CMC), respectively, and subsequent analyses with an amino acid analyzer. CGUA was determined by a coloration method employing an acidic ninhydrin reagent. Total cysteine contents in liver, kidney and plasma rapidly increased to 2.3, 2.7 and 6.5 times the levels of the controls, respectively, after CGUA administration at a dose of 5 mmol/kg of body weight. Total glutathione content did not change significantly in the liver or blood except for the kidney with a significant increase during the first 1-h period after administration. CGUA content increased markedly in these tissues, especially in the kidney, and 30% of administered CGUA was excreted in urine within 2h. These results indicate that CGUA is converted into cysteine in vivo, suggesting the usefulness of this compound for protection of the kidney and the liver.

Isolation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine.

S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid (CIE-TL), a novel imidazole compound with a sulphur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving m.s., i.r. spectrophotometry, high-voltage paper electrophoresis and elemental analysis as well as chemical synthesis. CIE-TL was synthesized by the reaction of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (CIE-Cys) with NaNO2 in HCl. CIE-TL was also formed during enzymic degradation of CIE-Cys by rat liver or kidney homogenate in a phosphate buffer, possibly via the metabolic intermediate S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiopyruvic acid, and this was accompanied by the formation of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid, a compound previously found in human urine [Kinuta, Yao, Masuoka, Ohta, Teraoka and Ubuka (1991) Biochem. J. 275, 617-621]. These results suggest that CIE-Cys [Kinuta, Ubuka, Yao, Futani, Fujiwara and Kurozumi (1992) Biochem. J. 283, 39-40] is a physiological precursor of the urinary compounds and that L-histidine is metabolized in part via an alternative pathway initiated by the adduction of natural thiol compounds such as cysteine and GSH to urocanic acid, the first catabolite of histidine.

Effect ofN-acetylcysteine administration on cysteine and glutathione contents in liver and kidney and in perfused liver of intact and diethyl maleate-treated rats.

Effect ofN-acetyl-L-cysteine (NAC) administration on cysteine and glutathione (GSH) contents in rat liver and kidney was studied using intact and diethyl maleate (DEM)-treated rats and perfused rat liver. Cysteine contents increased rapidly, reaching peak at 10 min after intraperitoneal NAC administration. In liver mitochondria it increased slowly, reaching peak at 60 min. GSH content did not change significantly in these tissues. However, in liver and kidney depleted of GSH with DEM, NAC administration restored GSH contents in 60 and 120 min, respectively. Perfusion with 10 mM NAC resulted in 76% increase in liver cysteine content, but not in GSH content. Liver perfusion of DEM-injected rats with 10 mM NAC restored GSH content by 15%. Present findings indicate that NAC is an effective precursor of cysteine in the intact liver and kidney and in the perfused rat liver, and that NAC stimulated GSH synthesis in GSH-depleted tissues.

L-Cysteine metabolism via 3-mercaptopyruvate pathway and sulfate formation in rat liver mitochondria.

We have studied the 3-mercaptopyruvate pathway (transamination pathway) ofL-cysteine metabolism in rat liver mitochondria.L-Cysteine and other substrates at 10 mM concentration were incubated with mitochondrial fraction at pH 8.4, and sulfate and thiosulfate were determined by ion chromatography. WhenL-cysteine alone was incubated, sulfate formed was 0.7µmol per mitochondria from one g of liver per 60 min. Addition of 2-oxoglutarate and GSH resulted in more than 3-fold increase in sulfate formation, and thiosulfate was formed besides sulfate. The sum (A + 2B) of sulfate (A) and thiosulfate (B) formed was approximately 7-times that withL-cysteine alone. Incubation with 3-mercaptopyruvate resulted in sulfate and thiosulfate formation, and sulfate was formed with thiosulfate. These reactions were stimulated with glutathione. Sulfate formation fromL-cysteinesulfinate and 2-oxoglutarate was not enhanced by glutathione and thiosulfate was not formed. These findings indicate thatL-cysteine was metabolized and sulfate was formed through 3-mercaptopyruvate pathway in mitochondria.

An additional promoter within the protein-coding region of the psbD-psbC gene cluster in tobacco chloroplast DNA.

Transcription of the psbD-psbC gene cluster in tobacco chloroplasts has been studied. This cluster contains in linear sequence the overlapping genes encoding the D2 and 43 kDa proteins of Photosystem II (psbD and psbC, respectively), and ORF62. Eight major transcripts ranging from 1.5 to 4.4 kb were detected by northern blot analysis. S1 mapping experiments revealed that these multiple transcripts comprise five distinct 5' ends whose precise positions were further determined by primer extension analysis. Two of the five 5' ends were determined to be the transcriptional initiation sites by in vitro capping assays: the main site is located 905 bp upstream from the ATG codon of psbD and the additional site is 194 bp upstream from the first ATG codon of psbC. The latter site and the preceding prokaryotic promoter motif are within the protein-coding region of psbD. The 3' ends of transcripts were determined by S1 mapping.