Toxicity Attenuation Mechanism on Processing Method for Aconiti Lateralis Radix Praeparata in Guilingji Based on Urine Metabolomics / 中国实验方剂学杂志

ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.

Metabolomics-based study on the improvement mechanism of the Mongolian drug Sugemule-4 on insomnia rats / 中国药房

OBJECTIVE To study the effects of the Mongolian medicine Sugemule-4 on the metabolism of insomnia rats， and to preliminarily explore its possible mechanisms for improving insomnia. METHODS The rat model of chronic stress insomnia was established by tail clipping stimulation and intraperitoneal injection of p-chlorophenyl alanine solution. Twenty-four male rats were randomly divided into the normal group， model group， diazepam group （positive control， 0.92 mg/kg）， and Sugemule-4 group （5.2 g/kg）， with 6 rats in each group. Since the 7th day of tail clipping stimulation， the Sugemule-4 group and diazepam group began to be intragastrically administered with relevant medicine； the normal group and model group were intragastrically administered with an equal volume of distilled water， once a day， for 14 consecutive days. The learning and memory abilities of rats were tested using a water maze experiment， and the non-invasive sleep activity monitoring system was used to monitor the 24- hour sleep time of rats. A metabolomics study was conducted on rat serum and hippocampal tissue by using ultra-high-performance liquid chromatography-tandem mass spectrometry. The multivariate statistical analysis method was adopted to analyze the differential metabolites in serum and hippocampal tissue of rats， and screen for differential metabolites and metabolic pathways among those groups. RESULTS Compared with the normal group， the escape latency of rats in the model group was significantly increased， the times of crossing platforms were significantly reduced， and the percentage of average 24-hour sleep time was significantly reduced （P＜0.05）. Compared with the model group， the levels of the above indicators were significantly reversed in the diazepam group and Sugemule-4 group （P＜0.05）. Metabolomics studies found that a total of 9 differential metabolites were identified in rat serum and hippocampal tissue， including 5-hydroxyindoleacetic acid， canine urate， canine urinary quinolinic acid， 5-hydroxytryptamine， phenol sulfate， 1-carboxyethyltyrosine， 3-（4-hydroxyphenyl） lactate， N-acetyl tyrosine， tyrosine and phenol sulfate， mainly involving 2 metabolic pathways of tryptophan and tyrosine.CONCLUSIONS Sugemule-4 can improve the sleep time and behavioral performance of insomnia rats， and its mechanism may be associated with affecting amino acid metabolic pathways such as tryptophan and tyrosine.

Exploring Central Regulatory Effect of Chaishao Liujuntang on Chronic Atrophic Gastritis Rats with Liver Depression and Spleen Deficiency Syndrome Based on Metabolomics / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-mass spectrometry（UPLC-MS） and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis（CAG） rats with liver-depression and spleen-deficiency， and to look for the correlation between cerebral cortex， hypothalamus and metabolic status of gastric tissues. MethodA CAG rat model with liver-depression and spleen-deficiency was established by chemical induction， hunger and satiety disorders， chronic restraint and tail clamping stimulation， lasting for 16 weeks. Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats. After the completion of modeling， 4 rats in the model group were taken to observe the pathological changes of gastric mucosa. The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats. Chaishao Liujuntang group rats were given 5.1 g·kg-1 by gavage， and the remaining rats were given equal volume sterilized water by gavage for 4 weeks. Macroscopic characteristics， behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared. UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex， hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency. Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites. ResultCompared with the model group， the macroscopic characteristics of rats in Chaishao Liujuntang group were improved， such as hair color， mental state and stool properties， and the number of times of crossing and standing in the open field experiment was significantly increased， and the static time of forced swimming was significantly reduced（P<0.01）， and the gastric mucosa atrophy was reduced. The metabolic data from the cerebral cortex of rats in each group identified a total of 3 common potential biomarkers， but not enriched in pathways， 26 common potential biomarkers were identified in the hypothalamus， and the key metabolic pathways involved were mainly enriched in purine metabolism， glycerol phospholipid metabolism， D-glutamine and D-glutamic acid metabolism. Seventeen common potential biomarkers were identified in the stomach， and the key metabolic pathways involved were mainly enriched in thiamine metabolism， valine， leucine and isoleucine biosynthesis， and taurine and taurine metabolism. Correlation analysis of metabolites in different tissues revealed that multiple amino acids and their derivatives mediated metabolic connections between the cerebral cortex， hypothalamus and stomach of rats. ConclusionThe metabolic disorders in the cerebral cortex， hypothalamus and stomach of CAG rats with liver-depression and spleen-deficiency have their own characteristics， mainly manifested by changes in the content of glycerol phospholipids， fatty acids and bile acid metabolites. Moreover， Chaishao Liujuntang may play a central regulatory role in CAG rats with liver-depression and spleen-deficiency by correcting the metabolic disorders of amino acids.

Comparative Analysis of the Elementary and Amino Acid Composition of Nepeta olgae Regel L. Plants Growing in Uzbekistan

This article for the first time presents the results of the study of qualitative and quantitative elemental and amino acid composition of the aboveground part of the plant Nepeta olgae Regel (L.) taken in the territory of Chust and Kosonsai districts (from the slopes of Gova and Kosonsai mountains) of Namangan region during the period before and during flowering (May-June, 2021-2022). The use of instrumental analysis of high-throughput energy dispersive X-ray fluorescence spectrometry, allowed to establish 20 mineral elements in the plant Nepeta olgae Regel (L.), among which to vital 9 elements and 3 to conditionally necessary. The amino acid composition of the plant Nepeta olgae Regel (L.) was studied by high performance liquid chromatography (HPLC) and 17 compounds were identified. Of these, 8 were substitutable and 9 essential amino acids.

Causal relationship between branched-chain amino acids and peripheral atherosclerosis： a Mendelian randomization study / 上海预防医学

ObjectiveWe conducted a two-sample Mendelian randomization （MR） study to assess the causal relationship between circulating isoleucine， leucine and valine levels and the risk of peripheral atherosclerosis. MethodsBased on the large-scale genome-wide association study （GWAS） database， single nucleotide polymorphisms （SNPs） closely related to the circulating levels of isoleucine， leucine and valine were identified as instrumental variables （IVs）. Two-sample MR analysis applying the inverse variance weighted （IVW） method and the weighted median estimator （WME） method were performed to estimate the causal relationship between the risk of peripheral atherosclerosis and the exposure with more than three SNPs that were available as IVs. The pleiotropy was evaluated by using the MR-Egger regression and MR-PRESSO method， and the leave-one-out method was used in sensitivity analysis. ResultsFour， one and one SNPs were identified as IVs for circulating isoleucine， leucine and valine levels， respectively. For isoleucine， the IVW model demonstrated there was no evidence of heterogeneity among the IVs （P=0.715）， and there was a significant causal relationship between the increase of circulating isoleucine level and a higher risk of peripheral atherosclerosis risk. Per every 1 elevated standard deviation （SD） of circulating isoleucine level resulted in increasing 31% of peripheral atherosclerosis risk （OR=1.31， 95%CI： 1.07‒1.61）. Similarly， the OR（95%CI） was 1.33 （1.04‒1.71） in the WME model. The MR-Egger regression and MR-PRESSO analysis indicated no evidence of pleiotropy in IVs （all P>0.05）. The result of the leave-one-out sensitivity analysis was stable. The Wald ratio model displayed that the causal relationship between circulating leucine and valine levels and the risk of peripheral atherosclerosis was not statistically significant. The OR （95%CI） for leucine and valine was 1.13 （0.78‒1.63） and 1.11 （0.82‒1.50）， respectively. ConclusionThere is a significant causal relationship between the increase of circulating isoleucine level and a higher peripheral atherosclerosis risk. The causal relationships between circulating leucine and valine levels and the risk of peripheral atherosclerosis need to be further confirmed in future studies.

Research progress of active probes targeting specific aminoacids / 药学学报

Activity-based protein (proteomic) profiling (ABPP) has emerged as a key component of the broad field of chemical techniques capable of directly analyzing enzyme activity in living systems. With the deepening of research on electrophilic warheads and nucleophilic amino acids, and the continuous proposal and improvement of effective development strategies, the application of amino acid-targeting active probes in various biological systems has facilitated the identification, development of new targets in various disease contexts and discovery of inhibitors. The purpose of this review is to summarize the latest progress in the design and application of active probes targeting specific amino acids, in order to provide support for the further development of amino acid-targeted covalent inhibitordrugs.

Simultaneous determination of 17 kinds of free amino acid concentrations in cell culture medium by UPLC / 药学学报

To establish an ultra high performance liquid chromatography coupled with pre-column derivatization method for simultaneous determination of 17 kinds of free amino acid concentrations in CHO cell which expressed high levels of programmed death protein-1 (PD-1) antibody, and its amino acid metabolism was analyzed by this method. Using 6-aminoquinoline-N-hydroxysuccinimidyl carbamate (AQC) as a derivatization reagent, the free amino acids in different concentrations of amino acid standards or cell lines were transformed into stable UV-absorbent compounds, which were separated by gradient elution through ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm) column. The flow rate was set at 0.7 mL·min-1, the column temperature at 55 ℃, the loading amount of sample at 1 µL, the UV detection wavelength at 260 nm, and then the free amino acid concentration in cell lines which expressed PD-1 antibody was determined by external standard method. According to the changes of amino acids concentration during the process of cell culture, the amino acid metabolism was analyzed. The results showed that pre-column derivatization high performance liquid chromatography could completely separate 17 kinds of amino acids within 11 minutes, has good linear relationship (R2 ≥ 0.999 3) in the range of 0.75-500 μmol·L-1, the limits of detection was 0.1-0.3 μmol·L-1, the limits of quantitative was 0.5-1 μmol·L-1. The established method is quickly and reproducibility. Amino acid metabolism revealed that methionine, isoleucine and leucine may be the restrictive factors of expression for cell line. This method can be used for detection changes of free amino acid concentration in cell line.

Allium polyrhizum Turcz.ex Regel results of aboveground research / Монголын Анагаах Ухаан

Introduction@#Human beings have been using raw materials of plant and animal origin for the treatment of various diseases. Nowadays, in developed and developing countries, plant raw materials are widely used in traditional medicine, health care, and food supplements, and they are used as raw materials in pharmaceutical production, making up a large part of the world pharmaceutical market. Therefore, research activities are intensively carried out to determine the chemical composition and mineral content of plant-derived raw materials and explain the mechanism of action.@*Goal@#Allium polyrhizum Turcz.ex Regel determination of chemical compounds macro and micro elements and amino acids@*Material and Methods@#Allium polyrhizum Turcz.ex Regel was collected and prepared from Huvut shar Khoshun, Shili River Province, Institute of Mongolia medicine chemistry, Inner Mongolia university, Inner Mongolia Key Laboratory Medicine Chemistry. then it was made into a type with 0.075 mm particle size by a grinding machine. @*Result@#Dete-rmining the elemental composition of plant raw materials is important for determining the therapeutic value and safety of the plant. Some elements in Allium polyrhizum Turcz.ex Regel were determined by X-ray fluorescence method.@*Conclusions@#</br>1. In this study, the content of 7 elements in the above-ground part of Allium polyrhizum Turcz was determined using the XRF analysis method. Of the macro and micro elements such as Ca, K, Mn, Fe, Na, Zn, and Mg, which are essential for the human body, potassium (K) 49.7 mg/kg, calcium (Ca) 45.7 mg/kg, and sodium (Na) 31.0 mg/kg are the most had a high concentration. </br>2. Among various amino acids involved in protein synthesis, glutamic acid 1.89 mg, aspartic acid 1.48 mg, and alanine 1.00 mg were identified.

Polymorphisms of host tropism relating amino acid sites in influenza A virus / 上海预防医学

ObjectiveTo discover and analyze single or several correlative key amino acid sites that influence the host tropism during the influenza A virus （IAV） infection based on complete internal protein gene segments of IAV strains， and to provide evidence for the study of human host-adaptive mutations of IAV. MethodsThe full-length nucleotide sequences of 43 671 IAV strains containing 6 complete internal gene segments were downloaded from the GISAID EpiFluTM database， and 698 human-tropic （HU） and 1 266 avian-tropic （AV） representative strains were included. The consensus coding sequences of the representative strains from the amphitropic category were compared by R script， and the differential amino acid sites and their polymorphisms were then obtained. The multi-site combination analysis of differential sites was conducted with R script. ResultsA total of 49 and 57 conserved differential sites were obtained from the consensus sequence comparison between AV and H1N1 （subtype from HU）， and comparison between AV and H3N2 （another subtype from HU）， separately. 79 and 65 multi-site combinations were found between HU and AV strains through 3 and 4 sites combination analysis， respectively， and a total of 11 conserved sites were involved： site 271 and 684 in PB2； site 336， 486， 581 and 621 in PB1； site 204 and 356 in PA； site 33， 305 and 357 in NP. No eligible differential sites were found in M1 and NS1. ConclusionSeveral conserved amino acid differential sites， between HU and AV strains of IAV， are found in PB2， PB1， PA and NP proteins. Instead of working as single units， these sites may have interactions， forming specific amino acid combinations that determine the host tropism of IAV collectively.

Breeding of Chlorella mutants deficient in chlorophyll synthesis and evaluation of its protein yield and quality / 生物工程学报

The aim of this study was to construct Chlorella mutants deficient in chlorophyll synthesis by atmospheric pressure room temperature plasma (ARTP) mutagenesis, and screen novel algal species with very low chlorophyll content which is suitable for protein production by fermentation. Firstly, the lethal rate curve of mixotrophic wild type cells was established by optimizing the mutagenesis treatment time. The mixotrophic cells in early exponential phase were treated by the condition of over 95% lethal rate, and 4 mutants with the visual change of colony color were isolated. Subsequently, the mutants were cultured in shaking flasks heterotrophically for evaluation of their protein production performance. P. ks 4 mutant showed the best performance in Basal medium containing 30 g/L glucose and 5 g/L NaNO3. The protein content and productivity reached 39.25% dry weight and 1.15 g/(L·d), with an amino acid score of 101.34. The chlorophyll a content decreased 98.78%, whereas chlorophyll b was not detected, and 0.62 mg/g of lutein content made the algal biomass appear golden yellow. This work provides a novel germplasm, the mutant P. ks 4 with high yield and high quality, for alternative protein production by microalgal fermentation.

Immobilizing engineered Escherichia coli cells into zeolitic imidazolate framework 8 for efficient biosynthesis of Ala-Gln / 生物工程学报

The α-amino acid ester acyltransferase (SAET) from Sphingobacterium siyangensis is one of the enzymes with the highest catalytic ability for the biosynthesis of l-alanyl-l-glutamine (Ala-Gln) with unprotected l-alanine methylester and l-glutamine. To improve the catalytic performance of SAET, a one-step method was used to rapidly prepare the immobilized cells (SAET@ZIF-8) in the aqueous system. The engineered Escherichia coli (E. coli) expressing SAET was encapsulated into the imidazole framework structure of metal organic zeolite (ZIF-8). Subsequently, the obtained SAET@ZIF-8 was characterized, and the catalytic activity, reusability and storage stability were also investigated. Results showed that the morphology of the prepared SAET@ZIF-8 nanoparticles was basically the same as that of the standard ZIF-8 materials reported in literature, and the introduction of cells did not significantly change the morphology of ZIF-8. After repeated use for 7 times, SAET@ZIF-8 could still retain 67% of the initial catalytic activity. Maintained at room temperature for 4 days, 50% of the original catalytic activity of SAET@ZIF-8 could be retained, indicating that SAET@ZIF-8 has good stability for reuse and storage. When used in the biosynthesis of Ala-Gln, the final concentration of Ala-Gln reached 62.83 mmol/L (13.65 g/L) after 30 min, the yield reached 0.455 g/(L·min), and the conversion rate relative to glutamine was 62.83%. All these results suggested that the preparation of SAET@ZIF-8 is an efficient strategy for the biosynthesis of Ala-Gln.

Design, synthesis and biological activity of DB02 amino acid derivatives as HIV-1 non-nucleoside reverse transcriptase inhibitors / 药学学报

To improve the stability of amino acid ester derivatives of DB02, a series of 24 amide derivatives of DB02 amino acids as non-nucleoside HIV-1 reverse transcriptase inhibitor were designed and synthesized based on bioisosterism by replacing amino acid ester scaffold with more stable amide bond. The anti-HIV-1 activity of these compounds was evaluated by MTT assay and counting the number of syncytia. Most of the target compounds showed a potential anti-HIV-1 activity, among which compounds 2d, 2i, 2l, 2s, and 2w had better antiviral effect than lead compound DB02, with a therapeutic index > 1 000.00. Finally, the structure-activity relationship of these compounds was discussed, which provided new ideas for the further development of DB02 derivatives.

Amino acid metabolism characteristics of Banxia Baizhu Tianma Decoction in realizing drug withdrawal based on transcriptomic analysis / 中国中药杂志

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD & antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.

Advances of development and application amino acid biosensors / 生物工程学报

Amino acids are the basic building blocks of protein that are very important to the nutrition and health of humans and animals, and widely used in feed, food, medicine and daily chemicals. At present, amino acids are mainly produced from renewable raw materials by microbial fermentation, forming one of the important pillar industries of biomanufacturing in China. Amino acid-producing strains are mostly developed through random mutagenesis- and metabolic engineering-enabled strain breeding combined with strain screening. One of the key limitations to further improvement of production level is the lack of efficient, rapid, and accurate strain screening methods. Therefore, the development of high-throughput screening methods for amino acid strains is very important for the mining of key functional elements and the creation and screening of hyper-producing strains. This paper reviews the design of amino acid biosensors and their applications in the high-throughput evolution and screening of functional elements and hyper-producing strains, and the dynamic regulation of metabolic pathways. The challenges of existing amino acid biosensors and strategies for biosensor optimization are discussed. Finally, the importance of developing biosensors for amino acid derivatives is prospected.

Dietary amino acids and anthropometric indices: Tehran Lipid and Glucose Study

ABSTRACT Objective: Recent studies investigated the role of amino acids (AAs) in weight management. We aimed to determine the association between AAs and three-year change of anthropometric indices and incident obesity. Materials and methods: Height, weight, hip, and waist circumference (WC) were collected at baseline and follow up. Three-year changes in anthropometric indices and obesity incident according to body mass index (BMI) (overweight & obesity) and WC cutoffs (obesity-WC) were ascertained. Dietary intakes of AAs were collected at baseline, using a food frequency questionnaire. Data analyses were conducted on 4976 adult participants and two subsamples, including 1,570 and 2,918 subjects, for assessing the AAs relationship with 3-year changes on anthropometric indices and obesity incident. Results: Lysine and aspartic acid were positively associated with higher weight change, whereas acidic AAs, cysteine, and glutamic acid showed a negative correlation with weight change. Furthermore, a weak positive correlation was shown for alkaline AAs, lysine, and valine with WC; however, acidic AAs, tryptophan, cysteine, and glutamic acid were negatively associated with WC. Aromatic and acidic AAs also demonstrated a weak negative relation with changes in BAI. Phenylalanine and Aromatic AAs showed a negative association with overweight &obesity incidence adjusting for potential confounders. Each quartile increases the dietary lysine, arginine, alanine, methionine, aspartic acid, and alkaline AAs related to a greater risk of obesity-WC, while tryptophan, glutamic acid, proline, and acidic AAs associated with lower obesity-WC risk. Conclusion: Our results suggested that certain dietary AAs may potentially change anthropometric indices and risk of obesity incident.

Oromandibular Dystonia is a Prominent Feature in Patients with Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency

Abstract Aromatic L-Amino acid decarboxylase (AADC) deficiency is a rare neurometabolic disorder due to a homozygous or compound heterozygous pathogenic variant of the DDC gene, resulting in low synthesis of the biogenic amines dopamine, serotonin, epinephrine, and norepinephrine. Most patients had severe expression of the disease with global developmental delay, early hypotonia, movement disorders such as oculogyric crises, tremor, and dystonia. Oromandibular dystonia (OMD) is rarely recognized in patients with AADC deficiency. The aim of this study was to describe OMD in detail in 4 patients with AADC deficiency. OMD occurred in isolated form or in association with oculogyric crises, increasing the difficulty in care patients during the crises. The main form of OMD was tongue dystonia associated with mouth opening dystonia. AADC deficiency must be included in the list of genetic causes of OMD.

Progress on nutritional assessment and nutritional support for liver transplant recipients / 器官移植

Patients with end-stage liver disease after liver transplantation constantly suffer from malnutrition due to primary diseases and transplantation-related factors. Malnutrition will worsen clinical condition of the patients, increase the incidence of complication, length of hospital stay and medical expense after transplantation, and lower the survival rate. Sufficient nutritional support at all stages of liver transplantation is of significance. Accurate assessment of nutritional status and timely intervention are prerequisites for perioperative nutritional treatment in liver transplantation. In this article, the latest nutritional risk screening indexes and evaluation tools, nutritional support methods and other perioperative nutritional intervention measures for liver transplantation were reviewed, aiming to deepen the understanding and cognition of perioperative nutritional therapy for liver transplantation and provide reference for improving nutritional status and clinical prognosis of liver transplant recipients.

Effect of Polysaccharides and n-Butanol Fractions of Atractylodis Rhizoma Stir-fried with Bran on Metabonomics in Rats with Spleen Deficiency / 中国实验方剂学杂志

ObjectiveTo explore the regulatory effect of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran on the plasma metabolites of spleen-deficient rats， and then to elucidate their mechanisms of spleen-enhancing effects. MethodForty male SD rats were randomly divided into the blank group， model group， polysaccharide group （FD group， 0.075 6 g·mL-1·d-1）， n-butanol fractions group （FZ group， 0.012 1 g·mL-1·d-1）， with 10 rats in each group. Except the blank group， the other three groups used the compound factors of overwork， dietary disorders and intragastric administration of Sennae Folium decoction to replicate the rat model of spleen deficiency. After the end of modeling， the FD group and FZ group were given the corresponding medicinal solution by gavage for 7 d， meanwhile， the blank group and model group were given an equal volume of saline. The plasma samples from rats in the blank， model， FZ and FD groups were analyzed by ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap-MS）， multivariate statistical methods were used to process the data and screen differential metabolites， and metabolic pathway enrichment analysis of the screened differential metabolites was performed using the Kyoto Encyclopedia of Genes and Genomes （KEGG)）database and MetaboAnalyst 5.0. ResultThe results of multivariate statistical analysis showed that there were significant differences in plasma metabolites between the model group and blank group， FZ group and model group， FD group and model group. There were 380 differential metabolites between the blank group and the model group， of which 78 and 57 were called back by polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran， respectively. Metabolic pathway enrichment results showed that the n-butanol fractions mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， D-arginine and D-ornithine metabolism， which were summarized as amino acid metabolism， while the polysaccharides mainly affected glycine， serine and threonine metabolism， alanine， aspartate and glutamate metabolism， tricarboxylic acid cycle， biotin metabolism and thiamine metabolism. ConclusionBoth of polysaccharides and n-butanol fractions of Atractylodis Rhizoma stir-fried with bran have significant regulating effects on the metabolic abnormalities in spleen-deficient rats， in which the n-butanol fractions is mainly involved in amino acid metabolism， and the polysaccharides are involved in energy metabolism and cofactor and vitamin metabolism in addition to regulating amino acid metabolism.

Extraction and partial characterization of exopolysaccharides and pigments from cyanobacterium Oscillatoria pseudogeminata G.Schmid

Cyanobacterial pigments such as chlorophyll, carotenoids and phycobiliproteins are considered as ecofriendly natural colourants used in food and food additives as they have nutraceutical value, non-toxic and non-carcinogenic. The present study focused on extraction, partial characterization of extracellular polysaccharides (EPS), phycocyanin and mycosporin like amino acid (MAA) from a freshwater cyanobacterium Oscillatoria pseudogeminata G.Schmid.The purified isolate of O.pseudogeminatawas deposited and maintained in the NRMC-F, Bharathidasan University. The EPS was extracted withthe help of double volume of ice-cold acetone and confirmed by UV (260 and 280 nm), FTIR and XRD analyses.Phycocyanin and MAA were also extracted from O. pseudogeminata biomass using double distilled water. The UV-VisSpectrophotometric results revealed that 520 and 230 nm peaks represent phycocyanin and MAA, respectively. Further, theprocess of scaling-up the biomass and increase the productivity of EPS, Phycocyanin and MAA from Oscillatoriapseudogeminata is under raceway pond system, already initialed in our laboratory.

Síntesis y actividad antifúngica in vitro frente a Fusarium oxysporum de amidas N-alquilsustituidas derivadas de 2-aminoácidos

Una serie de amidas N-alquilsustituidas 1-16 fueron sintetizadas a partir de malonato de dietilo y ésteres de alquilo derivados de los aminoácidos L-triptófano, L-alanina, L-fenilalanina y L-tirosina. Los métodos de síntesis empleados involucraron calentamiento por irradiación de microondas empleando tanto un ácido de Lewis (AlCl3) o 4-dimetilaminopiridina (DMAP) como catalizador y auxiliar nucleofílico, respectivamente. Los resultados sugieren que el uso de irradiación de microondas y de DMAP conlleva mejores rendimientos en un tiempo de reacción más corto. Para ilustrar las diferencias observadas, se presentan las propuestas mecanísticas de cada método de reacción para la formación de amidas N-alquilsustituidas. Finalmente, las amidas sintetizadas se evaluaron en condiciones in vitro frente a Fusarium oxysporum; mostraron actividad antifúngica a diferentes niveles (0,40 mM < IC50 < 29,1 mM), lo cual indicó que las variaciones de la actividad observada de este grupo de compuestos pueden deberse al efecto de la amida acíclica como bioisóstero no clásico de algunas fitoalexinas heterocíclicas.

N-alkyl substituted amides 1-16 were synthesized from diethyl malonate and alkyl esters derived from the amino acids L -tryptophan, L -alanine, L -phenylalanine, and L -tyrosine. In addition, a microwave-assisted protocol was employed using a Lewis acid (AlCl3) or dimethylaminopyridine (DMAP) as a catalyst and nucleophilic auxiliary, respectively, affording the desired compounds. The results suggest that DMAP-catalyzed reactions under microwave irradiation yield higher during short reaction times. Each reaction method's mechanistic proposals for forming N-alkyl-substituted amides are presented to illustrate the observed differences. The synthesized amides were evaluated under in vitro conditions against Fusarium oxysporum. The compounds exhibited antifungal activity at different levels (0.40 mM < IC50 < 29.1 mM). These results indicated that the observed activity variations of this compound group might be due to the effect of acyclic amide as a non-classical bioisostere of some heterocyclic phytoalexins.

Uma série de amidas N-alquil substituídas foram sintetizadas a partir de malonato de dietila e ésteres alquílicos derivados dos aminoácidos ʟ-triptofano, L -alanina, L-fenilalanina e L-tirosina. Os métodos de síntese empregados foram realizados usando aquecimento por irradiação de micro-ondas empregando um ácido de Lewis (AlCl3) ou dimetilaminopiridina (DMAP) como catalisador. Os resultados sugerem que a irradiação de micro-ondas usando DMAP leva a melhores rendimentos em um tempo de reação mais curto. Para ilustrar as diferenças observadas, são apresentadas as propostas mecanísticas de cada método de reação para a formação de amidas N-alquilsubstituídas. Finalmente, as amidas sintetizadas foram avaliadas in vitro contra Fusarium oxysporum, mostrando atividade antifúngica em diferentes níveis (0.40 mM < IC50 < 29.1 mM), o que indica que as variações observadas na atividade desse grupo de compostos podem ser devidas ao efeito de amida acíclica como um bioisóstero não clássico de algumas fitoalexinas heterocíclicas.