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Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integratemolecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Ab1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Ab1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Ab1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calciumresponses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Ab1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Ab in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches. [ABSTRACT FROM AUTHOR]

Background: Townes-Brocks syndrome (TBS) is a rare genetic disorder characterized by imperforate anus, dysplastic ears, thumb malformations, and other abnormalities. Previous studies have revealed that mutations in the SALL1 gene can disrupt normal development, resulting in the characteristic features of Townes-Brocks syndrome. Spalt-like transcription factors (SALLs) are highly conserved proteins that play important roles in various cellular processes, including embryonic development, cell differentiation, and cell survival. Over 400 different variants or mutations have been reported in the SALL1 gene in individuals with TBS. Most of these variants lead to the formation of premature termination codons (PTCs), also known as nonsense mutations. The majority of these PTCs occur in a specific region of the SALL1 gene called the "hotspot region", which is particularly susceptible to mutation. Methods: In this study, we conducted whole-exome sequencing on a three-generation Chinese family with anorectal malformations. Results: We identified a novel heterozygous mutation (chr16:51175376:c.757 C > T p.Gln253*) in the SALL1 gene. Molecular analysis revealed a heterozygous C to T transition at nucleotide position 757 in exon 2 of the SALL1 (NM_002968) gene. This mutation is predicted to result in the substitution of the Gln253 codon with a premature stop codon (p.Gln253*). The glutamine-rich domain forms a long alpha helix, enabling the mutant protein to interact with the wild-type SALL1 protein. This interaction may result in steric hindrance effects on the wild-type SALL1 protein. Conclusions: Our findings have expanded the mutation database of the SALL1 gene, which is significant for genetic counseling and clinical surveillance in the affected family. Furthermore, our study enhances the understanding of Townes-Brocks syndrome and has the potential to improve its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

To retrospectively explore the characteristics of plasma amino acids (PAAs) in children with autism spectrum disorder and their clinical association via case-control study. A total of 110 autistic and 55 healthy children were recruited from 2014 to 2018. The clinical phenotypes included severity of autism, cognition, adaptability, and regression. Compared with the control group, autistic children had significantly elevated glutamate, γ-Amino-n-butyric acid, glutamine, sarcosine, δ-aminolevulinic acid, glycine and citrulline. In contrast, their plasma level of ethanolamine, phenylalanine, tryptophan, homocysteine, pyroglutamic acid, hydroxyproline, ornithine, histidine, lysine, and glutathione were significantly lower. Elevated neuroactive amino acids (glutamate) and decreased essential amino acids were mostly distinct characteristics of PAAs of autistic children. Increased level of tryptophan might be associated with severity of autism. [ABSTRACT FROM AUTHOR]

The Tibetan cashmere goat is a prolific goat breed in China. In sheep breeds, natural mutations have demonstrated that the transforming growth factor beta (TGF-β) super family ligands, such as growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and their type I receptor (bone morphogenetic protein receptor (BMPR1B), are essential for ovulation and increasing litter size. In this study, 216 female Tibetan cashmere goats were sampled, and candidate genes with fecundity traits were detected via restriction fragment length polymorphism (RFLP) and sequenced. Four polymorphic loci were found in specific amplification fragments of BMP15 and GDF9. Two SNP sites of the BMP15 gene were discovered, namely G732A and C805G. The G732A mutation did not cause the change in amino acids, and the frequencies of each genotype were 0.695 for the GG type, 0.282 for the GA type and 0.023 for the AA type. The C805G mutation caused amino acids to change from glutamine to glutamate. The genotype frequencies were 0.620 for the CC type, 0.320 for the CG type and 0.320 for the CG type. For the GG type 0.060, the G3 and G4 mutations of the GDF9 gene were all homozygous mutations. Two known SNP sites, C719T and G1189A, were detected in the Tibetan cashmere goat GDF9 gene, of which the C719T mutation caused a change of alanine to valine, with a genotype frequency of 0.944 for the CC type and 0.056 for the CT type, whereas no TT type was found. The G1189A mutation caused valine to become isoleucine, and the frequencies of each genotype were 0.579 for the GG type, 0.305 for the GA type and 0.116 for the AA type; G1, B2, B3, B4, FecXH, FecXI, FecXL, G2, G5, G6, G7, G8, FecGE, FecTT and FecB mutations were not found in Tibetan cashmere goats. The results of this study provide a data basis for future studies of BMP15, GDF9 and BMPR1B gene mutations in goats. [ABSTRACT FROM AUTHOR]

Elevated ammonia levels in aquaculture systems could reduce fish growth and survival rates and produce a range of physiological problems. Ammonia toxicity in aquatic environments was regulated by various factors. Feeding was usually reported to help in the detoxification of fish, thereby increasing their capacity to tolerate ammonia nitrogen. However, the impact of different feeding amounts on fish in relation to ammonia exposure stress remains to be determined. To determine how feeding levels affected fish's responses to different ammonia nitrogen concentrations, two acute toxicity experiments were conducted with Carassius auratus gibelio, the major strain of gibel carp in aquaculture systems in China. In Test I, fed Carassius auratus gibelio (3 % body weight) showed a higher survival rate under a specific ammonia exposure stress. 96-h LC 50 of NH 3 -N to 3 %F gibel carp was 1.1 times greater than that for NF (no feeding). In Test II, all fed groups (2 %F and 4 %F) under low and high ammonia stress exhibited improved ammonia detoxification, evidenced by higher liver GSase, GDH, and glutamine concentrations compared with the NF treatment. Muscle glycogen levels in feeding treatments were higher than those in NF, indicating that fed fish have more energy for ammonia detoxification. While compared with low ammonia treatment (2.70 mg L -1 TAN; NH 3 0.06 mg L -1 ), fish exposed to high ammonia levels (26.03 mg L -1 TAN; NH 3 0.57 mg L -1 ) demonstrated a decrease in food consumption, severe histopathological alterations in their liver, gill, and kidney, and decreased GSase, GDH, and glutamine production in the liver and brain. The results partly supported our hypothesis and suggested that increasing feeding enhances gibel carp's tolerance to ammonia nitrogen. The highest detoxification metabolism was observed under low ammonia stress. While excessive ammonia exposure could inhibit feeding and damage the detoxification organs of fish, and thus reduce the detoxification metabolism of gibel carp., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Simple Summary: Multiple myeloma (MM) is characterized by the presence of systemic clinical manifestations. Among them, pneumonia accounts for a significant cause of morbidity and mortality, highlighting an urgent need to explore possible susceptibility and potential mechanisms of pneumonia in MM. Recently, the gut–lung axis has emphasized the relevance of gut microbiota and pneumonia, indicating that the compromised function of gut microbiota may be susceptible to pneumonia. It has been previously shown that intestinal Klebsiella pneumonia enriches in MM patients and promotes MM progression in our previous work. In addition, host metabolism has been identified as a key regulator of MM. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. In this study, we explored the association between gut microbiota and MM with pneumonia. This is the first study to identify and elucidate the function of gut microbiota involved in MM with pneumonia. Pneumonia accounts for a significant cause of morbidity and mortality in multiple myeloma (MM) patients. It has been previously shown that intestinal Klebsiella pneumonia (K. pneumonia) enriches in MM and promotes MM progression. However, what role the altered gut microbiota plays in MM with pneumonia remains unknown. Here, we show that intestinal K. pneumonia is significantly enriched in MM with pneumonia. This enriched intestinal K. pneumonia links to the incidence of pneumonia in MM, and intestinal colonization of K. pneumonia contributes to pneumonia in a 5TGM1 MM mice model. Further targeted metabolomic assays reveal the elevated level of glutamine, which is consistently increased with the enrichment of K. pneumonia in MM mice and patients, is synthesized by K. pneumonia, and leads to the elevated secretion of TNF-α in the lung normal fibroblast cells for the higher incidence of pneumonia. Inhibiting glutamine synthesis by establishing glnA-mutated K. pneumonia alleviates the incidence of pneumonia in the 5TGM1 MM mice model. Overall, our work proposes that intestinal K. pneumonia indirectly contributes to pneumonia in MM by synthesizing glutamine. Altogether, we unveil a gut–lung axis in MM with pneumonia and establish a novel mechanism and a possible intervention strategy for MM with pneumonia. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine (TCM) is widely used as an alternative therapy for cancer treatment in China. Glutamine catabolism plays an important role in cancer development. Qici Sanling decoction (QCSL) suppresses bladder cancer growth. However, the association between QCSL and glutamine catabolism remains unknown. In this study, different doses of QCSL were applied to T24 cells, followed by the measurements of cell viability and apoptosis using CCK-8 and Annexin V/PI assay, respectively. Furthermore, glutamine consumption was detected using the glutamine assay kit. QCSL was observed to inhibit cell growth and induced cell apoptosis in a dose-dependent manner. Analysis of glutamine consumption revealed that QCSL suppressed glutamine consumption in T24 cells. Furthermore, QCSL decreased the mRNA and protein levels of c-Myc, GLS1, and SLC1A5. All these effects induced by QCSL could be alleviated by c-Myc overexpression, indicating c-Myc was involved in the protective role of QCSL in bladder cancer. In addition, QCSL was found to inhibit tumor growth in the xenograft tumor model. The similar results were obtained in tumor samples that protein levels of c-Myc, GLS1, and SLC1A5 were decreased upon treatment with QCSL. In conclusion, QCSL suppresses glutamine consumption and bladder cancer cell growth through inhibiting c-Myc expression. [ABSTRACT FROM AUTHOR]

Turbot (Scophthalmus maximus) is an economically important marine fish cultured in China. In this study, fish in the experimental group were exposed to four temperatures: 15, 20, 25 and 28 °C. Metabolomics analysis and quantitative real-time PCR were used to assess changes in metabolic profiling and gene expression associated with thermal stress. The results showed the levels of heat shock protein 70 (HSP70), heat shock protein 90 (HSP90), blood creatinine and cortisol in S. maximus were all significantly upregulated (P < 0.05), indicating a stress response at 25 °C or higher. Challenge with thermal stress significantly increased expression levels of succinate dehydrogenase (SDH), fructose-1, 6-bisphosphatase (FBPase), malate dehydrogenase (MDH), cytosolic phosphoenolpyruvate carboxykinase (cPEPCK), glucose-6-phosphatase (G6Pase) and aspartate aminotransferase (AST) (P < 0.05). However, there was no effect on the expression levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and mitochondrial phosphoenolpyruvate carboxykinase (mPEPCK). Moreover, high temperature decreased levels of glycogenic amino acids, including histidine, threonine, glutamine, phenylalanine, arginine, serine, tyrosine, methionine and isoleucine. These findings suggest a significant correlation between gene expression and regulation of carbohydrate and amino acid metabolism in heat-stressed S. maximus kidney. In addition, the maintenance of aerobic metabolism and activation of gluconeogenesis appeared to be a critical metabolic strategy in combating heat stress in turbot kidney. • Creatinine, cortisol, HSP70 , and HSP90 can be used as biomarkers related to heat stress in turbot. • This is the first study to integrate the expression profiles of key metabolic enzymes and metabolomics changes in turbot kidney under heat stress. • Renal carbohydrate and amino acid metabolism are regulated by heat stress in turbot. • Maintaining aerobic metabolism and activating gluconeogenesis may be key strategies for turbot kidney to combat heat stress. [ABSTRACT FROM AUTHOR]

Paper mulberry, a vigorous pioneer species used for ecological reclamation and a high-protein forage plant for economic development, has been widely planted in China. To further develop its potential value, it is necessary to explore the regulatory mechanism of nitrogen metabolism for rational nitrogen utilization. In this study, we investigated the morphology, physiology and transcriptome of a paper mulberry hybrid (Broussonetia kazinoki  ×  B. papyrifera) in response to different nitrogen concentrations. Moderate nitrogen promoted plant growth and biomass accumulation. Photosynthetic characteristics, concentration of nitrogenous compounds and activities of enzymes were stimulated under nitrogen treatment. However, these enhancements were slightly or severely inhibited under excessive nitrogen supply. Nitrite reductase and glutamate synthase were more sensitive than nitrate reductase and glutamine synthetase and more likely to be inhibited under high nitrogen concentrations. Transcriptome analysis of the leaf transcriptome identified 161,961 unigenes. The differentially expressed genes associated with metabolism of nitrogen, alanine, aspartate, glutamate and glycerophospholipid showed high transcript abundances after nitrogen application, whereas those associated with glycerophospholipid, glycerolipid, amino sugar and nucleotide sugar metabolism were down-regulated. Combined with weighted gene coexpression network analysis, we uncovered 16 modules according to similarity in expression patterns. Asparagine synthetase and inorganic pyrophosphatase were considered two hub genes in two modules, which were associated with nitrogen metabolism and phosphorus metabolism, respectively. The expression characteristics of these genes may explain the regulation of morphological, physiological and other related metabolic strategies harmoniously. This multifaceted study provides valuable insights to further understand the mechanism of nitrogen metabolism and to guide utilization of paper mulberry. [ABSTRACT FROM AUTHOR]

Background: Inhibition of fatty acid synthase (FAS) plays a crucial protective role in pulmonary hypertension (PH). Our aim was to identify novel metabolites in mice with hypoxia-induced PH after treatment with C75 (FAS inhibitor) and to confirm the presence of these metabolites in paediatric patients with PH., Methods: The PH mouse model was built by chronic hypoxia and ovalbumin (OVA) assistance. Untargeted metabolomics was used to analyse mouse serum. Six children with PH and six relative controls (patients without lung and heart disease) were selected in Shanghai Children's Hospital and they all performed blood tandem mass spectrometry during hospitalization., Results: First, a total of 29 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified as differential metabolites in the hypoxia group compared with the control group. After C75 treatment, symptoms were partially relieved in the PH mouse, and 15 differential metabolites, including lipid metabolites, polyamine, and glutamine were identified in the hypoxia + C75 group compared with the hypoxia group. These differential metabolites were enriched in arginine and glycerolipid metabolism through metabolite set enrichment analyses and were involved in excessive cell proliferation, which was a characteristic of PH. Second, glutamine and caproyl carnitine levels were increased in paediatric patients with PH., Conclusions: FAS may be a potential PH therapeutic target. Lipid metabolites, polyamine, and glutamine, are closely related to PH. Putrescine and glutamine might be biomarkers for PH., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

With global warming on the rise, hypersalinity events are occurring with increasing frequency due to accelerated evaporation rates of seawater. Hypersalinity affects the distribution, growth, and physiological processes of aquatic organisms, especially for osmoconforming bivalves that lack complete means of osmoregulation. In this way, knowledge concerning comprehensive metabolic regulation is limited in hypersalinity-stressed bivalves. The hard clam, Mercenaria mercenaria , is an important pond-farmed bivalve in China, with an annual output value of 150 million USD. This species can be farmed in salt pans because it is highly resistant to hypersalinity. In this study, we investigated the comprehensive pattern of metabolic regulation in hard clams under hypersalinity stress. We identified 979 metabolites in the gills of hard clams, 295 of which were differentially accumulated after different periods of exposure to hypersalinity (8 h, 1 day, and 5 days), compared with the control. Critical hypersalinity-responsive metabolites, including acyl carnitine, oxidized lipids, and several antioxidants were identified using K-means analysis. During hypersalinity exposure, the activities of hexokinase and pyruvate kinase, and the pyruvic acid content significantly increased, suggesting that glycolysis was enhanced. Alanine and glycine were identified as key free amino acids involved in osmoregulaion. After 5 days of hypersalinity exposure, the accumulation of alanine and lactic acid marked the initiation of anaerobic glycolysis. The up-regulation of amino acid catabolism and inhibition of ammonia excretion led to ammonia accumulation in the gills. Glutamine synthetase and glutamate dehydrogenase activities significantly increased to reduce ammonia toxicity. Many antioxidant metabolites, such as allantoin, cinnamic acid, and trigonelline, were dramatically up-regulated to relieve hypersalinity-induced oxidative stress. The accumulation of lysophosphatides suggested that cell membranes damaged by prolonged oxidative stress and/or hyperosmosis were dissolved by phospholipase A1. This process helped to maintain overall cellular homeostasis. Potential biomarkers of hypersalinity stress in hard clams were identified. These results will facilitate the assessment of the physiological status of hard clam in aquaculture and provide novel insights into the metabolic regulatory mechanisms of bivalves under hypersalinity stress. [Display omitted] • Hard clam, Mercenaria mercenaria , has become the main pond-farmed bivalve in China. • Enhanced glycolysis and fatty acid β-oxidation provide energy for osmoregulation. • Hypersalinity induces oxidative stress and excessive ammonia accumulation in gills. • Glutamine synthesis is enhanced to reduce ammonia accumulation. [ABSTRACT FROM AUTHOR]

Objectives: The gut-associated lymphoid tissue is continuously exposed to antigens in the gut lumen and becomes the first line of defense against enteric bacteria and associated toxin. The aim of this study was to investigate the effects of parenteral glutamine (GLN) supplementation in combination with enteral nutrition (EN) on intestinal mucosal immunity in septic rats by cecal ligation and puncture (CLP). Methods: Male Sprague-Dawley rats were randomly assigned into four groups: A sham CLP + EN + saline group (n = 10), a sham CLP + EN + GLN group (n = 10), a CLP + EN + saline group (n = 10), and a CLP + EN + GLN group (n = 10). At 2 h after CLP or sham CLP, all rats in each of the four groups received an identical enteral nutrition solution as their base formula. Then, the rats in the sham CLP + EN + GLN group and CLP + EN + GLN group were given 0.35 g GLN/kg body weight daily for 7 d, all at the same time, via a tail vein injection; whereas those in the sham CLP + EN + saline group and CLP + EN + saline group were daily administered isovolumic sterile 0.9% saline for comparison. All rats in each of the four groups were given 290 kcal/kg body wt/d for 7 d. At the end of the seventh day after the nutritional program was finished, all rats were euthanized and the entire intestine was collected. Total Peyer's patches (PP) cell yield was counted by a hemocytometer. The percentage of PP lymphocyte subsets was analyzed by flow cytometry. The number of intestinal lamina propria IgA plasma cells was determined by the immunohisto-chemistry technique. The intestinal immunoglobulin A (IgA) levels were assessed by ELISA. PP apoptosis was evaluated by terminal deoxyuridine nick-end labeling. Results: The results revealed total PP cell yield, the numbers of PP lymphocyte subsets, intestinal lamina propria IgA plasma cells, and intestinal IgA levels in the CLP + EN + GLN group were significantly increased when compared with the CLP + EN + saline group (P < 0.05). On the other hand, the number of TUNEL-stained cells within PPs in the CLP + EN + GLN group was markedly decreased as compared with the CLP + EN + saline group (P < 0.05). Conclusion: The results of this study show that parenteral glutamine supplementation in combination with enteral nutrition may attenuate PP apoptosis, increase PP cell yield and intestinal lamina propria IgA plasma cells, and subsequently improve intestinal mucosal immunity. Clinically, these results suggest therapeutic efforts at improving intestinal immunity may contribute to the prevention and treatment of sepsis. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the effects of alanyl-glutamine (Ala-Gln) on keletal muscle protein synthetic and degradative signaling in piglets challenged with Escherichia coli lipopolysaccharide (LPS). Methods: Piglets were arranged in a 2 X 2 factorial design and the main effects were LPS challenge (0 or 100 units) and diets (0.62% Ala or 0.5% Ala-Gln). After treatment with either Ala or Ala-Gln for 10 d, piglets were injected twice with either saline or LPS on days 11 and 15. Results: During days 11 to 15 (postchallenge), LPS challenge affected the growth performance of piglets. Ala-Gln supplementation tended to alleviate the reduction of the average daily weight gain (P = 0.071) and the average daily feed intake (P = 0.087) of the LPS-challenged piglets. LPS challenge increased the concentrations of cytokines in plasma (P < 0.05), however, Ala-Gln supplementation prevented the elevation of cortisol induced by LPS challenge (P < 0.05). Moreover, Ala-Gln supplementation increased the mRNA expressions of insulin-like growth factor-1 signaling and Akt (P < 0.05). Ala-Gln supplementation also increased the phosphorylation abundance of the mammalian target of rapamycin, eIF-4 E binding protein 1 and ribosomal protein S6 kinase 1 (P < 0.05). Additionally, Ala-Gln supplementation down-regulated the mRNA abundances of toll-like receptor 4 (TLR4), muscle atrophy F-box, and muscle RING finger 1, which are associated with protein degradation induced by LPS challenge. Conclusion: Ala-Gln supplementation had beneficial effects in improving protein synthesis signaling of skeletal muscle, and reversed the deleterious changes of signaling molecules in muscle atrophy mainly through down-regulation of Akt/FOXO and TLR4 signaling pathways induced by LPS challenge. [ABSTRACT FROM AUTHOR]

Summary. This study aimed to explore significant differences in chemical composition among maca (Lepidium meyenii Walp.) types with different colors in Yunnan province, China. 1H-NMR spectroscopy, in combination with principal component analysis and partial least squares discriminant analysis, was used to investigate the compounds responsible for compositional differences. Different maca color types in Yunnan were clearly distinguished by 11 differential metabolites. Furthermore, network pharmacology results showed that 30 active components were related to Alzheimer's disease. Nine intersecting compounds among the 11 differential metabolites and 30 active components, namely, lysine, isoleucine, phenylalanine, β-hydroxybutyrate, tryptophan, pyroglutamate, proline, glutamine, and fructose, were used as bioactive markers to identify different maca color types. The results showed the bioactive markers among different maca color types holistically, providing a scientific basis for assessing the quality of commercial products derived from different maca color types. [ABSTRACT FROM AUTHOR]

Abstract: Berberine was reported to protect against the intestinal injury and improve the survival rate in sepsis, and glutamine deficiency was considered to be correlated with mortality in sepsis. We found that berberine pretreatment ameliorated lipopolysaccharide-induced direct intestinal injury and mucosal hypoplasia and attenuated impairments of intestinal glutamine transport and glutaminase activity, B0AT1 mRNA and protein expressions, and glutaminase protein expression. These findings showed the first time that berberine pretreatment could improve intestinal recovery and attenuate the impairment of glutamine transport and glutaminase activity in rat sepsis. This might be one of the mechanisms for the beneficial effect of berberine on sepsis. [Copyright &y& Elsevier]

Background: Chicken anemia virus (CAV) is the causative agent of chicken infectious anemia (CIA). A high prevalence of CAV has been reported in China. However, VP1 sequences of Chinese isolates show no clear genotype clustering or correlation with geographic origin. Therefore, the present study aimed to detect and characterize CAV isolates from China based on sequence and phylogenetic analysis of the VP1, VP2 and VP3 genes. Results: Of 460 spleen samples tested by PCR, 47 (10.22%) were found to be positive for CAV. A total of 25 CAV, approximately full genomes, from different commercial farms were characterized. Phylogenetic analysis of the Chinese CAV sequences together with strains from different countries resulted in four distinct groups (A-D) with significant high bootstrap values. The Chinese viral sequences were located as four different clusters within groups A and D. All the Chinese CAV genomes characterized in this study had glutamine (Q) at amino acid position 394, which indicated that all are highly pathogenic. Mutations associated with attenuation and weaker reactivity with monoclonal antibody 2A9 were absent in the Chinese sequences. Conclusions: We revealed that CAV prevalence was lower than that reported previously in commercial farms in China. We also showed four distinct sequence groups (A-D), and genetic variability in local CAV sequences that could be divided into four groups based on phylogenetic analysis. [ABSTRACT FROM AUTHOR]

Serum paraoxonase (PON) is a high-density lipoprotein-bound enzyme that can prevent oxidation of low-density lipoprotein by hydrolyzing lipid peroxides and thus exert an anti-atherogenic effect. Recent studies have suggested that glutamine(Q isoform)/arginine(R isoform) polymorphism at position 192 of PON1 gene is associated with macrovascular disease of type 2 diabetes mellitus (T2DM). We re-investigated this relationship using carotid intima-media thickness (IMT) as a surrogate continuous variable for macroangiopathy. The genotype and allele frequency of PON1 192 Q/R polymorphism was assayed by polymerase chain reaction–restriction fragment length polymorphism in 152 type 2 diabetic patients and 128 healthy subjects from a population of Chinese Han nationality in ChengDu area. The carotid IMT was measured by B-mode ultrasonography in type 2 diabetic patients. No differences were found in PON1 gene Q/R polymorphism in the type 2 diabetic patients when compared with the control group. The mean carotid IMT in type 2 diabetic subjects with the QQ, QR and RR genotype was 0.65±0.27, 0.83±0.27 and 1.05±0.32 mm, respectively. One-way ANOVA showed that IMT was significantly greater in the RR subgroup than in both QR and QQ subgroups (P<0.01). Multivariate logistic regression analysis showed R allele to be the main determinant of IMT variability (OR 4.0 95% CI 2.10–7.40 P=0.005). Our data support the view that 192 R allele of PON1 gene is a risk factor for macrovascular disease of T2DM in Chinese. [Copyright &y& Elsevier]

Bostrichthys sinensis inhabits brackish water, living in the crevices of the river mouths of Shang Xi andGuangdong, China. In its natural habitat, it may encounter aerial exposure frequently during low tides, and it usually remains quiescent in the absence of water. Upon aerial exposure in the laboratory, the ammonia excretion rate decreased to one-fourth that of the submerged control. Although all the enzymes of the ornithine-urea cycle were detected in the liver of this fish, the activity of hepatic carbamoyl phosphate synthetase was too low for the cycle to be functioning. Indeed, ammonia accumulated in the tissues and was not converted to urea. Results indicate that ammonia produced through amino acid catabolism was detoxified to glutamine during the first 24 h of aerial exposure. The excess amount of glutamine stored in the muscle during this period couldaccount approximately for the reduction in ammonia equivalent excreted. There was indeed a significant increase in the activity of glutamine synthetase from the liver of specimens exposed to terrestrial conditions. In contrast to the production of alanine, formation of glutamine is energetically expensive. Since B. sinensis remained relatively inactive on land, the reduction in energy demand for muscular activity might provide it with the opportunity to exploit glutamine formation as a means to detoxify ammonia. After 72 h of aerial exposure, B. sinensis reduced internal ammonia production, possibly through reductions in proteolysis and amino acid catabolism, to avoid excessive accumulation of ammonia. [ABSTRACT FROM AUTHOR]

α-EPTX-Na1a (MW 6949) is a short-chain postsynaptic neurotoxin isolated from the venom of the Chinese cobra (Naja naja) which shows pseudo-irreversible antagonism at the acetylcholine nicotinic receptor on skeletal muscle. The Chinese Cobra (Naja atra) is an elapid snake of major medical importance in southern China. Although previous studies have shown that postsynaptic neurotoxins account for 11–23% of N. atra venom, envenomed patients do not display marked signs of neurotoxicity. We have previously shown that the lack of clinical neurotoxicity following snake envenoming by some species with 'neurotoxic' venoms may be related to the high prevalence of short-chain postsynaptic neurotoxins in these venoms. In this study, we describe the isolation and characterization of α-Elapitoxin-Na1a (α-EPTX-Na1a; 6949 Da), a short-chain postsynaptic neurotoxin, which accounts for approximately 9% of N. atra crude venom. α-EPTX-Na1a (30–300 nM) produced concentration-dependent inhibition of indirect-twitches, with a t 90 value of 17 ± 2 min at 300 nM, and abolished contractile responses to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior addition of either Chinese N. atra monovalent antivenom (0.3 U/ml) or Australian polyvalent snake antivenom (2.4 U/ml), prevented the in vitro neurotoxic effects of α-EPTX-Na1a (30 nM). Addition of each of these antivenoms at the t 90 time point partially reversed the in vitro neurotoxicity caused by α-EPTX-Na1a (30 nM). The inhibition of indirect twitches by α-EPTX-Na1a (30 nM) was not reversed by repeatedly washing the tissue. α-EPTX-Na1a displayed pseudo-irreversible antagonism of concentration-response curves to carbachol with a pA 2 value of 8.21. De novo protein sequencing of α-EPTX-Na1a revealed a typical short-chain postsynaptic neurotoxin profile of 62 amino acids which shared >98% amino acid sequence similarity with short-chain postsynaptic neurotoxins from other Naja species. When compared to short-chain neurotoxins isolated from cobras in China, α-EPTX-Na1a contained novel residues K47Q (i.e. lysine to glutamine), N48T (i.e. asparagine to threonine) and G49A (i.e. glycine to alanine). In conclusion, α-EPTX-Na1a is a potent, pseudo-irreversible, short-chain neurotoxin. The high prevalence of α-EPTX-Na1a in Chinese N. atra venom is likely to explain the mild neurotoxicity experienced by envenomed patients. [ABSTRACT FROM AUTHOR]

2,2′,3,5',6-Pentachlorobiphenyl (PCB95) is known as a persistent pollutant that was found in eggs in China. PCB 95 can be metabolized into OH-PCB95 and MeO-PCB95 in liver microsomes. However, the toxicity and its mechanism of PCB95 or its metabolites have been little studied on laying hens. Herein, chicken embryo liver cells of laying hens were selected and treated with different levels of PCB95 and its two metabolites, and the EC 50 of PCB95, OH-PCB95, MeO-PCB95 was 80.85, 4.81 and 107.04 μg/mL respectively, indicating that OH-PCB95 is much more cytotoxic than PCB95 or MeO-PCB95. Targeted metabolomics was further used to study the effects of the parent compound and its metabolites on cell metabolism. The results showed that four primary types of glycerophospholipids were down-regulated after exposure to PCB95 and its metabolites, especially PE and PS (60% more than the control for PCB95, 40% for OH-PCB95, and less than 40% for MeO-PCB95). KEGG pathway analysis based on amino acid metabolism showed that PCB95 may mainly interfere with the amino acids involved in immune regulation (phenylalanine and tyrosine), and OH-PCB95 may be associated with genetic disoders (cysteine, methionine and purine metabolism). However, the metabolic pathways induced by MeO-PCB95 are quite different from those induced by PCB95 and OH-PCB95, affecting mainly D-glutamine and D-glutamate metabolism, alanine and glutamate metabolism, and arginine and proline metabolism; these pathways mainly regulate the elimination of excess purines and are involved in the synthesis of the amino acids required by cells. These results showed that OH-PCB95 has the highest toxicity on chicken embryo liver cells and MeO-PCB95 could be a detoxification product of PCB95 and OH-PCB95. This study contributes to the understanding of the different effects of PCB95 and its metabolites on cellular metabolism, and the data are helpful in evaluating the hepatotoxic effects of these compounds. Image 1 • Most PCBs contamination was reported only in eggs, but not in Chicken Embryo Liver Cells of Laying Hens. • The cytotoxicity of PCB95 and its metabolites was compared. • The mechanism of PCBS on cells was analysed for the perspective of metabolome. • Further demonstration that methoxyl metabolites may be detoxifying substances of hydroxyl metabolites. [ABSTRACT FROM AUTHOR]

Enterovirus 71 (EV71) infection is an endemic disease in Southeast Asia and China. We have previously shown that EV71 virus causes functional changes in mitochondria. It is speculative whether EV71 virus alters the host cell metabolism to its own benefit. Using a metabolomics approach, we demonstrate that EV71-infected Vero cells had significant changes in metabolism. Glutathione and its related metabolites, and several amino acids, such as glutamate and aspartate, changed significantly with the infectious dose of virus. Other pathways, including glycolysis and tricarboxylic acid cycle, were also altered. A change in glutamine/glutamate metabolism is critical to the viral infection. The presence of glutamine in culture medium was associated with an increase in viral replication. Dimethyl α-ketoglutarate treatment partially mimicked the effect of glutamine supplementation. In addition, the immunoblot analysis revealed that the expression of glutamate dehydrogenase (GDH) and trifunctional carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) increased during infection. Knockdown of expression of glutaminase (GLS), GDH and CAD drastically reduced the cytopathic effect (CPE) and viral replication. Furthermore, we found that CAD bound VP1 to promote the de novo pyrimidine synthesis. Our findings suggest that virus may induce metabolic reprogramming of host cells to promote its replication through interactions between viral and host cell proteins. [ABSTRACT FROM AUTHOR]

Background: To conduct a meta-analysis of the effect of glutamine supplements on prognosis in adult critical-ill patients., Methods: We searched the Web of Science, Cochrane library, PubMed, the Wanfang Database, and the China National Knowledge Infrastructure (CNKI)/CBMdisc database. The primary outcome was hospital mortality, or if not reported, 28-day/6-month/intensive care unit (ICU) mortality. The secondary outcomes were duration of mechanical ventilation (MV), length of stay (LOS) in the ICU, LOS in the hospital, and nosocomial infections., Results: In 599 related articles, 47 randomized controlled trials, including 6,198 patients, met all the inclusion criteria. Hospital mortality was not significantly different between the glutamine group and the control group. Length of MV was significantly higher in the control group than that of the glutamine group. In a subgroup analysis of severely burned patients, hospital mortality had the same trend. In other subgroups, there was no significant difference between the two groups., Conclusions: We suggest that supplemental glutamine need not be routinely added to the diet of criticalill patients to reduce hospital mortality, with the exception of the diet of severely burned patients.

Infectious spleen and kidney necrosis virus (ISKNV) has caused serious economic losses in the cultured mandarin fish (Siniperca chuatsi) industry in China. Host metabolism alteration induced by disease infection may be the core problem of pathogenesis. However, to date, little is known about the disease-induced fish metabolism changes. In this study, we first reported ISKNV, the fish virus, induced metabolism alteration. The metabolomics profiles of Chinese perch brain cells (CPB) post-ISKNV infection at progressive time points were analyzed using the UHPLC-Q-TOF/MS technique. A total of 98 differential metabolites were identified. In the samples harvested at 24 hours post-infection (hpi; the early stage of ISKNV infection), 49 differential metabolites were identified comparing with control cells, including 31 up-regulated and 18 down-regulated metabolites. And in the samples harvested at 72 hpi (the late stage of ISKNV infection), 49 differential metabolites were identified comparing with control cells, including 27 up-regulated and 22 down-regulated metabolites. These differential metabolites were involved in many pathways related with viral pathogenesis. Further analysis on the major differential metabolites related to glucose metabolism and amino acid metabolism revealed that both glucose metabolism and glutamine metabolism were altered and a metabolic shift was determined from glucose to glutamine during ISKNV infection cycle. In ISKNV-infected cells, CPB cells prefer to utilize glucose for ISKNV replication at the early stage of infection, while they prefer to utilize glutamine to synthetize lipid for ISKNV maturation at the late stage of infection. These findings may improve the understanding of the interaction between ISKNV and host, as well as provide a new insight for elucidating the ISKNV pathogenic mechanism. [ABSTRACT FROM AUTHOR]

In this report, we describe the identification of a novel allele HLA-A*0128, which was found in a registered donor from China Marrow Donor Program. The A*0128 allele differs from the A*0113 by one nucleotide substitutions in exon 2 at position 282 (G→C). The mutation results in a codon change: at codon 70 where a glutamine acid is substituted by a histidine acid. [ABSTRACT FROM AUTHOR]

Background: Plasma glutamine (Gln) level has been negatively correlated with the severity of severe acute pancreatitis (SAP). Although Gln is widely used today, the results of individual randomized controlled trials of Gln-enriched nutrition support for patients with SAP are conflicting., Methods: PubMed, EMBASE, HighWire, Cochrane Central Register of Controlled Trials, Wanfang, China Journals Full-Text Database, and the Chinese Biomedical Literature Database were searched. Literature published before June 2014 was searched. Randomized controlled trials investigating the comparison of conventional and Gln-enriched nutrition support were included; a random effect model using Rev Man 5.2 software was chosen to complete this meta-analysis. The count data were analyzed using the risk ratio (RR) and 95% confidence interval (CI), and the measurement data were analyzed using the standard mean difference or weighted mean difference and 95% CI. Heterogeneity analyses were conducted by I(2) test; publication bias analyses were conducted by Begg test., Results: Ten studies were eventually chosen for analysis, including 218 patients who received conventional methods (control group) and 215 patients who received Gln-enriched nutrition support (experimental group). Compared with the control group, Gln is helpful in elevating the albumin level, decreasing C-reaction protein (standard mean difference = 1.01, -1.89; 95% CI: 0.50 to 1.51, -3.23 to -0.56; P < .05), decreasing the incidence of infectious complication and mortality (RR = 0.62, 0.36; 95% CI: 0.46 to 0.83, 0.16 to 0.83; P < .05), and shortening the hospital stay length (weighted mean difference [WMD] = -3.89; 95% CI: -4.98 to -2.81; P < .05) without increasing expenses (WMD = -0.16; 95% CI: -1.34 to 1.02; P > .05). Intravenous infusion manifested more advantages by decreasing the incidence of infectious complications and mortality., Conclusions: Gln-enriched nutrition support is superior to conventional methods for SAP, and intravenous infusion may be a better choice for drug administration., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Abstract: Intermediate-length polyglutamine (polyQ) expansions in the ataxin-2 (ATXN2) gene have recently been identified as a risk factor for sporadic amyotrophic lateral sclerosis (SALS). Our study aims to analyze cytosine, adenine, guanine (CAG)n expansions in the ATXN2 gene among Chinese patients with SALS. All patients diagnosed with adult-onset sporadic amyotrophic lateral sclerosis (ALS) were consecutively followed up, and their clinical characteristics were collected. To measure the repeat length of ATXN2 polyQ, fluorescence-polymerase chain reaction products were analyzed on a 3100-Avant Genetic Analyzer Applied Biosystem (Foster City, CA, USA) using the ROC-500 size standard. Three hundred forty-five patients with SALS were studied. The mean age of onset was 51.38 ± 12.45 years. ATXN2 polyQ with a repeat length greater than 27 was found to be weakly associated with amyotrophic lateral sclerosis in our study. There was no significant difference in mean age of onset, gender, and onset site between the group of SALS patients with and without ATXN2 polyQ expansion greater than 27. Our finding provides evidence that the ATXN2 polyQ expansion greater than 27 might be a risk factor for Chinese SALS patients. [Copyright &y& Elsevier]

Background and Objective: Adrenergic β2 receptors (ADRB2) play an important role in regulating pulmonary function. Many previous studies have investigated possible associations between polymorphisms in the ADRB2 gene and asthma, but have yielded conflicting results. Furthermore, little is known regarding the possible role of the Arg19Cys polymorphism in susceptibility to asthma among Chinese., Methods: This case-control association study involved 238 patients with asthma and 265 healthy subjects from a Han population in southwest China. For all subjects, the 5' leader cistron Arg19Cys, Arg16Gly and Gln27Glu polymorphisms in the ADRB2 gene were characterized by direct sequencing. Genotype, allele and haplotype frequencies were determined. In addition, to evaluate the association between the ADRB2 polymorphisms and lung function, bronchodilator response to inhaled β2 agonists (400 µg of albuterol) was assessed in the asthmatic patients., Results: There were no significant differences in genotype or allele frequencies for the three ADRB2 polymorphisms between the two cohorts. The Arg19/Arg16/Gln27 haplotype was more frequent among asthmatic patients than control subjects (odds ratio 2.24, 95% confidence interval (CI): 1.05-4.73, P=0.04). Moreover, the Arg19/Cys19 genotype was associated with a lower FEV₁% (mean difference -4.5, 95% CI: -12.5 to 3.6, P=0.02) and FEV₁/FVC (mean difference 8.9, 95% CI: 8.5-9.4, P=0.01). The bronchodilator response to albuterol was also marginally lower in individuals who were homozygous for the Arg19 genotype (mean difference 4.2, 95% CI: 3.7-4.8, P=0.03)., Conclusions: The Arg19/Cys19 genotype was an independent risk factor for lower FEV₁% and FEV₁/FVC. Asthmatic patients with the Arg19/Arg19 genotype showed decreased responsiveness to albuterol. Furthermore, the Arg19/Arg16/Gln27 haplotype may contribute to increased susceptibility to asthma in the Chinese population., (© 2011 The Authors. Respirology © 2011 Asian Pacific Society of Respirology.)

The aim of this study was to investigate the role of FcgammaRIIB gene in susceptibility to systemic lupus erythematosus (SLE) using family-based association methods. In total, 119 patients with SLE from 95 nuclear families, aged from 14 to 78 years, who met the American College of Rheumatology (ACR) 1997 criteria, were recruited, as were 316 family members of these patients. A family-based association analysis was used to explore the relationship between gene polymorphism and SLE. We studied three single-nucleotide polymorphisms (SNPs, rs10917661, rs5017567, and rs1050499) encoding non-synonymous substitution in the FcgammaRIIB gene with respect to genetic susceptibility to SLE in collection of 435 subjects from 95 nuclear families. We performed the genotyping using PCR-restriction fragment length polymorphism method. Among 119 SLE patients, the frequencies of FcgammaRIIB Gln/Gln,Gln/Ter and Ter/Ter genotypes were 12.7, 60.7 and 26.6%. Univariate (single-marker) family-based association tests (FBATs) demonstrated that variant alleles at a SNP, rs10917661, in exon 2 of FcgammaRIIB gene were significantly associated with genetic susceptibility to SLE in additive model (exon 2, Z = 3.444, P = 0.00057). transmission/disequilibrium test (TDT) and sibship disequilibuium test (SDT) analysis showed an excess of the alleles of 50Ter from heterozygous parents to affected offspring (chi(2) = 10.88, P = 0.0013). However, the rs5017567 and rs1050499 SNPs were not found in Chinese population. Our findings provide strong evidence suggesting that a FcgammaRIIB-Gln50Ter loci might be the susceptible factor of SLE in Chinese population.

Chelant-enhanced phytoextraction is one of the most promising technologies to remove heavy metals from soil. The key of the technology is to choose suitable additives in combination with a suitable plant. In the present study, laboratory batch experiment of metal solubilization, cress seeds germination were undertaken to investigate the metal-mobilizing capability and the phytotoxicity of organic additives, including ethylene diamine triacetic acid (EDTA), citric acid, acetic acid, oxalic acid, glutamine and monosodium glutamate waste liquid (MGWL) from food industry. Experiments in pots were carried out to study the effects of the additives on Zn and Cd phytoextraction. Furthermore, a leaching experiment with lysimeter was performed to evaluate the environmental risks of additive-induced leaching to underground water. The results showed that EDTA had a strong mobilizing ability for Zn and Cd, followed by mixed reagent (MR) and MGWL. MGWL and acetic acid at 5 mmol equivalent per liter resulted in seed germination index less than 2%. Experiments in pots verified the phytotoxicity of acetic acid and MGWL. Addition of the mixed reagent at 6-10 mmol/kg significantly increased Zn phytoextraction by Thlaspi caerulescens. The same for EDTA and the mixed reagent at 10 mmol/kg by Sedum alfredii. But only mixed reagents could significantly increase Cd phytoextraction by the studied hyperaccumulators. This suggested that the strong chelant was not always the good agent to enhance phytoextraction. S. alfredii combined with 2-10 mmol/kg soil MR was preferred for phytoremediation of Cd/Zn contaminated soils in southern China, this could result in high phytoextraction of Cd/Zn and reduce the leaching risk to underground water than EDTA assisted phytoextration.

Allergic rhinitis is a major public health problem and has seen its prevalence increase during the past few decades. Interleukin 13 (IL-13) has been implicated in the pathogenesis and in the regulation of immunoglobulin E (IgE) production. Single nucleotide polymorphisms (SNPs) have been found in both the coding sequence and the promoter region of IL-13, and such SNPs have been associated with allergic asthma. We have investigated whether IL-13 SNPs are associated with allergic rhinitis. Among 188 Chinese adult patients with allergic rhinitis and 87 normal controls, no significant difference was found in either allele or haplotype frequency of the SNPs between the two groups. Within patients, there was a significant association of the IL-13 Arg130Gln SNP, but not of the IL-13 promoter -1112(C/T) SNP, with serum total IgE levels. Patients with a Gln/Gln genotype showed much higher serum total IgE than those with an Arg/Arg genotype. When tested for serum-specific IgE, patients allergic to Derp 1, but not those allergic to Artemisia pollen, showed a significant association with the IL-13 promoter SNP. Thus, our results suggest a possible involvement of IL-13 SNPs in the regulation of IgE production in response to allergens in this Chinese population.

Familial defective apolipoprotein (apo) B-100 together with familial hypercholesterolemia are the two common genetic conditions that cause hypercholesterolemia. Familial defective apolipoprotein B-100 is due to mutations around codon 3500 of the apo B gene. The most-characterized mutation is a G>A transition at nucleotide 10,708 that results in the substitution of arginine by glutamine at codon 3500 (Apo B Arg3500Gln). Two other mutations are caused by a C>T transition, one at nucleotide 10,800 (Apo B Arg3531Cys) and the other at nucleotide 10,707 (apo B Arg3500Trp). In the present study we describe three new Italian cases of familial defective apolipoprotein B-100 (Apo B Arg3500Gln), one from the Liguria region and two from Sicily, and the haplotype of the apo B gene co-segregating with the mutation. By screening two groups of probands, clinically diagnosed as having Familial Hypercholesterolemia (700 from mainland Italy and 305 from Sicily), the prevalence of familial defective apolipoprotein B-100 due to Arg3500Gln was found to be very low (0.28% and 0.65%, respectively). The Arg3531Cys mutation was not detected in any proband. In the three new families with Arg3500Gln mutation in the present study and in one previously described in Italy, the mutation was associated with a unique apo B haplotype, which is consistent with data previously reported for Caucasian patients [XbaI-, MspI+, EcoRI-, presence of the 5' signal peptide insertion (Ins) allele, and the 49-repeat allele of the 3'-VNTR].

We investigated the prevalence of the factor V (FV) Arg 506 Gln mutation in healthy subjects from three eastern Asian countries (Japan, n = 270; China, n = 113; and Korea, n = 93) and in 26 Japanese patients showing venous thromboembolic events. The patients were also examined for activated protein C (APC) resistance by using the Coatest APC resistance kit. The FV mutation was investigated by polymerase chain reaction and restricted enzyme digestion with MnlI RFLP assay of the FV gene. None of the patients showed APC resistance, while all subjects examined were homozygous for Arg at position 506 of the FV gene. Our results imply that FV mutation and APC resistance contribute little to venous thrombotic diseases in eastern Asia.