Active Components of Pueraria lobata through the MAPK/ERK Signaling Pathway Alleviate Iron Overload in Alcoholic Liver Disease.

OBJECTIVE: To delve into the primary active ingredients and mechanism of Pueraria lobata for alleviating iron overload in alcoholic liver disease. METHODS: Pueraria lobata's potential targets and signaling pathways in treating alcohol-induced iron overloads were predicted using network pharmacology analysis. Then, animal experiments were used to validate the predictions of network pharmacology. The impact of puerarin or genistein on alcohol-induced iron accumulation, liver injury, oxidative stress, and apoptosis was assessed using morphological examination, biochemical index test, and immunofluorescence. Key proteins implicated in linked pathways were identified using RT-qPCR, western blot analysis, and immunohistochemistry. RESULTS: Network pharmacological predictions combined with animal experiments suggest that the model group compared to the control group, exhibited activation of the MAPK/ERK signaling pathway, suppression of hepcidin expression, and aggravated iron overload, liver damage, oxidative stress, and hepatocyte death. Puerarin and genistein, the active compounds in Pueraria lobata, effectively mitigated the aforementioned alcohol-induced effects. No statistically significant disparities were seen in the effects above between the two groups receiving drug therapy. CONCLUSION: This study preliminarily demonstrated that puerarin and genistein in Pueraria lobata may increase hepcidin production to alleviate alcohol-induced iron overload by inhibiting the MAPK/ERK signaling pathway.

Structural Characterization of Polygonatum Cyrtonema Polysaccharide and Its Immunomodulatory Effects on Macrophages.

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.

Arabidopsis CBP60b is a central transcriptional activator of immunity.

Plants use a dual defense system to cope with microbial pathogens. The first involves pathogen-associated molecular pattern-triggered immunity which is conferred by membrane receptors, and the second involves effector-triggered immunity (ETI), which is conferred by disease-resistance proteins (nucleotide-binding leucine-rich repeat-containing proteins; NLRs). Calmodulin-Binding Protein 60 (CBP60) family transcription factors are crucial for pathogen defense: CBP60g and Systemic Acquired Resistance Deficient 1 (SARD1) positively regulate immunity, whereas CBP60a negatively regulates immunity. The roles of other Arabidopsis (Arabidopsis thaliana) CBP60s remain unclear. We report that CBP60b positively regulates immunity and is redundant with-yet distinct from-CBP60g and SARD1. By combining chromatin immunoprecipitation-PCRs and luciferase reporter assays, we demonstrate that CBP60b is a transcriptional activator of immunity genes. Surprisingly, CBP60b loss-of-function results in autoimmunity, exhibiting a phenotype similar to that of CBP60b gain-of-function. Mutations at the ENHANCED DISEASE SUSCEPTIBILITY 1-PHYTOALEXIN DEFICIENT 4-dependent ETI pathway fully suppressed the defects of CBP60b loss-of-function but not those of CBP60b gain-of-function, suggesting that CBP60b is monitored by NLRs. Functional loss of SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1, an R-gene, partially rescued the phenotype of cbp60b, further supporting that CBP60b is a protein targeted by pathogen effectors, that is, a guardee. Unlike CBP60g and SARD1, CBP60b is constitutively and highly expressed in unchallenged plants. Transcriptional and genetic studies further suggest that CBP60b plays a role redundant with CBP60g and SARD1 in pathogen-induced defense, whereas CBP60b has a distinct role in basal defense, partially via direct regulation of CBP60g and SARD1.

A Review of Polygonatum Mill. Genus: Its Taxonomy, Chemical Constituents, and Pharmacological Effect Due to Processing Changes.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Polygonatum Tourn, ex Mill. contains numerous chemical components, such as steroidal saponins, polysaccharides, flavonoids, alkaloids, and others, it possesses diverse pharmacological activities, such as anti-aging, anti-tumor, immunological regulation, as well as blood glucose management and fat reducing properties. AIM OF THE REVIEW: This study reviews the current state of research on the systematic categorization, chemical composition, pharmacological effects, and processing changes of the plants belonging to the genus Polygonatum, to provide a theoretical foundation for their scientific development and rational application. MATERIALS AND METHODS: The information was obtained by searching the scientific literature published between 1977 and 2022 on online databases (including PubMed, CNKI, SciFinder, and Web of Science) and other sources (such as the Chinese Pharmacopoeia 2020 edition, and Chinese herbal books). RESULTS: The genus Polygonatum contains 79 species, and 233 bioactive chemical compounds were identified in them. The abundance of pharmacological activities, such as antioxidant activities, anti-fatigue activities, anti-inflammatory activities, etc., were revealed for the representatives of this genus. In addition, there are numerous processing methods, and many chemical constituents and pharmacological activities change after the unappropriated processing. CONCLUSIONS: This review summarizes the taxonomy classification, chemical composition, pharmacological effects, and processing of the plants belonging to the genus Polygonatum, providing references and research tendencies for plant-based drug development and further clinical applications.

The traditional ethnic herb Tadehagi triquetrum from China: a review of its phytochemistry and pharmacological activities.

CONTEXT: Tadehagi triquetrum (Linn.) Ohashi (Fabaceae) (TT), is a traditional herbal medicine used especially in China's ethnic-minority communities, such as the Zhuang, Dai, Li and Wa aeras. As an ethnic medicine, it has long been used to treat various diseases. OBJECTIVE: This review summarised the phytochemical and pharmacological progress on TT from 1979 to October, 2021 by highlighting its chemical classification, structural features, pharmacological applications and folk applications to provide inspirations and suggestions for accelerating further research of this traditional phytomedicine. METHODS: The information on TT in this article has been obtained using these multiple scientific databases including Scifinder, Web of Science, ScienceDirect, Wiley, ACS publications, Springer, PubMed, China Knowledge Resource Integrated Database from the China National Knowledge Infrastructure (CNKI), Google Scholar and Baidu Scholar. Some information was also collected from classic literature on traditional Chinese medicines. RESULTS: More than 70 compounds have been isolated and reported from TT to date by the comprehensive analysis of the current literature. A large number of traditional uses and pharmacological studies have exhibited diversified bioactivities of various TT extracts and its metabolites, including anti-inflammatory, antimicrobial, anti-hepatitis B virus, hepatoprotective, insecticidal, etc. CONCLUSIONS: As a famous traditional medicine with a long history, TT has various medicinal uses and some of them have been supported by modern pharmacological researches. Further detailed studies on the action mechanisms, pharmacodynamics and structure-function relationships of single compounds or active constituents from TT are also required.

Variants of Unknown Significance in Genes Associated with Heritable Thoracic Aortic Disease Can Be Low Penetrant "Risk Variants".

Thoracic aortic aneurysms leading to acute aortic dissections are a preventable cause of premature deaths if individuals at risk can be identified. Individuals with early-onset aortic dissections without a family history or syndromic features have an increased burden of rare genetic variants of unknown significance (VUSs) in genes with pathogenic variants for heritable thoracic aortic disease (HTAD). We assessed the role of VUSs in the development of disease using both in vitro enzymatic assays and mouse models. VUSs in LOX and MYLK identified in individuals with acute aortic dissections were assayed to determine whether they disrupted enzymatic activity. A subset of VUSs reduced enzymatic activity compared to the wild-type proteins but less than pathogenic variants. Additionally, a Myh11 variant, p.Arg247Cys, which does not cause aortic disease in either humans or mice, was crossed with the Acta2-/- mouse, which has aortic enlargement with age while Acta2+/- mice do not. Acta2+/-Myh11R247C/R247C mice have aortic dilation by 3 months of age without medial degeneration, indicating that two variants not known to cause disease do lead to aortic enlargement in combination. Furthermore, the addition of Myh11R247C/R247C to the Acta2-/- mouse model accelerates aortic enlargement and increases medial degeneration. Therefore, our results emphasize the need for a classification system for variants in Mendelian genes that goes beyond the 5-tier system of pathogenic, likely pathogenic, VUS, likely benign, and benign, and includes a designation for low-penetrant "risk variants" that trigger disease either in combination with other risk factors or in a stochastic manner.

COPII Components Sar1b and Sar1c Play Distinct Yet Interchangeable Roles in Pollen Development.

The development of pollen is a prerequisite for double fertilization in angiosperms. Coat protein complex II (COPII) mediates anterograde transport of vesicles from the endoplasmic reticulum to the Golgi. Components of the COPII complex have been reported to regulate either sporophytic or gametophytic control of pollen development. The Arabidopsis (Arabidopsis thaliana) genome encodes five Sar1 isoforms, the small GTPases essential for COPII formation. By using a dominant negative approach, Sar1 isoforms were proposed to have distinct cargo specificity despite their sequence similarity. Here, we examined the functions of three Sar1 isoforms through analysis of transfer DNA insertion mutants and CRISPR/Cas9-generated mutants. We report that functional loss of Sar1b caused malfunction of tapetum, leading to male sterility. Ectopic expression of Sar1c could compensate for Sar1b loss of function in sporophytic control of pollen development, suggesting that they are interchangeable. Functional distinction between Sar1b and Sar1c may have resulted from their different gene transcription levels based on expression analyses. On the other hand, Sar1b and Sar1c redundantly mediate male gametophytic development such that the sar1b;sar1c microspores aborted at anther developmental stage 10. This study uncovers the role of Sar1 isoforms in both sporophytic and gametophytic control of pollen development. It also suggests that distinct functions of Sar1 isoforms may be caused by their distinct transcription programs.

Exogenous Adenosine Antagonizes Excitatory Amino Acid Toxicity in Primary Astrocytes.

Excitatory toxicity is still a hot topic in the study of ischemic stroke, and related research has focused mainly on neurons. Adenosine is an important neuromodulator that is known as a "biosignature" in the central nervous system (CNS). The protective effect of exogenous adenosine on neurons has been confirmed, but its mechanism remains elusive. In this study, astrocytes were pretreated with adenosine, and the effects of an A2a receptor (A2aR) inhibitor (SCH58261) and A2b receptor (A2bR) inhibitor (PSB1115) on excitatory glutamate were investigated. An oxygen glucose deprivation/reoxygenation (OGD/R) and glutamate model was generated in vitro. Post-model assessment included expression levels of glutamate transporters (glt-1), gap junction protein (Cx43) and glutamate receptor (AMPAR), Na+-K+-ATPase activity, and diffusion distance of dyes. Glutamate and glutamine contents were determined at different time points. The results showed that (1) adenosine could improve the function of Na+-K+-ATPase, upregulate the expression of glt-1, and enhance the synthesis of glutamine in astrocytes. This effect was associated with A2aR activation but not with A2bR activation. (2) Adenosine could inhibit the expression of gap junction protein (Cx43) and reduce glutamate diffusion. Inhibition of A2aR attenuated adenosine inhibition of gap junction intercellular communication (GJIC) in the OGD/R model, while it enhanced adenosine inhibition of GJIC in the glutamate model, depending on the glutamate concentration. (3) Adenosine could cause AMPAR gradually entered the nucleus from the cytoplasm, thereby reducing the expression of AMPAR on the cell membrane. Taken together, the results indicate that adenosine plays a role of anti-excitatory toxicity effect in protection against neuronal death and the functional recovery of ischemic stroke mainly by targeting astrocytes, which are closely related to A2aR. The present study provided a scientific basis for adenosine prevention and ischemic stroke treatment, thereby providing a new approach for alleviating ischemic stroke.

Identification of Antifungal Bisphosphocholines from Medicinal Gentiana Species.

Gentiana species including G. crassicaulis, G. macrophylla, G. dahurica, and G. straminea are used in traditional Chinese medicine as "Qinjiao" for the treatment of rheumatism, hepatitis, and pain. Four antifungal bisphosphocholines [irlbacholine (2) and three new analogues, gentianalines A-C (1, 3, and 4)] were identified from G. crassicaulis by a bioassay-guided fractionation and structure elucidation approach. Subsequent chemical analysis of 56 "Qinjiao" samples (45 from G. crassicaulis, five from G. macrophylla, three from G. dahurica, and three from G. straminea) showed that bisphosphocholines were present in all four Gentiana species, with irlbacholine as the major compound ranging from 2.0 to 6.2 mg per gram of dried material. Irlbacholine exhibited potent in vitro antifungal activity against Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans, and Candida glabrata with minimum inhibitory concentration (MIC) values of 0.63, 1.25, 10.0, and 5.0 µg/mL, respectively. Identification of the bisphosphocholines, a rare class of antifungal natural products, in these medicinal plants provides scientific evidence to complement their medicinal use. The bisphosphocholines carrying a long aliphatic chain possess amphiphilic molecule-like properties with a tendency of retention in both normal and reversed-phase silica gel column chromatography and thereby may be neglected in natural products discovery. This report may stimulate interest in this class of compounds, which warrant the further study of other biological activities as well.

Effects of sweetener sucralose on diet preference, growth performance and hematological and biochemical parameters of weaned piglets.

OBJECTIVE: Two experiments were conducted to investigate the effects of dietary sucralose on diet preference and growth performance of weaned piglets, and a third experiment was a 28-d safety study to examine if high-dose sucralose could affect the health state of weaned piglets. METHODS: In experiment one, 48 piglets had free access to a corn-soybean based diet and the same diet supplemented with 150 mg/kg sucralose for 15 d. In experiment two, 180 piglets were blocked into 5 treatments with 6 replications. They were fed basal diets supplemented with 0, 75, 150, 225, and 300 mg/kg sucralose for 28 days. In experiment three, 108 piglets were randomly assigned to 3 treatments and fed diets supplemented with 0, 150 (suitable level), and 1,500 (ten-fold suitable level) mg/kg sucralose for 28 d. RESULTS: The experiment 1 showed that piglets preferred (p < 0.05) diets containing sucralose during experimental period. In experiment 2, piglets fed a diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than pigs in the control group and other treatment groups during the experiment period. The concentrations of sucralose over 150 mg/kg may decrease feed intake. However, no difference in feed conversion ratio was observed. In experiment 3, piglets fed diet supplemented with 150 mg/kg sucralose had a higher average daily gain (ADG) and average daily feed intake (ADFI) than that of pigs in the control group and 1500 mg/kg treatment groups during the experiment period. Clinical blood metabolites, organ index and histological morphology were not significantly different between sucralose treatments. CONCLUSION: Sucralose can promote feed intake and thereby improve growth performance of weaned piglets. Moreover, inclusion of 1,500 mg/kg sucralose was demonstrated to have no observed adverse effects. Supplementing 150 mg/kg sucralose for weaned piglets is recommended in this study.

Effects of supplemented culture media from solid-state fermented Isaria cicadae on performance, serum biochemical parameters, serum immune indexes, antioxidant capacity and meat quality of broiler chickens.

OBJECTIVE: The objective of this study was to investigate effects of supplementation of culture media from solid-state fermented Isaria cicadae (I. cicadae) on performance, serum biochemical parameters, serum immune indexes, antioxidant capacity and meat quality of broiler chickens. METHODS: A total of 648 Arbor Acres male broiler chickens(1 d; average body weight, 42.93± 0.47 g) were randomly assigned to 6 treatments, each with six replicates and 18 broiler chickens per replicate. Broiler chickens were fed phase I (d 1 to 21) and phase II (d 22 to 42) diets. The phase I diets were corn and soybean-meal based diets supplemented with 0%, 2%, 4%, 6%, 8%, or 10% culture media from solid-state fermented I. cicadae respectively. The phase II diets were corn and soybean-meal based diets supplemented with 0%, 1.33%, 2.67%, 4.00%, 5.32%, or 6.67% culture media from solid-state fermented I. cicadae respectively. RESULTS: In phase I, the broiler chickens with the supplementation of culture media had increased body weight gain and feed intake (linear and quadratic, p<0.05) with increasing inclusion of culture media. The levels of serum total antioxidant capacity (T-AOC), glutathione (GSH) and superoxide dismutase (SOD) increased linearly (p<0.05). In phase II, levels of serum T-AOC and interleukin-1ß increased linearly (p<0.05), and GSH increased (p<0.05). In the kidney, GSH and glutathione peroxidase (GSH-Px) concentrations increased (linear and quadratic, p<0.05) and SOD concentration increased linearly (p<0.05). Compared to the control, shear force and drip loss of breast muscle decreased (linear and quadratic, p<0.05). Drip loss of leg muscle decreased linearly and quadratically (p<0.05). CONCLUSION: Dietary supplementation of culture media from solid-state fermented I.cicadae which was enriched in both wheat and residual bioactive components of I. cicadae enhanced the growth performance of broiler chickens. It also improved body anti-oxidative status and contributed to improve broiler meat quality.

Mutagenesis of FAD2 genes in peanut with CRISPR/Cas9 based gene editing.

BACKGROUND: Increasing the content of oleic acid in peanut seeds is one of the major goals in peanut breeding due to consumer and industry benefits, such as anti-oxidation and long shelf-life. Homeologous ahFAD2A and ahFAD2B genes encode fatty acid desaturases, which are the key enzymes for converting oleic acid to linoleic acid that oxidizes readily. To date, all high oleic acid peanut varieties result from natural mutations occurred in both genes. A method to induce mutations in the genes of other elite cultivars could speed introgression of this valuable trait. The gene-editing approach utilizing CRISPR/Cas9 technology was employed to induce de novo mutations in the ahFAD2 genes using peanut protoplasts and hairy root cultures as models. RESULTS: The hot spot of natural mutation in these genes was selected as the target region. Appropriate sgRNAs were designed and cloned into a CRISPR/Cas9 expression plasmid. As a result of CRISPR/Cas9 activity, three mutations were identified - G448A in ahFAD2A, and 441_442insA and G451T in ahFAD2B. The G448A and 441_442insA mutations are the same as those seen in existing high oleate varieties and the G451T is new mutation. Because natural mutations appear more often in the ahFAD2A gene than in the ahFAD2B gene in subspecies A. hypogaea var. hypogaea, the mutations induced in ahFAD2B by gene editing may be useful in developing high oleate lines with many genetic backgrounds after validation of oleic acid content in the transformed lines. The appearance of the G448A mutation in ahFAD2A is a further benefit for high oleic acid oil content. CONCLUSIONS: Overall, these results showed that mutations were, for the first time, induced by CRISPR-based gene editing approach in peanut. This research demonstrated the potential application of gene editing for mutagenesis in peanut and suggested that CRISPR/Cas9 technology may be useful in the peanut breeding programs.

MYLK pathogenic variants aortic disease presentation, pregnancy risk, and characterization of pathogenic missense variants.

PURPOSE: Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. METHODS: Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. RESULTS: Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK. CONCLUSION: These data further define the aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

Loss of Smooth Muscle α-Actin Leads to NF-κB-Dependent Increased Sensitivity to Angiotensin II in Smooth Muscle Cells and Aortic Enlargement.

RATIONALE: Mutations in ACTA2, encoding the smooth muscle isoform of α-actin, cause thoracic aortic aneurysms, acute aortic dissections, and occlusive vascular diseases. OBJECTIVE: We sought to identify the mechanism by which loss of smooth muscle α-actin causes aortic disease. METHODS AND RESULTS: Acta2-/- mice have an increased number of elastic lamellae in the ascending aorta and progressive aortic root dilation as assessed by echocardiography that can be attenuated by treatment with losartan, an angiotensin II (AngII) type 1 receptor blocker. AngII levels are not increased in Acta2-/- aortas or kidneys. Aortic tissue and explanted smooth muscle cells from Acta2-/- aortas show increased production of reactive oxygen species and increased basal nuclear factor κB signaling, leading to an increase in the expression of the AngII receptor type I a and activation of signaling at 100-fold lower levels of AngII in the mutant compared with wild-type cells. Furthermore, disruption of smooth muscle α-actin filaments in wild-type smooth muscle cells by various mechanisms activates nuclear factor κB signaling and increases expression of AngII receptor type I a. CONCLUSIONS: These findings reveal that disruption of smooth muscle α-actin filaments in smooth muscle cells increases reactive oxygen species levels, activates nuclear factor κB signaling, and increases AngII receptor type I a expression, thus potentiating AngII signaling in vascular smooth muscle cells without an increase in the exogenous levels of AngII.

MAT2A mutations predispose individuals to thoracic aortic aneurysms.

Up to 20% of individuals who have thoracic aortic aneurysms or acute aortic dissections but who do not have syndromic features have a family history of thoracic aortic disease. Significant genetic heterogeneity is established for this familial condition. Whole-genome linkage analysis and exome sequencing of distant relatives from a large family with autosomal-dominant inheritance of thoracic aortic aneurysms variably associated with the bicuspid aortic valve was used for identification of additional genes predisposing individuals to this condition. A rare variant, c.1031A>C (p.Glu344Ala), was identified in MAT2A, which encodes methionine adenosyltransferase II alpha (MAT IIα). This variant segregated with disease in the family, and Sanger sequencing of DNA from affected probands from unrelated families with thoracic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His). Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. Structural analysis suggested that p.Glu344Ala and p.Arg356His disrupt MAT IIα enzyme function. Knockdown of mat2aa in zebrafish via morpholino oligomers disrupted cardiovascular development. Co-transfected wild-type human MAT2A mRNA rescued defects of zebrafish cardiovascular development at significantly higher levels than mRNA edited to express either the Glu344 or Arg356 mutants, providing further evidence that the p.Glu344Ala and p.Arg356His substitutions impair MAT IIα function. The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease.

LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections.

RATIONALE: Mutations in several genes have been identified that are responsible for 25% of families with familial thoracic aortic aneurysms and dissections. However, the causative gene remains unknown in 75% of families. OBJECTIVES: To identify the causative mutation in families with autosomal dominant inheritance of thoracic aortic aneurysms and dissections. METHODS AND RESULTS: Exome sequencing was used to identify the mutation responsible for a large family with thoracic aortic aneurysms and dissections. A heterozygous rare variant, c.839G>T (p.Ser280Arg), was identified in LOX, encoding a lysyl oxidase, that segregated with disease in the family. Sanger and exome sequencing was used to investigate mutations in LOX in an additional 410 probands from unrelated families. Additional LOX rare variants that segregated with disease in families were identified, including c.125G>A (p.Trp42*), c.604G>T (p.Gly202*), c.743C>T (p.Thr248Ile), c.800A>C (p.Gln267Pro), and c.1044T>A (p.Ser348Arg). The altered amino acids cause haploinsufficiency for LOX or are located at a highly conserved LOX catalytic domain, which is relatively invariant in the population. Expression of the LOX variants p.Ser280Arg and p.Ser348Arg resulted in significantly lower lysyl oxidase activity when compared with the wild-type protein. Individuals with LOX variants had fusiform enlargement of the root and ascending thoracic aorta, leading to ascending aortic dissections. CONCLUSIONS: These data, along with previous studies showing that the deficiency of LOX in mice or inhibition of lysyl oxidases in turkeys and rats causes aortic dissections, support the conclusion that rare genetic variants in LOX predispose to thoracic aortic disease.

Effects of zinc sources and levels of zinc amino acid complex on growth performance, hematological and biochemical parameters in weanling pigs.

OBJECTIVE: The objective of the study was to investigate the effects of zinc amino acid complex (ZnAA) on growth performance, hematological and biochemical parameters in weanling pigs. METHODS: In Exp. 1, a total of 216 Duroc×Landrace×Large White weanling pigs were assigned randomly to 6 dietary treatments. Each treatment had 6 replicates (pens) with 6 pigs each. The diets were corn-soybean meal based with supplementation of 0, 20, 40, 80, 120 mg Zn/kg from ZnAA or 40 mg Zn/kg from feed-grade zinc sulfate. The experiment lasted 42 days. In Exp. 2, a total of 180 weanling pigs were assigned randomly to 3 dietary treatments supplemented with 0, 80, or 800 mg Zn/kg from ZnAA. RESULTS: In Exp. 1, pigs fed 40 to 80 mg Zn/kg from ZnAA had higher (p<0.05) average daily gain (ADG) than the unsupplemented group during d 0 to 14. During d 0 to 42, the pigs fed 20 to 120 mg Zn/kg from ZnAA had increased (p<0.05) ADG. Pigs fed 20 to 120 mg/kg Zn from ZnAA had lower feed:gain (p<0.05), increased the activity of serum Cu-Zn superoxide dismutase on d 14, and increased serum Zn levels on d 42 (p<0.05). In Exp. 2, pigs fed diets with 800 mg Zn/kg had increased average daily feed intake during d 15 to 28 (p<0.05) compared to the unsupplemented group. During d 0 to 28, the pigs fed supplemental Zn had increased ADG (p<0.05). On d 14 and d 28, pigs fed supplemental Zn had higher the serum alkaline phosphatase activities (p<0.05). No significant differences were observed in the hematological parameters and organ indices. CONCLUSION: Supplementation with 20 to 80 mg/kg Zn from ZnAA improved the growth performance in weaned pigs. The piglets can tolerate up to 800 mg/kg Zn from ZnAA with limited potential health effects.

[Status of Yingyangbao's compliance and its affected factors among infants in three poor rural provinces].

OBJECTIVE: This study aimed to analyze the consumption status of Yingyangbao and its affected factors in 3 poor rural Provinces. METHODS: Appling stratified cluster sampling method, 447 caregivers from Guizhou, Yunnan and Shanxi Provinces were investigated to analyze the compliance and caregivers' awareness of Yingyangbao, as well as the method to acquire the knowledge of Yingyangbao in 2014. Affected factors were detected by Chi-square test and multiple logistic regression. 43 caregivers with poor compliance were interviewed under the guidance of interview outline. The matic framework was applied to do interview data analysis, including infants, caregivers and village doctors. RESULTS: 81. 0% infants and children ate more than 3sachets of Yingyangbao last week. More than half of the caregivers( 83. 0% and 66. 0%)knew that the Yingyangbao can prevent malnutrition and anemia. 80. 8% caregivers achieved the knowledge of Yingyangbao through village doctors. Compared withbreastfeeding, mixed feeding( OR = 26. 698, 95% CI 4. 411 ~ 161. 614) and formulas feeding( OR = 4. 709, 95% CI 1. 089 ~ 20. 369) were the protecting factors, children who like eating Yingyangbao( OR = 4. 369, 95% CI 1. 859 ~ 10. 395) and caregivers who know that Yingyangbao( OR = 4. 421, 95% CI 1. 335 ~ 14. 638) can prevent malnutrition were the protecting factors. CONCLUSION: Infants and caregivers were the key factors affecting children eating Yingyangbao effectively.

[Studies on identification of Phragmitis Rhizoma and its counterfeits].

The study aims to explore the main differential characteristics of Phragmites Rhizoma and its counterfeits (rhizomes of Arundo donax, Triarrhena lutarioriparia and Miscanthus sinensis) and provide experimental basis for the reasonable applications of gramineous plants through system research and comparison of plant morphogenesis, character, transverse organization characteristics and powder microscopic characteristics.

Recurrent gain-of-function mutation in PRKG1 causes thoracic aortic aneurysms and acute aortic dissections.

Gene mutations that lead to decreased contraction of vascular smooth-muscle cells (SMCs) can cause inherited thoracic aortic aneurysms and dissections. Exome sequencing of distant relatives affected by thoracic aortic disease and subsequent Sanger sequencing of additional probands with familial thoracic aortic disease identified the same rare variant, PRKG1 c.530G>A (p.Arg177Gln), in four families. This mutation segregated with aortic disease in these families with a combined two-point LOD score of 7.88. The majority of affected individuals presented with acute aortic dissections (63%) at relatively young ages (mean 31 years, range 17-51 years). PRKG1 encodes type I cGMP-dependent protein kinase (PKG-1), which is activated upon binding of cGMP and controls SMC relaxation. Although the p.Arg177Gln alteration disrupts binding to the high-affinity cGMP binding site within the regulatory domain, the altered PKG-1 is constitutively active even in the absence of cGMP. The increased PKG-1 activity leads to decreased phosphorylation of the myosin regulatory light chain in fibroblasts and is predicted to cause decreased contraction of vascular SMCs. Thus, identification of a gain-of-function mutation in PRKG1 as a cause of thoracic aortic disease provides further evidence that proper SMC contractile function is critical for maintaining the integrity of the thoracic aorta throughout a lifetime.