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Background: A genome-wide assessment of nucleotide diversity in a polyploid species must minimize the inclusion of homoeologous sequences into diversity estimates and reliably allocate individual haplotypes into their respective genomes. The same requirements complicate the development and deployment of single nucleotide polymorphism (SNP) markers in polyploid species. We report here a strategy that satisfies these requirements and deploy it in the sequencing of genes in cultivated hexaploid wheat (Triticum aestivum, genomes AABBDD) and wild tetraploid wheat (Triticum turgidum ssp. dicoccoides, genomes AABB) from the putative site of wheat domestication in Turkey. Data are used to assess the distribution of diversity among and within wheat genomes and to develop a panel of SNP markers for polyploid wheat.Results: Nucleotide diversity was estimated in 2114 wheat genes and was similar between the A and B genomes and reduced in the D genome. Within a genome, diversity was diminished on some chromosomes. Low diversity was always accompanied by an excess of rare alleles. A total of 5,471 SNPs was discovered in 1791 wheat genes. Totals of 1,271, 1,218, and 2,203 SNPs were discovered in 488, 463, and 641 genes of wheat putative diploid ancestors, T. urartu, Aegilops speltoides, and Ae. tauschii, respectively. A public database containing genome-specific primers, SNPs, and other information was constructed. A total of 987 genes with nucleotide diversity estimated in one or more of the wheat genomes was placed on an Ae. tauschii genetic map, and the map was superimposed on wheat deletion-bin maps. The agreement between the maps was assessed.Conclusions: In a young polyploid, exemplified by T. aestivum, ancestral species are the primary source of genetic diversity. Low effective recombination due to self-pollination and a genetic mechanism precluding homoeologous chromosome pairing during polyploid meiosis can lead to the loss of diversity from large chromosomal regions. The net effect of these factors in T. aestivum is large variation in diversity among genomes and chromosomes, which impacts the development of SNP markers and their practical utility. Accumulation of new mutations in older polyploid species, such as wild emmer, results in increased diversity and its more uniform distribution across the genome. © 2010 Akhunov et al; licensee BioMed Central Ltd.

Single-nucleotide polymorphism was used in the construction of an expressed sequence tag map of Aegilops tauschii, the diploid source of the wheat D genome. Comparisons of the map with the rice and sorghum genome sequences revealed 50 inversions and translocations; 2, 8, and 40 were assigned respectively to the rice, sorghum, and Ae. tauschii lineages, showing greatly accelerated genome evolution in the large Triticeae genomes. The reduction of the basic chromosome number from 12 to 7 in the Triticeae has taken place by a process during which an entire chromosome is inserted by its telomeres into a break in the centromeric region of another chromosome. The original centromere-telomere polarity of the chromosome arms is maintained in the new chromosome. An intrachromosomal telomere-telomere fusion resulting in a pericentric translocation of a chromosome segment or an entire arm accompanied or preceded the chromosome insertion in some instances. Insertional dysploidy has been recorded in three grass subfamilies and appears to be the dominant mechanism of basic chromosome number reduction in grasses. A total of 64% and 66% of Ae. tauschii genes were syntenic with sorghum and rice genes, respectively. Synteny was reduced in the vicinity of the termini of modern Ae. tauschii chromosomes but not in the vicinity of the ancient termini embedded in the Ae. tauschii chromosomes, suggesting that the dependence of synteny erosion on gene location along the centromere-telomere axis either evolved recently in the Triticeae phylogenetic lineage or its evolution was recently accelerated.

Background: Acute ischemic stroke (AIS) is a significant global health issue with increasing incidence owing to aging populations and rising cardiovascular risk factors. In addition to physical impairments, AIS frequently leads to neuropsychiatric complications, such as cognitive impairment, anxiety, and depressive symptoms, which adversely affect patients' quality of life and rehabilitation. Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a potential biomarker for various conditions, including AIS. This study investigated the association between serum NGAL levels at admission and neuropsychiatric complications in patients with AIS., Aim: To investigate the relationship between serum NGAL levels at admission and neuropsychiatric complications in patients with AIS., Methods: Between January 2022 and December 2023, 150 patients with AIS were enrolled. Serum NGAL levels were measured at admission using an enzyme-linked immunosorbent assay. Cognitive function was assessed using the Mini-Mental State Examination, while anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale at discharge. The relationship between serum NGAL levels and cognitive impairment, anxiety, and depressive symptoms was analyzed using multivariate logistic regression, adjusted for potential confounders of age, sex, body mass index, smoking status, hypertension, diabetes mellitus, dyslipidemia, previous stroke, and stroke severity., Results: The mean age of the participants was 65.4 ± 10.2 years, and 58% were males. Prevalence rates of cognitive impairment, anxiety, and depressive symptoms at discharge were 34.7%, 28.0%, and 32.0%, respectively. Serum NGAL levels were significantly higher in patients with cognitive impairment (median: 5.6 ng/mL vs 3.2 ng/mL, P < 0.001), anxiety (median: 5.1 ng/mL vs 3.5 ng/mL, P = 0.002), and depressive symptoms (median: 5.4 ng/mL vs 3.3 ng/mL, P < 0.001), compared to those without these conditions. Multivariate logistic regression analysis showed that higher serum NGAL levels at admission were independently associated with cognitive impairment [odds ratio (OR) = 1.42, 95% confidence interval (CI): 1.18-1.71, P < 0.001], anxiety (OR = 1.28, 95%CI: 1.09-1.51, P = 0.003), and depressive symptoms (OR = 1.39, 95%CI: 1.16-1.67, P < 0.001) after adjusting for potential confounders., Conclusion: Elevated serum NGAL levels were independently associated with cognitive impairment, anxiety, and depressive symptoms in patients with AIS; and may function as potential biomarkers for patients at risk., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bread wheat (Triticum aestivum) is a globally dominant crop and major source of calories and proteins for the human diet. Compared with its wild ancestors, modern bread wheat shows lower genetic diversity, caused by polyploidisation, domestication and breeding bottlenecks 1,2 . Wild wheat relatives represent genetic reservoirs, and harbour diversity and beneficial alleles that have not been incorporated into bread wheat. Here we establish and analyse extensive genome resources for Tausch's goatgrass (Aegilops tauschii), the donor of the bread wheat D genome. Our analysis of 46 Ae. tauschii genomes enabled us to clone a disease resistance gene and perform haplotype analysis across a complex disease resistance locus, allowing us to discern alleles from paralogous gene copies. We also reveal the complex genetic composition and history of the bread wheat D genome, which involves contributions from genetically and geographically discrete Ae. tauschii subpopulations. Together, our results reveal the complex history of the bread wheat D genome and demonstrate the potential of wild relatives in crop improvement., (© 2024. The Author(s).)

Powdery mildew, caused by the fungal pathogen Blumeria graminis (DC.) E. O. Speer f. sp. tritici Em. Marchal (Bgt), is a constant threat to global wheat (Triticum aestivum L.) production. Although ∼100 powdery mildew (Pm) resistance genes and alleles have been identified in wheat and its relatives, more is needed to minimize Bgt's fast evolving virulence. In tetraploid wheat (Triticum turgidum L.), wild emmer wheat [T. turgidum ssp. dicoccoides (Körn. ex Asch. & Graebn.) Thell.] accessions from Israel have contributed many Pm resistance genes. However, the diverse genetic reservoirs of cultivated emmer wheat [T. turgidum ssp. dicoccum (Schrank ex Schübl.) Thell.] have not been fully exploited. In the present study, we evaluated a diverse panel of 174 cultivated emmer accessions for their reaction to Bgt isolate OKS(14)-B-3-1 and found that 66% of accessions, particularly those of Ethiopian (30.5%) and Indian (6.3%) origins, exhibited high resistance. To determine the genetic basis of Bgt resistance in the panel, genome-wide association studies were performed using 46,383 single nucleotide polymorphisms (SNPs) from genotype-by-sequencing and 4331 SNPs from the 9K SNP Infinium array. Twenty-five significant SNP markers were identified to be associated with Bgt resistance, of which 21 SNPs are likely novel loci, whereas four possibly represent emmer derived Pm4a, Pm5a, PmG16, and Pm64. Most novel loci exhibited minor effects, whereas three novel loci on chromosome arms 2AS, 3BS, and 5AL had major effect on the phenotypic variance. This study demonstrates cultivated emmer as a rich source of powdery mildew resistance, and the resistant accessions and novel loci found herein can be utilized in wheat breeding programs to enhance Bgt resistance in wheat., (© 2024 The Author(s). The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L 1 )(H 2 O)Cl 3 ] (1), [Rh(L 2 )(CH 3 OH)Cl 3 ] (2), [Rh(L 3 )(H 2 O)Cl 3 ] (3), [Rh 2 (L 4 )Cl 6 ]·CH 3 OH (4), [Rh(L 5 )(CH 3 CN)Cl 3 ]·0.5CH 3 CN (5), and [Pd(L 5 )Cl 2 ] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6., 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 © 2023 Elsevier Inc. All rights reserved.)

Diploid A-genome wheat (einkorn wheat) presents a nutrition-rich option as an ancient grain crop and a resource for the improvement of bread wheat against abiotic and biotic stresses. Realizing the importance of this wheat species, reference-level assemblies of two einkorn wheat accessions were generated (wild and domesticated). This work reports an einkorn genome database that provides an interface to the cereals research community to perform comparative genomics, applied genetics and breeding research. It features queries for annotated genes, the use of a recent genome browser release, and the ability to search for sequence alignments using a modern BLAST interface. Other features include a comparison of reference einkorn assemblies with other wheat cultivars through genomic synteny visualization and an alignment visualization tool for BLAST results. Altogether, this resource will help wheat research and breeding. Database URL  https://wheat.pw.usda.gov/GG3/pangenome., (© The Author(s) 2023. Published by Oxford University Press.)

MicroRNAs (miRNAs) are mediators of the aging process. The purpose of this work was to analyze the miRNA expression profiles of spermatozoa from men of different ages with normal fertility. Twenty-seven donors were divided into three groups by age (Group A, n = 8, age: 20-30 years; Group B, n = 10, age: 31-40 years; and Group C, n = 9, age: 41-55 years) for high-throughput sequencing analysis. Samples from 65 individuals (22, 22, and 21 in Groups A, B, and C, respectively) were used for validation by quantitative real-time polymerase chain reaction (qRT-PCR). A total of 2160 miRNAs were detected: 1223 were known, 937 were newly discovered and unnamed, of which 191 were expressed in all donors. A total of 7, 5, and 17 differentially expressed microRNAs (DEMs) were found in Group A vs B, Group B vs C, and Group A vs C comparisons, respectively. Twenty-two miRNAs were statistically correlated with age. Twelve miRNAs were identified as age-associated miRNAs, including hsa-miR-127-3p, mmu-miR-5100&#95;L+2R-1, efu-miR-9226&#95;L-2&#95;1ss22GA, cgr-miR-1260&#95;L+1, hsa-miR-652-3p&#95;R+1, pal-miR-9993a-3p&#95;L+2R-1, hsa-miR-7977&#95;1ss6AG, hsa-miR-106b-3p&#95;R-1, hsa-miR-186-5p, PC-3p-59611&#95;111, hsa-miR-93-3p&#95;R+1, and aeca-mir-8986a-p5&#95;1ss1GA. There were 9165 target genes of age-associated miRNAs. Gene Ontology (GO) analysis of the target genes identified revealed enrichment of protein binding, membrane, cell cycle, and so on. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of age-related miRNAs for target genes revealed 139 enriched pathways, such as signaling pathways regulating stem cell pluripotency, metabolic pathways, and the Hippo signaling pathway. This suggests that miRNAs play a key role in male fertility changes with increasing age and provides new evidence for the study of the mechanism of age-related male fertility decline., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

A mild and elegant multicomponent protocol for construction of CF 2 H-containing carbazoles was accomplished by visible-light photoredox catalysis with formation of two new C-C bonds in a single step to deliver a wide variety of structurally diverse difluoroalkylated carbazoles in moderate to good yields, featuring mild reaction conditions, synthetic simplicity, broad substrates, and good functional group tolerance.

Wheat is one of the most important cereal crops for the global food security. Due to its narrow genetic base, modern bread wheat cultivars face challenges from increasing abiotic and biotic stresses. Since genetic improvement is the most sustainable approach, finding novel genes and alleles is critical for enhancing the genetic diversity of wheat. The tertiary gene pool of wheat is considered a gold mine for genetic diversity as novel genes and alleles can be identified and transferred to wheat cultivars. Aegilops geniculata and Ae. umbellulata are the key members of the tertiary gene pool of wheat and harbor important genes against abiotic and biotic stresses. Homoeologous-group five chromosomes (5U u and 5M g ) have been extensively studied from Ae. geniculata and Ae. umbellulata as they harbor several important genes including Lr57, Lr76, Yr40, Yr70, Sr53 and chromosomal pairing loci. In the present study, using chromosome DNA sequencing and RNAseq datasets, we performed comparative analysis to study homoeologous gene evolution in 5M g , 5U u, and group 5 wheat chromosomes. Our findings highlight the diversity of transcription factors and resistance genes, resulting from the differential expansion of the gene families. Both the chromosomes were found to be enriched with the "response to stimulus" category of genes providing resistance against biotic and abiotic stress. Phylogenetic study positioned the M genome closer to the D genome, with higher proximity to the A genome than the B genome. Over 4000 genes were impacted by SNPs on 5D, with 4-5% of those genes displaying non-disruptive variations that affect gene function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yadav, Rawat, Chhuneja, Kaur, Uauy, Lazo, Gu, Doležel and Tiwari.)

Endophytic fungi can promote host plant growth, enhance antioxidant defense enzyme activity, and induce the biosynthesis and accumulation of secondarymetabolites. Therefore, using endophytic fungi to improve the quality and yield of medicinal plants or important crops is an effective means of regulation. Colletotrichum sp. AP12 has been reported to produce andrographolide compounds (ADCs). This study aimed to investigate the effects of AP12 and its elicitors on the growth, defense enzyme activity, accumulation, and transcription levels of key genes in Andrographis paniculata (Burm. f.) Nees ( A. paniculata ). Using fermentation method to prepare AP12 into the inactivated fermentation solution (IFS), fermentation solution (FS), inactivated mycelium solution (IMS), and mycelium solution (MS), and the results showed that all four fungal elicitor components (ECs) could promote A. paniculata growth, enhance antioxidant defense enzymes, and increase ADC content and yield, especially the IMS group that had the highest leaf area, whole plant dry weight, superoxide dismutase (SOD), catalase (CAT) enzyme activities, total lactone contents, and yields, which were 2.37-, 1.60-, 2.20-, 3.27-, 1.59-, and 2.65-fold of the control, respectively. The 14-deoxyandrographolide (NAD) in the host irrigated with MS was 3.35-fold that of the control. In addition, AP12-infected A. paniculata sterile seedlings could significantly increase ADC content and expression levels of key enzyme genes, especially on day 12, when the total lactone content of the host reached 88.881± 5.793 mg/g DW, while on day 6, CPS gene expression level reached 10.79-fold that of the control, in turn promoting the biosynthesis and accumulation of andrographolide. In conclusion, the endophytic fungus AP12 is beneficial to the growth and secondary metabolism of A. paniculata , which is helpful for the cultivation and application of the biological bacterial fertilizer in A. paniculata , providing a theoretical and research basis for the use of endophytic fungi as a microbial resource to improve the quality and yield of medicinal plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, Li, Gu, Huang, Hu, Zheng, Hu and Du.)

Aristolochic acid I (AAI) is a well established nephrotoxin and human carcinogen. Cytosolic NAD(P)H quinone oxidoreductase 1 (NQO1) plays an important role in the nitro reduction of aristolochic acids, leading to production of aristoloactam and AA-DNA adduct. Application of a potent NQO1 inhibitor dicoumarol is limited by its life-threatening side effect as an anticoagulant and the subsequent hemorrhagic complications. As traditional medicines containing AAI remain available in the market, novel NQO1 inhibitors are urgently needed to attenuate the toxicity of AAI exposure. In this study, we employed comprehensive 2D NQO1 biochromatography to screen candidate compounds that could bind with NQO1 protein. Four compounds, i.e., skullcapflavone II (SFII), oroxylin A, wogonin and tectochrysin were screened out from Scutellaria baicalensis. Among them, SFII was the most promising NQO1 inhibitor with a binding affinity (K D  = 4.198 μmol/L) and inhibitory activity (IC 50  = 2.87 μmol/L). In human normal liver cell line (L02) and human renal proximal tubular epithelial cell line (HK-2), SFII significantly alleviated AAI-induced DNA damage and apoptosis. In adult mice, oral administration of SFII dose-dependently ameliorated AAI-induced renal fibrosis and dysfunction. In infant mice, oral administration of SFII suppressed AAI-induced hepatocellular carcinoma initiation. Moreover, administration of SFII did not affect the coagulation function in short term in adult mice. In conclusion, SFII has been identified as a novel NQO1 inhibitor that might impede the risk of AAI to kidney and liver without obvious side effect., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

CF 2 H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF 2 H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF 2 H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and S -(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.

Although some nucleotide binding, leucine-rich repeat immune receptor (NLR) proteins conferring resistance to specific viruses have been identified in dicot plants, NLR proteins involved in viral resistance have not been described in monocots. We have used map-based cloning to isolate the CC-NB-LRR (CNL) Barley stripe mosaic virus (BSMV) resistance gene barley stripe resistance 1 (BSR1) from Brachypodium distachyon Bd3-1 inbred line. Stable BSR1 transgenic Brachypodium line Bd21-3, barley (Golden Promise) and wheat (Kenong 199) plants developed resistance against BSMV ND18 strain. Allelic variation analyses indicated that BSR1 is present in several Brachypodium accessions collected from countries in the Middle East. Protein domain swaps revealed that the intact LRR domain and the C-terminus of BSR1 are required for resistance. BSR1 interacts with the BSMV ND18 TGB1 protein in planta and shows temperature-sensitive antiviral resistance. The R 390 and T 392 residues of TGB1 ND (ND18 strain) and the G 196 and K 197 residues within the BSR1 P-loop motif are key amino acids required for immune activation. BSR1 is the first cloned virus resistance gene encoding a typical CNL protein in monocots, highlighting the utility of the Brachypodium model for isolation and analysis of agronomically important genes for crop improvement., (© 2022 The Authors. New Phytologist © 2022 New Phytologist Foundation. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Understanding neuropsychological mechanisms of mindfulness meditation (MM) has been a hot topic in recent years. This review was conducted with the goal of synthesizing empirical relationships via the genomics, circuits and networks between MM and mental disorders. We describe progress made in assessing the effects of MM on gene expression in immune cells, with particular focus on stress-related inflammatory markers and associated biological pathways. We then focus on key brain circuits associated with mindfulness practices and effects on symptoms of mental disorders, and expand our discussion to identify three key brain networks associated with mindfulness practices including default mode network, central executive network, and salience network. More research efforts need to be devoted into identifying underlying neuropsychological mechanisms of MM on how it alleviates the symptoms of mental disorders., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Cry toxins produced by Bacillus thuringiensis (Bt) are well known for their insecticidal activities against Lepidopteran, Dipteran, and Coleopteran species. In our previous work, we showed that trypsin-digested full-length Cry7Ab4 protoxin did not have insecticidal activity against Plutella xylostella larvae but strongly inhibited their growth. In this paper, we expressed and purified recombinant active Cry7Ab4 toxic core from Escherichia coli for bioassay and identified its binding proteins. Interestingly, Cry7Ab4 toxic core exhibited activity to delay the pupation of P. xylostella larvae. Using protein pull-down assay, several proteins, including basic juvenile hormone-suppressible protein 1-like (BJSP-1), were identified from the midgut juice of P. xylostella larvae as putative Cry7Ab4-binding proteins. We showed that feeding P. xylostella larval Cry7Ab4 toxic core upregulated the level of BJSP-1 mRNA in the hemocytes and fat body and decreased the free juvenile hormone (JH) level in larvae. BJSP-1 interacted with Cry7Ab4 and bound to free JH in vitro . A possible mechanism of Cry7Ab4 in delaying the pupation of P. xylostella larvae was proposed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lu, Jin, Li, Yu, Wen, Gu, Lin and Yu.)

The highly conserved Sal1 encodes a bifunctional enzyme with inositol polyphosphate-1-phosphatase and 3' (2'), 5'-bisphosphate nucleotidase activity and has been shown to alter abiotic stress tolerance in plants when disrupted. Precise gene editing techniques were used to generate Sal1 mutants in hexaploid bread wheat. The CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats) Cas9 system with three guide RNAs (gRNAs) was used to inactivate six Sal1 homologous genes within the Bobwhite wheat genome. The resulting mutant wheat plants with all their Sal1 genes disabled had slimmer stems, had a modest reduction in biomass and senesced more slowly in water limiting conditions, but did not exhibit improved yield under drought conditions. Our results show that multiplexed gRNAs enabled effective targeted gene editing of the Sal1 gene family in hexaploid wheat. These Sal1 mutant wheat plants will be a resource for further research studying the function of this gene family in wheat.

Liver fibrosis is the common consequence of almost all liver diseases and has become an urgent clinical problem without efficient therapies. Recent evidence has shown that hepatocytes-derived extracellular vesicles (EVs) play important roles in liver pathophysiology, but little is known about the role of damaged hepatocytes-derived EVs in hepatic stellate cell (HSC) activation and following fibrosis. Tetramethylpyrazine (TMP) from Ligusticum wallichii Franchat exhibits a broad spectrum of biological activities including liver protection. In this study, we investigated whether TMP exerted liver-protective action through regulating EV-dependent intercellular communication between hepatocytes and HSCs. Chronic liver injury was induced in mice by CCl 4 (1.6 mg/kg, i.g.) twice a week for 8 weeks. In the last 4 weeks of CCl 4 administration, mice were given TMP (40, 80, 160 mg·kg -1 ·d -1 , i.g.). Acute liver injury was induced in mice by injection of a single dose of CCl 4 (0.8 mg/kg, i.p.). After injection, mice were treated with TMP (80 mg/kg) every 24 h. We showed that TMP treatment dramatically ameliorated CCl 4 -induced oxidative stress and hepatic inflammation as well as acute or chronic liver fibrosis. In cultured mouse primary hepatocytes (MPHs), treatment with CCl 4 or acetaminophen resulted in mitochondrial dysfunction, release of mitochondrial DNA (mtDNA) from injured hepatocytes to adjacent hepatocytes and HSCs through EVs, mediating hepatocyte damage and fibrogenic responses in activated HSCs; pretreatment of MPHs with TMP (25 μM) prevented all these pathological effects. Transplanted serum EVs from TMP-treated mice prevented both initiation and progression of liver fibrosis caused by CCl 4 . Taken together, this study unravels the complex mechanisms underlying the protective effects of TMP against mtDNA-containing EV-mediated hepatocyte injury and HSC activation during liver injury, and provides critical evidence inspiring the development of TMP-based innovative therapeutic agents for the treatment of liver fibrosis., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Endophytic fungi of medicinal plants are abundant, and their metabolites often have antioxidant, antibacterial, and antitumor effects and can produce secondary metabolites identical or similar to those of their hosts, which can mitigate the problem of insufficient supply of medicinal plants. In this study, we screened endophytic fungi for strains that produce the same diterpene lactones as Andrographis paniculata based on their biological activity. Firstly, the dominant group of endophytic fungi of Andrographis paniculata was screened and pathogenicity was studied using Koch's rule. Secondly, DPPH, ABTS, OH, PTIO radical scavenging, and FRAP assays were used to detect the antioxidant activity of the extracellular extracts of the strains, and total phenol and total flavonoid contents of the strains with high antioxidant capacity were determined. S. aureus , B. subtilis , E. coli , and P. aeruginosa were used to determine the antibacterial activity of the mycelial extracts of the strains. Finally, the secondary metabolites of the mycelial extracts of the strains were examined by high-performance liquid chromatography. The results showed that 32 strains of Andrographis paniculata were relatively isolated > 70% and non-pathogenic. Extracellular extracts of strains AP-1 and AP-4 showed vigorous antioxidant activity, and AP-4, AP-12, AP-47, and AP-48 showed antibacterial activity against four strains of bacteria. The HPLC results indicated that the mycelial extracts of AP-4 and AP-12 contained diterpene lactones. The two endophytic fungi were recognized as Colletotrichum sp. The study successfully obtained diterpene lactones from the endophytic fungus of Andrographis paniculata and confirmed the feasibility of using endophytic fungal strains to produce active substances consistent with the host. It was also useful for exploring endophytic fungi and medicinal plants. The relationship provides theoretical guidance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Xu, Huang, Zheng, Liu, Hu, Gu and Du.)

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Aegilops tauschii is the donor of the D subgenome of hexaploid wheat and an important genetic resource. The reference-quality genome sequence Aet v4.0 for Ae. tauschii acc. AL8/78 was therefore an important milestone for wheat biology and breeding. Further advances in sequencing acc. AL8/78 and release of the Aet v5.0 sequence assembly are reported here. Two new optical maps were constructed and used in the revision of pseudomolecules. Gaps were closed with Pacific Biosciences long-read contigs, decreasing the gap number by 38,899. Transposable elements and protein-coding genes were reannotated. The number of annotated high-confidence genes was reduced from 39,635 in Aet v4.0 to 32,885 in Aet v5.0. A total of 2245 biologically important genes, including those affecting plant phenology, grain quality, and tolerance of abiotic stresses in wheat, was manually annotated and disease-resistance genes were annotated by a dedicated pipeline. Disease-resistance genes encoding nucleotide-binding site domains, receptor-like protein kinases, and receptor-like proteins were preferentially located in distal chromosome regions, whereas those encoding transmembrane coiled-coil proteins were dispersed more evenly along the chromosomes. Discovery, annotation, and expression analyses of microRNA (miRNA) precursors, mature miRNAs, and phasiRNAs are reported, including miRNA target genes. Other small RNAs, such as hc-siRNAs and tRFs, were characterized. These advances enhance the utility of the Ae. tauschii genome sequence for wheat genetics, biotechnology, and breeding., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

High-molecular-weight glutenin subunits (HMW-GS) account for only 10% of total wheat storage proteins, but play an important role in the processing quality of wheat flour. Therefore, identifying HMW-GS alleles associated with good end-use quality provides important information for wheat breeders. To rapidly, accurately and reproducibly identify HMW-GS, we established an optimized reversed-phase ultra-performance liquid chromatography (RP-UPLC) method. Separation parameters were optimized using an ACQUITY UPLC Protein BEH C 4 column and stepwise ACN gradient, and the separation patterns and retention times (RTs) of 22 subunits were comparatively analyzed in 16 standard wheat cultivars. All HMW-GS proteins were well separated within about 5.5 min, and all analyses were complete within 12 min. We distinguished the 16 subunits based on RT, although three subunits in 1Bx (1Bx7/1Bx7 OE and 1Bx17) and three subunits in 1By (1By8*, 1By9 and 1By15) had overlapping RTs; these were differentiated by SDS-PAGE. To distinguish 1Bx7 and 1Bx7 OE , which differ in protein abundance, RP-UPLC was combined with PCR analysis of DNA junction markers. The optimized method was successfully applied to determine HMW-GS alleles in a large collection of bread wheat germplasm (1787 lines). This protocol is an appropriate option for selecting lines harboring favorable HMW-GS alleles in wheat breeding.

The low-molecular weight glutenin subunit (LMW-GS) composition of wheat ( Triticum aestivum ) flour has important effects on end-use quality. However, assessing the contributions of each LMW-GS to flour quality remains challenging because of the complex LMW-GS composition and allelic variation among wheat cultivars. Therefore, accurate and reliable determination of LMW-GS alleles in germplasm remains an important challenge for wheat breeding. In this study, we used an optimized reversed-phase HPLC method and proteomics approach comprising 2-D gels coupled with liquid chromatography-tandem mass spectrometry (MS/MS) to discriminate individual LMW-GSs corresponding to alleles encoded by the Glu-A3 , Glu-B3 , and Glu-D3 loci in the 'Aroona' cultivar and 12 'Aroona' near-isogenic lines (ARILs), which contain unique LMW-GS alleles in the same genetic background. The LMW-GS separation patterns for 'Aroona' and ARILs on chromatograms and 2-D gels were consistent with those from a set of 10 standard wheat cultivars for Glu-3 . Furthermore, 12 previously uncharacterized spots in 'Aroona' and ARILs were excised from 2-D gels, digested with chymotrypsin, and subjected to MS/MS. We identified their gene haplotypes and created a 2-D gel map of LMW-GS alleles in the germplasm for breeding and screening for desirable LMW-GS alleles for wheat quality improvement.

Until recently, achieving a reference-quality genome sequence for bread wheat was long thought beyond the limits of genome sequencing and assembly technology, primarily due to the large genome size and > 80% repetitive sequence content. The release of the chromosome scale 14.5-Gb IWGSC RefSeq v1.0 genome sequence of bread wheat cv. Chinese Spring (CS) was, therefore, a milestone. Here, we used a direct label and stain (DLS) optical map of the CS genome together with a prior nick, label, repair and stain (NLRS) optical map, and sequence contigs assembled with Pacific Biosciences long reads, to refine the v1.0 assembly. Inconsistencies between the sequence and maps were reconciled and gaps were closed. Gap filling and anchoring of 279 unplaced scaffolds increased the total length of pseudomolecules by 168 Mb (excluding Ns). Positions and orientations were corrected for 233 and 354 scaffolds, respectively, representing 10% of the genome sequence. The accuracy of the remaining 90% of the assembly was validated. As a result of the increased contiguity, the numbers of transposable elements (TEs) and intact TEs have increased in IWGSC RefSeq v2.1 compared with v1.0. In total, 98% of the gene models identified in v1.0 were mapped onto this new assembly through development of a dedicated approach implemented in the MAGAAT pipeline. The numbers of high-confidence genes on pseudomolecules have increased from 105 319 to 105 534. The reconciled assembly enhances the utility of the sequence for genetic mapping, comparative genomics, gene annotation and isolation, and more general studies on the biology of wheat., (© 2021 The Authors. The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l -1 combined with the presence of ≥ 3 sexual symptoms was used as the criterion of LOH. Among them, 26.1% (103/395) and 73.9% (292/395) had primary and secondary hypogonadism, respectively. After adjustment for confounding factors, primary and secondary hypogonadism was positively related to age and comorbidities. Body mass index was an independent risk factor for secondary hypogonadism. The results suggest that the AMS total score is not an appropriate indicator for decreased testosterone, and that the cFT level is more reliable than TT for LOH diagnosis. Secondary hypogonadism is the most common form of LOH., Competing Interests: None

Objective: This paper retrospectively reviews our experience with endovascular and hybrid treatments for subclavian artery aneurysms (SAA)., Methods: Seventeen patients with SAAs were treated at our center between July 2011 and October 2018. Clinical and follow-up data were extracted from the hospital records and retrospectively reviewed. We routinely use endovascular treatments and stenting or axillary-axillary bypass to treat SAA if vertebral artery blood flow requires restoration. Patients were followed up at 3, 6, and 12 months after their operations and yearly thereafter., Results: Median follow-up was 30.5 months. In 6 patients, the SAAs involved the ipsilateral vertebral artery. Simple coil embolization was performed for 1 patient; endovascular covered stenting and coil embolization for 4 patients; and hybrid treatment for 1 patient. In 11 patients, the SAAs did not involve the ipsilateral vertebral artery. Hybrid treatment was performed for 1 patient; thoracic aortic stent implantation with coil embolization for 1 patient; and covered stent placement in the subclavian artery for 9 patients. Among the 9 patients who were symptomatic at presentation, 8 had relief of symptoms. Leakage was observed in 1 patient, but it stopped spontaneously. Stent occlusion occurred in 18.8% (3/16), but all were asymptomatic, and no interventions were necessary., Conclusion: Endovascular and hybrid treatments appear to be effective for SAAs with few complications and good clinical outcomes., Key Words: Covered stent, Coil embolization, Endovascular treatment, Hybrid, Subclavian artery aneurysm.

The wheat gliadins are a complex group of flour proteins that can trigger celiac disease and serious food allergies. As a result, mutation breeding and biotechnology approaches are being used to develop new wheat lines with reduced immunogenic potential. Key to these efforts is the development of rapid, high-throughput methods that can be used as a first step in selecting lines with altered gliadin contents. In this paper, we optimized matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and reversed-phase high-performance liquid chromatography (RP-HPLC) methods for the separation of gliadins from Triticum aestivum cv. Chinese Spring (CS). We evaluated the quality of the resulting profiles using the complete set of gliadin gene sequences recently obtained from this cultivar as well as a set of aneuploid lines in CS. The gliadins were resolved into 13 peaks by MALDI-TOF-MS. α- or γ-gliadins that contain abundant celiac disease epitopes and are likely targets for efforts to reduce the immunogenicity of flour were found in several peaks. However, other peaks contained multiple α- and γ-gliadins, including one peak with as many as 12 different gliadins. In comparison, separation of proteins by RP-HPLC yielded 28 gliadin peaks, including 13 peaks containing α-gliadins and eight peaks containing γ-gliadins. While the separation of α- and γ-gliadins gliadins achieved by RP-HPLC was better than that achieved by MALDI-TOF-MS, it was not possible to link peaks with individual protein sequences. Both MALDI-TOF-MS and RP-HPLC provided adequate separation of ω-gliadins. While MALDI-TOF-MS is faster and could prove useful in studies that target specific gliadins, RP-HPLC is an effective method that can be applied more broadly to detect changes in gliadin composition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Jang, Cho, Kim, Sim, Lee, Kim, Gu, Altenbach, Lim, Goo and Lee.)

Powdery mildew poses severe threats to wheat production. The most sustainable way to control this disease is through planting resistant cultivars. We report the map-based cloning of the powdery mildew resistance allele Pm5e from a Chinese wheat landrace. We applied a two-step bulked segregant RNA sequencing (BSR-Seq) approach in developing tightly linked or co-segregating markers to Pm5e. The first BSR-Seq used phenotypically contrasting bulks of recombinant inbred lines (RILs) to identify Pm5e-linked markers. The second BSR-Seq utilized bulks of genetic recombinants screened from a fine-mapping population to precisely quantify the associated genomic variation in the mapping interval, and identified the Pm5e candidate genes. The function of Pm5e was validated by transgenic assay, loss-of-function mutants and haplotype association analysis. Pm5e encodes a nucleotide-binding domain leucine-rich-repeat-containing (NLR) protein. A rare nonsynonymous single nucleotide variant (SNV) within the C-terminal leucine rich repeat (LRR) domain is responsible for the gain of powdery mildew resistance function of Pm5e, an allele endemic to wheat landraces of Shaanxi province of China. Results from this study demonstrate the value of landraces in discovering useful genes for modern wheat breeding. The key SNV associated with powdery mildew resistance will be useful for marker-assisted selection of Pm5e in wheat breeding programs., (© 2020 The Authors. New Phytologist © 2020 New Phytologist Trust.)

The purpose of this study was to investigate the prevalence and epidemiological characteristics of late-onset hypogonadism (LOH) in middle-aged and elderly Chinese men. Two cross-sectional studies were conducted at 5-year intervals in community-dwelling men living in the same area. A total of 1472 (Study 1, S1) and 944 (Study 2, S2) men aged 40-69 years old were recruited as subjects. Subjects were evaluated through combining serum reproductive hormone levels with the Androgen Deficiency in Aging Males (ADAM) questionnaire and the Aging Males' Symptoms (AMS) scale. A significant difference was found in mean testosterone deficiency (TD) prevalence between S1 and S2, using either serum total testosterone (TT; 14.02% vs. 6.36%) or serum calculated free testosterone (cFT; 43.69% vs. 16.53%) cutoff values. According to the S1 or S2 data, the mean prevalence of LOH was 37.85%/15.47% in the positive ADAM test and 15.42%/9.43% in the positive AMS test ( p < .01). According to classifications of TD based on gonadal status, the prevalence of secondary TD (27.34%) was higher than the primary (16.36%) and compensated (15.42%) TD in S1 ( p < .01). However, there were significant differences among the prevalence of primary (6.89%), secondary (9.64%), and compensated (27.65%) TD in S2 ( p < .05). Different types of testosterone levels, TD cutoff values, and questionnaires influenced the prevalence of TD and LOH. The serum FT cutoff value was an optimal threshold for evaluating and diagnosing TD and LOH, whose prevalence increased gradually with male aging.

Salvia miltiorrhiza Bunge, also known as red sage or Danshen, is an important traditional Chinese medicine (TCM) that has been used for thousands of years to treat cardiovascular and other diseases. It is also considered an important model TCM plant. Here, a high-quality reference genome of S. miltiorrhiza was generated by combining PacBio long-read sequencing and chromatin interaction mapping (Hi-C) technologies, resulting in the chromosome-scale assembly of a 594.75-Mb genome sequence with a contig N50 of 2.70 Mb. This assembly shows the highest level of continuity for a Danshen genome generated thus far. The S. miltiorrhiza genome contained 32,483 protein-coding genes, with a repetitive DNA content of approximately 64.84%. The high percentage of young LTRs suggests that multiple TE transposition bursts occurred recently in S. miltiorrhiza. Genes unique to secondary metabolism pathways were expanded in the S. miltiorrhiza genome. A new CYP450 gene cluster was identified in the phloem of red roots where active components were synthesized. This reference genome sequence will facilitate future studies aimed at the elucidation of the secondary metabolism synthesis pathway and the genetic improvement of S. miltiorrhiza., (© 2020 The Authors. The Plant Genome published by Wiley Periodicals, Inc. on behalf of Crop Science Society of America.)

Objective: Relatively little is known about the natural history of atherosclerotic common carotid artery occlusion and optimal treatment of these patients is still unclear. The aim of this retrospective study was to evaluate the immediate- and long-term outcomes of axillary to carotid bypass with polytetrafluoroethylene graft for symptomatic patients with chronic common carotid artery occlusion., Methods: From March 2001 to December 2017, 58 symptomatic patients (41 men; mean age 64.7 years) with chronic common carotid artery occlusion underwent axillary to carotid bypass at one academic hospital. The clinical data of this patient cohort were retrospectively analyzed. The cumulative graft patency, overall survival, freedom from symptoms, and freedom from ipsilateral stroke were calculated with Kaplan-Meier method., Results: Thirty-three patients presented with transient ischemic attack and 25 patients presented with minor stroke. At 30 days after bypass, the overall perioperative complication rate was 3.4% (2/58). Mild injuries of brachial plexus occurred in one (1.7%) patient and myocardial infarction occurred in one (1.7%) patient. No perioperative stroke or death occurred. The median follow-up was 51 months (range, 12-203) for this series. The cumulative graft patency rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 83%, respectively. The cumulative freedom from symptoms rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 75%, respectively. The cumulative freedom from ipsilateral stroke rates at 1, 3, 5, and 10 years were 100%, 100%, 94%, and 82%, respectively. The overall survival rates at 1, 3, 5, and 10 years were 98%, 89%, 81%, and 67%, respectively., Conclusions: Axillary to carotid bypass with polytetrafluoroethylene graft is safe and durable for symptomatic patients with chronic common carotid artery occlusion. The results of this study should be confirmed with a larger, randomized controlled trial in future., (Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Cancer immunotherapy is rapidly changing the paradigm of cancer care and treatment by evoking host immunity to kill cancer cells. As clinical approval of checkpoint inhibitors (e.g., ipilimumab and pembrolizumab) has been accelerated by a dramatic improvement of long-term survival in a small subset of patients compared to conventional chemotherapy, growing interesting research has focused on immunotherapy. However, majority of patients have not benefited from checkpoint therapies that only partially remove the inhibition of T cell functions. Insufficient systemic T cell responses, low immunogenicity and the immunosuppressive environment of tumors, create great challenges on therapeutic efficiency. Nanotechnology can integrate multiple functions within controlled size and shape, and has been explored as a unique avenue for the development of cancer immunotherapy. In this review, we mainly address how nanoengineered vaccines can induce robust T cell responses against tumors, as well as how nanomedicine can remodel the tumor immunosuppressive microenvironment to boost antitumor immune responses.

Objective: To analyze the improvement of clinical symptoms and recovery of neurological function in adult Japanese encephalitis, and study the prognostic factors. Methods: Follow-up was conducted for 112 hospitalized patients with Japanese encephalitis (JE) in adults at the Department of Neurology of three hospitals in Gansu province from July to October 2016, from July to October 2017, 6 months and 1 year after onset, respectively. The neurological functional recovery was evaluated by modified Ranking Scale (mRS).The influencing factors were analyzed by logistic regression model. Results: Among the 112 adult patients with JE after 1year follow-up, 57% (64/112) were completely recovered (mRS score=0), and 14%(16/112) had mild neurological dysfunction (mRS score=1 or 2 points), 20% (22/112) had moderate to severe neurological dysfunction (mRS score 3 to 5), and 9% (10/112) died. In 102 survivors, decreased consciousness were fully recovered (100%), 75% of the mental and behavior disorders, 64% of cognitive/memory impairment, 71% of language function disorder, 61% of paralysis, 73% of extrapyramidal symptoms were fully recovered, and 92% of the seizures were controlled. Comparison of clinical data of initial on-set between good prognosis group (mRS score≤2, 80 cases) and poor prognosis group (mRS score>2, 32 cases) showed that initial clinical manifestation with seizures, consciousness (GCS score), cerebrospinal fluid pressure, and lesion of MRI involved in midbrain had statistically significant differences (all P< 0.05) . Multivariate analysis demonstrated that cerebrospinal fluid (CSF) pressure>250 mmH(2)O and lesion of midbrain in MRI were independent risk factors of poor prognosis in adult patients with JE. Conclusion: JE is an acute and infectious viral encephalitis of the central nervous system with high disability and mortality. Most patients were completely recovered, and some had neurological sequelae. CSF pressure>250 mmH(2)O and lesion of midbrain in MRI are independent risk factors for poor prognosis.

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive diseases that pose a great threat to wheat production. Wheat landraces represent a rich source of powdery mildew resistance. Here, we report the map-based cloning of powdery mildew resistance gene Pm24 from Chinese wheat landrace Hulutou. It encodes a tandem kinase protein (TKP) with putative kinase-pseudokinase domains, designated WHEAT TANDEM KINASE 3 (WTK3). The resistance function of Pm24 was validated by transgenic assay, independent mutants, and allelic association analyses. Haplotype analysis revealed that a rare 6-bp natural deletion of lysine-glycine codons, endemic to wheat landraces of Shaanxi Province, China, in the kinase I domain (Kin I) of WTK3 is critical for the resistance function. Transgenic assay of WTK3 chimeric variants revealed that only the specific two amino acid deletion, rather than any of the single or more amino acid deletions, in the Kin I of WTK3 is responsible for gaining the resistance function of WTK3 against the Bgt fungus.

Although the economic value of wheat flour is determined by the complement of gluten proteins, these proteins have been challenging to study because of the complexity of the major protein groups and the tremendous sequence diversity among wheat cultivars. The completion of a high-quality wheat genome sequence from the reference wheat Chinese Spring recently facilitated the assembly and annotation of a complete set of gluten protein genes from a single cultivar, making it possible to link individual proteins in the flour to specific gene sequences. In a proteomic analysis of total wheat flour protein from Chinese Spring using quantitative two-dimensional gel electrophoresis combined with tandem mass spectrometry, gliadins or low-molecular-weight glutenin subunits were identified as the predominant proteins in 72 protein spots. Individual spots were associated with 40 of 56 Chinese Spring gene sequences, including 16 of 26 alpha gliadins, 10 of 11 gamma gliadins, six of seven omega gliadins, one of two delta gliadins, and nine of ten LMW-GS. Most genes that were not associated with protein spots were either expressed at low levels in endosperm or encoded proteins with high similarity to other proteins. A wide range of protein accumulation levels were observed and discrepancies between transcript levels and protein levels were noted. This work together with similar studies using other commercial cultivars should provide new insight into the molecular basis of wheat flour quality and allergenic potential.

To investigate the age-related nomograms and change trends of reproductive hormones, and prevalence of androgen deficiency (AD) in middle-aged and aging men from 2 studies.Two cross-sectional studies were conducted at 5-year intervals in Chinese community-dwelling men living in the same area. A total of 434 (Study 1, S1) and 944 (Study 2, S2) men aged 40 to 69 years were recruited as subjects and 59 (S1) and 98 (S2) men aged 20 to 39 years as controls to measure serum reproductive hormone levels.Serum total testosterone (TT) levels did not change significantly in S1, whereas TT levels increased in S2 with aging. Serum calculated free testosterone (cFT) levels gradually decreased with aging; however, only men aged 40 to 69 years showed this trend in S2. Serum luteinizing hormone (LH) and sex hormone binding globulin (SHBG) levels gradually increased, and serum testosterone secretion index (TSI) and free testosterone index (FTI) levels gradually decreased with male aging. The mean annual decrease values of serum cFT were 2.705 pmol/l in S1 and 1.060 pmol/l in S2. The cut-off values for AD in S1 and S2 were 9.13 nmol/l and 9.35 nmol/l for TT, and 169.00 pmol/l and 213.90 pmol/l for cFT. Using TT or cFT cut-off values, mean AD prevalence was 14.52% or 44.70% in S1, and 6.36% or 16.53% in S2. Based on cFT cut-off values, prevalence of AD increased gradually with male aging in a range of 25.30% to 61.63% in S1 and 1.20% to 23.03% in S2.The change patterns of serum LH, SHBG, TSI and FTI levels in middle-aged and aging males were consistent; however, there were differences in serum TT and cFT change patterns in S1 and S2 with male aging. cFT cut-off values were the optimal metric to evaluate AD, which can be present a ladder-like change in prevalence of different age groups.

Significant debate has been noted in the α-ω and ω-β phase transformations of zirconium. The initial pressure of the α-to-ω transformation at room temperature has been reported to vary from 0.25 to 7.0 GPa, while the hydrostatic transformation is believed to occur at approximately 2.2 GPa. Shear stress is commonly considered as a key factor leading to the discrepancy. However, the principal mechanisms previously proposed concluded that the phase transformation pressure would be decreased in the presence of shear stress. The experimental results of the α-ω transformation in zirconium are contrary to this conclusion. In the ω-β phase diagram of zirconium, the dT/dP along the phase boundary near the α-ω-β triple-point was reported to be either positive or negative, but no theoretical explanation, especially a quantitative one, has been proposed. This article aimed to quantitatively investigate and explain the controversies reported in the α-ω and ω-β phase transformations of zirconium by applying a new nonhydrostatic thermodynamic formalism for solid medium, which has recently been proposed and is capable of quantitatively estimating the impact of shear stress on phase transformations in solids.

Herein, a dual-response fluorescent sensor, L, based on pyrazolopyrimidine was designed and developed for the simultaneous detection of Ni 2+ and Cu 2+ ions in the presence of other metal ions; the structural characterization of L was carried out by FTIR spectroscopy, NMR spectroscopy, HRMS and X-ray diffraction analysis. The sensor L effectively displayed fluorescence quenching towards the Ni 2+ and Cu 2+ ions with high sensitivity without interference from other metal ions. The results reveal that L binds to Ni 2+ and Cu 2+ in a 2 : 1 pattern, which matches well with the result of the Job's plot. The association constants of L with Ni 2+ and Cu 2+ were 3.2 × 10 4 M -1 and 7.57 × 10 4 M -1 , respectively. The detection limits (DLs) are down to 8.9 nM for Ni 2+ and 8.7 nM for Cu 2+ . The fluorescence imaging of L in T-24 cells was investigated because of the low cytotoxicity of L, indicating that L could be used to detect Ni 2+ and Cu 2+ in living cells., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

α-Gliadins are a major group of gluten proteins in wheat flour that contribute to the end-use properties for food processing and contain major immunogenic epitopes that can cause serious health-related issues including celiac disease (CD). α-Gliadins are also the youngest group of gluten proteins and are encoded by a large gene family. The majority of the gene family members evolved independently in the A, B, and D genomes of different wheat species after their separation from a common ancestral species. To gain insights into the origin and evolution of these complex genes, the genomic regions of the Gli-2 loci encoding α-gliadins were characterized from the tetraploid wild emmer, a progenitor of hexaploid bread wheat that contributed the AABB genomes. Genomic sequences of Gli-2 locus regions for the wild emmer A and B genomes were first reconstructed using the genome sequence scaffolds along with optical genome maps. A total of 24 and 16 α-gliadin genes were identified for the A and B genome regions, respectively. α-Gliadin pseudogene frequencies of 86% for the A genome and 69% for the B genome were primarily caused by C to T substitutions in the highly abundant glutamine codons, resulting in the generation of premature stop codons. Comparison with the homologous regions from the hexaploid wheat cv. Chinese Spring indicated considerable sequence divergence of the two A genomes at the genomic level. In comparison, conserved regions between the two B genomes were identified that included α-gliadin pseudogenes containing shared nested TE insertions. Analyses of the genomic organization and phylogenetic tree reconstruction indicate that although orthologous gene pairs derived from speciation were present, large portions of α-gliadin genes were likely derived from differential gene duplications or deletions after the separation of the homologous wheat genomes ~ 0.5 MYA. The higher number of full-length intact α-gliadin genes in hexaploid wheat than that in wild emmer suggests that human selection through domestication might have an impact on α-gliadin evolution. Our study provides insights into the rapid and dynamic evolution of genomic regions harboring the α-gliadin genes in wheat.

OrthoVenn is a powerful web platform for the comparison and analysis of whole-genome orthologous clusters. Here we present an updated version, OrthoVenn2, which provides new features that facilitate the comparative analysis of orthologous clusters among up to 12 species. Additionally, this update offers improvements to data visualization and interpretation, including an occurrence pattern table for interrogating the overlap of each orthologous group for the queried species. Within the occurrence table, the functional annotations and summaries of the disjunctions and intersections of clusters between the chosen species can be displayed through an interactive Venn diagram. To facilitate a broader range of comparisons, a larger number of species, including vertebrates, metazoa, protists, fungi, plants and bacteria, have been added in OrthoVenn2. Finally, a stand-alone version is available to perform large dataset comparisons and to visualize results locally without limitation of species number. In summary, OrthoVenn2 is an efficient and user-friendly web server freely accessible at https://orthovenn2.bioinfotoolkits.net., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Embolic superior mesenteric artery (SMA) occlusion is associated with high mortality rates. Delayed treatment often leads to serious consequences, including intestinal necrosis, resection, and even patient death. Endovascular repair is being introduced, which can improve clinical symptoms and prognosis and decrease the incidence of exploratory laparotomy. Many reports have described successful endovascular revascularization of embolic SMA occlusion. However, most of those reports are case reports, and there are few reports on Chinese patients. In this paper, we describe the technical and clinical outcomes of aspiration therapy using a guiding catheter and long sheath technique which facilitates the endovascular repair procedure., Aim: To evaluate the complications, feasibility, effectiveness, and safety of endovascular treatment for the acute embolic occlusion of the SMA., Methods: This retrospective study reviewed eight patients (six males and two females) from August 2013 to October 2018 at Xuanwu Hospital, Capital Medical University. The patients presented with acute embolic occlusion of the SMA on admission and were initially diagnosed by computed tomography angiography (CTA). The patients who underwent endovascular treatment with a guiding catheter had no obvious evidence of bowel infarct. No intestinal necrosis was identified by gastrointestinal surgeons through peritoneal puncture or CTA. The complications, feasibility, effectiveness, safety, and mortality were assessed., Results: Six (75%) patients were male, and the mean patient age was 70.00 ± 8.43 years (range, 60-84 years). The acute embolic occlusion of the SMA was initially diagnosed by CTA. All patients had undertaken anticoagulation primarily, and percutaneous aspiration using a guiding catheter was then undertaken because the emboli had large amounts of thrombus residue. No death occurred among the patients. Complete patency of the suffering artery trunk was achieved in six patients, and defect filling was accomplished in two patients. The in-hospital mortality was 0%. The overall 12-mo survival rate was 100%. All patients survived, and two of the eight patients had complications (the clot broke off during aspiration)., Conclusion: Aspiration therapy is feasible, safe, and beneficial for acute embolic SMA occlusion. Aspiration therapy has many benefits for reducing patients' death, resolving thrombi, and improving symptoms., Competing Interests: Conflict-of-interest statement: All authors declare no conflicts of interest related to this article.

Ultrafast imaging and manipulating transient molecular structures in chemical reactions and photobiological processes is a fundamental but challenging goal for scientists. Theoretically, the challenge originates from the complex multiple-time-scale correlated electron dynamics and their coupling with the nuclei. Here, we employ classical polyatomic models for this kind of study and take the Coulomb explosion of argon and neon trimers in strong laser fields as an illuminating example. Our results demonstrate that the degree of asymmetry on the kinetic energy release (KER) spectrum, together with a Dalitz plot, constitutes a powerful tool for retrieving the ionization, excitation, and polarization configurations (femtosecond-to-attosecond time-scale electron dynamics) of trimers under strong-field radiation.