VEGF-B is involved in diabetic peripheral neuropathy in patients with type 2 diabetes.

Aims: This study aims to explore the potential role of vascular endothelial growth factor-B (VEGF-B) in the pathogenesis of diabetic peripheral neuropathy (DPN). The expression of VEGFRs were reanalysed by using gene arrays of peripheral nerve samples from mouse models of DPN retrieved from the GEO database. 213 T2D patients as well as 31 healthy individuals were recruited. The serum VEGF-B was detected and its relationship with DPN was analysed. The elevated VEGFR1 was the only change of VEGFR gene expression in the peripheral nerve from mouse models of DPN. The level of serum VEGF-B in T2D patients with DPN was higher than that in T2D patients without DPN and healthy people. Analysis of correlation and binary logistic regression confirmed that the increased serum VEGF-B level was an independent risk factor of DPN in T2D patients. VEGF-B-VEGFR1 signaling pathway may be involved in the development of DPN.

Heterologous expression of frog antimicrobial peptide Odorranain-C1 in Pichia pastoris: Biological characteristics and its application in food preservation.

To reduce food spoilage and deterioration caused by microbial contamination, antimicrobial peptides (AMPs) have gradually gained attention as a biological preservative. Odorranain-C1 is an α-helical cationic antimicrobial peptide extracted from the skin of frogs with broad-spectrum antimicrobial activity. In this study, we achieved the expression of Odorranain-C1 in Pichia pastoris (P. pastoris) (also known as Komagataella phaffii) by employing DNA recombination technology. The recombinant Odorranain-C1 showed broad-spectrum antibacterial activity and displayed a minimum inhibitory concentration within the range of 8-12 µg.mL-1. Meanwhile, Odorranain-C1 exhibited superior stability and lower hemolytic activity. Mechanistically, Odorranain-C1 disrupted the bacterial membrane's integrity, ultimately causing membrane rupture and subsequent cell death. In tilapia fillets preservation, Odorranain-C1 inhibited the total colony growth and pH variations, while also reducing the production of total volatile basic nitrogen (TVB-N) and thiobarbituric acid (TBA). In conclusion, these studies demonstrated the efficient recombinant expression of Odorranain-C1 in P. pastoris, highlighting its promising utilization in food preservation.

Association between blood chromium and hepatic steatosis assessed by liver ultrasound transient elastography: National Health and Nutrition Examination Survey 2017-2020.

Background: Hepatic steatosis is a significant pathological feature of fatty liver disease (FLD) which is widely spread with no effective treatment available. Previous studies suggest that chromium (Cr) intake reduces lipid deposition in the liver in animals. However, the connection between blood Cr and hepatic steatosis among humans remains inconclusive. Methods: Using the data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020, we performed a cross-sectional analysis, including 4,926 participants. The controlled attenuation parameter (CAP) measured by the vibration controlled transient elastography (VCTE) was used to evaluate the degree of liver steatosis. Weighted univariate regression, multivariate linear regression, smooth fitting curves and subgroup analysis were used. In addition, we carried out trend tests, multiple interpolations, and interaction analyses to conduct sensitivity analyses. Results: After adjusting with various covariables, multivariate linear regression analysis demonstrated a significant negative correlation between blood Cr and CAP [ß (95% CI) = -5.62 (-11.02, -0.21)]. The negative correlation between blood Cr and CAP was more significant in the males, 50-59 years, overweight, hypercholesterolemia, HDL-C ≥ 65 mg/dL, HbA1c (5.70-6.10 %), HOMA-IR (0.12-2.76), total bilirubin (0.30-0.40 mg/dL), ever alcohol consumption subjects. Of note, the relationships between blood Cr and CAP followed a U-shaped curve in the smokers and non-smokers, with blood Cr thresholds of 0.48, 0.69 µg/L, respectively. Conclusions: There is an independently negative correlation between blood Cr and hepatic steatosis in American. Our study provides clinical researchers with a new insight into the prospective prevention of hepatic steatosis.

Acetylation of p65Lys310 by p300 in macrophages mediates anti-inflammatory property of berberine.

Nuclear factor (NF)-κB plays a pivotal role in the regulation of inflammatory response in macrophages. Berberine (BBR), which is an active constituent isolated from Coptis rhizome, possesses a prominent anti-inflammatory activity. Here we show that BBR changes the global acetylation landscape in LPS-induced protein acetylation of macrophages and reduces the acetylation of NF-κB subunit p65 at site Lys310(p65Lys310), leading to the inhibition of NF-κB translocation and transcriptional activity to suppress the expressions of inflammatory factors. BBR resists the inflammatory response in acute LPS-stimulated mice through downregulation of p65Lys310 acetylation in peritoneal macrophages. In obese mice, BBR alleviates the metabolic disorder and inflammation with the reduced acetylation of p65Lys310 in white adipose tissue. Furthermore, we demonstrate that BBR acts as a regulator of p65Lys310 by inhibiting the expression of p300 in macrophages. Our findings elucidate a new molecular mechanism for the anti-inflammatory effect of BBR via the p300/p65Lys310 axis.

Emerging roles of histone deacetylases in adaptive thermogenesis.

Brown and beige adipose tissues regulate body energy expenditure through adaptive thermogenesis, which converts energy into heat by oxidative phosphorylation uncoupling. Although promoting adaptive thermogenesis has been demonstrated to be a prospective strategy for obesity control, there are few methods for increasing adipose tissue thermogenesis in a safe and effective way. Histone deacetylase (HDAC) is a category of epigenetic modifying enzymes that catalyzes deacetylation on both histone and non-histone proteins. Recent studies illustrated that HDACs play an important role in adipose tissue thermogenesis through modulating gene transcription and chromatin structure as well as cellular signals transduction in both deacetylation dependent or independent manners. Given that different classes and subtypes of HDACs show diversity in the mechanisms of adaptive thermogenesis regulation, we systematically summarized the effects of different HDACs on adaptive thermogenesis and their underlying mechanisms in this review. We also emphasized the differences among HDACs in thermogenesis regulation, which will help to find new efficient anti-obesity drugs targeting specific HDAC subtypes.

[Research progress in epigenetic pharmacological effects of rhein].

Rhein, which is one of the main active components of Rheum palmatum, has a range of pharmacological activities such as the regulation of the metabolism of glucose and lipids, anti-inflammatory, anti-tumor, anti-fibrosis, etc. Epigenetics refers to the heritable variation of gene expression without altering the DNA sequence. It is involved in the emergence and development of inflammation, renal fibrosis, diabetes, cancer, atherosclerosis, and other diseases, thus becoming a new strategy for the treatment of many di-seases. A series of studies have shown that epigenetic modification may be a common molecular mechanism of various pharmacological effects of rhein. This paper summarized the effects of rhein on the regulation of epigenetic modification and its underlying mechanisms, which involve the regulation of DNA methylation, protein acetylation, and RNA methylation, so as to provide a basis for the development and application of rhein.

Upregulation of adiponectin by Ginsenoside Rb1 contributes to amelioration of hepatic steatosis induced by high fat diet.

Background: Ginsenoside Rb1 (GRb1) is capable of regulating lipid and glucose metabolism through its action on adipocytes. However, the beneficial role of GRb1-induced up-regulation of adiponectin in liver steatosis remains unelucidated. Thus, we tested whether GRb1 ameliorates liver steatosis and insulin resistance by promoting the expression of adiponectin. Methods: 3T3-L1 adipocytes and hepatocytes were used to investigate GRb1's action on adiponectin expression and triglyceride (TG) accumulation. Wild type (WT) mice and adiponectin knockout (KO) mice fed high fat diet were treated with GRb1 for 2 weeks. Hepatic fat accumulation and function as well as insulin sensitivity was measured. The activation of AMPK was also detected in the liver and hepatocytes. Results: GRb1 reversed the reduction of adiponectin secretion in adipocytes. The conditioned medium (CM) from adipocytes treated with GRb1 reduced TG accumulation in hepatocytes, which was partly attenuated by the adiponectin antibody. In the KO mice, the GRb1-induced significant decrease of TG content, ALT and AST was blocked by the deletion of adiponectin. The elevations of GRb1-induced insulin sensitivity indicated by OGTT, ITT and HOMA-IR were also weakened in the KO mice. The CM treatment significantly enhanced the phosphorylation of AMPK in hepatocytes, but not GRb1 treatment. Likewise, the phosphorylation of AMPK in liver of the WT mice was increased by GRb1, but not in the KO mice. Conclusions: The up-regulation of adiponectin by GRb1 contributes to the amelioration of liver steatosis and insulin resistance, which further elucidates a new mechanism underlying the beneficial effects of GRb1 on obesity.

Increased Serum VEGF-B Level Is Associated With Renal Function Impairment in Patients With Type 2 Diabetes.

Aims/Introduction: Renal function impairment related to type 2 diabetes (T2DM) presents serious threat to public health. Previous studies suggest that vascular endothelial growth factor-B (VEGF-B) might contribute to renal injury. Therefore, this study investigated the association of serum VEGF-B level with the risk of renal function impairment in T2DM patients. Materials and Methods: Serum VEGF-B levels were measured in 213 patients with type 2 diabetes and 31 healthy participants. Participants with type 2 diabetes were further divided into a group of 112 participants with eGFR<90 mL/min/1.73m2 and 101 participants with eGFR≥ 90 mL/min/1.73m2. Clinical data were collected, and a binary logistic regression model was employed to test the association between potential predictors and eGFR. Results: Serum VEGF-B levels evaluated in type 2 diabetes patients compared with healthy controls. In patients with type 2 diabetes, serum VEGF-B level was positively correlated with triglyceride, serum creatinine and cystatin C while negatively correlated with HDL-C and eGFR. Binary logistic regression showed that serum VEGF-B level was an independent risk factor of eGFR<90 mL/min/1.73m2. Conclusions: Serum VEGF-B level is associated with renal function impairment in patients with type 2 diabetes and may be a potential drug target for diabetic kidney disease.

Enhanced Activation Energy Released by Coordination of Bifunctional Lewis Base d-Tryptophan for Highly Efficient and Stable Perovskite Solar Cells.

Perovskite defect passivation with molecule doping shows great potential in boosting the efficiency and stability of perovskite solar cells (PSCs). Herein, an efficient and low-cost bifunctional Lewis base additive d-tryptophan is introduced to control the crystallization and growth of perovskite grains and passivation defects. It is found that the additive doped in the solution precursors could retard crystal growth by increasing activation energy, resulting in improved crystallization of large grains with reduced grain boundaries, as well as inhibiting ion migration and PbI2 aggregation. As a result, the PSCs incorporated with d-tryptophan additives achieve an improved power conversion efficiency from 18.18 to 21.55%. Moreover, the d-tryptophan passivation agent improves the device stability, which retains 86.85% of its initial efficiency under ambient conditions at room temperature after 500 h. This work provides Lewis base small-molecule d-tryptophan for efficient defect passivation of the grain boundaries toward efficient and stable PSCs.

Strong Electron Acceptor of a Fluorine-Containing Group Leads to High Performance of Perovskite Solar Cells.

Organic-inorganic hybrid perovskites have become one of the most promising thin-film solar cell materials owing to their remarkable photovoltaic properties. However, nonradiative recombination of carriers usually leads to inferior performance of perovskite (PVK) devices. Interface modification is one of the effective ways to improve separation of charges for perovskite solar cells (PSCs). Here, a small organic molecule of tetrafluorophthalonitrile (TFPN) is used to enhance the extraction and transportation of carriers at the PVK/hole transport layer (HTL) interface. The electron-rich C-F group effectively reduces the trap state density in the perovskite through chemical combination with the empty orbital of Pb2+ or other electron traps on the PVK surface, resulting in enhanced interface contact between the PVK and HTL. Meanwhile, the C≡N group in TFPN also inactivates the defects caused by Pb2+. The Fermi level of the perovskite shifts by 0.15 eV to its valence band due to the strong electron acceptor nature of the F atom, indicating that positive dipoles and p-type doping emerge, which validly suppress the recombination of carriers for the PVK film. Therefore, the optimized PSC shows the highest power conversion efficiency (PCE) of 22.82% compared to 19.40% for the control one. The champion FF reaches up to 81.2% (PCE 21.44%) due to the effectively enhanced carrier separation. In addition, the unencapsulated device shows enhanced stability under air conditions.

Phenotypic and transcriptomic responses of two Nilaparvata lugens populations to the Mudgo rice containing Bph1.

The Bph1 gene was the first reported brown planthopper (BPH, Nilaparvata lugens) resistance gene in Mudgo rice and was widely used as a commercial cultivar for controlling BPH infestations. However, rapid adaptations of BPH on the Mudgo rice resulted in its resistance breakdown and the emergence of virulent BPH populations. Thus, specific BPH populations and rice varieties can serve as good model systems for studying the roles of different bio-compounds and proteins in the insect-plant interactions. Although our understandings have been improved on the complexity of BPH and rice interactions, the underlying molecular mechanisms remain largely unknown. Here we analyzed the feeding performances and the transcriptomic responses of two BPH populations (Mugdo-BPH and TN1-BPH) during compatible (Mudog-BPH feeding on Mudgo rice) and incompatible (TN1-BPH feeding on Mudgo rice) interactions. The electrical penetration graph (EPG) results indicated that the BPH feeding and performances during the incompatible interaction are significantly affected in terms of decreased honeydew, loss of weight, decreased phloem sap ingestion (N4 waveform), but increased non-penetration (NP waveform) phase. Abundance of glucose and trehalose was reduced in BPH during the incompatible interaction. Transcriptomic surveys of insects in both interactions revealed that genes involved in cuticle formation, detoxification, metabolite transport, digestion, RNA processing, lipid or fatty acid metabolism, and proteolysis were significantly down-regulated during the incompatible interaction, whereas genes involved in insulin signaling were significantly upregulated. Knockdown of four genes, including the sugar transporter NlST45, the serine and arginine-rich protein NlSRp54, the cytochrome P450 gene NlCYP6AY1, and the cuticle protein NlCPR70 through RNA-interference revealed thess genes are important for BPH survival. Overall, the results of this study will be helpful for the future researches on BPH virulence shifts.

High Resolution Genetic and Physical Mapping of a Major Powdery Mildew Resistance Locus in Barley.

Powdery mildew caused by Blumeria graminis f. sp. hordei is a foliar disease with highly negative impact on yield and grain quality in barley. Thus, breeding for powdery mildew resistance is an important goal and requires constantly the discovery of new sources of natural resistance. Here, we report the high resolution genetic and physical mapping of a dominant race-specific powdery mildew resistance locus, originating from an Ethiopian spring barley accession 'HOR2573,' conferring resistance to several modern mildew isolates. High-resolution genetic mapping narrowed down the interval containing the resistance locus to a physical span of 850 kb. Four candidate genes with homology to known disease resistance gene families were identified. The mapped resistance locus coincides with a previously reported resistance locus from Hordeum laevigatum, suggesting allelism at the same locus in two different barley lines. Therefore, we named the newly mapped resistance locus from HOR2573 as MlLa-H. The reported co-segregating and flanking markers may provide new tools for marker-assisted selection of this resistance locus in barley breeding.

High intraspecific diversity of Restorer-of-fertility-like genes in barley.

Nuclear restorer of fertility (Rf) genes suppress the effects of mitochondrial genes causing cytoplasmic male sterility (CMS), a condition in which plants fail to produce viable pollen. Rf genes, many of which encode RNA-binding pentatricopeptide repeat (PPR) proteins, are applied in hybrid breeding to overcome CMS used to block self-pollination of the seed parent. Here, we characterise the repertoire of restorer-of-fertility-like (RFL) PPR genes in barley (Hordeum vulgare). We found 26 RFL genes in the reference genome ('Morex') and an additional 51 putative orthogroups (POGs) in a re-sequencing data set from 262 barley genotypes and landraces. Whereas the sequences of some POGs are highly conserved across hundreds of barley accessions, the sequences of others are much more variable. High sequence variation strongly correlates with genomic location - the most variable genes are found in a cluster on chromosome 1H. A much higher likelihood of diversifying selection was found for genes within this cluster than for genes present as singlets. This work includes a comprehensive analysis of the patterns of intraspecific variation of RFL genes. The RFL sequences characterised in this study will be useful for the development of new markers for fertility restoration loci.

LAILAPS-QSM: A RESTful API and JAVA library for semantic query suggestions.

In order to access and filter content of life-science databases, full text search is a widely applied query interface. But its high flexibility and intuitiveness is paid for with potentially imprecise and incomplete query results. To reduce this drawback, query assistance systems suggest those combinations of keywords with the highest potential to match most of the relevant data records. Widespread approaches are syntactic query corrections that avoid misspelling and support expansion of words by suffixes and prefixes. Synonym expansion approaches apply thesauri, ontologies, and query logs. All need laborious curation and maintenance. Furthermore, access to query logs is in general restricted. Approaches that infer related queries by their query profile like research field, geographic location, co-authorship, affiliation etc. require user's registration and its public accessibility that contradict privacy concerns. To overcome these drawbacks, we implemented LAILAPS-QSM, a machine learning approach that reconstruct possible linguistic contexts of a given keyword query. The context is referred from the text records that are stored in the databases that are going to be queried or extracted for a general purpose query suggestion from PubMed abstracts and UniProt data. The supplied tool suite enables the pre-processing of these text records and the further computation of customized distributed word vectors. The latter are used to suggest alternative keyword queries. An evaluated of the query suggestion quality was done for plant science use cases. Locally present experts enable a cost-efficient quality assessment in the categories trait, biological entity, taxonomy, affiliation, and metabolic function which has been performed using ontology term similarities. LAILAPS-QSM mean information content similarity for 15 representative queries is 0.70, whereas 34% have a score above 0.80. In comparison, the information content similarity for human expert made query suggestions is 0.90. The software is either available as tool set to build and train dedicated query suggestion services or as already trained general purpose RESTful web service. The service uses open interfaces to be seamless embeddable into database frontends. The JAVA implementation uses highly optimized data structures and streamlined code to provide fast and scalable response for web service calls. The source code of LAILAPS-QSM is available under GNU General Public License version 2 in Bitbucket GIT repository: https://bitbucket.org/ipk_bit_team/bioescorte-suggestion.

Mutations in the gene of the Gα subunit of the heterotrimeric G protein are the cause for the brachytic1 semi-dwarf phenotype in barley and applicable for practical breeding.

BACKGROUND: Short-culm mutants have been widely used in breeding programs to increase lodging resistance. In barley (Hordeum vulgare L.), several hundreds of short-culm mutants have been isolated over the years. The objective of the present study was to identify the Brachytic1 (Brh1) semi-dwarfing gene and to test its effect on yield and malting quality. RESULTS: Double-haploid lines generated through a cross between a brh1.a mutant and the European elite malting cultivar Quench, showed good malting quality but a decrease in yield. Especially the activities of the starch degrading enzymes ß-amylase and free limit dextrinase were high. A syntenic approach comparing markers in barley to those in rice (Oryza sativa L.), sorghum (Sorghum bicolor Moench) and brachypodium (Brachypodium distachyon P. Beauv) helped us to identify Brh1 as an orthologue of rice D1 encoding the Gα subunit of a heterotrimeric G protein. We demonstrated that Brh1 is allelic to Ari-m. Sixteen different mutant alleles were described at the DNA level. CONCLUSIONS: Mutants in the Brh1 locus are deficient in the Gα subunit of a heterotrimeric G protein, which shows that heterotrimeric G proteins are important regulators of culm length in barley. Mutant alleles do not have any major negative effects on malting quality.

A sequence-ready physical map of barley anchored genetically by two million single-nucleotide polymorphisms.

Barley (Hordeum vulgare) is an important cereal crop and a model species for Triticeae genomics. To lay the foundation for hierarchical map-based sequencing, a genome-wide physical map of its large and complex 5.1 billion-bp genome was constructed by high-information content fingerprinting of almost 600,000 bacterial artificial chromosomes representing 14-fold haploid genome coverage. The resultant physical map comprises 9,265 contigs with a cumulative size of 4.9 Gb representing 96% of the physical length of the barley genome. The reliability of the map was verified through extensive genetic marker information and the analysis of topological networks of clone overlaps. A minimum tiling path of 66,772 minimally overlapping clones was defined that will serve as a template for hierarchical clone-by-clone map-based shotgun sequencing. We integrated whole-genome shotgun sequence data from the individuals of two mapping populations with published bacterial artificial chromosome survey sequence information to genetically anchor the physical map. This novel approach in combination with the comprehensive whole-genome shotgun sequence data sets allowed us to independently validate and improve a previously reported physical and genetic framework. The resources developed in this study will underpin fine-mapping and cloning of agronomically important genes and the assembly of a draft genome sequence.

Reticulate evolution of the rye genome.

Rye (Secale cereale) is closely related to wheat (Triticum aestivum) and barley (Hordeum vulgare). Due to its large genome (~8 Gb) and its regional importance, genome analysis of rye has lagged behind other cereals. Here, we established a virtual linear gene order model (genome zipper) comprising 22,426 or 72% of the detected set of 31,008 rye genes. This was achieved by high-throughput transcript mapping, chromosome survey sequencing, and integration of conserved synteny information of three sequenced model grass genomes (Brachypodium distachyon, rice [Oryza sativa], and sorghum [Sorghum bicolor]). This enabled a genome-wide high-density comparative analysis of rye/barley/model grass genome synteny. Seventeen conserved syntenic linkage blocks making up the rye and barley genomes were defined in comparison to model grass genomes. Six major translocations shaped the modern rye genome in comparison to a putative Triticeae ancestral genome. Strikingly dissimilar conserved syntenic gene content, gene sequence diversity signatures, and phylogenetic networks were found for individual rye syntenic blocks. This indicates that introgressive hybridizations (diploid or polyploidy hybrid speciation) and/or a series of whole-genome or chromosome duplications played a role in rye speciation and genome evolution.

Conserved synteny-based anchoring of the barley genome physical map.

Gene order is largely collinear in the small-grained cereals, a feature which has proved helpful in both marker development and positional cloning. The accuracy of a virtual gene order map ("genome zipper") for barley (Hordeum vulgare), developed by combining a genetic map of this species with a large number of gene locations obtained from the maps constructed in other grass species, was evaluated here both at the genome-wide level and at the fine scale in a representative segment of the genome. Comparing the whole genome "genome zipper" maps with a genetic map developed by using transcript-derived markers, yielded an accuracy of >94 %. The fine-scale comparison involved a 14 cM segment of chromosome arm 2HL. One hundred twenty-eight genes of the "genome zipper" interval were analysed. Over 95 % (45/47) of the polymorphic markers were genetically mapped and allocated to the expected region of 2HL, following the predicted order. A further 80 of the 128 genes were assigned to the correct chromosome arm 2HL by analysis of wheat-barley addition lines. All 128 gene-based markers developed were used to probe a barley bacterial artificial chromosome (BAC) library, delivering 26 BAC contigs from which all except two were anchored to the targeted zipper interval. The results demonstrate that the gene order predicted by the "genome zipper" is remarkably accurate and that the "genome zipper" represents a highly efficient informational resource for the systematic identification of gene-based markers and subsequent physical map anchoring of the barley genome.

From RNA-seq to large-scale genotyping - genomics resources for rye (Secale cereale L.).

BACKGROUND: The improvement of agricultural crops with regard to yield, resistance and environmental adaptation is a perpetual challenge for both breeding and research. Exploration of the genetic potential and implementation of genome-based breeding strategies for efficient rye (Secale cereale L.) cultivar improvement have been hampered by the lack of genome sequence information. To overcome this limitation we sequenced the transcriptomes of five winter rye inbred lines using Roche/454 GS FLX technology. RESULTS: More than 2.5 million reads were assembled into 115,400 contigs representing a comprehensive rye expressed sequence tag (EST) resource. From sequence comparisons 5,234 single nucleotide polymorphisms (SNPs) were identified to develop the Rye5K high-throughput SNP genotyping array. Performance of the Rye5K SNP array was investigated by genotyping 59 rye inbred lines including the five lines used for sequencing, and five barley, three wheat, and two triticale accessions. A balanced distribution of allele frequencies ranging from 0.1 to 0.9 was observed. Residual heterozygosity of the rye inbred lines varied from 4.0 to 20.4% with higher average heterozygosity in the pollen compared to the seed parent pool. CONCLUSIONS: The established sequence and molecular marker resources will improve and promote genetic and genomic research as well as genome-based breeding in rye.