Harnessing nature's pharmacy: investigating natural compounds as novel therapeutics for ulcerative colitis.

Backgrounds: Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease, and UC diagnosis rates continue to rise throughout the globe. The research and development of new drugs for the treatment of UC are urgent, and natural compounds are an important source. However, there is a lack of systematic summarization of natural compounds and their mechanisms for the treatment of UC. Methods: We reviewed the literature in the databases below from their inception until July 2023: Web of Science, PubMed, China National Knowledge Infrastructure, and Wanfang Data, to obtain information on the relationship between natural compounds and UC. Results: The results showed that 279 natural compounds treat UC through four main mechanisms, including regulating gut microbiota and metabolites (Mechanism I), protecting the intestinal mucosal barrier (Mechanism II), regulating intestinal mucosal immune response (Mechanism III), as well as regulating other mechanisms (Mechanism Ⅳ) such as cellular autophagy modulation and ferroptosis inhibition. Of these, Mechanism III is regulated by all natural compounds. The 279 natural compounds, including 62 terpenoids, 57 alkaloids, 52 flavonoids, 26 phenols, 19 phenylpropanoids, 9 steroids, 9 saponins, 8 quinonoids, 6 vitamins, and 31 others, can effectively ameliorate UC. Of these, terpenoids, alkaloids, and flavonoids have the greatest potential for treating UC. It is noteworthy to highlight that a total of 54 natural compounds exhibit their therapeutic effects by modulating Mechanisms I, II, and III. Conclusion: This review serves as a comprehensive resource for the pharmaceutical industry, researchers, and clinicians seeking novel therapeutic approaches to combat UC. Harnessing the therapeutic potential of these natural compounds may significantly contribute to the improvement of the quality of life of patients with UC and promotion of disease-modifying therapies in the future.

Investigation of the mechanical behavior of rock-like material with two flaws subjected to biaxial compression.

The biaxial compression experiments of rock-like materials with two flaws are carried out under different flaw inclination angle, rock bridge ligament angle, lateral stress. The experimental studies show that crack propagation modes of rock-like material are as follows: wing crack through mode (Y mode), shear crack through mode (J mode), mixed crack through mode (wing shear JY mode), longitudinal extension of crack and transverse shear splitting. prefabricated fractured rock specimens have experienced the closing stage of prefabricated fractures, the elastic deformation stage, the generation and expansion of cracks (or plastic strengthening), and the residual loading stage. The peak strength of the specimen is increases with the increase of flaw inclination angle and lateral stress. With the increase of the rock bridge ligament angle, the failure of the rock bridge region changes from the shear crack failure to composite failure of shear crack and the wing type tensile crack failure, and then to the wing crack failure. With the increase of the lateral pressure, the failure of the specimen changes from the wing type tensile crack failure to the wing type and shear crack failure, and then to shear crack failure. The flaw inclination angle mainly changes the form of crack growth but does not effect on the failure modes. The counting number of acoustic emission events at the center of the sample is relative large, indicating that the cacks appear in the part of the rock bridge firstly. With the increasing of loads, the cracks of the rock bridge expanding constantly and connecting finally. The changes of acoustic emission event counts is consistent with the macroscopic damage form obtained from the experiments.

Mapping QTLs for adult-plant resistance to powdery mildew and stripe rust using a recombinant inbred line population derived from cross Qingxinmai × 041133.

A recombinant inbred line (RIL) population derived from wheat landrace Qingxinmai and breeding line 041133 exhibited segregation in resistance to powdery mildew and stripe rust in five and three field tests, respectively. A 16K genotyping by target sequencing (GBTS) single-nucleotide polymorphism (SNP) array-based genetic linkage map was used to dissect the quantitative trait loci (QTLs) for disease resistance. Four and seven QTLs were identified for adult-plant resistance (APR) against powdery mildew and stripe rust. QPm.caas-1B and QPm.caas-5A on chromosomes 1B and 5A were responsible for the APR against powdery mildew in line 041133. QYr.caas-1B, QYr.caas-3B, QYr.caas-4B, QYr.caas-6B.1, QYr.caas-6B.2, and QYr.caas-7B detected on the five B-genome chromosomes of line 041133 conferred its APR to stripe rust. QPm.caas-1B and QYr.caas.1B were co-localized with the pleiotropic locus Lr46/Yr29/Sr58/Pm39/Ltn2. A Kompetitive Allele Specific Polymorphic (KASP) marker KASP_1B_668028290 was developed to trace QPm/Yr.caas.1B. Four lines pyramiding six major disease resistance loci, PmQ, Yr041133, QPm/Yr.caas-1B, QPm.caas-2B.1, QYr.caas-3B, and QPm.caas-6B, were developed. They displayed effective resistance against both powdery mildew and stripe rust at the seedling and adult-plant stages.

Alleles on locus chromosome 4B from different parents confer tiller number and the yield-associated traits in wheat.

Pleiotropy is frequently detected in agronomic traits of wheat (Triticum aestivum). A locus on chromosome 4B, QTn/Ptn/Sl/Sns/Al/Tgw/Gl/Gw.caas-4B, proved to show pleiotropic effects on tiller, spike, and grain traits using a recombinant inbred line (RIL) population of Qingxinmai × 041133. The allele from Qingxinmai increased tiller numbers, and the allele from line 041133 produced better performances of spike traits and grain traits. Another 52 QTL for the eight traits investigated were detected on 18 chromosomes, except for chromosomes 5D, 6D, and 7B. Several genes in the genomic interval of the locus on chromosome 4B were differentially expressed in crown and inflorescence samples between Qingxinmai and line 041133. The development of the KASP marker specific for the locus on chromosome 4B is useful for molecular marker-assisted selection in wheat breeding.

A membrane associated tandem kinase from wild emmer wheat confers broad-spectrum resistance to powdery mildew.

Crop wild relatives offer natural variations of disease resistance for crop improvement. Here, we report the isolation of broad-spectrum powdery mildew resistance gene Pm36, originated from wild emmer wheat, that encodes a tandem kinase with a transmembrane domain (WTK7-TM) through the combination of map-based cloning, PacBio SMRT long-read genome sequencing, mutagenesis, and transformation. Mutagenesis assay reveals that the two kinase domains and the transmembrane domain of WTK7-TM are critical for the powdery mildew resistance function. Consistently, in vitro phosphorylation assay shows that two kinase domains are indispensable for the kinase activity of WTK7-TM. Haplotype analysis uncovers that Pm36 is an orphan gene only present in a few wild emmer wheat, indicating its single ancient origin and potential contribution to the current wheat gene pool. Overall, our findings not only provide a powdery mildew resistance gene with great potential in wheat breeding but also sheds light into the mechanism underlying broad-spectrum resistance.

Efficacy and safety of mesenchymal stem cell-derived microvesicles in mouse inflammatory arthritis.

OBJECTIVE: To determine the effective and safe intravenous doses of mesenchymal stem cells (MSCs)-derived microvesicles (MVs) and to elucidate the possible causes of death in mice receiving high-dose MVs. METHODS: MVs were isolated from human MSCs by gradient centrifugation. Mice with collagen-induced arthritis were treated with different doses of intravenous MVs or MSCs. Arthritis severity, white blood cell count, and serum C-reactive protein levels were measured. To assess the safety profile of MSCs and MVs, mice were treated with different doses of MSCs and MVs, and LD50 was calculated. Mouse lungs and heart were assessed by live fluorescence imaging, histopathological measurements, and immunohistochemistry to explore the possible causes of death. Serum concentrations of cTnT, cTnI, and CK-MB were determined by ELISA. With the H9C2 cardiomyocyte cell line,  cellular uptake of MVs was observed using confocal microscopy and cell toxicity was assessed by CCK-8 and flow cytometry. RESULTS: Intravenous treatment with MSCs and MVs alleviated inflammatory arthritis, while high doses of MSCs and MVs were lethal. Mice receiving a maximum dose of MSCs (0.1 mL of MSCs at 109/mL) died immediately, while mice receiving a maximum dose of MVs (0.1 mL of MVs at 1012/mL) exhibited tears, drooling, tachycardia, shortness of breath, unbalanced rollover, bouncing, circular crawling, mania, and death. Some mice died after exhibiting convulsions and other symptoms. All mice died shortly after injecting the maximum dose of MSCs. Histologically, mice receiving high doses of MSCs frequently developed pulmonary embolism, while those receiving high doses of MVs died of myocardial infarction. Consistently, the serum levels of cTnT, cTnI, and CK-MB were significantly increased in the MVs-treated group (P < 0.05). The LD50 of intravenous MVs was 1.60 × 1012/kg. Further, MVs could enter the cell. High doses of MVs induced cell apoptosis, though low concentrations of MVs induced cell proliferation. CONCLUSIONS: Appropriate dosages of MVs and MSCs are effective treatments for inflammatory arthritis while MVs and MSCs overdose is unsafe by causing cardiopulmonary complications.

Effect of gender and age on bDMARD efficacy for axial spondyloathritis patients: a meta-analysis of randomized controlled trials.

OBJECTIVE: To study the therapeutic variations of biological and targeted synthetic disease-modifying antirheumatic drugs(b/tsDMARDs) between genders and across age stages in axial spondyloarthritis (axSpA) patients through meta-analysis. METHODS: Randomized controlled trials (RCTs), published by Pubmed, Scopus, and Embase before August 10, 2023, testing the efficiency of b/tsDMARDs in axSpA, were searched and systematically reviewed. The Assessment of Spondyloarthritis International Society ≥40% improvement (ASAS40) response was used as the primary outcome of treatment response. RESULTS: : Only one study meet the inclusion criteria was related to tsDMARD, which was excluded from further data combination. Nine studies of bDMARDs, with the involvement of 4127 patients, were included for final analysis. When compared with placebo, both males (OR = 3.14; 95%CI, 2.66-3.70) and females (2.32; 1.82-2.82), younger (4.00; 2.50-6.40) and older (2.21; 1.15-4.22) patients, presented significantly better responses to bDMARDs. Besides, the efficacies were more evident in males (1.89; 1.56-2.30) and younger patients (2.07; 1.42-3.02). Subgroup analysis revealed that gender difference in efficacy was more obvious in non-radiographic-axSpA (nr-axSpA) patients (Pheterogeneity=0.03, I2=78.1%). Moreover, males with radiographic-axSpA (r-axSpA) and nr-axSpA shared similar responses to bDMARDs (Pheterogeneity=0.87, I2=0%), while females with r-axSpA showed greater response than those with nr-axSpA (Pheterogeneity=0.005, I2=87.4%). CONCLUSIONS: BioDMARDs were efficient in all axSpA patients regardless of gender or age stage. However, the treatment responses were more evident in male and younger patients. Besides, females with r-axSpA had greater responses than those with nr-axSpA, whereas no relevant difference was observed in males, indicating that the gender difference on efficacy was larger in nr-axSpA patients.

Hormonal Regulation and Stimulation Response of Jatropha curcas L. Homolog Overexpression on Tobacco Leaf Growth by Transcriptome Analysis.

The Flowering locus T (FT) gene encodes the florigen protein, which primarily regulates the flowering time in plants. Recent studies have shown that FT genes also significantly affect plant growth and development. The FT gene overexpression in plants promotes flowering and suppresses leaf and stem development. This study aimed to conduct a transcriptome analysis to investigate the multiple effects of Jatropha curcas L. homolog (JcFT) overexpression on leaf growth in tobacco plants. The findings revealed that JcFT overexpression affected various biological processes during leaf development, including plant hormone levels and signal transduction, lipid oxidation metabolism, terpenoid metabolism, and the jasmonic-acid-mediated signaling pathway. These results suggested that the effects of FT overexpression in plants were complex and multifaceted, and the combination of these factors might contribute to a reduction in the leaf size. This study comprehensively analyzed the effects of JcFT on leaf development at the transcriptome level and provided new insights into the function of FT and its homologous genes.

Mesenchymal stem-cell-derived microvesicles ameliorate MPTP-induced neurotoxicity in mice: a role of the gut-microbiota-brain axis.

RATIONALE: Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. Increasing evidence suggests the role of the gut-microbiota-brain axis in the pathogenesis of PD. Mesenchymal stem-cell-derived microvesicles (MSC-MVs) have emerged as a therapeutic potential for neurological disorders over the last years. OBJECTIVE: The objective of this study was to investigate whether MSC-MVs could improve PD-like neurotoxicity in mice after administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). RESULTS: MPTP-induced reductions in the dopamine transporter and tyrosine hydroxylase expressions in the striatum and substantia nigra (SNr) were attenuated after a subsequent single administration of MSC-MVs. Increases in the phosphorylated α-synuclein (p-α-Syn)/α-Syn ratio in the striatum, SNr, and colon after MPTP injection were also attenuated after MSC-MVs injection. Furthermore, MSC-MVs restored MPTP-induced abnormalities of the gut microbiota composition. Interestingly, positive correlations between the genus Dubosiella and the p-α-Syn/α-Syn ratio were observed in the brain and colon, suggesting their roles in the gut-microbiota-brain communication. Moreover, MSC-MVs attenuated MPTP-induced reduction of the metabolite, 3,6-dihydroxy-2-[3-methoxy-4-(sulfooxy)phenyl]-7-(sulfinooxy)-3,4-dihydro-2H-1-benzopyran-5-olate, in the blood. Interestingly, a negative correlation between this compound and the p-α-Syn/α-Syn ratio was observed in the brain and colon. CONCLUSIONS: These data suggest that MSC-MVs could ameliorate MPTP-induced neurotoxicity in the brain and colon via the gut-microbiota-brain axis. Therefore, MSC-MVs would have a new therapeutic potential for neurological disorders such as PD.

Resistance to Powdery Mildew Is Conferred by Different Genetic Loci at the Adult-Plant and Seedling Stages in Winter Wheat Line Tianmin 668.

Winter wheat line Tianmin 668 was crossed with susceptible cultivar Jingshuang 16 to develop 216 recombinant inbred lines (RILs) for dissecting its adult-plant resistance (APR) and all-stage resistance (ASR) against powdery mildew. The RIL population was genotyped on a 16K genotyping by target sequencing single-nucleotide polymorphism array and phenotyped in six field trials and in the greenhouse. Three loci-QPmtj.caas-2BL, QPmtj.caas-2AS, and QPmtj.caas-5AL-conferring APR to powdery mildew were detected on chromosomes 2BL, 2AS, and 5AL, respectively, of Tianmin 668. The effect of resistance to powdery mildew for QPmtj.caas-2BL was greater than that of the other two loci. A Kompetitive allele-specific PCR marker specific for QPmtj.caas-2BL was developed and verified on 402 wheat cultivars or breeding lines. Results of virulence and avirulence patterns to 17 Blumeria graminis f. sp. tritici isolates, bulked segregant analysis-RNA-sequencing, and a genetic linkage mapping identified a resistance allele at locus Pm4 in Tianmin 668 based on the seedling phenotypes of the RIL population. The PCR-based DNA sequence alignment and cosegregation of the functional marker with the phenotypes of the RIL population demonstrated that Pm4d was responsible for the ASR to isolate Bgt1 in Tianmin 668. The dissection of genetic loci for APR and ASR may facilitate the application of Tianmin 668 in developing powdery mildew-resistant wheat cultivars.

The association between adverse pregnancy outcomes with genital Chlamydia Trachomatis infection among pre-pregnancy couples in Shenzhen, China: A cross-sectional study.

Objectives: To investigate the prevalence of adverse pregnancy outcomes (APOs) in women and the impact of pre-pregnancy couples' genital Chlamydia Trachomatis (GCT) infection and other infections on APOs. Study design: Data on genital infections were collected from the Free Pre-pregnancy Health Check (FPHC) in Shenzhen, China. Data on APOs were collected from a 1-year telephone follow-up of pregnancy status and subsequent pregnancy outcomes. Methods: APO data were used to count adverse outcomes, and logistic regression was conducted to determine the association between APOs and GCT infection. Results: From December 2018 to December 2019, among 4,429 couples who underwent FPHC; 1,925 were pregnant, and 1,816 couples were tracked for pregnancy outcomes, including 1,471 normal pregnancies and 345 (19.00%) APOs. The rest of 109 pregnant couples did not answer the phone or refused to answer the pregnancy outcome during the follow-up. Among APOs, the number of spontaneous abortions was 122 (35.36%), the number of macrosomia was 85 (24.64%), the number of low birth weight (LBW) & preterm births (PTB) was 39 (11.30%), the number of LBW was 34 (9.86%), and the number of PTB was 31 (8.99%). The prevalence of GCT infection in females and males was 4.24% [95% Confidence Interval, (CI): 3.41-5.27%] and 3.58% (95% CI: 2.79-4.57%), respectively. More than half (52.69%, 49/93) of the couples were GCT-concordant. The prevalence of APOs in couples without GCT infection was 18.74% (332/1,772). The prevalence of APOs in female GCT-discordant was 32.14% (9/28), and the prevalence of APOs in male GCT-discordant was 25% (4/16). The prevalence of APOs in GCT-concordant was 12.24% (6/49). Multivariable analysis indicated that females 30-35 years old [adjusted Odds Ratio (aOR) = 1.08, 95% CI: 1.01-1.17] and over 35 years old (aOR = 1.16, 95% CI: 1.03-1.32) were more likely to experiencing APOs. Conclusion: Although only women's age was found to be associated with APOs, the prevalence of APOs with GCT-discordant in couples, especially female GCT-discordant, was higher than in those without infection or who were GCT-concordant, suggesting that these groups, especially in older women, should be paid more attention to in follow-ups to improve reproductive health.

Distribution of Chlamydia trachomatis ompA genotypes and its association with abnormal cervical cytology among women of reproductive age in Shenzhen, China.

Background: Many studies have focused on the distribution and specific clinical symptoms caused by Chlamydia trachomatis. Still, relatively few studies have focused on the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions. Objectives: This study was conducted to determine the distribution of Chlamydia trachomatis genotypes and its associations with cervical intraepithelial lesions among women of reproductive age. The presence of other STIs coinfection was also evaluated. Method: 375 Chlamydia trachomatis positive cervical swabs collected from women of reproductive age were analyzed though molecular assay. Multivariate logistic regression analyses (covariates include contraception, gravidity (≥1), abnormal vaginal discharge, adverse pregnancy outcomes, reproductive tract symptoms and abnormal cervical cytology) were performed to evaluate the associations between Chlamydia trachomatis genotypes and cervical intraepithelial lesions and genital clinical symptoms. Results: Among 375 Chlamydia trachomatis positive cervical swabs, the prevalence of coinfection with Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginitis, Vulvovaginal candidiasis, and HPV were 0.8%, 2.7%, 2.4%, 10.1% and 15.5%, respectively. 306 were genotyped successfully, and nine genotypes were identified. The most common genovar was E (25.16%, 77/306), followed by J (22.55%, 69/306), F (17%, 52/306), D (14.4%, 44/306), K (7.2%, 22/306), G (6.9%, 21/306), H (5.2%, 16/306), B (1.0%, 3/306), Ia (0.7%, 2/306). Genotype H was associated with abnormal cervical cytology [p = 0.006, aOR = 8.16 (1.86-36.6)]. However, this study observed no association between Chlamydia trachomatis genotypes and any genital clinical symptoms. Conclusions: Chlamydia trachomatis genotype H may be a high risk factor for cervical intraepithelial lesions, which is useful for treatment and management measures for patients with cervical intraepithelial lesions.

The CC-NB-LRR protein BSR1 from Brachypodium confers resistance to Barley stripe mosaic virus in gramineous plants by recognising TGB1 movement protein.

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 R390 and T392 residues of TGB1ND (ND18 strain) and the G196 and K197 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.

Comprehensive Effects of Flowering Locus T-Mediated Stem Growth in Tobacco.

In flowering plants, Flowering locus T (FT) encodes a major florigen. It is a key flowering hormone in controlling flowering time and has a wide range of effects on plant development. Although the mechanism by which FT promotes flowering is currently clearly understood, comprehensive effects of the FT gene on plant growth have not been evaluated. Therefore, the effects of FT on vegetative growth need to be explored for a complete understanding of the molecular functions of the FT gene. In this study, the Jatropha curcas L. FT gene was overexpressed in tobacco (JcFTOE) in order to discover multiple aspects and related mechanisms of how the FT gene affects plant development. In JcFTOE plants, root, stem, and leaf development was strongly affected. Stem tissues were selected for further transcriptome analysis. In JcFTOE plants, stem growth was affected because of changes in the nucleus, cytoplasm, and cell wall. In the nucleus of JcFTOE plants, the primary effect was to weaken all aspects of DNA replication, which ultimately affected the cell cycle and cell division. The number of stem cells decreased significantly in JcFTOE plants, which decreased the thickness and height of tobacco stems. In the cell wall of JcFTOE plants, hemicellulose and cellulose contents increased, with the increase in hemicellulose associated with up-regulation of xylan synthase-related genes expression. In the cytoplasm of JcFTOE plants, the primary effects were on biogenesis of ribonucleoprotein complexes, photosynthesis, carbohydrate biosynthesis, and the cytoskeleton. In addition, in the cytoplasm of JcFTOE plants, there were changes in certain factors of the core oscillator, expression of many light-harvesting chlorophyll a/b binding proteins was down-regulated, and expression of fructose 1,6-bisphosphatase genes was up-regulated to increase starch content in tobacco stems. Changes in the xylem and phloem of JcFTOE plants were also identified, and in particular, xylem development was affected by significant increases in expression of irregular xylem genes.

Genome-Wide Identification and Analysis of the NAC Transcription Factor Gene Family in Garden Asparagus (Asparagus officinalis).

As a large plant-specific gene family, the NAC (NAM, ATAF1/2, and CUC2) transcription factor is related to plant growth, development, and response to abiotic stresses. Although the draft genome of garden asparagus (Asparagus officinalis) has been released, the genome-wide investigation of the NAC gene family is still unavailable. In this study, a total of 85 A. officinalis NAC genes were identified, and a comprehensive analysis of the gene family was performed, including physicochemical properties, phylogenetic relationship, chromosome localization, gene structure, conserved motifs, intron/exon, cis-acting elements, gene duplication, syntenic analysis, and differential gene expression analysis. The phylogenetic analysis demonstrated that there were 14 subgroups in both A. officinalis and Arabidopsis thaliana, and the genes with a similar gene structure and motif distribution were clustered in the same group. The cis-acting regulatory analysis of AoNAC genes indicated four types of cis-acting elements were present in the promoter regions, including light-responsive, hormone-responsive, plant-growth-and-development-related, and stress-responsive elements. The chromosomal localization analysis found that 81 NAC genes in A. officinalis were unevenly distributed on nine chromosomes, and the gene duplication analysis showed three pairs of tandem duplicated genes and five pairs of segmental duplications, suggesting that gene duplication is possibly associated with the amplification of the A. officinalis NAC gene family. The differential gene expression analysis revealed one and three AoNAC genes that were upregulated and downregulated under different types of salinity stress, respectively. This study provides insight into the evolution, diversity, and characterization of NAC genes in garden asparagus and will be helpful for future understanding of their biological roles and molecular mechanisms in plants.

Utility of Triti-Map for bulk-segregated mapping of causal genes and regulatory elements in Triticeae.

Triticeae species, including wheat, barley, and rye, are critical for global food security. Mapping agronomically important genes is crucial for elucidating molecular mechanisms and improving crops. However, Triticeae includes many wild relatives with desirable agronomic traits, and frequent introgressions occurred during Triticeae evolution and domestication. Thus, Triticeae genomes are generally large and complex, making the localization of genes or functional elements that control agronomic traits challenging. Here, we developed Triti-Map, which contains a suite of user-friendly computational packages specifically designed and optimized to overcome the obstacles of gene mapping in Triticeae, as well as a web interface integrating multi-omics data from Triticeae for the efficient mining of genes or functional elements that control particular traits. The Triti-Map pipeline accepts both DNA and RNA bulk-segregated sequencing data as well as traditional QTL data as inputs for locating genes and elucidating their functions. We illustrate the usage of Triti-Map with a combination of bulk-segregated ChIP-seq data to detect a wheat disease-resistance gene with its promoter sequence that is absent from the reference genome and clarify its evolutionary process. We hope that Triti-Map will facilitate gene isolation and accelerate Triticeae breeding.

Comprehensive Analysis and Validation of Competing Endogenous RNA Network and Tumor-infiltrating Immune Cells in Lung Adenocarcinoma.

OBJECTIVE: The potential pathogenesis of LUAD remains largely unknown. In the present study, we evaluated the competing endogenous RNA (ceRNA) regulatory network and tumorinfiltrating immune cells in LUAD. METHODS: We obtained the RNA profiles and corresponding clinical information of LUAD patients from the TCGA data portal, and identified differentially expressed mRNAs (DEmRNAs), lncRNAs (DElncRNAs), and miRNAs (DEmiRNAs) between LUAD samples and normal controls to build a ceRNA network. Additionally, the CIBERSORT algorithm was employed to analyze the patterns of immune cell infiltration. Then, two survival-predicting models were constructed based on the ceRNA network and tumor-infiltrating immune cells, which were validated by an independent GEO dataset GSE50081. Moreover, the correlation between prognosis-related ceRNAs and immune cells was also evaluated. RESULTS: In total, 484 LUAD samples and 59 normal controls were included in this study, and 15 DEmiRNAs, 94 DEmRNAs, and 7 DElncRNAs were integrated to construct the ceRNA network of LUAD. Meanwhile, differentially expressed tumor-infiltrating immune cells were also identified, and the expressions of monocytes and regulatory T cells were related to the overall survival (OS) of LUAD patients. Moreover, the prognostic prediction model based on ceRNA network or tumor-infiltrating immune cells exhibited significant power in predicting the survival of LUAD patients. Furthermore, co-expression analysis revealed that some prognosis-related ceRNAs, such as CCT6A, E2F7, SLC16A1, and SNHG3, were positively or negatively correlated with several tumorinfiltrating immune cells, such as monocytes and M1 macrophages. CONCLUSION: This study improves our understanding of the pathogenesis of LUAD and is helpful in exploring the potential therapeutic targets and prognostic biomarkers for LUAD.

Functional characterization of powdery mildew resistance gene MlIW172, a new Pm60 allele and its allelic variation in wild emmer wheat.

Wild emmer wheat (Triticum dicoccoides, WEW) is an immediate progenitor of both the cultivated tetraploid and hexaploid wheats and it harbors rich genetic diversity against powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt). A powdery mildew resistance gene MlIW172 originated from WEW accession IW172 (G-797-M) is fine mapped in a 0.048 centimorgan (cM) genetic interval on 7AL, corresponding to a genomic region spanning 233 kb, 1 Mb and 800 kb in Chinese Spring, WEW Zavitan, and T. urartu G1812, respectively. MlIW172 encodes a typical NLR protein NLRIW172 and physically locates in an NBS-LRR gene cluster. NLRIW172 is subsequently identified as a new allele of Pm60, and its function is validated by EMS mutagenesis and transgenic complementation. Haplotype analysis of the Pm60 alleles reveals diversifications in sequence variation in the locus and presence and absence variations (PAV) in WEW populations. Four common single nucleotide variations (SNV) are detected between the Pm60 alleles from WEW and T. urartu, indicative of speciation divergence between the two different wheat progenitors. The newly identified Pm60 alleles and haplotypes in WEW are anticipated to be valuable for breeding powdery mildew resistance wheat cultivars via marker-assisted selection.