GenomeMUSter mouse genetic variation service enables multitrait, multipopulation data integration and analysis.

Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense variant resource by harmonizing multiple data sets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extendable to other model organisms. The result is a web- and programmatically accessible data service called GenomeMUSter, comprising single-nucleotide variants covering 657 strains at 106.8 million segregating sites. Interoperation with phenotype databases, analytic tools, and other resources enable a wealth of applications, including multitrait, multipopulation meta-analysis. We show this in cross-species comparisons of type 2 diabetes and substance use disorder meta-analyses, leveraging mouse data to characterize the likely role of human variant effects in disease. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.

Chromosomal-scale genomes of two Rosa species provide insights into genome evolution and ascorbate accumulation.

Rosa roxburghii and Rosa sterilis, two species belonging to the Rosaceae family, are widespread in the southwest of China. These species have gained recognition for their remarkable abundance of ascorbate in their fresh fruits, making them an ideal vitamin C resource. In this study, we generated two high-quality chromosome-scale genome assemblies for R. roxburghii and R. sterilis, with genome sizes of 504 and 981.2 Mb, respectively. Notably, we present a haplotype-resolved, chromosome-scale assembly for diploid R. sterilis. Our results indicated that R. sterilis originated from the hybridization of R. roxburghii and R. longicuspis. Genome analysis revealed the absence of recent whole-genome duplications in both species and identified a series of duplicated genes that possibly contributing to the accumulation of flavonoids. We identified two genes in the ascorbate synthesis pathway, GGP and GalLDH, that show signs of positive selection, along with high expression levels of GDP-d-mannose 3', 5'-epimerase (GME) and GDP-l-galactose phosphorylase (GGP) during fruit development. Furthermore, through co-expression network analysis, we identified key hub genes (MYB5 and bZIP) that likely regulate genes in the ascorbate synthesis pathway, promoting ascorbate biosynthesis. Additionally, we observed the expansion of terpene synthase genes in these two species and tissue expression patterns, suggesting their involvement in terpenoid biosynthesis. Our research provides valuable insights into genome evolution and the molecular basis of the high concentration of ascorbate in these two Rosa species.

Mouse Phenome Database: towards a more FAIR-compliant and TRUST-worthy data repository and tool suite for phenotypes and genotypes.

The Mouse Phenome Database (MPD; https://phenome.jax.org; RRID:SCR_003212), supported by the US National Institutes of Health, is a Biomedical Data Repository listed in the Trans-NIH Biomedical Informatics Coordinating Committee registry. As an increasingly FAIR-compliant and TRUST-worthy data repository, MPD accepts phenotype and genotype data from mouse experiments and curates, organizes, integrates, archives, and distributes those data using community standards. Data are accompanied by rich metadata, including widely used ontologies and detailed protocols. Data are from all over the world and represent genetic, behavioral, morphological, and physiological disease-related characteristics in mice at baseline or those exposed to drugs or other treatments. MPD houses data from over 6000 strains and populations, representing many reproducible strain types and heterogenous populations such as the Diversity Outbred where each mouse is unique but can be genotyped throughout the genome. A suite of analysis tools is available to aggregate, visualize, and analyze these data within and across studies and populations in an increasingly traceable and reproducible manner. We have refined existing resources and developed new tools to continue to provide users with access to consistent, high-quality data that has translational relevance in a modernized infrastructure that enables interaction with a suite of bioinformatics analytic and data services.

Mouse phenome database: curated data repository with interactive multi-population and multi-trait analyses.

The Mouse Phenome Database continues to serve as a curated repository and analysis suite for measured attributes of members of diverse mouse populations. The repository includes annotation to community standard ontologies and guidelines, a database of allelic states for 657 mouse strains, a collection of protocols, and analysis tools for flexible, interactive, user directed analyses that increasingly integrates data across traits and populations. The database has grown from its initial focus on a standard set of inbred strains to include heterogeneous mouse populations such as the Diversity Outbred and mapping crosses and well as Collaborative Cross, Hybrid Mouse Diversity Panel, and recombinant inbred strains. Most recently the system has expanded to include data from the International Mouse Phenotyping Consortium. Collectively these data are accessible by API and provided with an interactive tool suite that enables users' persistent selection, storage, and operation on collections of measures. The tool suite allows basic analyses, advanced functions with dynamic visualization including multi-population meta-analysis, multivariate outlier detection, trait pattern matching, correlation analyses and other functions. The data resources and analysis suite provide users a flexible environment in which to explore the basis of phenotypic variation in health and disease across the lifespan.

The chromosome-scale genomes of Dipterocarpus turbinatus and Hopea hainanensis (Dipterocarpaceae) provide insights into fragrant oleoresin biosynthesis and hardwood formation.

Dipterocarpaceae are typical tropical plants (dipterocarp forests) that are famous for their high economic value because of their production of fragrant oleoresins, top-quality timber and usage in traditional Chinese medicine. Currently, the lack of Dipterocarpaceae genomes has been a limiting factor to decipher the fragrant oleoresin biosynthesis and gain evolutionary insights into high-quality wood formation in Dipterocarpaceae. We generated chromosome-level genome assemblies for two representative Dipterocarpaceae species viz. Dipterocarpus turbinatus Gaertn. f. and Hopea hainanensis Merr. et Chun. Our whole-genome duplication (WGD) analysis revealed that Dipterocarpaceae underwent a shared WGD event, which showed significant impacts on increased copy numbers of genes related to the biosynthesis of terpene, BAHD acyltransferases, fatty acid and benzenoid/phenylpropanoid, which probably confer to the formation of their characteristic fragrant oleoresin. Additionally, compared with common soft wood plants, the expansion of gene families was also found to be associated with wood formation, such as in CESA (cellulose synthase), CSLE (cellulose synthase-like protein E), laccase and peroxidase in Dipterocarpaceae genomes, which might also contribute to the formation of harder, stronger and high-density timbers. Finally, an integrative analysis on a combination of genomic, transcriptomic and metabolic data from different tissues provided further insights into the molecular basis of fragrant oleoresins biosynthesis and high-quality wood formation of Dipterocarpaceae. Our study contributes the first two representative genomes for Dipterocarpaceae, which are valuable genetic resources for further researches on the fragrant oleoresins and superior-quality timber, genome-assisted breeding and improvement, and conservation biology of this family.

Chromosome-level genome of Pedinomonas minor (Chlorophyta) unveils adaptations to abiotic stress in a rapidly fluctuating environment.

The Pedinophyceae (Viridiplantae) comprise a class of small uniflagellate algae with a pivotal position in the phylogeny of the Chlorophyta as the sister group of the 'core chlorophytes'. We present a chromosome-level genome assembly of the freshwater type species of the class, Pedinomonas minor. We sequenced the genome using Pacbio, Illumina and Hi-C technologies, performed comparative analyses of genome and gene family evolution, and analyzed the transcriptome under various abiotic stresses. Although the genome is relatively small (55 Mb), it shares many traits with core chlorophytes including number of introns and protein-coding genes, messenger RNA (mRNA) lengths, and abundance of transposable elements. Pedinomonas minor is only bounded by the plasma membrane, thriving in temporary habitats that frequently dry out. Gene family innovations and expansions and transcriptomic responses to abiotic stresses have shed light on adaptations of P. minor to its fluctuating environment. Horizontal gene transfers from bacteria and fungi have possibly contributed to the evolution of some of these traits. We identified a putative endogenization site of a nucleocytoplasmic large DNA virus and hypothesized that endogenous viral elements donated foreign genes to the host genome, their spread enhanced by transposable elements, located at gene boundaries in several of the expanded gene families.

Association between Vaginal Infections and the Types and Viral Loads of Human Papillomavirus: A Clinical Study Based on 4,449 Cases of Gynecologic Outpatients.

OBJECTIVE: We here evaluated the association between human papillomavirus (HPV) infection and vaginal infections, including bacterial vaginosis (BV), trichomonas vaginalis (TV), and vulvovaginal candidiasis (VVC). METHODS: A total of 4,449 women were enrolled in this study and given gynecological examinations. HPV genotyping and viral load determination were performed using a real-time PCR. Vaginal infections were diagnosed using wet mounts of vaginal secretions, gram-stained vaginal secretion smears, and chemical enzyme kits. RESULTS: In this study, the overall HPV-positive rate was 25.06%, and vaginal infection tended to occur in women with HPV infection (P < 0.05). HPV infection tended to occur in BV- and TV-positive women (P < 0.05) and not in women with microecological disorders, intermediate type BV, VVC, or coinfection (P > 0.05). The most common genotypes were HPV58 and HPV53 in women with normal vaginal microecology and HPV16 and HPV52 in the women suffering from vaginal infection. The viral loads among groups for HPV16 and HPV52 showed no statistically significant differences (P=0.940; P=0.167). CONCLUSIONS: Our study revealed that BV and TV are associated with HPV infection, especially high-risk HPV infection, while VVC has no association with HPV infection. Further studies are needed to explore the detailed mechanism.

Phylogenomics Provides New Insights into Gains and Losses of Selenoproteins among Archaeplastida.

Selenoproteins that contain selenocysteine (Sec) are found in all kingdoms of life. Although they constitute a small proportion of the proteome, selenoproteins play essential roles in many organisms. In photosynthetic eukaryotes, selenoproteins have been found in algae but are missing in land plants (embryophytes). In this study, we explored the evolutionary dynamics of Sec incorporation by conveying a genomic search for the Sec machinery and selenoproteins across Archaeplastida. We identified a complete Sec machinery and variable sizes of selenoproteomes in the main algal lineages. However, the entire Sec machinery was missing in the Bangiophyceae-Florideophyceae clade (BV) of Rhodoplantae (red algae) and only partial machinery was found in three species of Archaeplastida, indicating parallel loss of Sec incorporation in different groups of algae. Further analysis of genome and transcriptome data suggests that all major lineages of streptophyte algae display a complete Sec machinery, although the number of selenoproteins is low in this group, especially in subaerial taxa. We conclude that selenoproteins tend to be lost in Archaeplastida upon adaptation to a subaerial or acidic environment. The high number of redox-active selenoproteins found in some bloom-forming marine microalgae may be related to defense against viral infections. Some of the selenoproteins in these organisms may have been gained by horizontal gene transfer from bacteria.

CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma.

BACKGROUND/AIMS: CD24 is a highly glycosylated mucin-like antigen on the cell surface, which has recently emerged as a novel oncogene and metastasis promoter. We performed bioinformatics analysis to investigate whether CD24 can serve as a prognostic indicator in breast cancer. METHODS: CD24 expression was assessed using SAGE Genie tools and Oncomine analysis. The PrognoScan database, Kaplan-Meier Plotter, and bc-GenExMiner were used to identify the prognostic roles of CD24 in breast cancer. RESULTS: We found that CD24 was more frequently overexpressed in breast cancer than in normal breast tissue and correlated with worse prognosis. Meanwhile, high CD24 expression was associated with increased risk of HER2, basal-like, triple-negative breast cancer, and higher Scarff-Bloom-Richardson grade. Data mining in multiple big databases confirmed a positive correlation between CD24 mRNA expression and SDC1 mRNA expression in breast cancer tissue. CONCLUSIONS: Our findings suggest that CD24 overexpression is more common in breast cancer than in corresponding normal tissue. In addition, CD24 and SDC1 can serve as prognostic indicators for breast cancer. However, large-scale and comprehensive research is needed to further confirm these results.

Effect of honghua (Flos Carthami) on nitric oxide production in RAW 264.7 cells and alpha-glucosidase activity.

OBJECTIVE: To study the effects of extracts from Honghua (Flos Carthami) on lipopolysaccharide induced nitric oxide (NO) production in RAW 264.7 cells and the influence of the extracts on yeast a-glucosidase activity. The total flavonoid content of the extracts was also determined. METHODS: Cytotoxicity of the extracts to RAW 264.7 cells was evaluated by the ATPlite method. Inhibitory effects of the extracts on NO production were evaluated by Griess assay. Curcumin was used as a positive control. Screening of extracts for potential a-glucosidase inhibitors was done by a fluorometric assay. The assay was based on the hydrolysis of 4-methylumbelliferyl-a-D-glucopyranoside to form the fluorescent product, 4-methylumbelliferone. Acarbose was used as a positive control. The total flavonoid content was tested using kaempferol as the standard. RESULTS: There were significant inhibitory effects on NO production when the extracts were 25-100 microg/ mL (P < 0.05) and curcumin was 2-4 microg/mL (P < 0.001). The extracts showed an inhibitory effect on alpha-glucosidase activity at the concentrations of 15.6-125 microg/mL with a half maximal (50%) inhibitory concentration (IC50) of (32.8 +/- 5.7) microg/mL, compared with the IC50 of acarbose at (1.8 +/- 0.4) microg/mL. There was a significant difference between the two IC50 values (P < 0.001). The total content of flavonoids per gram of dried herb was 1.14 mg. CONCLUSION: Honghua (Flos Carthami) showed inhibitory effects on NO production in activated RAW 264.7 macrophage cells and an inhibitory effect on yeast alpha-glucosidase. There might be a relationship between these pharmacological effects and its flavonoid content.

The role of serum markers PAPP-A ß-hCG, AFP, and uE3 in predicting the risk of preeclampsia in early, middle, and late pregnancy.

BACKGROUND: Preeclampsia (PE) has adverse effects on pregnant women, fetuses, and newborns [1], and accounts for 3%-10% of pregnancy-related diseases globally. OBJECTIVE: This study aimed to screen a series of prenatal markers (pregnancy-associated plasma protein [PAPP-A], ß-human chorionic gonadotropin [ß-hCG], alpha fetoprotein [AFP], and estriol [uE3]) to establish a risk model and evaluate the diagnostic values of the markers for predicting PE. METHODS: Sixty-five pregnant women were enrolled in this study. They were divided into two groups containing healthy pregnant women (n= 51, the non-PE group) and pregnant women with PE (n= 14, the PE group). According to the stage of pregnancy, the pregnant women in each group were divided into early, middle, and late pregnancy groups for statistical analysis. The levels of PAPPA-A ß-hCG, AFP, and uE3 were compared among these groups. Then, a risk model was established, and PE was diagnosed using receiver operating characteristic (ROC) curve results. RESULTS: In the early pregnancy group, the differences in the levels of PAPP-A, AFP, and uE3 between the PE and non-PE groups were statistically significant (P< 0.001, P= 0.029, and P= 0.033, respectively), while the difference in the single remaining marker was not statistically significant. A ROC curve analysis revealed that in early pregnancy, the sensitivity and specificity of PAPP-A were 76.5% and 71.4%, respectively, and the sensitivity and specificity of ß-hCG were 82.4% and 57.1%, respectively. The sensitivity and specificity of the combination of the two markers for diagnosing PE were 86.3% and 57.1%, respectively. CONCLUSION: This study demonstrated that the combination of PAPP-A and ß-hCG has diagnostic value for PE in pregnant women. Accordingly, we should formulate innovative PE screening strategies to target the prevention of PE and create important conditions for predictive and preventive personalized medical treatments.

Relationships Between Maternal Selected Metals (Cu, Mg, Zn and Fe), Thyroid Function and Blood Glucose Levels During Pregnancy.

The aim of this study were to understand the intake of selected metals (copper (Cu), zinc (Zn), iron (Fe) and magnesium (Mg)) during pregnancy; to detect serum Cu, Mg, Zn and Fe levels in pregnant women; to analyze the relationships among the selected metals, maternal thyroid function and fasting blood glucose (FBG) levels; to investigate the impact of the selected metals and maternal thyroid function on the risk of gestational diabetes mellitus (GDM); and to provide clinical value for the rational intake of the selected metals and iodine during pregnancy to ensure normal fetal development. The population was recruited from pregnant women presenting to the obstetrics outpatient clinic of Shanxi Provincial People's Hospital (February 2021 to April 2022). Selected metal, thyroid hormone (TH (free thyroxine (FT4), free tri-iodothyronine (FT3), and thyroid-stimulating hormone (TSH)) and FBG levels were measured in pregnant women during early, middle and late pregnancy. Covariance analysis was used to analyze the overall trends in selected metal, TH and FBG levels during pregnancy, and binary logistic regression models were used to assess the impacts of the selected metals and thyroid function on the risk of GDM. In addtion, the potential mediation effects of thyroid functions were explored in the mediation analyses. A total of 65 pregnant women were included in this study. Regression models showed that maternal Mg and Cu levels were positively associated with the risk of GDM, conversely, logFT4 was negatively associated with the risk of GDM. Mediation analyses suggested that the associations between the selected metals (Zn, Cu and Mg) and GDM might be mediated by FT3 levels, and that the Cu-GDM and Zn-GDM association could be explained by FT4 levels. Additionally, the Zn-GDM association could also potentially be mediated by the FT3/FT4 ratio. Our findings suggest that Mg, Cu and FT4 levels may act as influencing factors for the development of GDM, and maternal FT3, FT4 and the FT3/FT4 ratio might be the potential mediators of the associations between the selected metals and GDM risk during pregnancy.

Antimycobacterial Activities of Hydroxamic Acids and Their Iron(II/III), Nickel(II), Copper(II) and Zinc(II) Complexes.

Hydroxamic acid (HA) derivatives display antibacterial and antifungal activities. HA with various numbers of carbon atoms (C2, C6, C8, C10, C12 and C17), complexed with different metal ions, including Fe(II/III), Ni(II), Cu(II) and Zn(II), were evaluated for their antimycobacterial activities and their anti-biofilm activities. Some derivatives showed antimycobacterial activities, especially in biofilm growth conditions. For example, 20-100 µM of HA10Fe2, HA10FeCl, HA10Fe3, HA10Ni2 or HA10Cu2 inhibited Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium marinum biofilm development. HA10Fe2, HA12Fe2 and HA12FeCl could even attack pre-formed Pseudomonas aeruginosa biofilms at higher concentrations (around 300 µM). The phthiocerol dimycocerosate (PDIM)-deficient Mycobacterium tuberculosis H37Ra was more sensitive to the ion complexes of HA compared to other mycobacterial strains. Furthermore, HA10FeCl could increase the susceptibility of Mycobacterium bovis BCG to vancomycin. Proteomic profiles showed that the potential targets of HA10FeCl were mainly related to mycobacterial stress adaptation, involving cell wall lipid biosynthesis, drug resistance and tolerance and siderophore metabolism. This study provides new insights regarding the antimycobacterial activities of HA and their complexes, especially about their potential anti-biofilm activities.

Large-Area and Visible-Light-Driven Heterojunctions of In2O3/Graphene Built for ppb-Level Formaldehyde Detection at Room Temperature.

Achieving convenient and accurate detection of indoor ppb-level formaldehyde is an urgent requirement to ensure a healthy working and living environment for people. Herein, ultrasmall In2O3 nanorods and supramolecularly functionalized reduced graphene oxide are selected as hybrid components of visible-light-driven (VLD) heterojunctions to fabricate ppb-level formaldehyde (HCHO) gas sensors (named InAG sensors). Under 405 nm visible light illumination, the sensor exhibits an outstanding response toward ppb-level HCHO at room temperature, including the ultralow practical limit of detection (pLOD) of 5 ppb, high response (Ra/Rg = 2.4, 500 ppb), relatively short response/recovery time (119 s/179 s, 500 ppb), high selectivity, and long-term stability. The ultrasensitive room temperature HCHO-sensing property is derived from visible-light-driven and large-area heterojunctions between ultrasmall In2O3 nanorods and supramolecularly functionalized graphene nanosheets. The performance of the actual detection toward HCHO is evaluated in a 3 m3 test chamber, confirming the practicability and reliability of the InAG sensor. This work provides an effective strategy for the development of low-power-consumption ppb-level gas sensors.

GenomeMUSter mouse genetic variation service enables multi-trait, multi-population data integration and analyses.

Hundreds of inbred laboratory mouse strains and intercross populations have been used to functionalize genetic variants that contribute to disease. Thousands of disease relevant traits have been characterized in mice and made publicly available. New strains and populations including the Collaborative Cross, expanded BXD and inbred wild-derived strains add to set of complex disease mouse models, genetic mapping resources and sensitized backgrounds against which to evaluate engineered mutations. The genome sequences of many inbred strains, along with dense genotypes from others could allow integrated analysis of trait - variant associations across populations, but these analyses are not feasible due to the sparsity of genotypes available. Moreover, the data are not readily interoperable with other resources. To address these limitations, we created a uniformly dense data resource by harmonizing multiple variant datasets. Missing genotypes were imputed using the Viterbi algorithm with a data-driven technique that incorporates local phylogenetic information, an approach that is extensible to other model organism species. The result is a web- and programmatically-accessible data service called GenomeMUSter ( https://muster.jax.org ), comprising allelic data covering 657 strains at 106.8M segregating sites. Interoperation with phenotype databases, analytic tools and other resources enable a wealth of applications including multi-trait, multi-population meta-analysis. We demonstrate this in a cross-species comparison of the meta-analysis of Type 2 Diabetes and of substance use disorders, resulting in the more specific characterization of the role of human variant effects in light of mouse phenotype data. Other applications include refinement of mapped loci and prioritization of strain backgrounds for disease modeling to further unlock extant mouse diversity for genetic and genomic studies in health and disease.

Assembling Hollow Cactus-Like ZnO Nanorods with Dipole-Modified Graphene Nanosheets for Practical Room-Temperature Formaldehyde Sensing.

Formaldehyde (HCHO) sensing plays a critical role for indoor environment monitoring in smart home systems. Inspired by the unique hierarchical structure of cactus, we have prepared a ZnO/ANS-rGO composite for room-temperature (RT) HCHO sensing, through assembling hollow cactus-like ZnO nanorods with 5-aminonaphthalene-1-sulfonic acid (ANS)-modified graphene nanosheets in a facile and template-free manner. Interestingly, it was found that the ZnO morphology could be simply tuned from flower clusters to hollow cactus-like nanostructures, along with the increase of the reaction time during the assembly process. The ZnO/ANS-rGO-based sensors exhibited superior RT HCHO-sensing performance with an ultrahigh response (68%, 5 ppm), good repeatability, long-term stability, and an outstanding practical limit of detection (LOD: 0.25 ppm) toward HCHO, which is the lowest practical LOD reported so far. Furthermore, for the first time, a 30 m3 simulation test cabinet was adapted to evaluate the practical gas-sensing performance in an indoor environment. As a result, an instantaneous response of 5% to 0.4 ppm HCHO was successfully achieved in the simulation test. The corresponding sensing mechanism was interpreted from two aspects including high charge transport capability of ANS-rGO and the distinct gas adsorbability derived from nanostructures, respectively. The combination of a biomimetic hierarchical structure and supramolecular assembly provides a promising strategy to design HCHO-sensing materials with high practicability.

The Cycas genome and the early evolution of seed plants.

Cycads represent one of the most ancient lineages of living seed plants. Identifying genomic features uniquely shared by cycads and other extant seed plants, but not non-seed-producing plants, may shed light on the origin of key innovations, as well as the early diversification of seed plants. Here, we report the 10.5-Gb reference genome of Cycas panzhihuaensis, complemented by the transcriptomes of 339 cycad species. Nuclear and plastid phylogenomic analyses strongly suggest that cycads and Ginkgo form a clade sister to all other living gymnosperms, in contrast to mitochondrial data, which place cycads alone in this position. We found evidence for an ancient whole-genome duplication in the common ancestor of extant gymnosperms. The Cycas genome contains four homologues of the fitD gene family that were likely acquired via horizontal gene transfer from fungi, and these genes confer herbivore resistance in cycads. The male-specific region of the Y chromosome of C. panzhihuaensis contains a MADS-box transcription factor expressed exclusively in male cones that is similar to a system reported in Ginkgo, suggesting that a sex determination mechanism controlled by MADS-box genes may have originated in the common ancestor of cycads and Ginkgo. The C. panzhihuaensis genome provides an important new resource of broad utility for biologists.

Liraglutide preconditioning attenuates myocardial ischemia/ reperfusion injury via homer1 activation.

Myocardial infarction (MI) is one of most common cardiovascular diseases, and ischemia/reperfusion (I/R) injury is one of the risk factors for severe myocardial injury and dysfunction, even leading to high mortality of myocardial infarction. Liraglutide, a novel glucagon-like peptide 1 (GLP-1) analogue, has been reported to reduce cardiac rupture and infarct size and improve cardiac function in normal and diabetic rodents, however, the mechanisms of liraglutide on cardiomyocytes is not clear. The current research was designed to investigate the hypothesis that liraglutide would protect cardiomyocytes through regulating homer1 expression under hypoxia/reoxygenation (H/R) condition. The results of the present study indicated liraglutide reduced hypoxia-reoxygenation induced cell death and attenuated intracellular calcium overload in H9C2 cardiomyocytes under H/R condition. Moreover, liraglutide significantly increased the Homer1 protein expression, and this protection might be related to Homer1-dependent regulation of endoplasmic reticulum (ER) calcium homeostasis. Taken together, liraglutide protects H9C2 cell against H/R induced cell injury, and this protective effect may inhibit intracellular calcium overload to some extent, through Homer1-dependent regulation of ER calcium homeostasis.

The Draft Genome of the Centric Diatom Conticribra weissflogii (Coscinodiscophyceae, Ochrophyta).

Here, we present a 231 Mb draft genome of the centric diatom Conticribra weissflogii CCMP1336. Comparative genomics of C. weissflogii and other Ochrophyta support the existence of unique carbon-concentrating mechanisms and chitin metabolic processes in diatoms. The whole-genome project is available at CNSA (https://db.cngb.org/search/project/CNP0001903/).

Genome-wide analyses across Viridiplantae reveal the origin and diversification of small RNA pathway-related genes.

Small RNAs play a major role in the post-transcriptional regulation of gene expression in eukaryotes. Despite the evolutionary importance of streptophyte algae, knowledge on small RNAs in this group of green algae is almost non-existent. We used genome and transcriptome data of 34 algal and plant species, and performed genome-wide analyses of small RNA (miRNA & siRNA) biosynthetic and degradation pathways. The results suggest that Viridiplantae started to evolve plant-like miRNA biogenesis and degradation after the divergence of the Mesostigmatophyceae in the streptophyte algae. We identified two major evolutionary transitions in small RNA metabolism in streptophyte algae; during the first transition, the origin of DCL-New, DCL1, AGO1/5/10 and AGO4/6/9 in the last common ancestor of Klebsormidiophyceae and all other streptophytes could be linked to abiotic stress responses and evolution of multicellularity in streptophytes. During the second transition, the evolution of DCL 2,3,4, and AGO 2,3,7 as well as DRB1 in the last common ancestor of Zygnematophyceae and embryophytes, suggests their possible contribution to pathogen defense and antibacterial immunity. Overall, the origin and diversification of DICER and AGO along with several other small RNA pathway-related genes among streptophyte algae suggested progressive adaptations of streptophyte algae during evolution to a subaerial environment.