MFA-ICPS: Semi-supervised medical image segmentation with improved cross pseudo supervision and multi-dimensional feature attention.

BACKGROUND: In the medical field, medical image segmentation plays a pivotal role in facilitating disease evaluation and supporting treatment decision-making for doctors. Recently, deep learning methods have been employed in the field of medical image segmentation. However, the manual annotation of a large number of reliable labels is a costly and time-consuming process. PURPOSE: To address this challenge, a semi-supervised learning framework is required to alleviate the burden of reliable labeling and enhance segmentation accuracy in challenging areas of medical images. METHODS: Therefore, this paper presents MFA-ICPS framework, a semi-supervised learning framework based on the improved cross pseudo supervision (ICPS) and multi-dimensional feature attention (MFA) modules. Medical images inevitably contain some noise that may affect the segmentation accuracy, so the proposed framework addresses this challenge by introducing noise disturbance, combining ICPS and MFA modules, and using pseudo-segmentation maps and MFA maps to maintain the consistency at both the output and feature levels. RESULTS: In the experiments, MFA-ICPS framework accurately obtains the following performances on the left atrial dataset: Dice, Jaccard, 95HD, and ASD values are 90.89 % $90.89\%$ , 83.40 % $83.40\%$ , 6.00 and 1.94 mm, respectively. And on the pancreas-CT dataset, the following performances are accurately obtained: Dice, Jaccard, 95HD, and ASD values are 79.55 % $79.55\%$ , 66.87 % $66.87\%$ , 7.67 and 1.65 mm, respectively. CONCLUSIONS: The segmentation performance of MFA-ICPS framework on different medical datasets demonstrates its remarkable capability to significantly enhance medical image segmentation.

Genome-Wide Identification of Seven Polyamine Oxidase Genes in Camellia sinensis (L.) and Their Expression Patterns Under Various Abiotic Stresses.

Polyamines (PAs) in plant play a critical role in growth and development and in response to environmental stress. Polyamine oxidase (PAO) is a flavin adenine dinucleotide dependent enzyme that plays a major role in PA catabolism. For the first time, PAO genes in tea plant were screened for the whole genome-wide and seven CsPAO genes were identified, which were named CsPAO1-7. Phylogenetic tree analysis revealed seven CsPAO protein sequences classed into three groups, including clade I, III, and IV. Compared with other plants, the tea plant lacked clade II members. Genetic structure and tissue specific expression analysis showed that there were significant differences among members of the CsPAO gene family. Among members of the CsPAOs family, CsPAO4 and CsPAO5 contain more introns and are highly expressed in various organizations. CsPAO1, CsPAO4, and CsPAO5 genes were cloned and expressed heterologously to verify theirs function. Heat map showed high response of CsPAO5 to drought stress, while CsPAO1 and CsPAO2 were sensitive to changes in nitrogen nutrition. Furthermore, exogenous abscisic acid (ABA) treatment indicated that the expression of most CsPAO genes in roots and leaves was significantly induced. In the root, Spm content increased significantly, while Put and Spd content decreased, suggesting that ABA has great influence on the biosynthesis of PAs. Anaerobic treatment of picked tea leaves showed that the decomposition of PAs was promoted to a certain extent. The above data help to clarify the role of CsPAO in response abiotic and nitrogen nutritional stresses in tea plants, and provide a reference perspective for the potential influence of PAs on the tea processing quality.

Improved hybrid de novo genome assembly and annotation of African wild rice, Oryza longistaminata, from Illumina and PacBio sequencing reads.

African wild rice Oryza longistaminata, one of the eight AA- genome species in the genus Oryza, possesses highly valued traits, such as the rhizomatousness for perennial rice breeding, strong tolerance to biotic and abiotic stresses, and high biomass production on poor soils. To obtain the high-quality reference genome for O. longistaminata we employed a hybrid assembly approach through incorporating Illumina and PacBio sequencing datasets. The final genome assembly comprised only 107 scaffolds and was approximately ∼363.5 Mb, representing ∼92.7% of the estimated African wild rice genome (∼392 Mb). The N50 lengths of the assembled contigs and scaffolds were ∼46.49 Kb and ∼6.83 Mb, indicating ∼3.72-fold and ∼18.8-fold improvement in length compared to the earlier released assembly (∼12.5 Kb and 364 Kb, respectively). Aided with Hi-C data and syntenic relationship with O. sativa, these assembled scaffolds were anchored into 12 pseudo-chromosomes. Genome annotation and comparative genomic analysis reveal that lineage-specific expansion of gene families that respond to biotic- and abiotic stresses are of great potential for mining novel alleles to overcome major diseases and abiotic adaptation in rice breeding programs. This reference genome of African wild rice will greatly enlarge the existing database of rice genome resources and unquestionably form a solid base to understand genomic basis underlying highly valued phenotypic traits and search for novel gene sources in O. longistaminata for the future rice breeding programs.

Transcriptome data reveal conserved patterns of fruiting body development and response to heat stress in the mushroom-forming fungus Flammulina filiformis.

Mushroom-forming fungi are complex multicellular organisms that form the basis of a large industry, yet, our understanding of the mechanisms of mushroom development and its responses to various stresses remains limited. The winter mushroom (Flammulina filiformis) is cultivated at a large commercial scale in East Asia and is a species with a preference for low temperatures. This study investigated fruiting body development in F. filiformis by comparing transcriptomes of 4 developmental stages, and compared the developmental genes to a 200-genome dataset to identify conserved genes involved in fruiting body development, and examined the response of heat sensitive and -resistant strains to heat stress. Our data revealed widely conserved genes involved in primordium development of F. filiformis, many of which originated before the emergence of the Agaricomycetes, indicating co-option for complex multicellularity during evolution. We also revealed several notable fruiting-specific genes, including the genes with conserved stipe-specific expression patterns and the others which related to sexual development, water absorption, basidium formation and sporulation, among others. Comparative analysis revealed that heat stress induced more genes in the heat resistant strain (M1) than in the heat sensitive one (XR). Of particular importance are the hsp70, hsp90 and fes1 genes, which may facilitate the adjustment to heat stress in the early stages of fruiting body development. These data highlighted novel genes involved in complex multicellular development in fungi and aid further studies on gene function and efforts to improve the productivity and heat tolerance in mushroom-forming fungi.

Draft genomes of two outcrossing wild rice, Oryza rufipogon and O. longistaminata, reveal genomic features associated with mating-system evolution.

Oryza rufipogon and O. longistaminata are important wild relatives of cultivated rice, harboring a promising source of novel genes for rice breeding programs. Here, we present de novo assembled draft genomes and annotation of O. rufipogon and O. longistaminata. Our analysis reveals a considerable number of lineage-specific gene families associated with the self-incompatibility (SI) and formation of reproductive separation. We show how lineage-specific expansion or contraction of gene families with functional enrichment of the recognition of pollen, thus enlightening their reproductive diversification. We documented a large number of lineage-specific gene families enriched in salt stress, antifungal response, and disease resistance. Our comparative analysis further shows a genome-wide expansion of genes encoding NBS-LRR proteins in these two outcrossing wild species in contrast to six other selfing rice species. Conserved noncoding sequences (CNSs) in the two wild rice genomes rapidly evolve relative to selfing rice species, resulting in the reduction of genomic variation owing to shifts of mating systems. We find that numerous genes related to these rapidly evolving CNSs are enriched in reproductive structure development, flower development, and postembryonic development, which may associate with SI in O. rufipogon and O. longistaminata.

SMRT sequencing of the Oryza rufipogon genome reveals the genomic basis of rice adaptation.

Asian cultivated rice is believed to have been domesticated from a wild progenitor, Oryza rufipogon, offering promising sources of alleles for world rice improvement. Here we first present a high-quality chromosome-scale genome of the typical O. rufipogon. Comparative genomic analyses of O. sativa and its two wild progenitors, O. nivara and O. rufipogon, identified many dispensable genes functionally enriched in the reproductive process. We detected millions of genomic variants, of which large-effect mutations could affect agronomically relevant traits. We demonstrate how lineage-specific expansion of gene families may have contributed to the formation of reproduction isolation. We document thousands of genes with signatures of positive selection that are mainly involved in the reproduction and response to biotic- and abiotic stresses. We show that selection pressures may serve as forces to govern substantial genomic alterations that form the genetic basis of rapid evolution of mating and reproductive systems under diverse habitats.

Tea plant genomics: achievements, challenges and perspectives.

Tea is among the world's most widely consumed non-alcoholic beverages and possesses enormous economic, health, and cultural values. It is produced from the cured leaves of tea plants, which are important evergreen crops globally cultivated in over 50 countries. Along with recent innovations and advances in biotechnologies, great progress in tea plant genomics and genetics has been achieved, which has facilitated our understanding of the molecular mechanisms of tea quality and the evolution of the tea plant genome. In this review, we briefly summarize the achievements of the past two decades, which primarily include diverse genome and transcriptome sequencing projects, gene discovery and regulation studies, investigation of the epigenetics and noncoding RNAs, origin and domestication, phylogenetics and germplasm utilization of tea plant as well as newly developed tools/platforms. We also present perspectives and possible challenges for future functional genomic studies that will contribute to the acceleration of breeding programs in tea plants.

Optimized sequencing depth and de novo assembler for deeply reconstructing the transcriptome of the tea plant, an economically important plant species.

BACKGROUND: Tea is the oldest and among the world's most popular non-alcoholic beverages, which has important economic, health and cultural values. Tea is commonly produced from the leaves of tea plants (Camellia sinensis), which belong to the genus Camellia of family Theaceae. In the last decade, many studies have generated the transcriptomes of tea plants at different developmental stages or under abiotic and/or biotic stresses to investigate the genetic basis of secondary metabolites that determine tea quality. However, these results exhibited large differences, particularly in the total number of reconstructed transcripts and the quality of the assembled transcriptomes. These differences largely result from limited knowledge regarding the optimized sequencing depth and assembler for transcriptome assembly of structurally complex plant species genomes. RESULTS: We employed different amounts of RNA-sequencing data, ranging from 4 to 84 Gb, to assemble the tea plant transcriptome using five well-known and representative transcript assemblers. Although the total number of assembled transcripts increased with increasing sequencing data, the proportion of unassembled transcripts became saturated as revealed by plant BUSCO datasets. Among the five representative assemblers, the Bridger package shows the best performance in both assembly completeness and accuracy as evaluated by the BUSCO datasets and genome alignment. In addition, we showed that Bridger and BinPacker harbored the shortest runtimes followed by SOAPdenovo and Trans-ABySS. CONCLUSIONS: The present study compares the performance of five representative transcript assemblers and investigates the key factors that affect the assembly quality of the transcriptome of the tea plants. This study will be of significance in helping the tea research community obtain better sequencing and assembly of tea plant transcriptomes under conditions of interest and may thus help to answer major biological questions currently facing the tea industry.

Genome Sequences Provide Insights into the Reticulate Origin and Unique Traits of Woody Bamboos.

Polyploidization is a major driver of speciation and its importance to plant evolution has been well recognized. Bamboos comprise one diploid herbaceous and three polyploid woody lineages, and are members of the only major subfamily in grasses that diversified in forests, with the woody members having a tree-like lignified culm. In this study, we generated four draft genome assemblies of major bamboo lineages with three different ploidy levels (diploid, tetraploid, and hexaploid). We also constructed a high-density genetic linkage map for a hexaploid species of bamboo, and used a linkage-map-based strategy for genome assembly and identification of subgenomes in polyploids. Further phylogenomic analyses using a large dataset of syntenic genes with expected copies based on ploidy levels revealed that woody bamboos originated subsequent to the divergence of the herbaceous bamboo lineage, and experienced complex reticulate evolution through three independent allopolyploid events involving four extinct diploid ancestors. A shared but distinct subgenome was identified in all polyploid forms, and the progenitor of this subgenome could have been critical in ancient polyploidizations and the origin of woody bamboos. Important genetic clues to the unique flowering behavior and woody trait in bamboos were also found. Taken together, our study provides significant insights into ancient reticulate evolution at the subgenome level in the absence of extant donor species, and offers a potential model scenario for broad-scale study of angiosperm origination by allopolyploidization.

Tea Plant Information Archive: a comprehensive genomics and bioinformatics platform for tea plant.

Tea is the world's widely consumed nonalcohol beverage with essential economic and health benefits. Confronted with the increasing large-scale omics-data set particularly the genome sequence released in tea plant, the construction of a comprehensive knowledgebase is urgently needed to facilitate the utilization of these data sets towards molecular breeding. We hereby present the first integrative and specially designed web-accessible database, Tea Plant Information Archive (TPIA; http://tpia.teaplant.org). The current release of TPIA employs the comprehensively annotated tea plant genome as framework and incorporates with abundant well-organized transcriptomes, gene expressions (across species, tissues and stresses), orthologs and characteristic metabolites determining tea quality. It also hosts massive transcription factors, polymorphic simple sequence repeats, single nucleotide polymorphisms, correlations, manually curated functional genes and globally collected germplasm information. A variety of versatile analytic tools (e.g. JBrowse, blast, enrichment analysis, etc.) are established helping users to perform further comparative, evolutionary and functional analysis. We show a case application of TPIA that provides novel and interesting insights into the phytochemical content variation of section Thea of genus Camellia under a well-resolved phylogenetic framework. The constructed knowledgebase of tea plant will serve as a central gateway for global tea community to better understand the tea plant biology that largely benefits the whole tea industry.

De novo transcriptome sequencing of Camellia sasanqua and the analysis of major candidate genes related to floral traits.

Camellia sasanqua is one of the most famous horticultural plants in Camellia (Theaceae) due to its aesthetic appeal as landscape plant. Knowledge regarding the genetic basis of flowering time, floral aroma and color in C. sasanqua is limited, but is essential to breed new varieties with desired floral traits. Here, we described the de novo transcriptome of young leaves, flower buds and flowers of C. sasanqua. A total of 60,127 unigenes were functionally annotated based on the sequence similarity. After analysis, we found that two floral integrator genes, SOC1 and AP1, in flowering time pathway showed evidence of gene family expansion. Compared with 1-deoxy-D-xylulose-5-phosphate pathway, some genes in the mevalonate pathway were most highly expressed, suggesting that this might represent the major pathway for terpenoid biosynthesis related to floral aroma in C. sasanqua. In flavonoid biosynthesis pathway, PAL, CHI, DFR and ANS showing significantly higher expression levels in flowers and flower buds might have important role in regulation of floral color. The top five most transcription factors (TFs) families in C. sasanqua transcriptome were MYB, MIKC, C3H, FAR1 and HD-ZIP, many of which have a direct relationship with floral traits. In addition, we also identified 33,540 simple sequence repeats (SSRs) in the C. sasanqua transcriptome. Collectively, the C. sasanqua transcriptome dataset generated from this study along with the SSR markers provide a new resource for the identification of novel regulatory transcripts and will accelerate the genetic improvement of C. sasanqua breeding programs.

Mixed-reproductive strategies, competitive mating-type distribution and life cycle of fourteen black morel species.

Morchella species are well known world-round as popular and prized edible fungi due to their unique culinary flavor. Recently, several species have been successfully cultivated in China. However, their reproductive modes are still unknown, and their basic biology needs to be elucidated. Here, we use the morel genome information to investigate mating systems and life cycles of fourteen black morel species. Mating type-specific primers were developed to screen and genotype ascospores, hymenia and stipes from 223 ascocarps of the 14 species from Asia and Europe. Our data indicated that they are all heterothallic and their life cycles are predominantly haploid, but sterile haploid fruiting also exists. Ascospores in all species are mostly haploid, homokaryotic, and multinuclear, whereas aborted ascospores without any nuclei were also detected. Interestingly, we monitored divergent spatial distribution of both mating types in natural morel populations and cultivated sites, where the fertile tissue of fruiting bodies usually harbored both mating types, whereas sterile tissue of wild morels constantly had one MAT allele, while the sterile tissue of cultivated strains always exhibited both MAT alleles. Furthermore, MAT1-1-1 was detected significantly more commonly than MAT1-2-1 in natural populations, which strongly suggested a competitive advantage for MAT1-1 strains.

The Tea Tree Genome Provides Insights into Tea Flavor and Independent Evolution of Caffeine Biosynthesis.

Tea is the world's oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich (80.9%), 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeine- but not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.

The caterpillar fungus, Ophiocordyceps sinensis, genome provides insights into highland adaptation of fungal pathogenicity.

To understand the potential genetic basis of highland adaptation of fungal pathogenicity, we present here the ~116 Mb de novo assembled high-quality genome of Ophiocordyceps sinensis endemic to the Qinghai-Tibetan Plateau. Compared with other plain-dwelling fungi, we find about 3.4-fold inflation of the O. sinensis genome due to a rapid amplification of long terminal repeat retrotransposons that occurred ~38 million years ago in concert with the uplift of the plateau. We also observe massive removal of thousands of genes related to the transport process and energy metabolism. O. sinensis displays considerable lineage-specific expansion of gene families functionally enriched in the adaptability of low-temperature of cold tolerance, fungal pathogenicity and specialized host infection. We detect signals of positive selection for genes involved in peroxidase and hypoxia to enable its highland adaptation. Resequencing and analyzing 31 whole genomes of O. sinensis, representing nearly all of its geographic range, exhibits latitude-based population divergence and nature selection for population inhabitation towards higher altitudes on the Qinghai-Tibetan Plateau.

Marine Peptides as Potential Agents for the Management of Type 2 Diabetes Mellitus-A Prospect.

An increasing prevalence of diabetes is known as a main risk for human health in the last future worldwide. There is limited evidence on the potential management of type 2 diabetes mellitus using bioactive peptides from marine organisms, besides from milk and beans. We summarized here recent advances in our understanding of the regulation of glucose metabolism using bioactive peptides from natural proteins, including regulation of insulin-regulated glucose metabolism, such as protection and reparation of pancreatic ß-cells, enhancing glucose-stimulated insulin secretion and influencing the sensitivity of insulin and the signaling pathways, and inhibition of bioactive peptides to dipeptidyl peptidase IV, α-amylase and α-glucosidase activities. The present paper tried to understand the underlying mechanism involved and the structure characteristics of bioactive peptides responsible for its antidiabetic activities to prospect the utilization of rich marine organism proteins.

Reproductive Outcome of Transcervical Uterine Incision in Unicornuate Uterus.

BACKGROUND: The pregnancy outcome of the unicornuate uterus is associated with an increased risk of miscarriage, cervical incompetence, and a number of obstetric complications. However, at present, there is no accepted treatment method for women with unicornuate uterus, other than expectant measures. The aim of this study was to evaluate the reproductive outcome of transcervical uterine incision (TCUI) in patients with unicornuate uterus. METHODS: Thirty-three patients with unicornuate uterus presented to our tertiary center for infertility or miscarriage. All 33 patients underwent TCUI and were followed up for 10-52 months. The pregnancy outcomes ( first-trimester miscarriage, second-trimester miscarriage, preterm, term, intrauterine death, ongoing pregnancy, and live birth) before and after TCUI were compared by t- test. RESULTS: Among 31 patients who attempted to conceive after TCUI, twenty conceived including one termination of pregnancy, one second-trimester miscarriage, one ectopic pregnancy, five preterm deliveries, 11 term delivery, and one ongoing pregnancy. There were 16 live births in total. There was significant reduction in the first-trimester miscarriage rate (t = 4.890; P< 0.001), increase in term delivery (t = -3.288; P = 0.002), and live birth rates (t = -4.073; P< 0.001) after TCUI. CONCLUSION: TCUI appeared to improve the pregnancy outcome in women with unicornuate uterus presenting with infertility or miscarriage.

Anticancer effects of morin-7-sulphate sodium, a flavonoid derivative, in mouse melanoma cells.

BACKGROUND: Increasing evidence supports the anticancer effects of morin in vitro and in vivo. However, the role of morin-7-sulphate sodium (NaMoS), a water-soluble flavonoid derivative synthesized from morin remains unclear. The present study investigated the tumor suppression by NaMoS in mouse melanoma cells. MATERIALS AND METHODS: We synthesized the flavonoid derivative morin-7-sulphate sodium according to the method described for quercetin-sulphate derivative, and further isolated, purified and identified the compound. Cell proliferation in vitro was assessed using a CCK-8 assay. The wound healing assay was performed to evaluate cell motility, and flow cytometry was used to detect cellular apoptosis. Protein levels of vimentin, matrix metalloproteinase 9 (MMP9), phosphorylation of Akt1/2/3 (p-Akt1/2/3), extracellular signal-regulated kinase 1/2 (p-ERK1/2) and Caspase3 in B16F10 cells were detected by immunohistochemistry and Western blot. RESULTS: The results suggest that cell proliferation was markedly decreased in NaMoS-treated groups (1, 10, 25, 50, 100, 500, 1000µM) in a dose-dependent manner compared with the Control group and the IC50 was 221.67µM at 48h. NaMoS at 200µM concentration significantly inhibited the invasion and promoted apoptosis of B16F10 cells. Moreover, protein level of Caspase3 increased significantly in B16F10 cells treated by NaMoS. Immunohistochemistry and Western blot further confirmed that NaMoS decreased the expression of vimentin, MMP9, p-Akt1/2/3 and p-ERK1/2 in B16F10 cells. CONCLUSIONS: This study provides robust evidence that NaMoS, a water-soluble flavonoid, manifests anticancer properties and may act as a signal transduction inhibitor in melanoma cells.

Full transcription of the chloroplast genome in photosynthetic eukaryotes.

Prokaryotes possess a simple genome transcription system that is different from that of eukaryotes. In chloroplasts (plastids), it is believed that the prokaryotic gene transcription features govern genome transcription. However, the polycistronic operon transcription model cannot account for all the chloroplast genome (plastome) transcription products at whole-genome level, especially regarding various RNA isoforms. By systematically analyzing transcriptomes of plastids of algae and higher plants, and cyanobacteria, we find that the entire plastome is transcribed in photosynthetic green plants, and that this pattern originated from prokaryotic cyanobacteria - ancestor of the chloroplast genomes that diverged about 1 billion years ago. We propose a multiple arrangement transcription model that multiple transcription initiations and terminations combine haphazardly to accomplish the genome transcription followed by subsequent RNA processing events, which explains the full chloroplast genome transcription phenomenon and numerous functional and/or aberrant pre-RNAs. Our findings indicate a complex prokaryotic genome regulation when processing primary transcripts.