The complete chloroplast genome sequence of a cultivar of Chrysanthemum, Chrysanthemum × morifolium 'Hangbaiju' (Asteraceae).

Chrysanthemum × morifolium Ramat 1792 cultivar 'Hangbaiju', also known as 'Hangzhou White Chrysanthemum', originates from Tongxiang City, Zhejiang Province, China. It is celebrated as one of Zhejiang's 'eight flavors'. In this study, we reported the complete chloroplast genome of Chrysanthemum × morifolium cultivar 'Hangbaiju'. The genome has a circular structure of 151,110 bp containing a large single-copy region (LSC) of 82,851 bp, a small copy region (SSC) of 18,351 bp, and two inverted repeats (IR) of 24,936 and 24,972 bp in length. It comprises 128 genes: 85 protein-coding gene, 8 ribosomal RNA (rRNA) genes, and 35 transfer RNA (tRNA) genes. Phylogenetic analysis, based on complete chloroplast genomes, demonstrates that Chrysanthemum × morifolium 'Hangbaiju' shares a close genetic cluster with Chrysanthemum × morifolium 'Fubaiju' (MT1919691.1). Notably, 'Fubaiju' was introduced to Macheng, Hubei Province from Tongxiang in 1968 according to public information. The chloroplast genome data, coupled with morphological and historical records, strongly suggest that they are the same variety known by different names based on their cultivation locations.

The complete chloroplast genome sequence of Prunus salicina cultivar 'Zuili' (Rosaceae).

'Zuili' is a distinguished plum (Prunus salicina Lindley 1830) originating from Tongxiang City, Zhejiang Province, China, and a nationally recognized geographical indication product. In this study, we reported the complete chloroplast genome of P. salicina cultivar 'Zuili'. The genome has a circular structure of 157,935 bp containing a large single-copy (LSC) region of 86,133 bp, a small single-copy (SSC) region of 19,028 bp, and two inverted repeats (IRs) of 26,387 by each. It harbors 130 genes (111 unique genes), including 85 protein-coding genes (78 are unique), eight ribosomal RNA genes (four are unique), and 37 transfer genes (29 are unique). The phylogenetic analysis based on whole chloroplast genomes showed 'Zuili' was clustered with Prunus salicina cultivar 'Wuyuecui' (MW406461.1) and 'No. 2 Guofeng' (MW406472.1). This study provides valuable information that can contribute to the identification and further evolutionary analysis of Prunus salicina cultivar 'Zuili'.

Genomic and Evolutionary Characterization of Concurrent Intraductal Carcinoma and Adenocarcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is a lethal prostate cancer subtype that generally coexists with invasive high-grade prostate acinar adenocarcinoma (PAC) but exhibits distinct biological features compared with concomitant adenocarcinoma. In this study, we performed whole-exome, RNA, and DNA-methylation sequencing of IDC-P, concurrent invasive high-grade PAC lesions, and adjacent normal prostate tissues isolated from 22 radical prostatectomy specimens. Three evolutionary patterns of concurrent IDC-P and PAC were identified: early divergent, late divergent, and clonally distant. In contrast to those with a late divergent evolutionary pattern, tumors with clonally distant and early divergent evolutionary patterns showed higher genomic, epigenomic, transcriptional, and pathologic heterogeneity between IDC-P and PAC. Compared with coexisting PAC, IDC-P displayed increased expression of adverse prognosis-associated genes. Survival analysis based on an independent cohort of 505 patients with metastatic prostate cancer revealed that IDC-P carriers with lower risk International Society of Urological Pathology (ISUP) grade 1-4 adenocarcinoma displayed a castration-resistant free survival as poor as those with the highest risk ISUP grade 5 tumors that lacked concurrent IDC-P. Furthermore, IDC-P exhibited robust cell-cycle progression and androgen receptor activities, characterized by an enrichment of cellular proliferation-associated master regulators and genes involved in intratumoral androgen biosynthesis. Overall, this study provides a molecular groundwork for the aggressive behavior of IDC-P and could help identify potential strategies to improve treatment of IDC-P. SIGNIFICANCE: The genomic, transcriptomic, and epigenomic characterization of concurrent intraductal carcinoma and adenocarcinoma of the prostate deepens the biological understanding of this lethal disease and provides a genetic basis for developing targeted therapies.

The WD40 domain-containing protein Ehd5 positively regulates flowering in rice (Oryza sativa).

Heading date (flowering time), which greatly influences regional and seasonal adaptability in rice (Oryza sativa), is regulated by many genes in different photoperiod pathways. Here, we characterized a heading date gene, Early heading date 5 (Ehd5), using a modified bulked segregant analysis method. The ehd5 mutant showed late flowering under both short-day and long-day conditions, as well as reduced yield, compared to the wild type. Ehd5, which encodes a WD40 domain-containing protein, is induced by light and follows a circadian rhythm expression pattern. Transcriptome analysis revealed that Ehd5 acts upstream of the flowering genes Early heading date 1 (Ehd1), RICE FLOWERING LOCUS T 1 (RFT1), and Heading date 3a (Hd3a). Functional analysis showed that Ehd5 directly interacts with Rice outermost cell-specific gene 4 (Roc4) and Grain number, plant height, and heading date 8 (Ghd8), which might affect the formation of Ghd7-Ghd8 complexes, resulting in increased expression of Ehd1, Hd3a, and RFT1. In a nutshell, these results demonstrate that Ehd5 functions as a positive regulator of rice flowering and provide insight into the molecular mechanisms underlying heading date.

Pegylated Liposomal Doxorubicin Combined with Ifosfamide for Treating Advanced or Metastatic Soft-tissue Sarcoma: A Prospective, Single-arm Phase II Study.

PURPOSE: This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS). PATIENTS AND METHODS: Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1-5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772). RESULTS: Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7-8.9] and 20.6 (95% CI: 16.3-25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3-4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056). CONCLUSIONS: Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.

A novel 8-gene panel for prediction of early biochemical recurrence in patients with prostate cancer after radical prostatectomy.

Approximately 25% of prostate cancer (PCa) cases experience biochemical recurrence (BCR) following radical prostatectomy (RP). The patients with BCR, especially with BCR ≤2 year after RP (early BCR), are more likely to develop clinical metastasis and castration resistance. Now decision-making regarding BCR after RP relies solely on clinical parameters. We thus attempted to establish an early BCR-risk prediction model by combining a molecular signature with clinicopathological features for guiding clinical decision-making. In this study, an 8-gene signature was derived, and these eight genes were SPTBN2, LGI3, TGM3, LENG9, HAS3, SLC25A27, PCDHGA1, and ADPRHL1. The Kaplan-Meier analysis revealed a significantly prolonged BCR-free survival in the patients with low-risk scores compared to those with high-risk scores in both training and validation datasets. Harrell's concordance index and time-dependent receiver operating characteristic analysis demonstrated that this gene signature tended to outperform three commercial panels at early BCR prediction. Moreover, this signature was also proven as an independent predictor of BCR-free survival. A nomogram, incorporating the gene signature and clinicopathologic features, was constructed and excellently predicted 1-, 2- and 3-year BCR-free survival of localized PCa patients after RP. Gene set enrichment analysis, tumor immunity, and mRNA expression profiling analysis showed that the high-risk group was more prone to the immunosuppressive microenvironment and impaired DNA damage response than the low-risk group. Collectively, we successfully developed a novel 8-gene signature as a powerful predictor for early BCR after RP and created a prognostic nomogram, which may help inform the clinical management of PCa.

NLRs guard metabolism to coordinate pattern- and effector-triggered immunity.

Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) in plants enable them to respond to pathogens by activating the production of defence metabolites that orchestrate immune responses1-4. How the production of defence metabolites is promoted by immune receptors and coordinated with broad-spectrum resistance remains elusive. Here we identify the deubiquitinase PICI1 as an immunity hub for PTI and ETI in rice (Oryza sativa). PICI1 deubiquitinates and stabilizes methionine synthetases to activate methionine-mediated immunity principally through biosynthesis of the phytohormone ethylene. PICI1 is targeted for degradation by blast fungal effectors, including AvrPi9, to dampen PTI. Nucleotide-binding domain, leucine-rich-repeat-containing receptors (NLRs) in the plant immune system, such as PigmR, protect PICI1 from effector-mediated degradation to reboot the methionine-ethylene cascade. Natural variation in the PICI1 gene contributes to divergence in basal blast resistance between the rice subspecies indica and japonica. Thus, NLRs govern an arms race with effectors, using a competitive mode that hinges on a critical defence metabolic pathway to synchronize PTI with ETI and ensure broad-spectrum resistance.

Subtelomeric assembly of a multi-gene pathway for antimicrobial defense compounds in cereals.

Non-random gene organization in eukaryotes plays a significant role in genome evolution. Here, we investigate the origin of a biosynthetic gene cluster for production of defence compounds in oat-the avenacin cluster. We elucidate the structure and organisation of this 12-gene cluster, characterise the last two missing pathway steps, and reconstitute the entire pathway in tobacco by transient expression. We show that the cluster has formed de novo since the divergence of oats in a subtelomeric region of the genome that lacks homology with other grasses, and that gene order is approximately colinear with the biosynthetic pathway. We speculate that the positioning of the late pathway genes furthest away from the telomere may mitigate against a 'self-poisoning' scenario in which toxic intermediates accumulate as a result of telomeric gene deletions. Our investigations reveal a striking example of adaptive evolution underpinned by remarkable genome plasticity.

Chromosome-scale assembly and analysis of biomass crop Miscanthus lutarioriparius genome.

Miscanthus, a rhizomatous perennial plant, has great potential for bioenergy production for its high biomass and stress tolerance. We report a chromosome-scale assembly of Miscanthus lutarioriparius genome by combining Oxford Nanopore sequencing and Hi-C technologies. The 2.07-Gb assembly covers 96.64% of the genome, with contig N50 of 1.71 Mb. The centromere and telomere sequences are assembled for all 19 chromosomes and chromosome 10, respectively. Allotetraploid origin of the M. lutarioriparius is confirmed using centromeric satellite repeats. The tetraploid genome structure and several chromosomal rearrangements relative to sorghum are clearly demonstrated. Tandem duplicate genes of M. lutarioriparius are functional enriched not only in terms related to stress response, but cell wall biosynthesis. Gene families related to disease resistance, cell wall biosynthesis and metal ion transport are greatly expanded and evolved. The expansion of these families may be an important genomic basis for the enhancement of remarkable traits of M. lutarioriparius.

Dissecting a heterotic gene through GradedPool-Seq mapping informs a rice-improvement strategy.

Hybrid rice breeding for exploiting hybrid vigor, heterosis, has greatly increased grain yield. However, the heterosis-related genes associated with rice grain production remain largely unknown, partly because comprehensive mapping of heterosis-related traits is still labor-intensive and time-consuming. Here, we present a quantitative trait locus (QTL) mapping method, GradedPool-Seq, for rapidly mapping QTLs by whole-genome sequencing of graded-pool samples from F2 progeny via bulked-segregant analysis. We implement this method and map-based cloning to dissect the heterotic QTL GW3p6 from the female line. We then generate the near isogenic line NIL-FH676::GW3p6 by introgressing the GW3p6 allele from the female line Guangzhan63-4S into the male inbred line Fuhui676. The NIL-FH676::GW3p6 exhibits grain yield highly increased compared to Fuhui676. This study demonstrates that it may be possible to achieve a high level of grain production in inbred rice lines without the need to construct hybrids.

The PLATZ Transcription Factor GL6 Affects Grain Length and Number in Rice.

Grain size is one of the key determinants of grain yield. Although a number of genes that control grain size in rice (Oryza sativa) have been identified, the overall regulatory networks behind this process remain poorly understood. Here, we report the map-based cloning and functional characterization of the quantitative trait locus GL6, which encodes a plant-specific plant AT-rich sequence- and zinc-binding transcription factor that regulates rice grain length and spikelet number. GL6 positively controls grain length by promoting cell proliferation in young panicles and grains. The null gl6 mutant possesses short grains, whereas overexpression of GL6 results in large grains and decreased grain number per panicle. We demonstrate that GL6 participates in RNA polymerase III transcription machinery by interacting with RNA polymerase III subunit C53 and transcription factor class C1 to regulate the expression of genes involved in rice grain development. Our findings reveal a further player involved in the regulation of rice grain size that may be exploited in future rice breeding.

Sequence divergence between spelt and common wheat.

KEY MESSAGE: Sequence comparison between spelt and common wheat reveals that the former has huge potential in enriching the genetic variation of the latter. Genetic variation is the foundation of crop improvement. By comparing genome sequences of a Triticum spelta accession and one of its derived hexaploid lines with the sequences of the international reference genotype Chinese Spring, we detected variants more than tenfold higher than those present among common wheat (T. aestivum L) genotypes. Furthermore, different from the typical 'V-shaped' pattern of variant distribution often observed along wheat chromosomes, the sequence variation detected in this study was more evenly distributed along the 3B chromosome. This was also the case between T. spelta and the wild emmer genome. Genetic analysis showed that T. spelta and common wheat formed discrete groups. These results showed that, although it is believed that the spelt and common wheat are evolutionarily closely related and belong to the same species, a significant sequence divergence exists between them. Thus, the values of T. spelta in enriching the genetic variation of common wheat can be huge.