Diversification of FT-like genes in the PEBP family contributes to the variation of flowering traits in Sapindaceae species.

Many species of Sapindaceae, such as lychee, longan, and rambutan, provide nutritious and delicious fruit. Understanding the molecular genetic mechanisms that underlie the regulation of flowering is essential for securing flower and fruit productivity. Most endogenous and exogenous flowering cues are integrated into the florigen encoded by FLOWERING LOCUS T. However, the regulatory mechanisms of flowering remain poorly understood in Sapindaceae. Here, we identified 60 phosphatidylethanolamine-binding protein-coding genes from six Sapindaceae plants. Gene duplication events led to the emergence of two or more paralogs of the FT gene that have evolved antagonistic functions in Sapindaceae. Among them, the FT1-like genes are functionally conserved and promote flowering, while the FT2-like genes likely serve as repressors that delay flowering. Importantly, we show here that the natural variation at nucleotide position - 1437 of the lychee FT1 promoter determined the binding affinity of the SVP protein (LcSVP9), which was a negative regulator of flowering, resulting in the differential expression of LcFT1, which in turn affected flowering time in lychee. This finding provides a potential molecular marker for breeding lychee. Taken together, our results reveal some crucial aspects of FT gene family genetics that underlie the regulation of flowering in Sapindaceae.

SapBase: A central portal for functional and comparative genomics of Sapindaceae species.

The Sapindaceae family, encompassing a wide range of plant forms such as herbs, vines, shrubs, and trees, is widely distributed across tropical and subtropical regions. This family includes economically important crops like litchi, longan, rambutan, and ackee. With the wide application of genomic technologies in recent years, several Sapindaceae plant genomes have been decoded, leading to an accumulation of substantial omics data in this field. This surge in data highlights the pressing need for a unified genomic data center capable of storing, sharing, and analyzing these data. Here, we introduced SapBase, that is, the Sapindaceae Genome Database. SapBase houses seven published plant genomes alongside their corresponding gene structure and functional annotations, small RNA annotations, gene expression profiles, gene pathways, and synteny block information. It offers user-friendly features for gene information mining, co-expression analysis, and inter-species comparative genomic analysis. Furthermore, we showcased SapBase's extensive capacities through a detailed bioinformatic analysis of a MYB gene in litchi. Thus, SapBase could serve as an integrative genomic resource and analysis platform for the scientific exploration of Sapinaceae species and their comparative studies with other plants.

The role of hydrogen-rich water in delaying the pulp breakdown of litchi fruit during postharvest storage.

Previous studies have indicated that hydrogen-rich water (HW) treatment can delay fruit ripening and senescence. However, little is known about the HW-delaying pulp breakdown. In this study, eight physiological characteristics revealed that HW treatment delayed both pericarp browning and pulp breakdown of litchi fruit. To gain a comprehensive understanding of the changes in litchi pulp, a combination of multiple metabolomics and gene expression analyses was conducted, assessing 67 primary metabolites, 103 volatiles, 31 amino acids, and 13 crucial metabolite-related genes. Results showed that HW treatment promoted starch degradation, decelerated cell wall degradation and glycolysis, and maintained the flavor and quality of litchi fruit. Furthermore, HW treatment stimulated the production of volatile alcohols, aldehydes, ketones, olefins, and amino acids, which might play a vital role in HW-delaying pulp breakdown. This study sheds light on the mechanism by which HW delayed pulp breakdown by investigating small molecule metabolites and metabolic pathways.

Genomic identification and expression analysis of acid invertase (AINV) gene family in Dendrobium officinale Kimura et Migo.

BACKGROUND: Dendrobium officinale Kimura et Migo, a renowned traditional Chinese orchid herb esteemed for its significant horticultural and medicinal value, thrives in adverse habitats and contends with various abiotic or biotic stresses. Acid invertases (AINV) are widely considered enzymes involved in regulating sucrose metabolism and have been revealed to participate in plant responses to environmental stress. Although members of AINV gene family have been identified and characterized in multiple plant genomes, detailed information regarding this gene family and its expression patterns remains unknown in D. officinale, despite their significance in polysaccharide biosynthesis. RESULTS: This study systematically analyzed the D. officinale genome and identified four DoAINV genes, which were classified into two subfamilies based on subcellular prediction and phylogenetic analysis. Comparison of gene structures and conserved motifs in DoAINV genes indicated a high-level conservation during their evolution history. The conserved amino acids and domains of DoAINV proteins were identified as pivotal for their functional roles. Additionally, cis-elements associated with responses to abiotic and biotic stress were found to be the most prevalent motif in all DoAINV genes, indicating their responsiveness to stress. Furthermore, bioinformatics analysis of transcriptome data, validated by quantitative real-time reverse transcription PCR (qRT-PCR), revealed distinct organ-specific expression patterns of DoAINV genes across various tissues and in response to abiotic stress. Examination of soluble sugar content and interaction networks provided insights into stress release and sucrose metabolism. CONCLUSIONS: DoAINV genes are implicated in various activities including growth and development, stress response, and polysaccharide biosynthesis. These findings provide valuable insights into the AINV gene amily of D. officinale and will aid in further elucidating the functions of DoAINV genes.

MicroRNA482/2118 is lineage-specifically involved in gibberellin signalling via the regulation of GID1 expression by targeting noncoding PHAS genes and subsequently instigated phasiRNAs.

MicroRNA482/2118 (miR482/2118) is a 22-nt miRNA superfamily, with conserved functions in disease resistance and plant development. It usually instigates the production of phased small interfering RNAs (phasiRNAs) from its targets to expand or reinforce its silencing effect. Using a new high-quality reference genome sequence and comprehensive small RNA profiling, we characterized a newly evolved regulatory pathway of miR482/2118 in litchi. In this pathway, miR482/2118 cleaved a novel noncoding trans-acting gene (LcTASL1) and triggered phasiRNAs to regulate the expression of gibberellin (GA) receptor gene GIBBERELLIN INSENSITIVE DWARF1 (GID1) in trans; another trans-acting gene LcTASL2, targeted by LcTASL1-derived phasiRNAs, produced phasiRNAs as well to target LcGID1 to reinforce the silencing effect of LcTASL1. We found this miR482/2118-TASL-GID1 pathway was likely involved in fruit development, especially the seed development in litchi. In vivo construction of the miR482a-TASL-GID1 pathway in Arabidopsis could lead to defects in flower and silique development, analogous to the phenotype of gid1 mutants. Finally, we found that a GA-responsive transcription factor, LcGAMYB33, could regulate LcMIR482/2118 as a feedback mechanism of the sRNA-silencing pathway. Our results deciphered a lineage-specifically evolved regulatory module of miR482/2118, demonstrating the high dynamics of miR482/2118 function in plants.

Multi-omics comparison of malignant and normal uveal melanocytes reveals molecular features of uveal melanoma.

Uveal melanoma (UM) is a rare cancer resulting from the transformation of melanocytes in the uveal tract. Integrative analysis has identified four molecular and clinical subsets of UM. To improve our molecular understanding of UM, we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis using Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM.

Cytological observation and RNA-seq analysis reveal novel miRNAs high expression associated with the pollen fertility of neo-tetraploid rice.

BACKGROUND: Neo-tetraploid rice lines exhibit high fertility and strong heterosis and harbor novel specific alleles, which are useful germplasm for polyploid rice breeding. However, the mechanism of the fertility associated with miRNAs remains unknown. In this study, a neo-tetraploid rice line, termed Huaduo21 (H21), was used. Cytological observation and RNA-sequencing were employed to identify the fertility-related miRNAs in neo-tetraploid rice. RESULTS: H21 showed high pollen fertility (88.08%), a lower percentage of the pollen mother cell (PMC) abnormalities, and lower abnormalities during double fertilization and embryogenesis compared with autotetraploid rice. A total of 166 non-additive miRNAs and 3108 non-additive genes were detected between H21 and its parents. GO and KEGG analysis of non-additive genes revealed significant enrichments in the DNA replication, Chromosome and associated proteins, and Replication and repair pathways. Comprehensive multi-omics analysis identified 32 pairs of miRNA/target that were associated with the fertility in H21. Of these, osa-miR408-3p and osa-miR528-5p displayed high expression patterns, targeted the phytocyanin genes, and were associated with high pollen fertility. Suppression of osa-miR528-5p in Huaduo1 resulted in a low seed set and a decrease in the number of grains. Moreover, transgenic analysis implied that osa-MIR397b-p3, osa-miR5492, and osa-MIR5495-p5 might participate in the fertility of H21. CONCLUSION: Taken together, the regulation network of fertility-related miRNAs-targets pairs might contribute to the high seed setting in neo-tetraploid rice. These findings enhance our understanding of the regulatory mechanisms of pollen fertility associated with miRNAs in neo-tetraploid rice.

TBtools-II: A "one for all, all for one" bioinformatics platform for biological big-data mining.

Since the official release of the stand-alone bioinformatics toolkit TBtools in 2020, its superior functionality in data analysis has been demonstrated by its widespread adoption by many thousands of users and references in more than 5000 academic articles. Now, TBtools is a commonly used tool in biological laboratories. Over the past 3 years, thanks to invaluable feedback and suggestions from numerous users, we have optimized and expanded the functionality of the toolkit, leading to the development of an upgraded version-TBtools-II. In this upgrade, we have incorporated over 100 new features, such as those for comparative genomics analysis, phylogenetic analysis, and data visualization. Meanwhile, to better meet the increasing needs of personalized data analysis, we have launched the plugin mode, which enables users to develop their own plugins and manage their selection, installation, and removal according to individual needs. To date, the plugin store has amassed over 50 plugins, with more than half of them being independently developed and contributed by TBtools users. These plugins offer a range of data analysis options including co-expression network analysis, single-cell data analysis, and bulked segregant analysis sequencing data analysis. Overall, TBtools is now transforming from a stand-alone software to a comprehensive bioinformatics platform of a vibrant and cooperative community in which users are also developers and contributors. By promoting the theme "one for all, all for one", we believe that TBtools-II will greatly benefit more biological researchers in this big-data era.

Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.

Gain-of-function mutations in NOTCH1 are among the most frequent genetic alterations in T-cell acute lymphoblastic leukemia (T-ALL), highlighting the Notch signaling pathway as a promising therapeutic target for personalized medicine. Yet, a major limitation for long-term success of targeted therapy is relapse due to tumor heterogeneity or acquired resistance. Thus, we performed a genome-wide CRISPR-Cas9 screen to identify prospective resistance mechanisms to pharmacological NOTCH inhibitors and novel targeted combination therapies to efficiently combat T-ALL. Mutational loss of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) causes resistance to Notch inhibition. PIK3R1 deficiency leads to increased PI3K/AKT signaling, which regulates cell cycle and the spliceosome machinery, both at the transcriptional and posttranslational level. Moreover, several therapeutic combinations have been identified, in which simultaneous targeting of the cyclin-dependent kinases 4 and 6 (CDK4/6) and NOTCH proved to be the most efficacious in T-ALL xenotransplantation models.

Electrochemical Restoration of Battery Materials Guided by Synchrotron Radiation Technology for Sustainable Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) have been ubiquitous in modern society, especially in the fields of electronic devices, electric vehicles and grid storage, while raising concerns about a tremendous number of spent batteries in the next five to ten years. As environmental awareness and resource security is gaining increasingly extensive attention, how to effectively deal with spent LIBs has become a challenging issue academically and industrially. Accordingly, the development of battery recycling has surfaced as a highly researched topic in the battery community. Recently, the structural and electrochemical restoration of recycled electrode materials have been proposed as a non-destructive method to save more energy and chemical agents compared with mature metallurgical methods. Such a refurbishment process of electrode materials is also regarded as a reverse process of their degradation in the working condition. Notably, synchrotron radiation technology, which is previously applied to diagnose battery degrade, has started to play major roles in gaining more insight into the structural restoration of electrode materials. Here, the contribution of synchrotron radiation technology to reveal the underlying degradation and regeneration mechanisms of LIBs cathodes is highlighted, providing a theoretical basis and guidance for the direct recycling and reuse of degraded cathodes.

Whole-genome doubling drives oncogenic loss of chromatin segregation.

Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies1-8. However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotypes are currently unknown. Here we show that in p53-deficient cells, WGD induces loss of chromatin segregation (LCS). This event is characterized by reduced segregation between short and long chromosomes, A and B subcompartments and adjacent chromatin domains. LCS is driven by the downregulation of CTCF and H3K9me3 in cells that bypassed activation of the tetraploid checkpoint. Longitudinal analyses revealed that LCS primes genomic regions for subcompartment repositioning in WGD cells. This results in chromatin and epigenetic changes associated with oncogene activation in tumours ensuing from WGD cells. Notably, subcompartment repositioning events were largely independent of chromosomal alterations, which indicates that these were complementary mechanisms contributing to tumour development and progression. Overall, LCS initiates chromatin conformation changes that ultimately result in oncogenic epigenetic and transcriptional modifications, which suggests that chromatin evolution is a hallmark of WGD-driven cancer.

Taxon-specific, phased siRNAs underlie a speciation locus in monkeyflowers.

Taxon-specific small RNA loci are widespread in eukaryotic genomes, yet their role in lineage-specific adaptation, phenotypic diversification, and speciation is poorly understood. Here, we report that a speciation locus in monkeyflowers (Mimulus), YELLOW UPPER (YUP), contains an inverted repeat region that produces small interfering RNAs (siRNAs) in a phased pattern. Although the inverted repeat is derived from a partial duplication of a protein-coding gene that is not involved in flower pigmentation, one of the siRNAs targets and represses a master regulator of floral carotenoid pigmentation. YUP emerged with two protein-coding genes that control other aspects of flower coloration as a "superlocus" in a subclade of Mimulus and has contributed to subsequent phenotypic diversification and pollinator-mediated speciation in the descendant species.

Dendritic cells direct circadian anti-tumour immune responses.

The process of cancer immunosurveillance is a mechanism of tumour suppression that can protect the host from cancer development throughout its lifetime1,2. However, it is unknown whether the effectiveness of cancer immunosurveillance fluctuates over a single day. Here we demonstrate that the initial time of day of tumour engraftment dictates the ensuing tumour size across mouse cancer models. Using immunodeficient mice as well as mice lacking lineage-specific circadian functions, we show that dendritic cells (DCs) and CD8+ T cells exert circadian anti-tumour functions that control melanoma volume. Specifically, we find that rhythmic trafficking of DCs to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8+ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80. As a consequence, cancer immunotherapy is more effective when synchronized with DC functions, shows circadian outcomes in mice and suggests similar effects in humans. These data demonstrate that the circadian rhythms of anti-tumour immune components are not only critical for controlling tumour size but can also be of therapeutic relevance.

The 3D architecture of the pepper genome and its relationship to function and evolution.

The organization of chromatin into self-interacting domains is universal among eukaryotic genomes, though how and why they form varies considerably. Here we report a chromosome-scale reference genome assembly of pepper (Capsicum annuum) and explore its 3D organization through integrating high-resolution Hi-C maps with epigenomic, transcriptomic, and genetic variation data. Chromatin folding domains in pepper are as prominent as TADs in mammals but exhibit unique characteristics. They tend to coincide with heterochromatic regions enriched with retrotransposons and are frequently embedded in loops, which may correlate with transcription factories. Their boundaries are hotspots for chromosome rearrangements but are otherwise depleted for genetic variation. While chromatin conformation broadly affects transcription variance, it does not predict differential gene expression between tissues. Our results suggest that pepper genome organization is explained by a model of heterochromatin-driven folding promoted by transcription factories and that such spatial architecture is under structural and functional constraints.

Clinical observation of posterior scleral reinforcement in the treatment of progressive high myopia in Chinese children: a retrospective study.

OBJECTIVE: To observe the efficacy and safety of posterior sclera reinforcement over time. METHODS: This retrospective single-arm cohort study included children with high myopia who underwent the modified Snyder-Thompson type posterior sclera reinforcement surgery from 03/2015 to 08/2018 at Fuzhou Children's Hospital of Fujian Medical University. Axial length (AL), corneal radius of curvature (CRC), AL/CRC, refractive error, and best-corrected visual acuity (BCVA) were observed from 1 year before the operation to 2 years after. RESULTS: Nineteen children (33 eyes) with high myopia were included. The patients were 4.9 ± 2.7 (range, 2-10) years of age (three patients were 10 years old, all others were ≤ 7 years old). AL increased from 1 year before surgery to 2 years after surgery (from 25.31 ± 1.59 to 26.76 ± 1.52, P < 0.001). The refractive error was smaller 1 year before surgery than at the other timepoints (all P < 0.05). BCVA improved over time (P < 0.001). Changes over time were also observed in horizontal CRC (hCRC), AL/hCRC, AL/vertical CRC (vCRC), and AL/CRC (all P < 0.001), but not in vCRC (P = 0.304). The increase of AL at 2 years after surgery was smaller than at 1 year before surgery and 1 year after surgery (both P < 0.001). The increase of AL/CRC at 2 years after surgery was smaller than at 1 year before surgery (0.04 ± 0.04 vs. 0.07 ± 0.04; P = 0.008). CONCLUSION: In the short term, posterior scleral reinforcement surgery can delay the increase of AL of progressive high myopia.

Tcf1 is essential for initiation of oncogenic Notch1-driven chromatin topology in T-ALL.

NOTCH1 is a well-established lineage specifier for T cells and among the most frequently mutated genes throughout all subclasses of T cell acute lymphoblastic leukemia (T-ALL). How oncogenic NOTCH1 signaling launches a leukemia-prone chromatin landscape during T-ALL initiation is unknown. Here we demonstrate an essential role for the high-mobility-group transcription factor Tcf1 in orchestrating chromatin accessibility and topology, allowing aberrant Notch1 signaling to convey its oncogenic function. Although essential, Tcf1 is not sufficient to initiate leukemia. The formation of a leukemia-prone epigenetic landscape at the distal Notch1-regulated Myc enhancer, which is fundamental to this disease, is Tcf1-dependent and occurs within the earliest progenitor stage even before cells adopt a T lymphocyte or leukemic fate. Moreover, we discovered a unique evolutionarily conserved Tcf1-regulated enhancer element in the distal Myc-enhancer, which is important for the transition of preleukemic cells to full-blown disease.

MicroRNA482/2118, a miRNA superfamily essential for both disease resistance and plant development.

MicroRNAs (miRNAs) are a class of 21-24 nucleotides (nt) noncoding small RNAs ubiquitously distributed across the plant kingdom. miR482/2118, one of the conserved miRNA superfamilies originating from gymnosperms, has divergent main functions in core-angiosperms. It mainly regulates NUCLEOTIDE BINDING SITE-LEUCINE-RICH REPEAT (NBS-LRR) genes in eudicots, functioning as an essential component in plant disease resistance; in contrast, it predominantly targets numerous long noncoding RNAs (lncRNAs) in monocot grasses, which are vital for plant reproduction. Usually, miR482/2118 is 22-nt in length, which can trigger the production of phased small interfering RNAs (phasiRNAs) after directed cleavage. PhasiRNAs instigated from target genes of miR482/2118 enhance their roles in corresponding biological processes by cis-regulation on cognate genes and expands their function to other pathways via trans activity on different genes. This review summarizes the origin, biogenesis, conservation, and evolutionary characteristics of the miR482/2118 superfamily and delineates its diverse functions in disease resistance, plant development, stress responses, etc.

Relationships between physical characteristics and biomechanics of lower extremity during the squat.

BACKGROUND/OBJECTIVE: There is a lack of information about relationship between physical characteristics and biomechanics of the lower extremity during the squat. Additionally, studies did not examine sex-related differences. The purpose of this study was to investigate relationships between physical characteristics and biomechanics of the lower extremity during the squat, and to determine if any sex differences are present. METHODS: Fifty three participants recruited (21.82 ± 2.3 years; 75.56 ± 14.98 kg; 171.57 ± 8.38 cm) performed three squats with 75% of one repetition maximum. Femur to tibia length ratio, hip and ankle joints' flexibilities, and relative muscular strength were measured and used as physical characteristics. Net joint torques (NJT) and flexion angles of the lower extremity were extracted as dependent variables. Multiple regression (stepwise) analysis was conducted to examine the relationships with physical characteristics being factors. Pearson correlation coefficients were calculated to determine intercorrelations among the dependent variables. RESULTS: Relative muscular strength was related to hip NJT and knee flexion angle, and hip flexibility was related to ankle dorsiflexion. Hip and knee NJT showed moderate correlations with the corresponding flexion angles (r = 0.48-0.53; p < .01). Ankle dorsiflexion angle showed weak to moderate correlations with hip NJT and hip flexion angle (r = -0.36-0.50; p < .01) and a moderate correlation with knee NJT. No significant sex difference was observed (r = 0.52; p < .05). CONCLUSION: Biomechanics of the lower extremity has been shown to correlate more with relative muscular strength and joint flexibility than with leg length ratio.

The GRAS gene family and its roles in seed development in litchi (Litchi chinensis Sonn).

BACKGROUND: The GRAS gene family plays crucial roles in multiple biological processes of plant growth, including seed development, which is related to seedless traits of litchi (Litchi chinensis Sonn.). However, it hasn't been fully identified and analyzed in litchi, an economic fruit tree cultivated in subtropical regions. RESULTS: In this study, 48 LcGRAS proteins were identified and termed according to their chromosomal location. LcGRAS proteins can be categorized into 14 subfamilies through phylogenetic analysis. Gene structure and conserved domain analysis revealed that different subfamilies harbored various motif patterns, suggesting their functional diversity. Synteny analysis revealed that the expansion of the GRAS family in litchi may be driven by their tandem and segmental duplication. After comprehensively analysing degradome data, we found that four LcGRAS genes belong to HAM subfamily were regulated via miR171-mediated degradation. The various expression patterns of LcGRAS genes in different tissues uncovered they were involved in different biological processes. Moreover, the different temporal expression profiles of LcGRAS genes between abortive and bold seed indicated some of them were involved in maintaining the normal development of the seed. CONCLUSION: Our study provides comprehensive analyses on GRAS family members in litchi, insight into a better understanding of the roles of GRAS in litchi development, and lays the foundation for further investigations on litchi seed development.