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1.
Nat Immunol ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38942990

ABSTRACT

The immunological mechanisms underlying chronic colitis are poorly understood. T follicular helper (TFH) cells are critical in helping B cells during germinal center reactions. In a T cell transfer colitis model, a lymphoid structure composed of mature dendritic cells (DCs) and TFH cells was found within T cell zones of colonic lymphoid follicles. TFH cells were required for mature DC accumulation, the formation of DC-T cell clusters and colitis development. Moreover, DCs promoted TFH cell differentiation, contributing to colitis development. A lineage-tracing analysis showed that, following migration to the lamina propria, TFH cells transdifferentiated into long-lived pathogenic TH1 cells, promoting colitis development. Our findings have therefore demonstrated the reciprocal regulation of TFH cells and DCs in colonic lymphoid follicles, which is critical in chronic colitis pathogenesis.

2.
Cell ; 169(7): 1342-1356.e16, 2017 Jun 15.
Article in English | MEDLINE | ID: mdl-28622514

ABSTRACT

Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory. Specific subsets such as exhausted CD8+ T cells and Tregs are preferentially enriched and potentially clonally expanded in hepatocellular carcinoma (HCC), and we identified signature genes for each subset. One of the genes, layilin, is upregulated on activated CD8+ T cells and Tregs and represses the CD8+ T cell functions in vitro. This compendium of transcriptome data provides valuable insights and a rich resource for understanding the immune landscape in cancers.


Subject(s)
Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Sequence Analysis, RNA , Single-Cell Analysis , T-Lymphocyte Subsets/immunology , CD8-Positive T-Lymphocytes/immunology , Humans , Lymphocytes, Tumor-Infiltrating/immunology , T-Lymphocytes, Regulatory/immunology , Tumor Microenvironment
3.
Proc Natl Acad Sci U S A ; 120(48): e2314408120, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37983506

ABSTRACT

Sodium-sulfur (Na-S) batteries are attracting intensive attention due to the merits like high energy and low cost, while the poor stability of sulfur cathode limits the further development. Here, we report a chemical and spatial dual-confinement approach to improve the stability of Na-S batteries. It refers to covalently bond sulfur to carbon at forms of C-S/N-C=S bonds with high strength for locking sulfur. Meanwhile, sulfur is examined to be S1-S2 small species produced by thermally cutting S8 large molecules followed by sealing in the confined pores of carbon materials. Hence, the sulfur cathode achieves a good stability of maintaining a high-capacity retention of 97.64% after 1000 cycles. Experimental and theoretical results show that Na+ is hosted via a coordination structure (N···Na···S) without breaking the C-S bond, thus impeding the formation and dissolution of sodium polysulfide to ensure a good cycling stability. This work provides a promising method for addressing the S-triggered stability problem of Na-S batteries and other S-based batteries.

4.
J Cell Mol Med ; 28(3): e18112, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38263865

ABSTRACT

The energy metabolic rearrangement of triple-negative breast cancer (TNBC) from oxidative phosphorylation to aerobic glycolysis is a significant biological feature and can promote the malignant progression. However, there is little knowledge about the functional mechanisms of methyltransferase-like protein 14 (METTL14) mediated contributes to TNBC malignant progression. Our study found that METTL14 expression was significantly upregulated in TNBC tissues and cell lines. Silencing METTL14 significantly inhibited TNBC cell growth and invasion in vitro, as well as suppressed tumour growth. Mechanically, METTL14 was first found to activate miR-29c-3p through m6A and regulate tripartite motif containing 9 (TRIM9) to promote ubiquitination of pyruvate kinase isoform M2 (PKM2) and lead to its transition from tetramer to dimer, resulting in glucose metabolic reprogramming from oxidative phosphorylation to aerobic glycolysis to promote the progress of TNBC. Taken together, these findings reveal important roles of METTL14 in TNBC tumorigenesis and energy metabolism, which might represent a novel potential therapeutic target for TNBC.


Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , Humans , MicroRNAs/metabolism , Triple Negative Breast Neoplasms/genetics , Cell Line, Tumor , Cell Proliferation , Glycolysis , Gene Expression Regulation, Neoplastic , Cell Movement , Methyltransferases/metabolism
5.
Plant J ; 116(2): 446-466, 2023 10.
Article in English | MEDLINE | ID: mdl-37428465

ABSTRACT

Although the South African Cape flora is one of the most remarkable biodiversity hotspots, its high diversity has not been associated with polyploidy. Here, we report the chromosome-scale genome assembly of an ephemeral cruciferous species Heliophila variabilis (~334 Mb, n = 11) adapted to South African semiarid biomes. Two pairs of differently fractionated subgenomes suggest an allo-octoploid origin of the genome at least 12 million years ago. The ancestral octoploid Heliophila genome (2n = 8x = ~60) has probably originated through hybridization between two allotetraploids (2n = 4x = ~30) formed by distant, intertribal, hybridization. Rediploidization of the ancestral genome was marked by extensive reorganization of parental subgenomes, genome downsizing, and speciation events in the genus Heliophila. We found evidence for loss-of-function changes in genes associated with leaf development and early flowering, and over-retention and sub/neofunctionalization of genes involved in pathogen response and chemical defense. The genomic resources of H. variabilis will help elucidate the role of polyploidization and genome diploidization in plant adaptation to hot arid environments and origin of the Cape flora. The sequenced H. variabilis represents the first chromosome-scale genome assembly of a meso-octoploid representative of the mustard family.


Subject(s)
Brassicaceae , Genome, Plant , Genome, Plant/genetics , Brassicaceae/genetics , Polyploidy , Plants/genetics , Biodiversity
6.
Article in English | MEDLINE | ID: mdl-38843782

ABSTRACT

BACKGROUND: Diabetes is a significant risk factor for cognitive impairment. Therefore early identification of cognitive impairment in diabetic patients is particularly important. The aim of this study was to assess the relationship between Cardiometabolic index(CMI) and cognitive function in a diabetic population. METHODS: A cross-sectional study was conducted by collecting information from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Multiple linear regression models were used to investigate the correlation between CMI and low cognitive function in a diabetic population. Threshold effects analysis and fitted smoothing curves were used to describe the nonlinear links. Interaction tests and subgroup analyses were also performed. RESULTS: A total of 1050 people participated in this study, including 561 men and 489 women. In the fully corrected model, CMI was positively associated with low cognitive performance as assessed by CERAD W-L, AFT and DSST [OR=1.37 (1.14, 1.72),P=0.0074], [OR=1.21 (1.04, 1.51),P=0.0126] and [OR=1.27 (1.08, 1.63),P= 0.0253]. Our study found that diabetic patients with higher CMI were at greater risk of developing low cognitive function. The effect of the subgroups on the positive association of CMI with cognitive impairment was not significant. A non-linear association between low cognitive performance and CMI was determined by CERAD W-L, AFT and DSST (log likelihood ratio < 0.05). In addition our also study found that CMI was a better predictor of cognitive impairment in diabetes than WWI. CONCLUSION: Increased CMI is associated with an increased risk of cognitive impairment in people with diabetes.CMI can be used as a new anthropometric measure for predicting cognitive impairment in diabetes.

7.
Nature ; 564(7735): 268-272, 2018 12.
Article in English | MEDLINE | ID: mdl-30479382

ABSTRACT

T cells are key elements of cancer immunotherapy1 but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8+ effector and 'exhausted' T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Treg cell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+ TH1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors -the GZMK+ effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13+BHLHE40+ TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like cells and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.


Subject(s)
CD4-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/cytology , Cell Lineage , Cell Movement , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Adaptor Proteins, Signal Transducing , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Carrier Proteins/metabolism , Cell Tracking , Cells, Cultured , Clone Cells/cytology , Clone Cells/immunology , Humans , Th1 Cells/cytology , Th1 Cells/immunology
8.
Article in English | MEDLINE | ID: mdl-38946427

ABSTRACT

The glucose-fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein (Gfo/Idh/MocA) family includes a variety of oxidoreductases with a wide range of substrates that utilize NAD or NADP as redox cofactor. Human contains two members of this family, namely glucose-fructose oxidoreductase domain-containing protein 1 and 2 (GFOD1 and GFOD2). While GFOD1 exhibits low tissue specificity, it is notably expressed in the brain, potentially linked to psychiatric disorders and severe diseases. Nevertheless, the specific function, cofactor preference, and enzymatic activity of GFOD1 remain largely unknown. In this work, we find that GFOD1 does not bind to either NAD or NADP. Crystal structure analysis unveils that GFOD1 exists as a typical homodimer resembling other family members, but lacks essential residues required for cofactor binding, suggesting that it may function as a pseudoenzyme. Exploration of GFOD1-interacting partners in proteomic database identifies NK-κB inhibitor-interacting Ras-like 2 (NKIRAS2) as one potential candidate. Co-immunoprecipitation (co-IP) analysis indicates that GFOD1 interacts with both GTP- and GDP-bound forms of NKIRAS2. The predicted structural model of the GFOD1-NKIRAS2 complex is validated in cells using point mutants and shows that GFOD1 selectively recognizes the interswitch region of NKIRAS2. These findings reveal the distinct structural properties of GFOD1 and shed light on its potential functional role in cellular processes.

9.
Phytother Res ; 38(6): 2892-2930, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38577989

ABSTRACT

Atherosclerotic cardiovascular disease remains a preeminent cause of morbidity and mortality globally. The onset of atherosclerosis underpins the emergence of ischemic cardiovascular diseases, including coronary heart disease (CHD). Its pathogenesis entails multiple factors such as inflammation, oxidative stress, apoptosis, vascular endothelial damage, foam cell formation, and platelet activation. Furthermore, it triggers the activation of diverse signaling pathways including Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), NF-E2-related factor 2/antioxidant response element (Nrf2/ARE), the Notch signaling pathway, peroxisome proliferator-activated receptor (PPAR), nucleotide oligo-structural domain-like receptor thermoprotein structural domain-associated protein 3 (NLRP3), silencing information regulator 2-associated enzyme 1 (Sirt1), nuclear transcription factor-κB (NF-κB), Circular RNA (Circ RNA), MicroRNA (mi RNA), Transforming growth factor-ß (TGF-ß), and Janus kinase-signal transducer and activator of transcription (JAK/STAT). Over recent decades, therapeutic approaches for atherosclerosis have been dominated by the utilization of high-intensity statins to reduce lipid levels, despite significant adverse effects. Consequently, there is a growing interest in the development of safer and more efficacious drugs and therapeutic modalities. Traditional Chinese medicine (TCM) offers a vital strategy for the prevention and treatment of cardiovascular diseases. Numerous studies have detailed the mechanisms through which TCM active ingredients modulate signaling molecules and influence the atherosclerotic process. This article reviews the signaling pathways implicated in the pathogenesis of atherosclerosis and the advancements in research on TCM extracts for prevention and treatment, drawing on original articles from various databases including Google Scholar, Medline, CNKI, Scopus, and Pubmed. The objective is to furnish a reference for the clinical management of cardiovascular diseases.


Subject(s)
Atherosclerosis , Drugs, Chinese Herbal , Signal Transduction , Atherosclerosis/drug therapy , Humans , Signal Transduction/drug effects , Drugs, Chinese Herbal/pharmacology , Animals , Oxidative Stress/drug effects
10.
Chem Biodivers ; : e202400817, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775105

ABSTRACT

Four undescribed sesquiterpenes, atramacrolodes A-D (1-4), along with six known compounds 5-10 were isolated from the rhizome of Atractylodes macrocephala. Compound 3 possessed a new skeleton based on an unprecedented carton-carton connection. Their structures were determined by UV, IR, HRESIMS, NMR spectra, 13C NMR calculation with DP4+ analysis, and the comparison of experimental and calculated ECD spectra. Compounds 5 and 8 showed protective effects against paracetamol-induced liver cell injury.

11.
Compr Rev Food Sci Food Saf ; 23(1): e13285, 2024 01.
Article in English | MEDLINE | ID: mdl-38284579

ABSTRACT

The use of biomolecules, such as proteins, polysaccharides, saponins, and phospholipids, instead of synthetic emulsifiers in food emulsion creation has generated significant interest among food scientists due to their advantages of being nontoxic, harmless, edible, and biocompatible. However, using a single biomolecule may not always meet practical needs for food emulsion applications. Therefore, biomolecules often require modification to achieve ideal interfacial properties. Among them, noncovalent interactions between biomolecules represent a promising physical modification method to modulate their interfacial properties without causing the health risks associated with forming new chemical bonds. Electrostatic interactions, hydrophobic interactions, and hydrogen bonding are examples of noncovalent interactions that facilitate biomolecules' effective applications in food emulsions. These interactions positively impact the physical stability, oxidative stability, digestibility, delivery characteristics, response sensitivity, and printability of biomolecule-based food emulsions. Nevertheless, using noncovalent interactions between biomolecules to facilitate their application in food emulsions still has limitations that need further improvement. This review introduced common biomolecule emulsifiers, the promotion effect of noncovalent interactions between biomolecules on the construction of emulsions with different biomolecules, their positive impact on the performance of emulsions, as well as their limitations and prospects in the construction of biomolecule-based emulsions. In conclusion, the future design and development of food emulsions will increasingly rely on noncovalent interactions between biomolecules. However, further improvements are necessary to fully exploit these interactions for constructing biomolecule-based emulsions.


Subject(s)
Emulsifying Agents , Proteins , Emulsions/chemistry , Emulsifying Agents/chemistry , Proteins/chemistry , Food
12.
BMC Genomics ; 24(1): 174, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-37020189

ABSTRACT

BACKGROUND: Eutrema salsugineum (2n = 14), a halophyte in the family Brassicaceae, is an attractive model to study abiotic stress tolerance in plants. Two versions of E. salsugineum genomes that previously reported were based on relatively short reads; thus, the repetitive regions were difficult to characterize. RESULTS: We report the sequencing and assembly of the E. salsugineum (Shandong accession) genome using long-read sequencing and chromosome conformation capture data. We generated Oxford Nanopore long reads at high depth (> 60X) of genome coverage with additional short reads for error correction. The new assembly has a total size of 295.5 Mb with 52.8% repetitive sequences, and the karyotype of E. salsugineum is consistent with the ancestral translocation Proto-Calepineae Karyotype structure in both order and orientation. Compared with previous assemblies, this assembly has higher contiguity, especially in the centromere region. Based on this new assembly, we predicted 25,399 protein-coding genes and identified the positively selected genes associated with salt and drought stress responses. CONCLUSION: The new genome assembly will provide a valuable resource for future genomic studies and facilitate comparative genomic analysis with other plants.


Subject(s)
Brassicaceae , Extremophiles , Brassicaceae/genetics , Genomics , Stress, Physiological , Chromosomes
13.
J Biochem Mol Toxicol ; 37(4): e23298, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36727417

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious Gram-positive pathogen known to cause severe diseases such as endocarditis, food poisoning, pneumonia, osteomyelitis, and septicemia. MRSA is a major public health issue. Among these, osteomyelitis is inflammation of the bone caused by the invasion of the bacterial pathogen in the bones. Its prominent symptoms include fever, pain, and redness of bones. In the case of children, it affects the long bones of arms and legs, whereas in the case of adults it affects the hip, feet, and spine. Bacterial osteomyelitis can trigger pathological remodeling of bones and hence causes substantial morbidity and mortality. The present study aims to evaluate the isoflavone genistein's (5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one,4',5,7 trihydroxyisoflavone) antimicrobial and anti-inflammatory effects against osteomyelitis induced by MRSA in male Wistar rats. Classification of the animals was into the following: sham (Group I), osteomyelitis (Group II, control), genistein (25 mg/kg body weight, Group III), and genistein (50 mg/kg body weight, Group IV). The rats did not receive any treatment for 4 weeks after bacterial inoculation. Genistein was then administered twice daily for 2 weeks. Bacterial growth, mean body weight bone infection status, and side effects of genistein treatment were assessed. Furthermore, lipid peroxidation, superoxide dismutase, glutathione (GSH) peroxidase, catalase, reduced GSH, tumor necrosis factor-α (TNF-α), and interleukin (IL)-6 were also determined. Two days after treatment, it was found that genistein significantly suppressed bacterial growth and reduced serum pro-inflammatory cytokines TNF-α and IL-6. Therefore, the study suggests that genistein could be a promising lead against MRSA-induced osteomyelitis.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Osteomyelitis , Staphylococcal Infections , Rats , Male , Animals , Staphylococcus aureus , Genistein/pharmacology , Genistein/therapeutic use , Tumor Necrosis Factor-alpha , Rats, Wistar , Anti-Bacterial Agents , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Staphylococcal Infections/pathology , Osteomyelitis/etiology , Osteomyelitis/microbiology , Glutathione , Interleukin-6/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
14.
Bioorg Chem ; 137: 106590, 2023 08.
Article in English | MEDLINE | ID: mdl-37163809

ABSTRACT

In view of the potential off-target effects of antitumor drugs, including proteolysis targeting chimera (PROTAC), certain toxic effects may be caused in normal tissues. Herein, based on the characteristics of the tumor microenvironment, we reported the first estrogen receptor α (ERα) targeting hypoxia-responsive PROTACs in order to improve their safety in breast cancer treatment by introducing two hypoxia-activated groups, nitroimidazole and nitrobenzene, into the ER ligand or E3 ligand of an active PROTAC, which has certain cytotoxicity in normal cells. Bioactivity studies showed that these hypoxia-responsive PROTACs exhibited excellent hypoxic responsiveness and ERα degradation activity under hypoxic conditions, and thus improved the toxic effects of the active PROTAC in normal cells. It is expected that our caged compounds provide a new strategy for precise functional control of PROTAC drugs for breast cancer treatment.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Estrogen Receptor alpha/metabolism , Proteolysis Targeting Chimera , Ligands , Hypoxia/drug therapy , Hypoxia/metabolism , Skeleton/metabolism , Skeleton/pathology , Proteolysis , Tumor Microenvironment
15.
Chin J Physiol ; 66(2): 103-110, 2023.
Article in English | MEDLINE | ID: mdl-37026213

ABSTRACT

This study aimed to explore the effects of PPAPDC1A on the malignant phenotype of breast cancer (BC) in vivo and in vitro. PPAPDC1A expression was examined in BC tissues and cell lines by real-time polymerase chain reaction and Western blot. In this article, cell proliferation was evaluated by Cell Counting Kit-8 assay and colony formation assay, and cell migration and invasion were evaluated by wound healing assay and transwell assays. Furthermore, in vivo cell growth and pulmonary metastasis experiments were also performed using nude mice. The results showed that compared with normal tissues and cells, the PPAPDC1A expression in BC tissues and cell lines were both significantly increased. The PPAPDC1A targeting sequence significantly inhibited the PPAPDC1A expression and cell proliferation, migration, and invasion. The results of xenograft showed that knockdown of PPAPDC1A inhibited tumor growth and lung metastasis of BC. Then, the Dual-Luciferase Reporter Assay confirmed that miR-598-5p targeted the regulation of PPAPDC1A expression. In addition, the miR-598-5p expression in BC tissues was lower than that in the normal tissues. The rescue experiment showed that PPAPDC1A overexpression reversed the inhibitory effect of miR-598-5p mimic on cell proliferation, migration, and invasion. In conclusion, PPAPDC1A was highly expressed in BC tissues and cell lines, and miR-598-5p inhibited the malignant phenotype of BC by targeting PPAPDC1A.


Subject(s)
Breast Neoplasms , Lung Neoplasms , MicroRNAs , Animals , Mice , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , Cell Line, Tumor , Mice, Nude , Breast Neoplasms/genetics , Cell Movement/genetics , Lung Neoplasms/genetics , Cell Proliferation , Gene Expression Regulation, Neoplastic
16.
Nano Lett ; 22(5): 2094-2102, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35226508

ABSTRACT

Color vision deficiency (CVD) is a common ocular disorder affecting more than 300 million people on the earth. Although no clinical cure for the disorder currently exists, some specialized color filtering glasses/lenses based on dyes, metasurfaces, or nanocomposites have been employed for CVD management. However, as CVD patients usually diversify in their classification and severity, none of the current lenses provides a customized correction for various CVD patients, resulting in undesirable correction effects. Here, we present an inverse-designed approach for the precise correction of CVD. The wavelength shift of a patient's abnormal cone photoreceptors was measured to inversely design the best blocking wavelength and blocking rate of the lens. Then the customized aid lenses were fabricated using silica-coated gold nanoparticles with appropriate sizes and concentrations, verified by the simulated color vision and human tests. This study demonstrates the potential of the inverse-designed aid lenses in precise color filtering and customized CVD management.


Subject(s)
Cardiovascular Diseases , Color Vision Defects , Metal Nanoparticles , Nanocomposites , Color , Color Vision Defects/therapy , Gold , Humans , Metal Nanoparticles/therapeutic use
17.
Mol Biol Evol ; 38(5): 1695-1714, 2021 05 04.
Article in English | MEDLINE | ID: mdl-33331908

ABSTRACT

Pervasive hybridization and whole-genome duplications (WGDs) influenced genome evolution in several eukaryotic lineages. Although frequent and recurrent hybridizations may result in reticulate phylogenies, the evolutionary events underlying these reticulations, including detailed structure of the ancestral diploid and polyploid genomes, were only rarely reconstructed. Here, we elucidate the complex genomic history of a monophyletic clade from the mustard family (Brassicaceae), showing contentious relationships to the early-diverging clades of this model plant family. Genome evolution in the crucifer tribe Biscutelleae (∼60 species, 5 genera) was dominated by pervasive hybridizations and subsequent genome duplications. Diversification of an ancestral diploid genome into several divergent but crossable genomes was followed by hybridizations between these genomes. Whereas a single genus (Megadenia) remained diploid, the four remaining genera originated by allopolyploidy (Biscutella, Lunaria, Ricotia) or autopolyploidy (Heldreichia). The contentious relationships among the Biscutelleae genera, and between the tribe and other early diverged crucifer lineages, are best explained by close genomic relatedness among the recurrently hybridizing ancestral genomes. By using complementary cytogenomics and phylogenomics approaches, we demonstrate that the origin of a monophyletic plant clade can be more complex than a parsimonious assumption of a single WGD spurring postpolyploid cladogenesis. Instead, recurrent hybridization among the same and/or closely related parental genomes may phylogenetically interlink diploid and polyploid genomes despite the incidence of multiple independent WGDs. Our results provide new insights into evolution of early-diverging Brassicaceae lineages and elucidate challenges in resolving the contentious relationships within and between land plant lineages with pervasive hybridization and WGDs.


Subject(s)
Biological Evolution , Brassicaceae/genetics , Chromosomes, Plant , Genome, Plant , Polyploidy , Gene Duplication , Hybridization, Genetic
18.
Biochem Biophys Res Commun ; 604: 63-69, 2022 05 14.
Article in English | MEDLINE | ID: mdl-35299072

ABSTRACT

Neuroblastoma(NB) is a common childhood solid tumor, and most patients in the high-risk group with MYCN gene amplification have a poor prognosis. Inhibition of bromodomain and extra terminal (BET) proteins has shown considerable promise in the investigation of MYCN-driven malignancies in recent years. MZ1 is a novel BET inhibitor that employs proteolytic-targeting chimera (PROTAC) technology for proteasomal degradation of target proteins and has shown excellent effects in some tumors, but its role in neuroblastoma remains poorly understood. Herein, we observed that MZ1 suppressed MYC-amplified NB cell proliferation and normal cell cycle, while simultaneously boosting cell apoptosis. MZ1 also provides a significant therapeutic impact in vivo. Mechanistically, MZ1 exhibits anti-tumor effect in NB cells by suppressing the expression of N-Myc or C-Myc as well as the MAPK signaling pathway. Overall, our data imply that MZ1 might be exploited as a possible therapeutic method for NB therapy.


Subject(s)
Cell Cycle Proteins , Dipeptides , Heterocyclic Compounds, 3-Ring , N-Myc Proto-Oncogene Protein , Neuroblastoma , Transcription Factors , Cell Cycle Proteins/antagonists & inhibitors , Cell Line, Tumor , Child , Dipeptides/pharmacology , Gene Expression Regulation, Neoplastic , Heterocyclic Compounds, 3-Ring/pharmacology , Humans , N-Myc Proto-Oncogene Protein/genetics , N-Myc Proto-Oncogene Protein/metabolism , Neuroblastoma/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism
19.
Microb Pathog ; 173(Pt A): 105877, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36371064

ABSTRACT

Yersinia enterocolitica (Y. enterocolitica) is a gastrointestinal pathogen that is distributed worldwide, involved in systemic, extraintestinal and invasive infections in immunocompromised patients. Establishment of antibiotic resistance in the pathogen has produced a need for new antibacterial agents. The purpose of this study was to elucidate antibacterial mechanism of protocatechualdehyde (PCA) extracted from the roots of Salvia miltiorrhiza towards Y. enterocolitica, and to investigate effects of PCA on key virulence factors associated with human infection. Present results indicated that PCA exerted its antibacterial activity against Y. enterocolitica mainly by the rapid rise of intracellular reactive oxygen species, leading to change in permeability and integrity of cell membrane, and ultimately decline of membrane potential and intracellular ATP. Furthermore, scanning electron microscopic analysis revealed that Y. enterocolitica presented gradually shrinkage in length and partial wrinkles upon PCA treatment. PCA also effectively decreased motility, biofilm formation, quorum sensing in a dose-dependent manner without affecting bacterial growth. Further, at SICs, PCA substantially suppressed the adhesion and invasion of Y. enterocolitica to HT-29 cells and the downregulation of essential virulence factor-encoding genes unveiled impaired virulence. Overall, the findings revealed the potential of PCA as an alternative antibacterial agent to combat Y. enterocolitica contamination and infections.


Subject(s)
Yersinia Infections , Yersinia enterocolitica , Humans , Yersinia enterocolitica/genetics , Yersinia Infections/microbiology , Virulence Factors/genetics , Anti-Bacterial Agents/pharmacology
20.
Am J Bot ; 109(8): 1273-1289, 2022 08.
Article in English | MEDLINE | ID: mdl-35912547

ABSTRACT

PREMISE: The monotypic Idahoa (I. scapigera) and the bispecific Subularia (S. aquatica and S. monticola) belong to Brassicaceae with unclear phylogenetic relationships and no tribal assignment. To fill this knowledge gap, we investigated these species and their closest relatives by combining cytogenomic and phylogenomic methods. METHODS: We used whole plastome sequences in maximum likelihood and Bayesian inference analyses. We tested the phylogenetic informativeness of shared genomic repeats. We combined nuclear gene tree reconciliation and comparative chromosome painting (CCP) to examine the occurrence of past whole-genome duplications (WGDs). RESULTS: The plastid data set corroborated the sister relationship between Idahoa and Subularia within the crucifer Lineage V but failed to resolve consistent topologies using both inference methods. The shared repetitive sequences provided conflicting pwhylogenetic signals. CCP analysis unexpectedly revealed that Idahoa (2n = 16) has a diploidized mesotetraploid genome, whereas two Subularia species (2n = 28 and 30) have diploidized mesoctoploid genomes. Several ancient allopolyploidy events have also been detected in closely related taxa (Chamira circaeoides, Cremolobeae, Eudemeae, and Notothlaspideae). CONCLUSIONS: Our results suggest that the contentious phylogenetic placement of Idahoa and Subularia is best explained by two WGDs involving one or more shared parental genomes. The newly identified mesopolyploid genomes highlight the challenges of studying plant clades with complex polyploidy histories and provide a better framework for understanding genome evolution in the crucifer family.


Subject(s)
Brassicaceae , Polyploidy , Bayes Theorem , Brassicaceae/genetics , Evolution, Molecular , Genome , Phylogeny
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