IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation.

Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that the RNA helicase DDX5 was downregulated in keratinocytes from the inflammatory skin lesions in patients with atopic dermatitis and psoriasis, and that mice with keratinocyte-specific deletion of Ddx5 (Ddx5∆KC) were more susceptible to cutaneous inflammation. Inhibition of DDX5 expression in keratinocytes was induced by the cytokine interleukin (IL)-17D through activation of the CD93-p38 MAPK-AKT-SMAD2/3 signaling pathway and led to pre-messenger RNA splicing events that favored the production of membrane-bound, intact IL-36 receptor (IL-36R) at the expense of soluble IL-36R (sIL-36R) and to the selective amplification of IL-36R-mediated inflammatory responses and cutaneous inflammation. Restoration of sIL-36R in Ddx5∆KC mice with experimental atopic dermatitis or psoriasis suppressed skin inflammation and alleviated the disease phenotypes. These findings indicate that IL-17D modulation of DDX5 expression controls inflammation in keratinocytes during inflammatory skin diseases.

Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.

The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d-/- mice were more susceptible to acute colitis, bacterial infection and experimentally induced colon cancer than their wildtype counterparts. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced expression of IL-22-dependent antimicrobial peptides, RegIIIß and RegIIIγ, in colon tissue at steady state and in colitis; this was associated with changes in microbial composition and dysbiosis. Protein purification studies revealed that IL-17D bound not canonical IL-17 receptors, but rather CD93, a glycoprotein expressed on mature ILC3s. Mice lacking Cd93 in ILC3s exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis. Thus, an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis.

The cellular function of ROP GTPase prenylation is important for multicellularity in the moss Physcomitrium patens.

A complete picture of how signaling pathways lead to multicellularity is largely unknown. Previously, we generated mutations in a protein prenylation enzyme, GGB, and showed that it is essential for maintaining multicellularity in the moss Physcomitrium patens. Here, we show that ROP GTPases act as downstream factors that are prenylated by GGB and themselves play an important role in the multicellularity of P. patens. We also show that the loss of multicellularity caused by the suppression of GGB or ROP GTPases is due to uncoordinated cell expansion, defects in cell wall integrity and the disturbance of the directional control of cell plate orientation. Expressing prenylatable ROP in the ggb mutant not only rescues multicellularity in protonemata but also results in development of gametophores. Although the prenylation of ROP is important for multicellularity, a higher threshold of active ROP is required for gametophore development. Thus, our results suggest that ROP activation via prenylation by GGB is a key process at both cell and tissue levels, facilitating the developmental transition from one dimension to two dimensions and to three dimensions in P. patens.

Multi-omics analyses provide insights into the genomic basis of differentiation among four sweet osmanthus groups.

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multi-omic and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multi-seasonal flowering variety 'Rixianggui' in the Asiaticus group and other autumn flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool, α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multi-season flowering of osmanthus and other flowers.

The maize single-nucleus transcriptome comprehensively describes signaling networks governing movement and development of grass stomata.

The unique morphology of grass stomata enables rapid responses to environmental changes. Deciphering the basis for these responses is critical for improving food security. We have developed a planta platform of single-nucleus RNA-sequencing by combined fluorescence-activated nuclei flow sorting, and used it to identify cell types in mature and developing stomata from 33,098 nuclei of the maize epidermis-enriched tissues. Guard cells (GCs) and subsidiary cells (SCs) displayed differential expression of genes, besides those encoding transporters, involved in the abscisic acid, CO2, Ca2+, starch metabolism, and blue light signaling pathways, implicating coordinated signal integration in speedy stomatal responses, and of genes affecting cell wall plasticity, implying a more sophisticated relationship between GCs and SCs in stomatal development and dumbbell-shaped guard cell formation. The trajectory of stomatal development identified in young tissues, and by comparison to the bulk RNA-seq data of the MUTE defective mutant in stomatal development, confirmed known features, and shed light on key participants in stomatal development. Our study provides a valuable, comprehensive, and fundamental foundation for further insights into grass stomatal function.

Horizontally acquired fungal killer protein genes affect cell development in mosses.

The moss Physcomitrium patens is crucial for studying plant development and evolution. Although the P. patens genome includes genes acquired from bacteria, fungi and viruses, the functions and evolutionary significance of these acquired genes remain largely unclear. Killer protein 4 (KP4) is a toxin secreted by the phytopathogenic fungus Ustilago maydis that inhibits the growth of sensitive target strains by blocking their calcium uptake. Here, we show that KP4 genes in mosses were acquired from fungi through at least three independent events of horizontal gene transfer. Two paralogous copies of KP4 (PpKP4-1 and PpKP4-2) exist in P. patens. Knockout mutants ppkp4-1 and ppkp4-2 showed cell death at the protonemal stage, and ppkp4-2 also exhibited defects in tip growth. We provide experimental evidence indicating that PpKP4-1/2 affects P. patens protonemal cell development by mediating cytoplasmic calcium and that KP4 genes are functionally conserved between P. patens and fungi. The present study provides additional insights into the role of horizontal gene transfer in land plant development and evolution.

Integrating high-throughput phenotyping and genome-wide association studies for enhanced drought resistance and yield prediction in wheat.

Drought, especially terminal drought, severely limits wheat growth and yield. Understanding the complex mechanisms behind the drought response in wheat is essential for developing drought-resistant varieties. This study aimed to dissect the genetic architecture and high-yielding wheat ideotypes under terminal drought. An automated high-throughput phenotyping platform was used to examine 28 392 image-based digital traits (i-traits) under different drought conditions during the flowering stage of a natural wheat population. Of the i-traits examined, 17 073 were identified as drought-related. A genome-wide association study (GWAS) identified 5320 drought-related significant single-nucleotide polymorphisms (SNPs) and 27 SNP clusters. A notable hotspot region controlling wheat drought tolerance was discovered, in which TaPP2C6 was shown to be an important negative regulator of the drought response. The tapp2c6 knockout lines exhibited enhanced drought resistance without a yield penalty. A haplotype analysis revealed a favored allele of TaPP2C6 that was significantly correlated with drought resistance, affirming its potential value in wheat breeding programs. We developed an advanced prediction model for wheat yield and drought resistance using 24 i-traits analyzed by machine learning. In summary, this study provides comprehensive insights into the high-yielding ideotype and an approach for the rapid breeding of drought-resistant wheat.

Phytochrome B enhances seed germination tolerance to high temperature by reducing S-nitrosylation of HFR1.

Light and ambient high temperature (HT) have opposite effects on seed germination. Light induces seed germination through activating the photoreceptor phytochrome B (phyB), resulting in the stabilization of the transcription factor HFR1, which in turn sequesters the suppressor PIF1. HT suppresses seed germination and triggers protein S-nitrosylation. Here, we find that HT suppresses seed germination by inducing the S-nitrosylation of HFR1 at C164, resulting in its degradation, the release of PIF1, and the activation of PIF1-targeted SOMNUS (SOM) expression to alter gibberellin (GA) and abscisic acid (ABA) metabolism. Active phyB (phyBY276H ) antagonizes HFR1 S-nitrosylation and degradation by increasing S-nitrosoglutathione reductase (GSNOR) activity. In line with this, substituting cysteine-164 of HFR1 with serine (HFR1C164S ) abolishes the S-nitrosylation of HFR1 and decreases the HT-induced degradation of HFR1. Taken together, our study suggests that HT and phyB antagonistically modulate the S-nitrosylation level of HFR1 to coordinate seed germination, and provides the possibility to enhance seed thermotolerance through gene-editing of HFR1.

FARPA-based tube array coupled with quick DNA extraction enables ultra-fast bedside detection of antibiotic-resistant pathogens.

Rapid and accurate detection of pathogens and antimicrobial-resistant (AMR) genes of the pathogens are crucial for the clinical diagnosis and effective treatment of infectious diseases. However, the time-consuming steps of conventional culture-based methods inhibit the precise and early application of anti-infection therapy. For the prompt treatment of pathogen-infected patients, we have proposed a novel tube array strategy based on our previously reported FARPA (FEN1-aided recombinase polymerase amplification) principle for the ultra-fast detection of antibiotic-resistant pathogens on site. The entire process from "sample to result" can be completed in 25 min by combining quick DNA extraction from a urine sample with FARPA to avoid the usually complicated DNA extraction step. Furthermore, a 36-tube array made from commercial 384-well titre plates was efficiently introduced to perform FARPA in a portable analyser, achieving an increase in the loading sample throughput (from several to several tens), which is quite suitable for the point-of-care testing (POCT) of multiple pathogens and multiple samples. Finally, we tested 92 urine samples to verify the performance of our proposed method. The sensitivities for the detection of E. coli, K. pneumoniae, E. faecium, and E. faecalis were 92.7%, 93.8%, 100% and 88.9%, respectively. The specificities for the detection of the four pathogens were 100%. Consequently, our rapid, low-cost and user-friendly POCT method holds great potential for guiding the rational use of antibiotics and reducing bacterial resistance.

Central Metal-Triggered Structural Transformation of a 2D Layered MOF: Mechanistic Studies and Applications.

The structural transformation of metal-organic frameworks (MOFs) has attracted increasing interests, which has not only produced various new structures but also served as a fantastic platform for MOF-based kinetic analysis. Multiple reaction conditions have been documented to cause structural transformation; nevertheless, central metal-induced topological alteration of MOFs is rare. Herein, we reported a structural transformation of a 2D layered Cd-MOF driven by Cd(II) ions. After being submerged in the aqueous solution of cadmium nitrate, the twofold interpenetrated 2D network of [Cd(hsb-2)(bdc)·5H2O]n [HSB-W10; bdc: 1,4-benzenedicarboxylate; hsb-2:1,2-bis(4'-pyridylmethylamino)-ethane] was converted into a novel noninterpenetrated 2D network [Cd1.5(hsb-2)(bdc)1.5(H2O)2·H2O]n (HSB-W16). This partial dissolution-recrystallization process was investigated by integrating controlled experiments, 1H NMR spectra, and photographic tracking analysis. Furthermore, a novel strategy combining in situ multicomponent dye encapsulation and central metal-triggered structural transformation was developed for the fabrication of MOF materials with white-light emission. By adopting this strategy, different dye guest molecules were concurrently introduced into the HSB-W16 host matrix, leading to a range of white-light-emitting MOF composites. This work will enable detailed studies of solid-state transformations and demonstrate a promising application prospect for structural transformation.

Metabolite profiling of liquiritin in acute myocardial infarction model rat after intragastric administration using an information-dependent acquisition-mediated ultra-high-performance liquid chromatography-tandem mass spectrometry method.

Liquiritin (LQ), a kind of flavonoid isolated from licorice, was proven to have great potential in treating heart failure. Pharmacokinetic evaluation is important for demonstrating clinical efficacy and mechanisms, and the prototype drug and its metabolite profiling are important for drug discovery and development. However, the metabolism of LQ in acute myocardial infarction (AMI) model rats still needs to be studied in depth. An information-dependent acquisition (IDA)-ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was applied to profile LQ metabolites in AMI model rat plasma. Protein precipitation and extraction were used for sample preparation. Chromatographic separation was achieved using an XSelect BEH C18 column (2.1 × 150 mm, 2.5 µm) using gradient elution method combining 0.1% formic acid and acetonitrile with a flow rate of 0.3 mL/min. Twelve metabolites were identified in IDA mode, sulfation, glucuronidation, methylation, methyl esterification, glutamine conjugation, and valine conjugation, and their composite reactions were presumed as the primary pathways of LQ metabolism. The variation in the peak areas showed that the time to reach the peak drug concentration of LQ and 12 metabolites was within 5 h. In summary, IDA-bridged UHPLC-MS/MS from characteristic fragment ions toward confidence-enhanced identification could effectively screen and profile metabolites.

[Effect and mechanism of Linggui Zhugan Decoction in regulating Sig1R on Angâ ¡-induced cardiomyocyte hypertrophy].

This study aims to explore the mechanism of Linggui Zhugan Decoction(LGZGD) in inhibiting Angiotensin Ⅱ(AngⅡ)-induced cardiomyocyte hypertrophy by regulating sigma-1 receptor(Sig1R). The model of H9c2 cardiomyocyte hypertrophy induced by AngⅡ in vitro was established by preparing LGZGD-containing serum and blank serum. H9c2 cells were divided into normal group, AngⅡ model group, 20% normal rat serum group(20% NSC), and 20% LGZGD-containing serum group. After the cells were incubated with AngⅡ(1 µmol·L~(-1)) or AngⅡ with serum for 72 h, the surface area of cardiomyocytes was detected by phalloidine staining, and the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase were detected by micromethod. The mitochondrial Ca~(2+) levels were detected by flow cytometry, and the expression levels of atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), Sig1R, and inositol 1,4,5-triphosphate receptor type 2(IP_3R_2) were detected by Western blot. The expression of Sig1R was down-regulated by transfecting specific siRNA for investigating the efficacy of LGZGD-containing serum on cardiomyocyte surface area, Na~+-K~+-ATPase activity, Ca~(2+)-Mg~(2+)-ATPase activity, mitochondrial Ca~(2+), as well as ANP, BNP, and IP_3R_2 protein expressions. The results showed that compared with the normal group, AngⅡ could significantly increase the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.01), and it could decrease the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+), and the expression of Sig1R(P<0.01). In addition, IP_3R_2 protein expression was significantly increased(P<0.01). LGZGD-containing serum could significantly decrease the surface area of cardiomyocytes and the expression of ANP and BNP(P<0.05, P<0.01), and it could increase the activities of Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase, the concentration of mitochondrial Ca~(2+ )(P<0.01), and the expression of Sig1R(P<0.05). In addition, IP_3R_2 protein expression was significantly decreased(P<0.05). However, after Sig1R was down-regulated, the effects of LGZGD-containing serum were reversed(P<0.01). These results indicated that the LGZGD-containing serum could inhibit cardiomyocyte hypertrophy induced by AngⅡ, and its pharmacological effect was related to regulating Sig1R, promoting mitochondrial Ca~(2+ )inflow, restoring ATP synthesis, and protecting mitochondrial function.

Identification of the deubiquitinase USP28 as a novel molecular therapeutic target of ovarian cancer.

Ubiquitin specific proteinase 28 (USP28) is a member of the deubiquitylating enzymes, which are mainly involved in cell cycle, apoptosis and DNA damage repair. Although USP28 has been found to be upregulated in some tumors, its role in ovarian cancer (OV) remains unclear. Here we show that USP28 was highly expressed in OV samples compared with normal ovarian tissue, and OV patients with higher USP28 levels had a worse prognosis. We found that the abnormal expression of USP28 mRNA in OV was related to the activation of ß-catenin signaling pathway, and USP28 was a transcriptional target gene of the ß-catenin/YAP1/TBX5 complex. In addition, genetic ablation or pharmacological inhibition of USP28 impaired the proliferation ability of OV cells in vitro and in vivo. In conclusion, our findings show that ß-catenin/YAP1/TBX5-mediated aberrant expression of USP28 promotes the malignant phenotype of OV, suggesting that USP28 may be a therapeutic target for OV.

ROS accumulation-induced tapetal PCD timing changes leads to microspore abortion in cotton CMS lines.

BACKGROUND: Cytoplasmic male sterility (CMS) is the basis of heterosis exploitation. CMS has been used to hybrid production in cotton, but its molecular mechanism remains unclear. CMS is associated with advanced or delayed tapetal programmed cell death (PCD), and reactive oxygen species (ROS) may mediate this process. In this study, we obtained Jin A and Yamian A, two CMS lines with different cytoplasmic sources. RESULTS: Compared with maintainer Jin B, Jin A anthers showed advanced tapetal PCD with DNA fragmentation, producing excessive ROS which accumulated around the cell membrane, intercellular space and mitochondrial membrane. The activities of peroxidase (POD) and catalase (CAT) enzymes which can scavenge ROS were significantly decreased. However, Yamian A tapetal PCD was delayed with lower ROS content, and the activities of superoxide dismutase (SOD) and POD were higher than its maintainer. These differences in ROS scavenging enzyme activities may be caused by isoenzyme gene expressions. In addition, we found the excess ROS generated in Jin A mitochondria and ROS overflow from complex III might be the source in parallel with the reduction of ATP content. CONCLUSION: ROS accumulation or abrogation were mainly caused by the joint action of ROS generation and scavenging enzyme activities transformation, which led to the abnormal progression of tapetal PCD, affected the development of microspores, and eventually contributed to male sterility. In Jin A, tapetal PCD in advance might be caused by mitochondrial ROS overproduction, accompanied by energy deficiency. The above studies will provide new insights into the cotton CMS and guide the follow-up research ideas.

A transcription factor WRKY36 interacts with AFP2 to break primary seed dormancy by progressively silencing DOG1 in Arabidopsis.

The phytohormones abscisic acid (ABA) and gibberellic acid (GA) antagonistically control the shift between seed dormancy and its alleviation. DELAY OF GERMINATION1 (DOG1) is a critical regulator that determines the intensity of primary seed dormancy, but its underlying regulatory mechanism is unclear. In this study, we combined physiological, biochemical, and genetic approaches to reveal that a bHLH transcriptional factor WRKY36 progressively silenced DOG1 expression to break seed dormancy through ABI5-BINDING PROTEIN 2 (AFP2) as the negative regulator of ABA signal. AFP2 interacted with WRKY36, which recognizes the W-BOX in the DOG1 promoter to suppress its expression; Overexpressing WRKY36 broke primary seed dormancy, whereas wrky36 mutants showed strong primary seed dormancy. In addition, AFP2 recruited the transcriptional corepressor TOPLESS-RELATED PROTEIN2 (TPR2) to reduce histone acetylation at the DOG1 locus, ultimately mediating WRKY36-dependent inhibition of DOG1 expression to break primary seed dormancy. Our result proposes that the WRKY36-AFP2-TPR2 module progressively silences DOG1 expression epigenetically, thereby fine-tuning primary seed dormancy.

Pharmacokinetic evaluation of 24 representative components of Ling-Gui-Zhu-Gan decoction in acute myocardial infarction model rats via a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry method.

RATIONALE: Ling-Gui-Zhu-Gan decoction (LGZGD), one of the 100 herbal classic formulas, is clinically used to treat chronic heart failure with remarkable curative effect. However, LGZGD pharmacokinetic parameters in pathological model rats are poorly understood, in particular for special components. As physicochemical properties are specific to each representative component, no standard sample preparation is available for absolute quantification of representative components of LGZGD in rat plasma. METHODS: A specific, sensitive and high-throughput ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC/MS/MS) method capturing 24 representative components was developed and applied to evaluate the pharmacokinetic parameters of LGZGD in acute myocardial infarction (AMI) rat plasma after intragastric administration (2.4, 4.8 and 9.6 g/kg). Precipitation and extraction were selected and optimized for plasma preparation, and isopropanol precipitation could offer higher recovery and broader coverage. RESULTS: It was expected that AMI could cause less absorption and slower elimination of most of active components of LGZGD. Most of newly reported special components absorbed quickly and eliminated slowly. The average elimination half-life of the 24 representative components was 10.09 h, which is consistent with the dosage of LGZGD (twice daily). CONCLUSIONS: The specificity, linearity, precision and accuracy, recovery, matrix effect and stability were validated according to Food and Drug Administration guidance. The validation results demonstrated that the method could be applied to evaluate the pharmacokinetic parameters of LGZGD in AMI rats. The pharmacokinetic parameters showed substantial improvement in quality research of LGZGD, thereby laying the groundwork for preclinical and clinical trials in chronic heart failure clinical efficacy.

Visualized RNA detection of SARS-CoV-2 in a closed tube by coupling RT-PCR with nested invasive reaction.

A simple, cost-effective and reliable diagnosis of pathogen nucleic acids assay is much required for controlling a pandemic of a virus disease, such as COVID-19. Our previously developed visualized detection of pathogen DNA in a single closed tube is very suitable for POCT. However, virus RNA could not be detected directly and should be reverse-transcribed into cDNA in advance. To enable this visualized assay to detect virus RNA directly, various types of reverse transcriptase were investigated, and finally we found that HiScript II reverse transcriptase could keep active and be well adapted to the one-pot visualized assay in optimized conditions. Reverse transcription, template amplification and amplicon identification by PCR coupled with invasive reaction, as well as visualization by self-assembling of AuNP probes could be automatically and sequentially performed in a closed tube under different temperature conditions, achieving "sample (RNA)-in-result (red color)-out" only by a simple PCR engine plus the naked eye. The visualized RT-PCR is sensitive to unambiguous detection of 5 copies of the N and ORFlab genes of SARS-CoV-2 RNA comparing favourably with qPCR methods (commercialized kit), is specific to genotype 3 variants (Alpha, Beta and Omicron) of SARS-CoV-2, and is very accurate for picking up 0.01% Omicron variant from a large amount of sequence-similar backgrounds. The method is employed in detecting 50 clinical samples, and 10 of them were detected as SARS-CoV-2 positive samples, identical to those by conventional RT-PCR, indicating that the method is cost-effective and labor-saving for pathogen RNA screening in resource-limited regions.

Repression of GhTUBB1 Reduces Plant Height in Gossypium hirsutum.

The original 'Green Revolution' genes are associated with gibberellin deficiency. However, in some species, mutations in these genes cause pleiotropic phenotypes, preventing their application in dwarf breeding. The development of novel genotypes with reduced plant height will resolve this problem. In a previous study, we obtained two dwarf lines, L28 and L30, by introducing the Ammopiptanthus mongolicus (Maxim. ex Kom.) Cheng f. C-repeat-binding factor 1 (AmCBF1) into the upland cotton variety R15. We found that Gossypium hirsutum Tubulin beta-1 (GhTUBB1) was downregulated in L28 and L30, which suggested that this gene may have contributed to the dwarf phenotype of L28 and L30. Here, we tested this hypothesis by silencing GhTUBB1 expression in R15 and found that decreased expression resulted in a dwarf phenotype. Interestingly, we found that repressing AmCBF1 expression in L28 and L30 partly recovered the expression of GhTUBB1. Thus, AmCBF1 expression presented a negative relationship with GhTUBB1 expression in L28 and L30. Moreover, yeast one-hybrid and dual-luciferase assays suggest that AmCBF1 negatively regulates GhTUBB1 expression by directly binding to C-repeat/dehydration-responsive (CRT/DRE) elements in the GhTUBB1 promoter, potentially explaining the dwarf phenotypes of L28 and L30. This study elucidates the regulation of GhTUBB1 expression by AmCBF1 and suggests that GhTUBB1 may be a new target gene for breeding dwarf and compact cultivars.

Beneficial effects of flavonoids on cardiovascular diseases by influencing NLRP3 inflammasome.

Cardiovascular diseases (CVDs) are a leading cause of global mortality and have a high incidence rate worldwide. The function of inflammasomes in CVDs has received a lot of attention recently, and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome may be a new target for the prevention and treatment of CVDs. Flavonoids, which are found in food and plant extracts, inhibited inflammation in CVDs by regulating the NLRP3 inflammasome. CB-Dock was used to investigate whether 34 flavonoids from natural products acted on NLRP3 inflammasome. In brief, the PDB format of NLRP3 was selected as a protein file, and 34 flavonoids in SDF format were selected as the ligand file, and then input to CB-Dock for molecular docking. The docking results showed that epigallocatechin-3-gallate (EGCG), amentoflavone, baicalin, scutellarin, vitexin, silibinin, and puerarin had good binding affinities to NLRP3, which could be used as NLRP3 inhibitors, and aid in the discovery of lead compounds for the design and development of CVDs.

Genomic convergence underlying high-altitude adaptation in alpine plants.

Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection. However, genomic evidence for convergent adaptation to extreme environments remains scarce. Here, we assembled reference genomes of two alpine plants, Saussurea obvallata (Asteraceae) and Rheum alexandrae (Polygonaceae), with 37,938 and 61,463 annotated protein-coding genes. By integrating an additional five alpine genomes, we elucidated genomic convergence underlying high-altitude adaptation in alpine plants. Our results detected convergent contractions of disease-resistance genes in alpine genomes, which might be an energy-saving strategy for surviving in hostile environments with only a few pathogens present. We identified signatures of positive selection on a set of genes involved in reproduction and respiration (e.g., MMD1, NBS1, and HPR), and revealed signatures of molecular convergence on genes involved in self-incompatibility, cell wall modification, DNA repair and stress resistance, which may underlie adaptation to extreme cold, high ultraviolet radiation and hypoxia environments. Incorporating transcriptomic data, we further demonstrated that genes associated with cuticular wax and flavonoid biosynthetic pathways exhibit higher expression levels in leafy bracts, shedding light on the genetic mechanisms of the adaptive "greenhouse" morphology. Our integrative data provide novel insights into convergent evolution at a high-taxonomic level, aiding in a deep understanding of genetic adaptation to complex environments.