Bifunctional transcription factors SlERF.H5 and H7 activate cell wall and repress gibberellin biosynthesis genes in tomato via a conserved motif.

The plant cell wall is a dynamic structure that plays an essential role in development, but the mechanism regulating cell wall formation remains poorly understood. We demonstrate that two transcription factors, SlERF.H5 and SlERF.H7, control cell wall formation and tomato fruit firmness in an additive manner. Knockout of SlERF.H5, SlERF.H7, or both genes decreased cell wall thickness, firmness, and cellulose contents in fruits during early development, especially in double-knockout lines. Overexpressing either gene resulted in thicker cell walls and greater fruit firmness with elevated cellulose levels in fruits but severely dwarf plants with lower gibberellin contents. We further identified that SlERF.H5 and SlERF.H7 activate the cellulose biosynthesis gene SlCESA3 but repress the gibberellin biosynthesis gene GA20ox1. Moreover, we identified a conserved LPL motif in these ERFs responsible for their activities as transcriptional activators and repressors, providing insight into how bifunctional transcription factors modulate distinct developmental processes.

Chitosan-fucoidan encapsulating cinnamaldehyde composite coating films: Preparation, pH-responsive release, antibacterial activity and preservation for litchi.

In this study, an edible composite film with pH-responsive release was prepared by the formation of Schiff-base imine bonds between chitosan (CS) and oxidized fucoidan (CS-FU) and encapsulating cinnamaldehyde (CA). Fourier-transform infrared, 1H nuclear magnetic resonance, X-ray photoelectron spectroscopy and gel permeation chromatography confirmed the formation of CS-FU. The result showed that, oxidation degree of FU, degrees of substitution, average molecular weight and yield of CS-FU were 25.57 %, 10.48 %, 23.3094 kDa and 45.63 ± 0.64 %, respectively. Scanning electron microscopy revealed that CA was encapsulated within the CS-FU matrix. Increasing the CA content could improve the mechanical properties and ultraviolet and visible-light resistances of the CS-FU coating films but enhance their water vapor permeabilities. The release of CA increased as the pH decreased, and the antibacterial rate at pH 5 was 2.3-fold higher than that at pH 7, indicating good pH-responsive release and antibacterial properties in mildly acidic environments. Owing to their excellent properties, the CA/CS-FU-0.1 coating films maintained the appearance and quality indices of litchis for at least eight days. Hence, multifunctional composite coating films are prospective eco-friendly and intelligently responsive controlled-release packaging materials for fruit preservation.

A transcriptional cascade mediated by two APETALA2 family members orchestrates carotenoid biosynthesis in tomato.

Carotenoids are important nutrients for human health that must be obtained from plants since they cannot be biosynthesized by the human body. Dissecting the regulatory mechanism of carotenoid metabolism in plants represents the first step toward manipulating carotenoid contents in plants by molecular design breeding. In this study, we determined that SlAP2c, an APETALA2 (AP2) family member, acts as a transcriptional repressor to regulate carotenoid biosynthesis in tomato (Solanum lycopersicum). Knockout of SlAP2c in both the "MicroTom" and "Ailsa Craig" backgrounds resulted in greater lycopene accumulation, whereas overexpression of this gene led to orange-ripe fruit with significantly lower lycopene contents than the wild type. We established that SlAP2c represses the expression of genes involved in lycopene biosynthesis by directly binding to the cis-elements in their promoters. Moreover, SlAP2c relies on its EAR motif to recruit the co-repressors TOPLESS (TPL)2/4 and forms a complex with histone deacetylase (had)1/3, thereby reducing the histone acetylation levels of lycopene biosynthesis genes. Furthermore, SlAP2a, a homolog of SlAP2c, acts upstream of SlAP2c and alleviates the SlAP2c-induced repression of lycopene biosynthesis genes by inhibiting SlAP2c transcription during fruit ripening. Therefore, we identified a transcriptional cascade mediated by AP2 family members that regulates lycopene biosynthesis during fruit ripening in tomato, laying the foundation for the manipulation of carotenoid metabolism in plants.

Gibberellins involved in fruit ripening and softening by mediating multiple hormonal signals in tomato.

The phytohormone ethylene is well known for its important role in the ripening of climacteric fruit, such as tomato (Solanum lycopersicum). However, the role and mode of action of other plant hormones in climacteric fruit ripening regulation are not fully understood. Here, we showed that exogenous GA treatment or increasing endogenous gibberellin content by overexpressing the gibberellin synthesis gene SlGA3ox2 specifically in fruit tissues delayed tomato fruit ripening, whereas treatment with the GA biosynthesis inhibitor paclobutrazol (PAC) accelerated fruit ripening. Moreover, exogenous ethylene treatment cannot completely reverse the delayed fruit ripening phenotype. Furthermore, exogenous GA treatment of ethylene signalling mutant Never ripe (Nr) or SlEBF3-overexpressing lines still delayed fruit ripening, suggesting that GA involved in fruit ripening partially depends on ethylene. Transcriptome profiling showed that gibberellin affect the ripening of fruits by modulating the metabolism and signal transduction of multiple plant hormones, such as auxin and abscisic acid, in addition to ethylene. Overall, the results of this study provide new insight into the regulation of gibberellin in fruit ripening through mediating multiple hormone signals.

Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature.

BACKGROUND: TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level. METHODS: Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA). RESULTS: A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion. CONCLUSIONS: Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

Genome-wide identification of MAPK family in papaya (Carica papaya) and their involvement in fruit postharvest ripening.

BACKGROUND: Papaya (Carica papaya) is an economically important fruit cultivated in the tropical and subtropical regions of China. However, the rapid softening rate after postharvest leads to a short shelf-life and considerable economic losses. Accordingly, understanding the mechanisms underlying fruit postharvest softening will be a reasonable way to maintain fruit quality and extend its shelf-life. RESULTS: Mitogen-activated protein kinases (MAPKs) are conserved and play essential roles in response to biotic and abiotic stresses. However, the MAPK family remain poorly studied in papaya. Here, a total of nine putative CpMAPK members were identified within papaya genome, and a comprehensive genome-wide characterization of the CpMAPKs was performed, including evolutionary relationships, conserved domains, gene structures, chromosomal locations, cis-regulatory elements and expression profiles in response to phytohormone and antioxidant organic compound treatments during fruit postharvest ripening. Our findings showed that nearly all CpMAPKs harbored the conserved P-loop, C-loop and activation loop domains. Phylogenetic analysis showed that CpMAPK members could be categorized into four groups (A-D), with the members within the same groups displaying high similarity in protein domains and intron-exon organizations. Moreover, a number of cis-acting elements related to hormone signaling, circadian rhythm, or low-temperature stresses were identified in the promoters of CpMAPKs. Notably, gene expression profiles demonstrated that CpMAPKs exhibited various responses to 2-chloroethylphosphonic acid (ethephon), 1-methylcyclopropene (1-MCP) and the combined ascorbic acid (AsA) and chitosan (CTS) treatments during papaya postharvest ripening. Among them, both CpMAPK9 and CpMAPK20 displayed significant induction in papaya flesh by ethephon treatment, and were pronounced inhibition after AsA and CTS treatments at 16 d compared to those of natural ripening control, suggesting that they potentially involve in fruit postharvest ripening through ethylene signaling pathway or modulating cell wall metabolism. CONCLUSION: This study will provide some valuable insights into future functional characterization of CpMAPKs, and hold great potential for further understanding the molecular mechanisms underlying papaya fruit postharvest ripening.

A new cytotoxic disaccharide glycoside from the tubers of Arisaema franchetianum.

A new disaccharide glycoside, franchoside A (1), and 17 known compounds were isolated from the tubers of Arisaema franchetianum Engler. The chemical structure of the previously undescribed compound 1 was elucidated on the basis of detailed spectroscopic analyses. Compounds 1, 2, 6, 10, 14 and 18 showed significant cytotoxic activities at varying IC50 values in the range of 4.0-10.6 µM against five cancer cell lines. Compounds 8, 10, 13 and 17 (10 µM) exhibited moderate anti-inflammatory activities by inhibiting the NF-κB signaling pathway and the release of NO from RAW264.7 macrophages induced by lipopolysaccharide (LPS), while compounds 1, 9, 14, 15 and 16 showed weak anti-inflammatory activities.

Biochemical and metabolomics analyses reveal the mechanisms underlying ascorbic acid and chitosan coating mediated energy homeostasis in postharvest papaya fruit.

Papaya is a climacteric fruit that undergoes rapid ripening and quality deterioration during postharvest storage, resulting in significant economic losses. This study employed biochemical techniques and targeted metabolomics to investigate the impact of exogenous AsA + CTS application on the energy metabolism regulation of papaya fruit during postharvest storage. We found that AsA + CTS treatment significantly increased the levels of key metabolic compounds and enzymes, such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), and the energy charge, as well as the succinic acid content and the activities of succinic dehydrogenase (SDH), cytochrome c oxidase (CCO), H+-ATPase, and Ca2+-ATPase. Moreover, AsA + CTS coating augmented the nicotinamide adenine dinucleotide kinase (NADK) activity and increased the NADH and NADPH concentrations. Regarding sugar metabolism, it increased the activities of 6-phosphogluconate dehydrogenase and glucose-6-phosphate dehydrogenase and raised d-glucose-6-phosphate levels. These findings suggest that AsA + CTS coating application can mitigate the metabolic deterioration and sustain a primary metabolism homeostasis in papaya fruit by enhancing the tricarboxylic acid (TCA) cycle and pentose phosphate pathway (PPP), thereby preserving their quality attributes during postharvest storage.

Up-regulated SPP1 increases the risk from IPF to lung cancer via activating the pro-tumor macrophages.

The incidence of lung cancer (LC) in Idiopathic Pulmonary Fibrosis (IPF) patients is more than twice that in non-IPF. This study aims to investigate IPF-to-LC pathogenesis and to develop a predictor for detecting IPF predisposing patients to LC. We conducted unsupervised clustering to detect high-risk subtypes from IPF to LC. Subsequently, we performed single-cell RNA-seq analysis to characterize high-risk IPF by examining the immune microenvironment. We identified 42 common immune function-related pathogenic genes between IPF and LC. We developed an LC risk classifier for IPF patients, comprising five genes: SPP1, MMP9, MMP12, FABP4, and IL1B. The five-gene classifier can successfully distinguish the high-risk population from IPF patients. High-risk IPF patients exhibited an immunosuppressive microenvironment with higher oncogene expression than low-risk patients. Single-cell analysis revealed that SPP1+ macrophages at the terminal of macrophages' developmental trajectory may promote the progression from IPF to LC. The strong crosstalk between SPP1+ macrophages and inflammation-related cancer-associated fibroblasts promoted the tumorigenic process in IPF. In vitro, assays showed that co-culturing macrophages overexpressing SPP1 with MRC-5 cells induced the transition of fibroblasts into cancer-associated fibroblasts. SPP1 produced by macrophages promoted epithelial-mesenchymal transition in alveolar epithelial cells via stimulating the upregulation of N-cadherin and Vimentin in MLE-12 cells. This study provided a novel method to identify the LC risk population from IPF, revealing the cellular interactions involved in the transition from IPF to LC. Our findings highlighted SPP1 as a critical driver in IPF progression, offering a potential target for therapy in fibrosis.

Physiological and transcriptomic analysis of IAA-induced antioxidant defense and cell wall metabolism in postharvest mango fruit.

Mango fruit tend to oxidize and senescence rapidly after harvesting, significantly reducing their commercial value. This study investigated the effect of exogenous auxin indole-3-acetic acid (IAA) on fruit quality, antioxidant system, and cell wall metabolism of mango fruit during storage. The results showed that the 1.0 mM IAA treatment delayed weight loss and maintained the firmness, pH and contents of total soluble solids (TSS) and titratable acidity (TA) of the mango fruit. The 1.0 mM IAA treatment increased the peroxidase (POD) and phenylalanine ammonia-lyase (PAL) activities and the ascorbic acid (AsA) and total phenols (TP) contents but decreased the polyphenol oxidase (PPO) activity in postharvest mango fruit. Moreover, beta-galactosidase (ß-Gal) and polygalacturonase (PG) activities were increased, but the pectinesterase (PME) activity was decreased in the IAA-treated fruit. Transcriptome analysis showed that the differentially expressed genes (DEGs) in the IAA vs. control groups were mainly associated with oxidative stress responses, cell wall metabolism, and transcription factors (TFs). The IAA treatment upregulated the antioxidant-related genes (SOD, CAT1, PODs, GSTs, Prxs, and Trxs) and MYB TFs, and downregulated cell wall metabolism-related genes (PG, PME31 and two PME63) and 11 ethylene-responsive transcription factors (ERFs). These results suggested that exogenous IAA could improve the antioxidant system and maintain the storage quality of mango fruit by regulating gene expression and metabolic pathways. The results provide insights into the mechanisms involved in IAA-mediated delayed ripening and senescence of mango fruit.

Mutant RB1 enhances therapeutic efficacy of PARPis in lung adenocarcinoma by triggering the cGAS/STING pathway.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are approved for cancer therapy according to their synthetic lethal interactions, and clinical trials have been applied in non-small cell lung cancer. However, the therapeutic efficacy of PARPis in lung adenocarcinoma (LUAD) is still unknown. We explored the effect of a mutated retinoblastoma gene (RB1) on PARPi sensitivity in LUAD. Bioinformatic screening was performed to identify PARPi-sensitive biomarkers. Here, we showed that viability of LUAD cell lines with mutated RB1 was significantly decreased by PARPis (niraparib, rucaparib, and olaparib). RB1 deficiency induced genomic instability, prompted cytosolic double-stranded DNA (dsDNA) formation, activated the cGAS/STING pathway, and upregulated downstream chemokines CCL5 and CXCL10, triggering immune cell infiltration. Xenograft experiments indicated that PARPi treatment reduced tumorigenesis in RB1-KO mice. Additionally, single-cell RNA sequencing analysis showed that malignant cells with downregulated expression of RB1 had more communications with other cell types, exhibiting activation of specific signaling such as GAS, IFN response, and antigen-presenting and cytokine activities. Our findings suggest that RB1 mutation mediates the sensitivity to PARPis through a synthetic lethal effect by triggering the cGAS/STING pathway and upregulation of immune infiltration in LUAD, which may be a potential therapeutic strategy.

Exogenous glutathione maintains the postharvest quality of mango fruit by modulating the ascorbate-glutathione cycle.

Background: Mango fruit is prone to decay after harvest and premature senescence, which significantly lowers its quality and commercial value. Methods: The mango fruit (Mangifera indica L.cv. Guixiang) was treated with 0 (control), 2, 5, and 8 mM of reduced glutathione (GSH) after harvest. The fruit was stored at 25 ± 1 °C for 12 days to observe the changes in the antioxidant capacity and postharvest quality. Results: Compared with the control, the 5 mM GSH treatment significantly decreased the weight loss by 44.0% and 24.4%, total soluble solids content by 25.1% and 4.5%, and soluble sugar content by 19.0% and 27.0%. Conversely, the 5 mM GSH treatment increased the firmness by 25.9% and 30.7% on days 4 and 8, respectively, and the titratable acidity content by 115.1% on day 8. Additionally, the 5 mM GSH treatment decreased the malondialdehyde and hydrogen peroxide contents and improved the antioxidant capacity of mango fruit by increasing the superoxide dismutase and peroxidase activities and upregulating the expression of the encoding genes. Meanwhile, the higher levels of monodehydroascorbate reductase, dehydroascorbate reductase, and glutathione reductase enzyme activities and gene expressions accelerated the AsA-GSH cycle, thereby increasing the accumulation of AsA and GSH and maintaining the redox balance. Conclusions: Overall, the experimental results suggest that 5 mM GSH maintains high antioxidant capacity and postharvest quality of mangoes and can use as an effective preservation technique for postharvest mangoes.

Synthetic viability induces resistance to immune checkpoint inhibitors in cancer cells.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized the treatment for multiple cancers. However, most of patients encounter resistance. Synthetic viability (SV) between genes could induce resistance. In this study, we established SV signature to predict the efficacy of ICI treatment for melanoma. METHODS: We collected features and predicted SV gene pairs by random forest classifier. This work prioritized SV gene pairs based on CRISPR/Cas9 screens. SV gene pairs signature were constructed to predict the response to ICI for melanoma patients. RESULTS: This study predicted robust SV gene pairs based on 14 features. Filtered by CRISPR/Cas9 screens, we identified 1,861 SV gene pairs, which were also related with prognosis across multiple cancer types. Next, we constructed the six SV pairs signature to predict resistance to ICI for melanoma patients. This study applied the six SV pairs signature to divide melanoma patients into high-risk and low-risk. High-risk melanoma patients were associated with worse response after ICI treatment. Immune landscape analysis revealed that high-risk melanoma patients had lower natural killer cells and CD8+ T cells infiltration. CONCLUSIONS: In summary, the 14 features classifier accurately predicted robust SV gene pairs for cancer. The six SV pairs signature could predict resistance to ICI.

The role of miR-369-3p in proliferation and differentiation of preadipocytes in Aohan fine-wool sheep.

MicroRNAs (miRNAs) are a large class of non-coding RNAs that play important roles in the proliferation and differentiation of adipocytes. Our previous sequencing analysis revealed higher expression of miR-369-3p in the longissimus muscle of 2-month-old Aohan fine-wool sheep (AFWS) compared to 12-month-old sheep (P<0.05), suggesting that miR-369-3p may regulate fat deposition in AFWS. To test this, miR-369-3p mimics, inhibitors, and negative controls (NCs) were constructed and transfected into AFWS preadipocytes. After transfection with miR-369-3p mimics, we found a decrease (P<0.05) in the expression of genes and proteins related to cell proliferation and differentiation, detected by RT-qPCR (quantitative reverse transcription PCR) and western blot analyses. Moreover, EdU (5-ethynyl-2'-deoxyuridine) detection and Oil Red O staining showed a decrease (P<0.05) in cell proliferation and lipid accumulation, respectively. The opposite trends (P<0.05) were obtained after transfection with miR-369-3p inhibitors. In conclusion, the results showed that miR-369-3p can inhibit the proliferation and differentiation of AFWS preadipocytes, providing a theoretical basis to further explore the molecular mechanism of fat deposition in sheep and other domestic animals.

The MADS-box protein SlTAGL1 regulates a ripening-associated SlDQD/SDH2 involved in flavonoid biosynthesis and resistance against Botrytis cinerea in post-harvest tomato fruit.

3-Dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) is a key rate-limiting enzyme that catalyzes the synthesis of the shikimate, which is an important metabolic intermediate in plants and animals. However, the function of SlDQD/SDH family genes in tomato (Solanum lycopersicum) fruit metabolites is still unknown. In the present study, we identified a ripening-associated SlDQD/SDH member, SlDQD/SDH2, that plays a key role in shikimate and flavonoid metabolism. Overexpression of this gene resulted in an increased content of shikimate and flavonoids, while knockout of this gene by CRISPR/Cas9 mediated gene editing led to a significantly lower content of shikimate and flavonoids by downregulation of flavonoid biosynthesis-related genes. Moreover, we showed that SlDQD/SDH2 confers resistance against Botrytis cinerea attack in post-harvest tomato fruit. Dual-luciferase reporter and EMSA assays indicated that SlDQD/SDH2 is a direct target of the key ripening regulator SlTAGL1. In general, this study provided a new insight into the biosynthesis of flavonoid and B. cinerea resistance in fruit tomatoes.

Genome-wide characterization of the tomato GASA family identifies SlGASA1 as a repressor of fruit ripening.

Gibberellins (GAs) play crucial roles in a wide range of developmental processes and stress responses in plants. However, the roles of GA-responsive genes in tomato (Solanum lycopersicum) fruit development remain largely unknown. Here, we identify 17 GASA (Gibberellic Acid-Stimulated Arabidopsis) family genes in tomato. These genes encode proteins with a cleavable signal peptide at their N terminus and a conserved GASA domain at their C terminus. The expression levels of all tomato GASA family genes were responsive to exogenous GA treatment, but adding ethylene eliminated this effect. Comprehensive expression profiling of SlGASA family genes showed that SlGASA1 follows a ripening-associated expression pattern, with low expression levels during fruit ripening, suggesting it plays a negative role in regulating ripening. Overexpressing SlGASA1 using a ripening-specific promoter delayed the onset of fruit ripening, whereas SlGASA1-knockdown fruits displayed accelerated ripening. Consistent with their delayed ripening, SlGASA1-overexpressing fruits showed significantly reduced ethylene production and carotenoid contents compared to the wild type. Moreover, ripening-related genes were downregulated in SlGASA1-overexpressing fruits but upregulated in SlGASA1-knockdown fruits compared to the wild type. Yeast two-hybrid, co-immunoprecipitation, transactivation, and DNA pull-down assays indicated that SlGASA1 interacts with the key ripening regulator FRUITFULL1 and represses its activation of the ethylene biosynthesis genes ACS2 and ACO1. Our findings shed new light on the role and mode of action of a GA-responsive gene in tomato fruit ripening.

Transcriptome and metabolome analyses of Shatian pomelo (Citrus grandis var. Shatinyu Hort) leaves provide insights into the overexpression of the gibberellin-induced gene CcGASA4.

The gibberellic acid (GA)-stimulated Arabidopsis (GASA) gene family is highly specific to plants and plays crucial roles in plant growth and development. CcGASA4 is a member of the GASA gene family in citrus plants; however, the current understanding of its function in citrus is limited. We used CcGASA4-overexpression transgenic citrus (OEGA) and control (CON) plants to study the role of CcGASA4 in Shatian pomelo. The RNA sequencing (RNA-seq) analysis showed that 3,522 genes, including 1,578 upregulated and 1,944 downregulated genes, were significantly differentially expressed in the CON versus OEGA groups. The Gene Ontology enrichment analysis showed that 178 of the differentially-expressed genes (DEGs) were associated with flowers. A Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in 134 pathways, including "plant-pathogen interaction", "MAPK signaling pathway-plant", "phenylpropane biosynthesis", "plant hormone signal transduction", "phenylalanine, tyrosine and tryptophan biosynthesis", and "flavonoid and flavonol biosynthesis". The most significantly-enriched pathway was "plant-pathogen interaction", in which 203 DEGs were enriched (126 DEGs were upregulated and 78 were downregulated). The metabolome analysis showed that 644 metabolites were detected in the OEGA and CON samples, including 294 differentially-accumulated metabolites (DAMs; 83 upregulated versus 211 downregulated in OEGA compared to CON). The metabolic pathway analysis showed that these DAMs were mainly involved in the metabolic pathways of secondary metabolites, such as phenylpropanoids, phenylalanine, flavone, and flavonol biosynthesis. Thirteen flavonoids and isoflavones were identified as DAMs in OEGA and CON. We also discovered 25 OEGA-specific accumulated metabolites and found 10 that were associated with disease resistance. CcGASA4 may therefore play a functional role in activating the expression of MAPK signaling transduction pathway and disease resistance genes, inhibiting the expression of auxin- and ethylene-related genes, and activating or inhibiting the expression of brassinosteroid biosynthesis- and abscisic acid-related genes. CcGASA4 may also play a role in regulating the composition and abundance of flavonoids, isoflavones, amino acids, purines, and phenolic compounds. This study provides new insights into the molecular mechanisms of action of CcGASA4 in citrus plants.

A genetic map of the chromatin regulators to drug response in cancer cells.

BACKGROUND: Diverse drug vulnerabilities owing to the Chromatin regulators (CRs) genetic interaction across various cancers, but the identification of CRs genetic interaction remains challenging. METHODS: In order to provide a global view of the CRs genetic interaction in cancer cells, we developed a method to identify potential drug response-related CRs genetic interactions for specific cancer types by integrating the screen of CRISPR-Cas9 and pharmacogenomic response datasets. RESULTS: Totally, 625 drug response-related CRs synthetic lethality (CSL) interactions and 288 CRs synthetic viability (CSV) interactions were detected. Systematically network analysis presented CRs genetic interactions have biological function relationship. Furthermore, we validated CRs genetic interactions induce multiple omics deregulation in The Cancer Genome Atlas. We revealed the colon adenocarcinoma patients (COAD) with mutations of a CRs set (EP300, MSH6, NSD2 and TRRAP) mediate a better survival with low expression of MAP2 and could benefit from taxnes. While the COAD patients carrying at least one of the CSV interactions in Vorinostat CSV module confer a poor prognosis and may be resistant to Vorinostat treatment. CONCLUSIONS: The CRs genetic interaction map provides a rich resource to investigate cancer-associated CRs genetic interaction and proposes a powerful strategy of biomarker discovery to guide the rational use of agents in cancer therapy.

Efficacy of Liquid Embolic Agent Treatment in Hemorrhagic Peripheral Intracranial Aneurysms: A Single-Center Experience.

Objective: To evaluate the efficacy of liquid embolization agents for treating various hemorrhagic peripheral intracranial aneurysms. Methods: We retrospectively analyzed 38 patients who suffered from hemorrhagic peripheral intracranial aneurysms and were treated with liquid embolization agents. We used the modified Rankin scale for follow-up at 6 months postoperatively, and digital subtraction angiography follow-up was performed 6 months postoperatively. Results: Of the 38 patients (ten of simple peripheral intracranial aneurysms, six of Moyamoya disease (MMD), and 22 of arteriovenous malformation (AVM)), posterior circulation accounted for the most significant proportion (57.9%), followed by anterior circulation (21.1%) and intranidal aneurysms (21.1%). Intraoperative hemorrhage occurred in four cases, postoperative cerebral infarction occurred in four cases, two patients encountered microcatheter retention, and intraoperative thrombosis took place in the basilar artery of a patient with an arteriovenous malformation. A postoperative hemorrhage occurred in only one patient. At 6-month follow-up, 84.2% of patients had good prognosis outcomes, and 13.5% had poor outcomes. Conclusion: Liquid embolization agents are effective for hemorrhagic peripheral intracranial aneurysms; however, safety depends on the subtypes. For peripheral hemorrhagic aneurysms in MMD, the vessel architecture must be carefully evaluated before embolization.

Phenolic constituents with anti-inflammatory and cytotoxic activities from the rhizomes of Iris domestica.

Four undescribed flavonoid glucosides (iridins B-C, tectoridin A and ampelopsinin A); one undescribed phenolic glucoside (diplostephioside B); one undescribed phenolic compound (phenanthrenetriol A); and seventeen known compounds were isolated from the rhizomes of Iris domestica. The chemical structures of the undescribed compounds were established by spectroscopic/spectrometric data interpretation using HRESIMS, NMR, and ECD. Tectoridin A, nigricin A and naringenin exhibited anti-inflammatory activities with inhibition rates of 53.71%, 57.68% and 88.71%, respectively, against the NF-κB signaling pathway at a concentration of 10 µM. 4'-O-methylnyasol (10 µM) exhibited 84.91% antiproliferative activity against the K562 human leukemia cell line with an IC50 value of 4.20 µM.