Distinct roles of TREM2 in central nervous system cancers and peripheral cancers.

Glioblastomas (GBM) are incurable central nervous system (CNS) cancers characterized by substantial myeloid cell infiltration. Whether myeloid cell-directed therapeutic targets identified in peripheral non-CNS cancers are applicable to GBM requires further study. Here, we identify that the critical immunosuppressive target in peripheral cancers, triggering receptor expressed on myeloid cells-2 (TREM2), is immunoprotective in GBM. Genetic or pharmacological TREM2 deficiency promotes GBM progression in vivo. Single-cell and spatial sequencing reveals downregulated TREM2 in GBM-infiltrated myeloid cells. TREM2 negatively correlates with immunosuppressive myeloid and T cell exhaustion signatures in GBM. We further demonstrate that during GBM progression, CNS-enriched sphingolipids bind TREM2 on myeloid cells and elicit antitumor responses. Clinically, high TREM2 expression in myeloid cells correlates with better survival in GBM. Adeno-associated virus-mediated TREM2 overexpression impedes GBM progression and synergizes with anti-PD-1 therapy. Our results reveal distinct functions of TREM2 in CNS cancers and support organ-specific myeloid cell remodeling in cancer immunotherapy.

Chrysanthemum morifolium as a traditional herb: A review of historical development, classification, phytochemistry, pharmacology and application.

ETHNOPHARMACOLOGICAL RELEVANCE: In recent years, Chinese herbal medicine has gained more and more recognition in disease prevention and control due to its low toxicity and comprehensive treatment. C. morifolium (Chrysanthemum morifolium Ramat.), as the medicine food homology plant with the bioactivity of anti-oxidation, anti-inflammatory, neuroprotection and cardiovascular protection, has important therapeutic effects and health benefits for colds, inflammation, cardiovascular diseases and various chronic diseases. AIM OF THE STUDY: By reviewing the historical development, classification and distribution of germplasm resources, phytochemistry, pharmacology, and modern application of C. morifolium, the paper provides a reliable basis for the further research and application of chrysanthemum as therapeutic agents and functional additives. MATERIALS AND METHODS: The literature and information about C. morifolium published in the last ten years were collected from various platforms, including Google Scholar, PubMed, ScienceDirect, Web of Science and China Knowledge Network. RESULTS: A comprehensive analysis confirmed that C. morifolium originated in China, and it went through the development process from food and tea to medicine for more than 3000 years. During this period, different cultivars emerged through several breeding techniques and were distributed throughout the world. Moreover, A variety of chemical components such as flavonoids, phenolic acids, volatile oils, and terpenes in chrysanthemum have been proven they possess various pharmacology of anti-inflammatory, anti-oxidant, and prevention of chronic diseases by regulating inflammatory cytokines, oxidative stress responses and signaling pathways, which are the essential conditions to play a role in TCM, nutraceuticals and diet. CONCLUSION: This paper provides a comprehensive review of historical development, classification, phytochemistry, pharmacology, and modern application of C. morifolium. However, future studies should continue to focus on the bioactive compounds and the synergistic mechanism of the "multi-component, multi-target, and multi-pathway" of chrysanthemum, and it is necessary to develop more innovative products with therapeutic effects.

IFI35 regulates non-canonical NF-κB signaling to maintain glioblastoma stem cells and recruit tumor-associated macrophages.

Glioblastoma (GBM) is the most aggressive malignant primary brain tumor characterized by a highly heterogeneous and immunosuppressive tumor microenvironment (TME). The symbiotic interactions between glioblastoma stem cells (GSCs) and tumor-associated macrophages (TAM) in the TME are critical for tumor progression. Here, we identified that IFI35, a transcriptional regulatory factor, plays both cell-intrinsic and cell-extrinsic roles in maintaining GSCs and the immunosuppressive TME. IFI35 induced non-canonical NF-kB signaling through proteasomal processing of p105 to the DNA-binding transcription factor p50, which heterodimerizes with RELB (RELB/p50), and activated cell chemotaxis in a cell-autonomous manner. Further, IFI35 induced recruitment and maintenance of M2-like TAMs in TME in a paracrine manner. Targeting IFI35 effectively suppressed in vivo tumor growth and prolonged survival of orthotopic xenograft-bearing mice. Collectively, these findings reveal the tumor-promoting functions of IFI35 and suggest that targeting IFI35 or its downstream effectors may provide effective approaches to improve GBM treatment.

Efficacy, tolerability and safety of add-on third-generation antiseizure medications in treating focal seizures worldwide: a network meta-analysis of randomised, placebo-controlled trials.

Background: Adjunctive newer antiseizure medications (ASMs) are being used in patients with treatment-resistant focal-onset seizures (FOS). An updated network meta-analysis (NMA) was necessary to compile evidence in this critical area. Methods: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, and Scopus from their inception until 17 January 2024, evaluating the efficacy, tolerability, and safety of rufinamide (RUF), brivaracetam (BRV), cenobamate (CNB), eslicarbazepine (ESL), lacosamide (LCM), retigabine (RTG), and perampanel (PER) as adjunctive treatments for FOS. Efficacy outcomes included seizure response and seizure freedom. Tolerability was assessed by discontinuation due to adverse events (AEs). Safety outcomes were evaluated based on the number of patients experiencing at least one AE and serious adverse events (SAEs). This review is registered with PROSPERO (CRD42023485130). Findings: A total of 29 studies involving 11,750 participants were included. For seizure response, all ASMs were significantly superior to placebo, with RTG ranking highest, followed by CNB. Considering dosage, CNB 400 mg/d was top-ranked, followed by RTG 1200 mg/d. For seizure freedom, BRV was highest-ranked, followed by CNB, with BRV 100 mg/d leading, followed by CNB 400 mg/d. Regarding tolerability, LCM 600 mg/d had the lowest ranking, followed by CNB 400 mg/d. For the safety outcome of AEs, ESL 1200 mg/d was ranked lowest, followed by CNB 400 mg/d. Regarding SAEs, LCM 400 mg/d was ranked lowest, followed by RTG 1200 mg/d. Interpretation: ASMs at different dosages have varying efficacy and tolerability profiles. We have provided hierarchical rankings of ASMs for efficacy and safety outcomes. Our findings offer the most comprehensive evidence available to inform patients, families, physicians, guideline developers, and policymakers about the choice of ASMs in patients with treatment-resistant FOS. Funding: None.

A comprehensive review of TGA transcription factors in plant growth, stress responses, and beyond.

TGA transcription factors (TFs), belonging to the D clade of the basic region leucine zipper (bZIP) family, exhibit a specific ability to recognize and bind to regulatory elements with TGACG as the core recognition sequence, enabling the regulation of target gene expression and participation in various biological regulatory processes. In plant growth and development, TGA TFs influence organ traits and phenotypes, including initial root length and flowering time. They also play a vital role in responding to abiotic stresses like salt, drought, and cadmium exposure. Additionally, TGA TFs are involved in defending against potential biological stresses, such as fungal bacterial diseases and nematodes. Notably, TGA TFs are sensitive to the oxidative-reductive state within plants and participate in pathways that aid in the elimination of reactive oxygen species (ROS) generated during stressful conditions. TGA TFs also participate in multiple phytohormonal signaling pathways (ABA, SA, etc.). This review thoroughly examines the roles of TGA TFs in plant growth, development, and stress response. It also provides detailed insights into the mechanisms underlying their involvement in physiological and pathological processes, and their participation in plant hormone signaling. This multifaceted exploration distinguishes this review from others, offering a comprehensive understanding of TGA TFs.

Noninvasive radiomics model reveals macrophage infiltration in glioma.

Preoperative MRI is an essential diagnostic and therapeutic reference for gliomas. This study aims to evaluate the prognostic aspect of a radiomics biomarker for glioma and further investigate its relationship with tumor microenvironment and macrophage infiltration. We covered preoperative MRI of 664 glioma patients from three independent datasets: Jiangsu Province Hospital (JSPH, n = 338), The Cancer Genome Atlas dataset (TCGA, n = 252), and Repository of Molecular Brain Neoplasia Data (REMBRANDT, n = 74). Incorporating a multistep post-processing workflow, 20 radiomics features (Rads) were selected and a radiomics survival biomarker (RadSurv) was developed, proving highly efficient in risk stratification of gliomas (cut-off = 1.06), as well as lower-grade gliomas (cut-off = 0.64) and glioblastomas (cut-off = 1.80) through three fixed cut-off values. Through immune infiltration analysis, we found a positive correlation between RadSurv and macrophage infiltration (RMΦ = 0.297, p < 0.001; RM2Φ = 0.241, p < 0.001), further confirmed by immunohistochemical-staining (glioblastomas, n = 32) and single-cell sequencing (multifocal glioblastomas, n = 2). In conclusion, RadSurv acts as a strong prognostic biomarker for gliomas, exhibiting a non-negligible positive correlation with macrophage infiltration, especially with M2 macrophage, which strongly suggests the promise of radiomics-based models as a preoperative alternative to conventional genomics for predicting tumor macrophage infiltration and provides clinical guidance for immunotherapy.

Dual Role of CXCL8 in Maintaining the Mesenchymal State of Glioblastoma Stem Cells and M2-Like Tumor-Associated Macrophages.

PURPOSE: The dynamic interplay between glioblastoma stem cells (GSC) and tumor-associated macrophages (TAM) sculpts the tumor immune microenvironment (TIME) and promotes malignant progression of glioblastoma (GBM). However, the mechanisms underlying this interaction are still incompletely understood. Here, we investigate the role of CXCL8 in the maintenance of the mesenchymal state of GSC populations and reprogramming the TIME to an immunosuppressive state. EXPERIMENTAL DESIGN: We performed an integrative multi-omics analyses of RNA sequencing, GBM mRNA expression datasets, immune signatures, and epigenetic profiling to define the specific genes expressed in the mesenchymal GSC subsets. We then used patient-derived GSCs and a xenograft murine model to investigate the mechanisms of tumor-intrinsic and extrinsic factor to maintain the mesenchymal state of GSCs and induce TAM polarization. RESULTS: We identified that CXCL8 was preferentially expressed and secreted by mesenchymal GSCs and activated PI3K/AKT and NF-κB signaling to maintain GSC proliferation, survival, and self-renewal through a cell-intrinsic mechanism. CXCL8 induced signaling through a CXCR2-JAK2/STAT3 axis in TAMs, which supported an M2-like TAM phenotype through a paracrine, cell-extrinsic pathway. Genetic- and small molecule-based inhibition of these dual complementary signaling cascades in GSCs and TAMs suppressed GBM tumor growth and prolonged survival of orthotopic xenograft-bearing mice. CONCLUSIONS: CXCL8 plays critical roles in maintaining the mesenchymal state of GSCs and M2-like TAM polarization in GBM, highlighting an interplay between cell-autonomous and cell-extrinsic mechanisms. Targeting CXCL8 and its downstream effectors may effectively improve GBM treatment.

Sterol regulatory element-binding protein 2 maintains glioblastoma stem cells by keeping the balance between cholesterol biosynthesis and uptake.

BACKGROUND: Glioblastomas (GBMs) display striking dysregulation of metabolism to promote tumor growth. Glioblastoma stem cells (GSCs) adapt to regions of heterogeneous nutrient availability, yet display dependency on de novo cholesterol biosynthesis. The transcription factor Sterol Regulatory Element-Binding Protein 2 (SREBP2) regulates cholesterol biosynthesis enzymes and uptake receptors. Here, we investigate adaptive behavior of GSCs under different cholesterol supplies. METHODS: In silico analysis of patient tumors demonstrated enrichment of cholesterol synthesis associated with decreased angiogenesis. Comparative gene expression of cholesterol biosynthesis enzymes in paired GBM specimens and GSCs were performed. In vitro and in vivo loss-of-function genetic and pharmacologic assays were conducted to evaluate the effect of SREBP2 on GBM cholesterol biosynthesis, proliferation, and self-renewal. Chromatin immunoprecipitation quantitative real-time PCR was leveraged to map the regulation of SREBP2 to cholesterol biosynthesis enzymes and uptake receptors in GSCs. RESULTS: Cholesterol biosynthetic enzymes were expressed at higher levels in GBM tumor cores than in invasive margins. SREBP2 promoted cholesterol biosynthesis in GSCs, especially under starvation, as well as proliferation, self-renewal, and tumor growth. SREBP2 governed the balance between cholesterol biosynthesis and uptake in different nutrient conditions. CONCLUSIONS: SREBP2 displays context-specific regulation of cholesterol biology based on its availability in the microenvironment with induction of cholesterol biosynthesis in the tumor core and uptake in the margin, informing a novel treatment strategy for GBM.

Bamboo leaf: A review of traditional medicinal property, phytochemistry, pharmacology, and purification technology.

ETHNOPHARMACOLOGICAL RELEVANCE: Bamboos are perennial evergreen plants that belong to the subfamily Bambusoideae of the true grass family Poaceae, with more than thousands of species distributed around the world. They are used as a traditional medicine with demonstrated effects of anti-oxidation, free radical scavenging, anti-inflammatory, liver protection and ameliorating cognitive deficits. Bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic and nervous system diseases. AIM OF THE STUDY: This review aims to provide up-to-date information on the traditional medicinal properties, phytochemistry, pharmacology, and purification technologies of bamboo leaf. MATERIALS AND METHODS: Relevant information on bamboo leaf was obtained by an online search of worldwide accepted scientific databases (Web of Science, ScienceDirect, Elsevier, SpringerLink, ACS Publications, Wiley Online Library and CNKI). RESULTS: More than 100 chemical compounds, including flavonoids and flavonoid glycosides, volatile components, phenolic acids, polysaccharide, coenzyme Q10, phenylpropanoid and amino acids have been reported to be present. These compounds were usually extracted by column chromatography and membrane separation technologies. Preparative high performance liquid chromatography (PHPLC), high-speed counter-current chromatography (HSCCC), simulated moving bed chromatography (SMB) and dynamic axial compression chromatography (DAC) were the advanced separation technologies have been used to isolate C-glycosides from bamboo leaf flavonoid, the main bioactive ingredient of bamboo leaf. Currently, bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic, hepatic diseases and nervous system related symptoms, which are attributed to the presence of bioactive components of bamboo leaf. CONCLUSIONS: Phytochemical and pharmacological analyses of bamboo leaf have been revealed in recent studies. However, most of the pharmacological studies on bamboo leaf have focused on bamboo leaf flavonoids. Further studies need to pay more attention to other phytochemical components of bamboo leaf. In addition, there is lack of sufficient clinical data and toxicity studies on bamboo leaf. Therefore, more clinical and toxicity researches on this plant and constituents are recommended.

PGC1α Degradation Suppresses Mitochondrial Biogenesis to Confer Radiation Resistance in Glioma.

Radiotherapy is a major component of standard-of-care treatment for gliomas, the most prevalent type of brain tumor. However, resistance to radiotherapy remains a major concern. Identification of mechanisms governing radioresistance in gliomas could reveal improved therapeutic strategies for treating patients. Here, we report that mitochondrial metabolic pathways are suppressed in radioresistant gliomas through integrated analyses of transcriptomic data from glioma specimens and cell lines. Decreased expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α), the key regulator of mitochondrial biogenesis and metabolism, correlated with glioma recurrence and predicted poor prognosis and response to radiotherapy of patients with glioma. The subpopulation of glioma cells with low-mitochondrial-mass exhibited reduced expression of PGC1α and enhanced resistance to radiotherapy treatment. Mechanistically, PGC1α was phosphorylated at serine (S) 636 by DNA-dependent protein kinase in response to irradiation. Phosphorylation at S636 promoted the degradation of PGC1α by facilitating its binding to the E3 ligase RNF34. Restoring PGC1α activity with expression of PGC1α S636A, a phosphorylation-resistant mutant, or a small-molecule PGC1α activator ZLN005 increased radiosensitivity of resistant glioma cells by reactivating mitochondria-related reactive oxygen species production and inducing apoptotic effects both in vitro and in vivo. In summary, this study identified a self-protective mechanism in glioma cells in which radiotherapy-induced degradation of PGC1α and suppression of mitochondrial biogenesis play a central role. Targeted activation of PGC1α could help improve response to radiotherapy in patients with glioma. SIGNIFICANCE: Glioma cells reduce mitochondrial biogenesis by promoting PGC1α degradation to promote resistance to radiotherapy, indicating potential therapeutic strategies to enhance radiosensitivity.

Temporal-spatial low shear stress induces heterogenous distribution of hematopoietic stem cell budding in zebrafish.

Hematopoietic stem/progenitor cells (HSPCs) originate from endothelial cells (ECs) localized on the ventral side of the dorsal aorta (DA), and hemodynamic parameters may suffer sharp changes in DA at HSPCs development stage for intersegmental vessel formation. However, the temporal-spatial shear stress parameters and biomechanics mechanisms of HSPC budding remain unknown. Here, we found that the hematopoietic endothelium (HE) in the aorta-gonad-mesonephros was heterogeneous; that is, HEs were mainly distributed at the ventral side of the vascular bifurcation in zebrafish embryos, which was found to show low shear stress (LSS) through numerical simulation analysis. Furthermore, HSPCs localized in the posterior somite of aorta-gonad-mesonephros with slow velocity. On the temporal scale, there was a slow velocity and LSS during HE budding from 36 h post-fertilization and decreased shear stress with drug expanded HSPC numbers. Mechanistically, matrix metalloproteinase (MMP) expression and macrophage chemotaxis were significantly increased in HEs by RNA-seq. After treatment with an MMP13 inhibitor, HSPCs were significantly reduced in both the aorta-gonad-mesonephros and caudal hematopoietic tissue in embryos. Our results show that HSPC budding is heterogeneous, and the mechanism is that physiological LSS controls the emergence of HSPCs by promoting the accumulation of macrophages and subsequent MMP expression.

ß2-Microglobulin Maintains Glioblastoma Stem Cells and Induces M2-like Polarization of Tumor-Associated Macrophages.

Glioblastoma (GBM) is a complex ecosystem that includes a heterogeneous tumor population and the tumor-immune microenvironment (TIME), prominently containing tumor-associated macrophages (TAM) and microglia. Here, we demonstrated that ß2-microglobulin (B2M), a subunit of the class I major histocompatibility complex (MHC-I), promotes the maintenance of stem-like neoplastic populations and reprograms the TIME to an anti-inflammatory, tumor-promoting state. B2M activated PI3K/AKT/mTOR signaling by interacting with PIP5K1A in GBM stem cells (GSC) and promoting MYC-induced secretion of transforming growth factor-ß1 (TGFß1). Inhibition of B2M attenuated GSC survival, self-renewal, and tumor growth. B2M-induced TGFß1 secretion activated paracrine SMAD and PI3K/AKT signaling in TAMs and promoted an M2-like macrophage phenotype. These findings reveal tumor-promoting functions of B2M and suggest that targeting B2M or its downstream axis may provide an effective approach for treating GBM. SIGNIFICANCE: ß2-microglobulin signaling in glioblastoma cells activates a PI3K/AKT/MYC/TGFß1 axis that maintains stem cells and induces M2-like macrophage polarization, highlighting potential therapeutic strategies for targeting tumor cells and the immunosuppressive microenvironment in glioblastoma.

Association of genetic polymorphisms of PCSK9 with type 2 diabetes in Uygur Chinese population.

BACKGROUND: PCSK9 gene expression is associated with biological processes such as lipid metabolism, glucose metabolism, and inflammation. In the present study, our primary objective was to assess the association between the single-nucleotide polymorphisms in the PCSK9 gene and type 2 diabetes in Uygur subjects, in Xinjiang, China. METHODS: We designed a case-control study including 662 patients diagnosed with T2DM and 1220 control subjects. Four single-nucleotide polymorphisms (rs11583680, rs2483205, rs2495477 and rs562556) of PCSK9 gene were genotyped using the improved multiplex ligation detection reaction technique. RESULTS: For rs2483205, the distribution of genotypes, dominant model (CC vs CT + TT), overdominant model (CC + TT vs CT) showed significant differences between T2DM patients and the controls (P = 0.011 and P = 0.041 respectively). For rs2495477, the distribution of genotypes, the dominant model (AA vs GA + GG) showed significant differences between T2DM patients and the controls (P = 0.024). Logistic regression analysis suggested after adjustment of other confounders, the differences remained significant between the two groups [for rs2483205 CC vs CT + TT: odds ratio (OR) = 1.321, 95% confidence interval (CI) 1.078-1.617, P = 0.007; CC + TT vs CT: OR = 1.255, 95% CI 1.021-1.542, P = 0.03; for rs2495477 AA vs GA + GG: OR = 1.297, 95% CI 1.060-1.588, P = 0.012]. CONCLUSION: The present study indicated that CT + TT genotype and CT genotype of rs2483205, as well as GA + GG genotype of rs2495477 in PCSK9 gene were associated with an increased risk of type 2 diabetes in the Uygur population in Xinjiang.

Functional analysis of the ScAG and ScAGL11 MADS-box transcription factors for anthocyanin biosynthesis and bicolour pattern formation in Senecio cruentus ray florets.

Cineraria (Senecio cruentus) is an ornamental plant with pure colour and bicolour cultivars, widely used for landscaping. Anthocyanin biosynthesis influences coloration patterns in cineraria. However, how anthocyanins accumulate and distribute in cineraria is poorly understood. This study investigated the molecular mechanisms underlying anthocyanin biosynthesis and bicolour formation in cineraria using pure colour and bicolour cultivars. Transcriptome and gene expression analysis showed that five genes, ScCHS2, ScF3H1, ScDFR3, ScANS, and ScbHLH17, were inhibited in the white cultivar and colourless regions of bicolour cultivars. In contrast, two MADS-box genes, ScAG and ScAGL11, showed significantly higher expression in the colourless regions of bicolour cultivars. ScAG and ScAGL11 were localized in the nucleus and co-expressed with the bicolour trait. Further functional analysis verified that ScAG inhibits anthocyanin accumulation in tobacco (Nicotiana tabacum). However, virus-induced gene silencing (VIGS) experiments showed that silencing of ScAG and ScAGL11 increases anthocyanin content in cineraria leaves. Similar results were observed when ScAG and ScAGL11 were silenced in the cineraria capitulum, accompanied by the smaller size of the colourless region, specifically in the ScAG/ScAGL11-silenced plants. The expression of ScCHS2, ScDFR3, and ScF3H1 increased in silenced cineraria leaves and capitulum. Furthermore, yeast two-hybrid and bimolecular fluorescence complementation experiments demonstrated that ScAG interacts with ScAGL11. Moreover, ScAG directly inhibited the transcription of ScF3H1 while ScAGL11 inhibited ScDFR3 expression by binding to their promoters separately. The findings reported herein indicate that ScAG and ScAGL11 negatively regulate anthocyanin biosynthesis in cineraria ray florets, and their differential expression in ray florets influences the bicolour pattern appearance.

Lattice QCD Calculation of the Two-Photon Exchange Contribution to the Muonic-Hydrogen Lamb Shift.

We develop a method for lattice QCD calculation of the two-photon exchange contribution to the muonic-hydrogen Lamb shift. To demonstrate its feasibility, we present the first lattice calculation with a gauge ensemble at m_{π}=142 MeV. By adopting the infinite-volume reconstruction method along with an optimized subtraction scheme, we obtain with statistical uncertainty ΔE_{TPE}=-28.9(4.9) µeV+93.72 µeV/fm^{2}·⟨r_{p}^{2}⟩, or ΔE_{TPE}=37.4(4.9) µeV, which is consistent with the previous theoretical results in a range of 20-50 µeV.

Copy number amplification and SP1-activated lncRNA MELTF-AS1 regulates tumorigenesis by driving phase separation of YBX1 to activate ANXA8 in non-small cell lung cancer.

Long non-coding RNAs (lncRNAs) are reported to play key roles in tumorigenesis. However, the mechanisms underlying lncRNA-mediated regulation of RNA-binding protein phase separation in tumorigenesis have not been completely elucidated. In this study, an oncogenic lncRNA MELTF-AS1 was identified using systematic data analysis, screening, and verification. MELTF-AS1 was markedly upregulated in non-small cell lung cancer (NSCLC). High MELTF-AS1 levels were associated with advanced tumor-node-metastasis stage (TNM), high tumor size, and decreased survival time. Functionally, MELTF-AS1 regulated cell proliferation and metastasis in vitro and in vivo. RNA sequencing analysis revealed that MELTF-AS1 knockdown specifically modulated genes associated with cell proliferation, apoptosis, and migration. Mechanistically, at the genome level, copy number amplification promoted MELTF-AS1 expression. At the transcriptional level, the transcription factor SP1 directly activated MELTF-AS1 transcription by binding to its promoter. Furthermore, MELTF-AS1 could directly bind and drive the phase separation of YBX1, which was an RNA-binding protein and involved in tumorigenesis, thus activating ANXA8 transcription and promoting tumorigenesis of NSCLC. Aberrant activation of ANXA8 and promotion of tumorigenesis have been found in a variety of tumors. These novel findings demonstrated the critical role of MELTF-AS1-driven phase separation-mediated transcriptional regulation and provided a potential novel diagnostic and therapeutic target for NSCLC.

The transcription factor complex CmAP3-CmPI-CmUIF1 modulates carotenoid metabolism by directly regulating carotenogenic gene CmCCD4a-2 in chrysanthemum.

Carotenoids are one of the most important pigments for the coloring in many plants, fruits and flowers. Recently, significant progress has been made in carotenoid metabolism. However, the specific understanding on transcriptional regulation controlling the expression of carotenoid metabolic genes remains extremely limited. Anemone-type chrysanthemum, as a special group of chrysanthemum cultivars, contain elongated disc florets in capitulum, which usually appear in different colors compared with the ray florets since accumulating distinct content of carotenoids. In this study, the carotenoid composition and content of the ray and disc florets of an anemone-type chrysanthemum cultivar 'Dong Li Fen Gui' were analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and the key structural gene CmCCD4a-2, of which differential expression resulted in the distinct content of carotenoids accumulated in these two types of florets, was identified. Then the promoter sequence of CmCCD4a-2 was used as bait to screen a chrysanthemum flower cDNA library and two transcription factors, CmAP3 and CmUIF1 were identified. Y2H, BiFC and Y3H experiments demonstrated that these two TFs were connected by CmPI to form CmAP3-CmPI-CmUIF1 TF complex. This TF complex regulated carotenoid metabolism through activating the expression of CmCCD4a-2 directly. Furthermore, a large number of target genes regulated directly by the CmAP3-CmPI-CmUIF1 TF complex, including carotenoid biosynthetic genes, flavonoid biosynthetic genes and flower development-related genes, were identified by DNA-affinity purification sequencing (DAP-seq), which indicated that the CmAP3-CmPI-CmUIF1 TF complex might participate in multiple processes. These findings expand our knowledge for the transcriptional regulation of carotenoid metabolism in plants and will be helpful to manipulating carotenoid accumulation in chrysanthemum.

Approach to breech face impression comparison based on the robust estimation of a correspondence function.

Forensic firearm analysis concerns an attempt to determine if ammunition is associated with a specific firearm based on tool-marks produced by it. A feature-based method using the Scale Invariant Feature Transform (SIFT) and RANdom SAmple Consensus (RANSAC) integration algorithm had been suggested to allow the automated comparison of breech face impressions. In this paper, an estimation method is proposed to establish a correspondence function among the features of comparison impression pairs, aiming to further improve the robustness and repeatability of automated feature matching. During the application of the iterative establishment algorithm, the Support Vector Regression (SVR) method is repeated to estimate the correspondence function based on current feature correspondences, and a robust weighting method excludes egregious outliers among putative correspondences by updating additional weightings. Moreover, the consistency detection method is adopted to overcome the over-fitting problem in SVR. Validation tests of the proposed method are conducted on three sets of cartridge case's breech face impressions; namely the Fadul set consisting of 40 cartridge cases ejected from 10 Ruger P95PR15 pistols, the Weller sets containing 95 cartridge cases obtained from 11 Ruger P95DC firearms and the Lightstone set containing 30 cartridge cases from 10 SW40VE S&W Sigma pistol slides. Test results show that most known matching (KM) pairs possess no less than 20 matching feature points while the non-matching (KNM) pairs all maintain 3-8 correspondences. It also indicates that the feature-based method has apparent advantages in dealing with granular impressions with local peaks and valleys features, and poor performance on the striation marks. The clear distinction between KM and KNM impression pairs demonstrates the feasibility of the proposed method in ballistic feature comparison. Compared to the random hypothesize-and-verify modeling of RANSAC, this method can retain more reliable matching feature points of the impression pair to ensure the repeatability of feature correspondence selection.

The chrysanthemum lavandulifolium genome and the molecular mechanism underlying diverse capitulum types.

Cultivated chrysanthemum (Chrysanthemum × morifolium Ramat.) is a beloved ornamental crop due to the diverse capitula types among varieties, but the molecular mechanism of capitulum development remains unclear. Here, we report a 2.60 Gb chromosome-scale reference genome of C. lavandulifolium, a wild Chrysanthemum species found in China, Korea and Japan. The evolutionary analysis of the genome revealed that only recent tandem duplications occurred in the C. lavandulifolium genome after the shared whole genome triplication (WGT) in Asteraceae. Based on the transcriptomic profiling of six important developmental stages of the radiate capitulum in C. lavandulifolium, we found genes in the MADS-box, TCP, NAC and LOB gene families that were involved in disc and ray floret primordia differentiation. Notably, NAM and LOB30 homologs were specifically expressed in the radiate capitulum, suggesting their pivotal roles in the genetic network of disc and ray floret primordia differentiation in chrysanthemum. The present study not only provides a high-quality reference genome of chrysanthemum but also provides insight into the molecular mechanism underlying the diverse capitulum types in chrysanthemum.

ScGST3 and multiple R2R3-MYB transcription factors function in anthocyanin accumulation in Senecio cruentus.

Anthocyanins are important flavonoid pigments involved in the colouring of flowers and fruits. They are synthesized on the cytoplasmic surface of the endoplasmic reticulum and transported into the vacuole for storage. Previous reports have suggested that glutathione S-transferase (GST) is involved in anthocyanin transport. However, due to the limitation of plant materials, most GSTs only participate in the cyanidin or delphinidin transport pathway. Here, an anthocyanin-related GST, ScGST3, was identified from the transcriptome of cineraria. The expression pattern of ScGST3 was highly consistent with anthocyanin accumulation in ray florets. Molecular complementation of Arabidopsis tt19 indicated that the overexpression of ScGST3 restores the anthocyanin-deficient phenotype of the mutant. Virus-induced gene silencing (VIGS) of ScGST3 in carmine and blue cineraria leaves could inhibit anthocyanin accumulation, further confirming the function of ScGST3 in anthocyanin accumulation. In vitro assays showed that ScGST3 increases the water solubility of cyanidin-3-O-glucoside (C3G) and delphinidin-3-O-glucosid (D3G). In addition, we also identified two anthocyanin-related MYB transcription factors, ScMYB3 and ScMYB6. The expression pattern of these two genes was also highly consistent with anthocyanin accumulation. Faded abaxial leaf phenotypes were observed after the silencing of ScMYB3 and ScMYB6, and the expression levels of partial structural genes were repressed. Based on the results from dual-luciferase assays and yeast one-hybrid assays, ScMYB3 can activate the promoter of ScGST3. Collectively, the transcription of ScGST3 is regulated by ScMYB3, which plays an important role in the transport of C3G and D3G in cineraria.