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The multi‐substituted anilines are widely found in organic synthesis, medicinal chemistry and material science. The quest for robust and efficient methods to construct a diverse array of these compounds using readily accessible starting materials under simple reaction conditions is of utmost importance. Here, we report an unprecedented and efficient approach for the synthesis of 2,4‐di and 2,4,6‐trisubstituted anilines. With a simple molybdenum(VI) catalyst, a wide range of 2,4‐di and 2,4,6‐trisubstituted anilines were efficiently prepared in generally good to excellent yields from readily accessible ynones and allylic amines. The synthetic potential of this methodology was further underscored by its applications in several synthetic transformations, gram‐scale reactions, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this aniline formation might involve a cascade of aza‐Michael addition, [1,6]‐proton shift, cyclization, dehydration, 6π‐electrocyclization, and aromatization. This novel strategy provided a robust, simple, and modular approach for the syntheses of various valuable di‐ or trisubstituted anilines, some of which were otherwise challenging to access. [ABSTRACT FROM AUTHOR]

Fruit colour is a critical determinant for the appearance quality and commercial value of apple fruits. Viroid‐induced dapple symptom severely affects the fruit coloration, however, the underlying mechanism remains unknown. In this study, we identified an apple dimple fruit viroid (ADFVd)‐derived small interfering RNA, named vsiR693, which targeted the mRNA coding for a bHLH transcription factor MdPIF1 (PHYTOCHROME‐INTERACTING FACTOR 1) to regulate anthocyanin biosynthesis in apple. 5' RLM‐RACE and artificial microRNA transient expression system proved that vsiR693 directly targeted the mRNA of MdPIF1 for cleavage. MdPIF1 positively regulated anthocyanin biosynthesis in both apple calli and fruits, and it directly bound to G‐box element in the promoter of MdPAL and MdF3H, two anthocyanin biosynthetic genes, to promote their transcription. Expression of vsiR693 negatively regulated anthocyanin biosynthesis in both apple calli and fruits. Furthermore, co‐expression of vsiR693 and MdPIF1 suppressed MdPIF1‐promoted anthocyanin biosynthesis in apple fruits. Infiltration of ADFVd infectious clone suppressed coloration surrounding the injection sites in apple fruits, while a mutated version of ADFVd, in which the vsiR693 producing region was mutated, failed to repress fruit coloration around the injection sites. These data provide evidence that a viroid‐derived small interfering RNA targets host transcription factor to regulate anthocyanin biosynthesis in apple. Summary Statement: Our work identifies an apple dimple fruit viroid‐derived small RNA that mediating the cleavage of mRNA of a bHLH transcription factor MdPIF1, a positive regulator in anthocyanin biosynthesis, resulting in decreased synthesis and accumulation of anthocyanin in apple (Malus domestica) fruits. [ABSTRACT FROM AUTHOR]

Encapsulation of transition metals represents a crucial method for modifying the electronic structure and regulating the reactivity of fullerene, thereby expanding its applications. Herein, we present calculations with density functional theory methods to investigate the mechanisms of the Diels‐Alder (DA) reactions of cyclopentadiene and La@C60 or Gd@C60 as well as their tricationic derivatives. Our findings indicate that the encapsulation of La and Gd into the C60 cage is thermodynamically favorable. The DA reactions are favored by the presence of La and Gd, with lower barriers, though the regioselectivity, favoring 6−6 bonds in the fullerene, is not affected. The effect of external electric fields has been also considered. [ABSTRACT FROM AUTHOR]

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 is an endogenous neuropeptide with diverse functions, notably its critical role in inhibiting tumor proliferation. Radiotherapy is an important step in the standard treatment modality of many tumors. Combining radiotherapy with therapeutic agents represents a new and promising trend aimed at enhancing radiation sensitivity and improving tumor treatment efficacy. However, the efficacy of PACAP38 combined with radiotherapy on tumors has not yet been studied. Objective: This study aimed to investigate the impact of PACAP38, both independently and in combination with irradiation, on glioma and breast cancer cells, while elucidating the underlying mechanisms involved. Methods: We investigated the impact of PACAP38 independently and combined it with irradiation on glioma and breast cancer cells in vitro through cell counting kit-8, clonogenic formation, Edu assays, and in vivo through a xenograft tumor model. We further explored the molecular mechanisms underlying the inhibitory effects of PACAP38 on tumors using RNA sequencing, western blotting assay, immunohistochemistry, and immunofluorescence analysis. Further investigation of gene function and the downstream mechanism was carried out through small interfering RNA and overexpression lentivirus targeting the SRY-related high-mobility group box 6 (SOX6) gene and western blotting assay. Results: Our findings revealed that PACAP38 could effectively synergize with radiation to suppress the proliferation of glioma and breast cancer cells in vivo and in vitro. Molecular studies revealed that the inhibitory effect of PACAP38 on tumor cell proliferation was mediated by upregulating SOX6 protein expression through histone acetylation, thereby inhibiting the Wnt-β-catenin signaling pathway. Conclusion: PACAP38 synergizes with irradiation to suppress the proliferation of multiple cancer cells via regulating SOX6/Wnt/β-catenin signaling. This combination may represent a promising therapeutic strategy for cancer treatment, potentially improving outcomes for patients undergoing radiotherapy. [ABSTRACT FROM AUTHOR]

Cytochrome b5 (CB5), a small heme-binding protein, plays an important role in plant biotic and abiotic stress. Anthocyanin is a critical determinant for fruit coloration, however, whether CB5 is involved in regulating anthocyanin biosynthesis has not yet been investigated in apple fruit (Malus domestica). In this study, we determined that MdCYB5, an apple CB5 gene, was a positive regulator for anthocyanin biosynthesis in apple fruit. We first found that MdCYB5 showed a high sequence and structural similarity with Arabidopsis cytochrome b5 isoform E (CB5E) at the protein level. Quantitative reverse transcription PCR (qRT-PCR) analysis showed that MdCYB5 responds to light signals. Subcellular localization showed that MdCYB5 is localized to the cytoplasmin inthe epidermal cells of Nicotiana benthamiana leaves. Further investigation revealed that overexpressing MdCYB5 promoted anthocyanin biosynthesis in both apple calli and tissue-cultured apple seedlings. Furthermore, results of transient expression assay showed that overexpressing MdCYB5 promoted anthocyanin accumulation and fruit coloration in apple fruit. Taken together, this study suggests that MdCYB5 has a positive regulatory effect on anthocyanin biosynthesis in apple fruit. [ABSTRACT FROM AUTHOR]

Aims Cardiac cycle morphological changes can accelerate plaque growth proximal to myocardial bridging (MB) in the left anterior descending artery (LAD). To assess coronary computed tomography angiography (CCTA)-based vascular radiomics for predicting proximal plaque development in LAD MB. Methods and results Patients with repeated CCTA scans showing LAD MB without proximal plaque in index CCTA were included from Jinling Hospital as a development set. They were divided into training and internal testing in an 8:2 ratio. Patients from four other tertiary hospitals were set as external validation set. The endpoint was proximal plaque development of LAD MB in follow-up CCTA. Four vascular radiomics models were built: MB centreline (MB CL), proximal MB CL (pMB CL), MB cross-section (MB CS), and proximal MB CS (pMB CS), whose performances were evaluated using area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI). In total, 295 patients were included in the development (n = 192; median age, 54 ± 11 years; 137 men) and external validation sets (n = 103; median age, 57 ± 9 years; 57 men). The pMB CS vascular radiomics model exhibited higher AUCs in training, internal test, and external sets (AUC = 0.78, 0.75, 0.75) than the clinical and anatomical model (all P < 0.05). Integration of the pMB CS vascular radiomics model significantly raised the AUC of the clinical and anatomical model from 0.56 to 0.75 (P = 0.002), along with enhanced NRI [0.76 (0.37–1.14), P < 0.001] and IDI [0.17 (0.07–0.26), P < 0.001] in the external validation set. Conclusion The CCTA-based pMB CS vascular radiomics model can predict plaque development in LAD MB. [ABSTRACT FROM AUTHOR]

SUMMARY: In the field, necrosis area induced by pathogens is usually surrounded by a red circle in apple fruits. However, the underlying molecular mechanism of this phenomenon remains unclear. In this study, we demonstrated that accumulated salicylic acid (SA) induced by fungal infection promoted anthocyanin biosynthesis through MdNPR1‐MdTGA2.2 module in apple (Malus domestica). Inoculating apple fruits with Valsa mali or Botryosphaeria dothidea induced a red circle surrounding the necrosis area, which mimicked the phenotype observed in the field. The red circle accumulated a high level of anthocyanins, which was positively correlated with SA accumulation stimulated by fungal invasion. Further analysis showed that SA promoted anthocyanin biosynthesis in a dose‐dependent manner in both apple calli and fruits. We next demonstrated that MdNPR1, a master regulator of SA signaling, positively regulated anthocyanin biosynthesis in both apple and Arabidopsis. Moreover, MdNPR1 functioned as a co‐activator to interact with and enhance the transactivation activity of MdTGA2.2, which could directly bind to the promoters of anthocyanin biosynthetic and regulatory genes to promote their transcription. Suppressing expression of either MdNPR1 or MdTGA2.2 inhibited coloration of apple fruits, while overexpressing either of them significantly promoted fruit coloration. Finally, we revealed that silencing either MdNPR1 or MdTGA2.2 in apple fruits repressed SA‐induced fruit coloration. Therefore, our data determined that fungal‐induced SA promoted anthocyanin biosynthesis through MdNPR1‐MdTGA2.2 module, resulting in a red circle surrounding the necrosis area in apple fruits. Significance Statement: Pathogen‐stimulated salicylic acid promotes anthocyanin biosynthesis through MdNPR1‐MdTGA2.2 module, which facilitates formation of a red circle surrounding the necrosis region induced by pathogens. This work not only dissects a possible pathway that uncovers the molecular mechanism of pathogen‐induced anthocyanin accumulation but also complements and extends the biotic factors that modulate anthocyanin synthesis in plants. [ABSTRACT FROM AUTHOR]