SUMMARY
Flavonoids are major secondary metabolites derived from the plant phenylpropanoid pathway that play important roles in plant development and also have benefits for human health. So‐called MBW ...ternary complexes involving R2R3‐MYB and basic helix‐loop‐helix (bHLH) transcription factors along with WD‐repeat proteins have been reported to regulate expression of the biosynthetic genes in the flavonoid pathway. MYB4 and its closest homolog MYB7 have been suggested to function as repressors of phenylpropanoid metabolism. However, the detailed mechanism by which they act has not been fully elucidated. Here, we show that Arabidopsis thaliana MYB4 and its homologs MYB7 and MYB32 interact with the bHLH transcription factors TT8, GL3 and EGL3 and thereby interfere with the transcriptional activity of the MBW complexes. In addition, MYB4 can also inhibit flavonoid accumulation by repressing expression of the gene encoding Arogenate Dehydratase 6 (ADT6), which catalyzes the final step in the biosynthesis of phenylalanine, the precursor for flavonoid biosynthesis. MYB4 potentially represses not only the conventional ADT6 encoding the plastidial enzyme but also the alternative isoform encoding the cytosolic enzyme. We suggest that MYB4 plays dual roles in modulating the flavonoid biosynthetic pathway in Arabidopsis.
Significance Statement
Our results indicate that MYB4 can attenuate the transcriptional function of MYB‐bHLH‐WDR complexes, which are major regulators of flavonoid metabolism, by interacting with bHLH proteins. MYB4 directly represses the transcription of ADT6 encoding the enzyme catalyzing the last step of phenylalanine biosynthesis. These observations reveal unexpected cross‐talk between primary and secondary metabolism.
In the research field of hollow-core optical fiber (HCF), one type of fiber geometry with a leaky mode nature has unexpectedly taken center stage over the last couple of years: the so-called ...hollow-core anti-resonant fiber (ARF). The guidance mechanism of this ARF has been elucidated explicitly, the optical performance of the fiber has improved significantly, and the range of potential fiber application areas has expanded steadily. This paper will review our continuous efforts to understand, design, and fabricate this hollow-core ARF with the aim of lower loss and wider bandwidth. We also explore the possibility of using an advanced form of ARF in communications applications. In the long journey of looking for optical fibers that provide better performance than conventional solid-core glass fibers, exploitation of the hidden potential of artificial photonic micro-structures will continue to advance.
We developed hydroxysulfurization and alkoxysulfurization of styrenes using a visible‐light synthetic strategy in the absence of photocatalyst and oxidant. This strategy provided the corresponding ...β‐hydroxysulfides and β‐alkoxysulfides in moderate to good yields with high regioselectivity. The reaction was tolerated by a wide range of functional groups. This is the first example of ArSSAr/CBr4 system has been introduced into organic transformation.
The pivotal roles of phosphatidylinositol 3-kinases （PI3Ks） in human cancers have inspired active development of small molecules to inhibit these lipid kinases. However, the first-generation pan-PI3K ...and dual-PI3K/mTOR inhibitors have encountered problems in clinical trials, with limited efficacies as a monotherapeutic agent as well as a relatively high rate of side effects. It is increasingly recognized that different PI3K isoforms play non-redundant roles in particular tumor types, which has prompted the development of isoform-selective inhibitors for pre-selected patients with the aim for improving efficacy while decreasing undesirable side effects. The success of PI3K isoform-selective inhibitors is represented by CAL101 （Idelalisib）, a first-in-class PI3Kδ-selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin’s lymphoma and relapsed small lymphocytic lymphoma. Inhibitors targeting other PI3K isoforms are also being extensively developed. This review focuses on the recent progress in development of PI3K isoform-selective inhibitors for cancer therapy. A deeper understanding of the action modes of novel PI3K isoform-selective inhibitors will provide valuable information to further validate the concept of targeting specific PI3K isoforms, while the identification of biomarkers to stratify patients who are likely to benefit from the therapy will be essential for the success of these agents.
Transition metal‐based nitrogen‐doped carbon (M‐Nx‐C) is considered as a promising catalyst for the oxygen reduction reaction (ORR) in clean energy storage and conversion devices. Herein, ZnCo ...dual‐atomic sites are incorporated in hierarchical N‐doped carbon (HNC), with 1D nanotubes wrapped in 2D nanosheets structure (termed as 1D@2D ZnCo‐HNC), via a one‐step bio‐inspired pyrolysis. The feeding ratio of Zn to Co precursor and pyrolytic temperature are critically modulated to achieve well‐defined morphologies of the products, endowing them with the integrated merits of nanotubes and nanosheets as efficient ORR catalysts. Benefiting from the particular structure and electronic regulation of Zn on Co, the ZnCo‐Nx dual‐atomic system exhibits excellent ORR catalytic characteristics with an onset potential of 1.05 V and a half‐wave potential of 0.82 V. Density functional theory calculations further explain the regulating role of Zn, such that the adjusted Co in ZnCo‐Nx sites significantly reduces the energy cost to ultimately facilitate the ORR. Moreover, the Zn–air battery assembled with ZnCo‐HNC is capable of delivering the maximum power density of 123.7 mW cm−2 and robust stability for 110 h (330 cycles). This method provides a promising strategy for fabricating efficient transition metal‐based carbon catalysts for green energy devices.
With the unique 1D@2D structure and abundant ZnCo dual‐atomic sites, bio‐inspired ZnCo‐HNC exhibits excellent catalytic performances for the oxygen reduction reaction and a home‐assembled Zn–air battery. Density functional theory calculations further demonstrate that Co is the main active center in the ZnCo‐Nx system, while Zn serves as the charge adjuster.
An efficient and regioselective 4‐dimethylaminopyridine catalyzed 3+2 cycloaddition of isatin‐derived Morita−Baylis−Hillman adducts with azo esters was developed for the construction of ...3‐spiropyrazole‐2‐oxindoles. This protocol generated the desired spiropyrazoles in good to excellent yields with good functional group compatibility under mild reaction conditions.
Deep sea has an extreme environment which leads to biodiversity of microorganisms and their unique physical and biochemical mechanisms. Deep-sea derived microorganisms are more likely to produce ...novel bioactive substances with special mechanism of action for drug discovery. This article reviews secondary metabolites with biological activities such as anti-tumor, anti-bacterial, anti-viral, and anti-inflammatory isolated from deep-sea fungi and bacteria during 2018-2020. Effective methods for screening and obtaining natural active compounds from deep-sea microorganisms are also summarized, including optimizing the culture conditions, using genome mining technology, biosynthesis and so on. The comprehensive application of these methods makes broader prospects for the development and application of deep sea microbial bioactive substances.
The investigation concerning the B7-H1 expression in colorectal cancer cells is at an early stage. It is unclear whether B7-H1 expression may have diagnostic or prognostic value in colorectal ...carcinoma. Additionally, how B7-H1 is associated with the clinical features of colorectal carcinoma is not known. In order to investigate the relationship between B7-H1 and colorectal cancer, we analyzed B7-H1 expression and its effect in clinical specimens and HCT116 cells.
Paraffin-embedded specimens from 143 eligible patients were used to investigate the expression of CD274 by immunohistochemistry. We also examined whether B7-H1 itself may be related to cell proliferation, apoptosis, migration and invasion in colon cancer HCT116 cells.
Our results show that B7-H1 was highly expressed in colorectal carcinoma and was significantly associated with cell differentiation status and TNM (Tumor Node Metastasis) stage. Patients with positive B7-H1 expression showed a trend of shorter survival time. Using multivariate analysis, we demonstrate that positive B7-H1 expression is an independent predictor of colorectal carcinoma prognosis. Our results indicate that B7-H1 silencing with siRNA inhibits cell proliferation, migration and invasion. Furthermore, cell apoptosis was also increased by B7-H1 inhibition.
Positive B7-H1 expression is an independent predictor for colorectal carcinoma prognosis. Moreover, knockdown of B7-H1 can inhibit cell proliferation, migration and invasion.
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