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"Yi, Fang"
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Selective autophagy of intracellular organelles: Recent research advances
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs,
. In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure,
. Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Journal Article
Solution structures of multiple G-quadruplex complexes induced by a platinum(II)-based tripod reveal dynamic binding
DNA G-quadruplexes are not only attractive drug targets for cancer therapeutics, but also have important applications in supramolecular assembly. Here, we report a platinum(II)-based tripod (Pt-tripod) specifically binds the biological relevant hybrid-1 human telomeric G-quadruplex (Tel26), and strongly inhibits telomerase activity. Further investigations illustrate Pt-tripod induces the formation of monomeric and multimeric Pt-tripod‒Tel26 complex structures in solution. We solve the 1:1 and the unique dimeric 4:2 Pt-tripod–Tel26 complex structures by NMR. The structures indicate preferential binding of Pt-tripod to the 5ʹ-end of Tel26 at a low Pt-tripod/Tel26 ratio of 0–1.0. After adding more Pt-tripod, the Pt-tripod binds the 3ʹ-end of Tel26, unexpectedly inducing a unique dimeric 4:2 structure interlocked by an A:A non-canonical pair at the 3ʹ-end. Our structures provide a structural basis for understanding the dynamic binding of small molecules with G-quadruplex and DNA damage mechanisms, and insights into the recognition and assembly of higher-order G-quadruplexes.
DNA G-quadruplexes occur in oncologically relevant regions, thus are interesting targets for cancer research and treatment. Here, the authors solved the 1:1 and 4:2 (ligand/DNA) NMR structures of human telomeric DNA in complex with platinum(II)-tripod ligand and show that the binding is dynamic.
Journal Article
Influence of differing nitrate and nitrogen availability on flowering control in Arabidopsis
Nitrogen, an essential macronutrient for plants, regulates many aspects of plant growth and development. Nitrate is one of the major forms of nitrogen taken up by plants from the soil. Nitrate and nitrogen have been reported to regulate flowering; while some studies have shown that lower nitrate/nitrogen promoted flowering, others have reported the opposite trend. To elucidate how nitrate/nitrogen affects flowering, we reviewed the existing literature and conducted experiments to examine flowering time under a wide range of nitrate concentrations using two growth systems. From the literature review and our experiments, we established that differing nitrate availability results in a U-shaped flowering curve, with an optimal concentration of nitrate facilitating flowering and concentrations above or below this optimal concentration delaying flowering. The role of nitrate and nitrogen in regulating flowering has been elucidated by several transcriptomic and mutant studies, which have suggested close interactions between nitrate/nitrogen, phosphate, the circadian clock, photosynthesis, and, potentially, hormones. We discuss several possible molecular mechanisms underlying the U-shaped flowering response.
Journal Article
CCL8 secreted by tumor-associated macrophages promotes invasion and stemness of glioblastoma cells via ERK1/2 signaling
Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.
Journal Article
Ampere-level current density ammonia electrochemical synthesis using CuCo nanosheets simulating nitrite reductase bifunctional nature
The development of electrocatalysts capable of efficient reduction of nitrate (NO
3
−
) to ammonia (NH
3
) is drawing increasing interest for the sake of low carbon emission and environmental protection. Herein, we present a CuCo bimetallic catalyst able to imitate the bifunctional nature of copper-type nitrite reductase, which could easily remove NO
2
−
via the collaboration of two active centers. Indeed, Co acts as an electron/proton donating center, while Cu facilitates NO
x
−
adsorption/association. The bio-inspired CuCo nanosheet electrocatalyst delivers a 100 ± 1% Faradaic efficiency at an ampere-level current density of 1035 mA cm
−2
at −0.2 V
vs
. Reversible Hydrogen Electrode. The NH
3
production rate reaches a high activity of 4.8 mmol cm
−2
h
−1
(960 mmol g
cat
−1
h
−1
). A mechanistic study, using electrochemical in situ Fourier transform infrared spectroscopy and shell-isolated nanoparticle enhanced Raman spectroscopy, reveals a strong synergy between Cu and Co, with Co sites promoting the hydrogenation of NO
3
−
to NH
3
via adsorbed *H species. The well-modulated coverage of adsorbed *H and *NO
3
led simultaneously to high NH
3
selectivity and yield.
Electroreduction of NO
3
−
to NH
3
is drawing increasing interest. Here, the authors designed a CuCo catalyst imitating the bifunctional nature of Cu-type nitrite reductase to deliver an ampere-level current density for NH
3
formation.
Journal Article
Non-Covalent Functionalization of Carbon Nanotubes for Electrochemical Biosensor Development
Carbon nanotubes (CNTs) have been widely studied and used for the construction of electrochemical biosensors owing to their small size, cylindrical shape, large surface-to-volume ratio, high conductivity and good biocompatibility. In electrochemical biosensors, CNTs serve a dual purpose: they act as immobilization support for biomolecules as well as provide the necessary electrical conductivity for electrochemical transduction. The ability of a recognition molecule to detect the analyte is highly dependent on the type of immobilization used for the attachment of the biomolecule to the CNT surface, a process also known as biofunctionalization. A variety of biofunctionalization methods have been studied and reported including physical adsorption, covalent cross-linking, polymer encapsulation etc. Each method carries its own advantages and limitations. In this review we provide a comprehensive review of non-covalent functionalization of carbon nanotubes with a variety of biomolecules for the development of electrochemical biosensors. This method of immobilization is increasingly being used in bioelectrode development using enzymes for biosensor and biofuel cell applications.
Journal Article
Maize ZmPT7 regulates Pi uptake and redistribution which is modulated by phosphorylation
Summary Phosphorus, an essential mineral macronutrient, is a major constituent of fertilizers for maize (Zea mays L.) production. However, the molecular mechanisms of phosphate (Pi) acquisition in maize plants and its redistribution remain unclear. This study presents the functional characterization of ZmPT7 in Pi uptake and redistribution in maize. The ZmPT7 was expressed in roots and leaves, and induced during Pi starvation. The ZmPT7 complemented the Pi‐uptake deficiency of yeast mutant phoΔnull and Arabidopsis mutant pht1;1Δ4Δ, indicating that ZmPT7 functioned as a Pi transporter. We generated zmpt7 mutants by CRISPR/Cas9 and ZmPT7‐overexpressing lines. The zmpt7 mutants showed reduced, whereas the ZmPT7‐overexpressing lines displayed increased Pi‐uptake capacity and Pi redistribution from old to young leaves, demonstrating that ZmPT7 played central roles in Pi acquisition and Pi redistribution from old to young leaves. The ZmCK2 kinases phosphorylated ZmPT7 at Ser‐521 in old maize leaves, which enhanced transport activity of ZmPT7. The Ser‐520 of Arabidopsis AtPHT1;1, a conserved residue of ZmPT7 Ser‐521, was also phosphorylated by AtCK2 kinase, and the mutation of Ser‐520 to Glu (phosphorylation mimic) yielded enhanced transport activity of AtPHT1;1. Taken together, these results indicate that ZmPT7 plays important roles in Pi acquisition and redistribution, and its transport activity is modulated by phosphorylation.
Journal Article
Strangeness production in Au+Au collisions at √SNN = 14.6, 19.6, and 200 GeV with the STAR experiment
Strangeness production has been suggested as a sensitive probe to the early dynamics of the deconfined matter created in heavy-ion collisions. In this presentation, we report new measurements of strange hadron (Ks0, Λ ¯Λ, Ξ, ¯Ξ, ϕ) production in Au+Au collisions at √SNN = 14.6, 19.6 GeV from STAR BESII and Ω(¯Ω) production in Au+Au collisions at √SNN = 200 GeV, including rapidity spectra, nuclear modification factors RCP and Ω-to-ϕ ratios. Benefiting from the iTPC upgrade, the strangeness measurements are now extended from mid-rapidity (|y| < 0.5, BES-I) to a larger rapidity range (|y| < 1.0).
Conference Proceeding
circ_PPAPDC1A promotes Osimertinib resistance by sponging the miR-30a-3p/ IGF1R pathway in non-small cell lung cancer (NSCLC)
Background
Recent evidence has demonstrated that abnormal expression and regulation of circular RNA (circRNAs) are involved in the occurrence and development of a variety of tumors. The aim of this study was to investigate the effects of circ_PPAPDC1A in Osimertinib resistance in NSCLC.
Methods
Human circRNAs microarray analysis was conducted to identify differentially expressed (DE) circRNAs in Osimertinib-acquired resistance tissues of NSCLC. The effect of circ_PPAPDC1A on cell proliferation, invasion, migration, and apoptosis was assessed in both in vitro and in vivo. Dual-luciferase reporter assay, RT-qPCR, Western-blot, and rescue assay were employed to confirm the interaction between circ_PPAPDC1A/miR-30a-3p/IGF1R axis.
Results
The results revealed that circ_PPAPDC1A was significantly upregulated in Osimertinib acquired resistance tissues of NSCLC. circ_PPAPDC1A reduced the sensitivity of PC9 and HCC827 cells to Osimertinib and promoted cell proliferation, invasion, migration, while inhibiting apoptosis in Osimertinib-resistant PC9/OR and HCC829/OR cells, both in vitro and in vivo. Silencing circ_PPAPDC1A partially reversed Osimertinib resistance. Additionally, circ_PPAPDC1A acted as a competing endogenous RNA (ceRNA) by targeting miR-30a-3p, and Insulin-like Growth Factor 1 Receptor (IGF1R) was identified as a functional gene for miR-30a-3p in NSCLC. Furthermore, the results confirmed that circ_PPAPDC1A/miR-30a-3p/IGF1R axis plays a role in activating the PI3K/AKT/mTOR signaling pathway in NSCLC with Osimertinib resistance.
Conclusions
Therefore, for the first time we identified that circ_PPAPDC1A was significantly upregulated and exerts an oncogenic role in NSCLC with Osimertinib resistance by sponging miR-30a-3p to active IGF1R/PI3K/AKT/mTOR pathway. circ_PPAPDC1A may serve as a novel diagnostic biomarker and therapeutic target for NSCLC patients with Osimertinib resistance.
Graphical Abstract
Journal Article