Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we ...catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.
Strategies that enable simultaneous morphology‐tuning and electroreduction performance boosting are much desired for the exploration of covalent organic frameworks in efficient CO2 electroreduction. ...Herein, a kind of functionalizing exfoliation agent has been selected to simultaneously modify and exfoliate bulk COFs into functional nanosheets and investigate their CO2 electroreduction performance. The obtained nanosheets (Cu−Tph−COF−Dct) with large‐scale (≈1.0 μm) and ultrathin (≈3.8 nm) morphology enable a superior FECH4 (≈80 %) (almost doubly enhanced than bare COF) with large current‐density (−220.0 mA cm−2) at −0.9 V. The boosted performance can be ascribed to the immobilized functionalizing exfoliation agent (Dct groups) with integrated amino and triazine groups that strengthen CO2 absorption/activation, stabilize intermediates and enrich the CO concentration around the Cu active sites as revealed by DFT calculations. The point‐to‐point functionalization strategy for modularly assembling Dct‐functionalized COF catalyst for CO2 electroreduction will open up the attractive possibility of developing COFs as efficient CO2RR electrocatalysts.
A kind of functionalizing exfoliation agent has been selected to simultaneously modify and exfoliate bulk COFs into functional nanosheets and the obtained materials can be applied in highly selective CO2 electroreduction into CH4.
Advanced organic bioelectronics enable smooth fusion between modern electronics and biological systems for better physiological monitoring and pathological examinations. Photon‐regulated ...bioelectronics are especially desirable due to the non‐contact impact, remote‐control, and even self‐powered operation. However, few studies have addressed the advanced photon‐enabled organic photoelectrochemical transistor (OPECT) biosensors capable of operation at zero gate bias. Here, on the basis of a hydrogel/graphene oxide hybrid (denoted as HGH), a multifunctional HGH‐gated OPECT biosensor is presented, which is exemplified by Ca2+‐triggered gelation on the CdS quantum dot (QD) photoelectrode linking with a sandwich immunoassay toward human IgG as the model target. Gelation of HGH on the CdS QD gate electrode can not only inhibit the interfacial mass transfer on the gate/electrolyte interface, but also significantly block the light absorption of CdS QDs, leading to the corresponding change of the channel currents of OPECT device. At zero gate bias, this OPECT biosensor exhibits high gain in response to light and good analytical performance for human IgG with a detection limit of 50 fg mL–1. Given the numerous intelligent hydrogel materials and their potential interactions with light, this work unveils a general platform for developing a new class of hydrogel‐gated OPECT bioelectronics and beyond.
A multifunctional hydrogel‐gated organic photoelectrochemical transistor biosensor is constructed using a Ca2+‐triggered hydrogel/graphene oxide hybrid on the CdS quantum dot photosensitive gate electrode linking with a sandwich immunoassay toward human IgG as the model target. The proposed biosensor exhibits high gain in response to light and good analytical performance at zero gate bias.
Prime editing is a novel and universal CRISPR/Cas-derived precision genome-editing technology that has been recently developed. However, low efficiency of prime editing has been shown in transgenic ...rice lines. We hypothesize that enhancing pegRNA expression could improve prime-editing efficiency. In this report, we describe two strategies for enhancing pegRNA expression. We construct a prime editing vector harboring two pegRNA variants for W542L and S621I double mutations in ZmALS1 and ZmALS2. Compared with previous reports in rice, we achieve much higher prime-editing efficiency in maize. Our results are inspiring and provide a direction for the optimization of plant prime editors.
The exploration of novel systems for the electrochemical CO2 reduction reaction (CO2RR) for the production of hydrocarbons like CH4 remains a giant challenge. Well‐designed electrocatalysts with ...advantages like proton generation/transferring and intermediate‐fixating for efficient CO2RR are much preferred yet largely unexplored. In this work, a kind of Cu‐porphyrin‐based large‐scale (≈1.5 μm) and ultrathin nanosheet (≈5 nm) has been successfully applied in electrochemical CO2RR. It exhibits a superior FECH4
of 70 % with a high current density (−183.0 mA cm−2) at −1.6 V under rarely reported neutral conditions and maintains FECH4
>51 % over a wide potential range (−1.5 to −1.7 V) in a flow cell. The high performance can be attributed to the construction of numerous hydrogen‐bonding networks through the integration of diaminotriazine with Cu‐porphyrin, which is beneficial for proton migration and intermediate stabilization, as supported by DFT calculations. This work paves a new way in exploring hydrogen‐bonding‐based materials as efficient CO2RR catalysts.
A Cu‐porphyrin‐based large‐scale, ultrathin nanosheet with numerous hydrogen‐bonding networks was developed for the highly selective electroreduction of CO2 to CH4 under neutral conditions. This catalyst exhibits a superior FECH4
of 70 % with a high current density (−183.0 mA cm−2) at −1.6 V under rarely reported neutral conditions and maintains FECH4
>51 % over a wide potential range (−1.5 to −1.7 V) in a flow cell.
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.
Porous heterostructured electrocatalysts with multifunctionality and synergistic effect have much benefit for efficient electrocatalytic CO2 reduction reaction (CO2RR), yet it still remains a ...daunting challenge to explore heterostructures based on covalent organic frameworks (COFs) and metal–organic frameworks (MOFs) in this field. Here, a series of honeycomb‐like porous crystalline hetero‐electrocatalysts (MCH‐X, X = 1–4, X stands for the numbered sample obtained from different MOF doses in the synthesis of the MCH) are synthesized, and these are successfully applied in electrocatalytic CO2RR. The specially designed heterostructures with integrated porous MOF‐template and ultrathin COF‐coating enable efficient CO2 adsorption/activation and conversion into CH4. The best of them, MCH‐3, shows greatly inhibited H2 evolution, excellent current density (−398.1 mA cm−2), and superior FECH4${\rm{F}}{{\rm{E}}_{{\rm{C}}{{\rm{H}}_4}}}$ (76.7%) to the physical mixture (38.0%), the MOF@COF without the honeycomb‐like morphology (47.7%), and the bare COF (37.5%) and MOF (15.9%) at −1.0 V. Based on the density functional theory calculations and various characterizations, the vital roles of the MOF in facilitating CO2 adsorption/activation, stabilizing intermediates, and conquering the energy barrier of rate‐determining step are intensively studied.
A series of honeycomb‐like metal–organic framework (MOF)@covalent organic framework (COF) heterostructures with integrated porous MOF template and ultrathin COF coating are synthesized and successfully applied in efficient CO2 electroreduction to CH4.
Summary
Although it is well known that miRNAs play crucial roles in multiple biological processes, there is currently no evidence indicating that milRNAs from Fusarium oxysporum f. sp. lycopersici ...(Fol) interfere with tomato resistance during infection.
Here, using sRNA‐seq, we demonstrate that Fol‐milR1, a trans‐kingdom small RNA, is exported into tomato cells after infection.
The knockout strain ∆Fol‐milR1 displays attenuated pathogenicity to the susceptible tomato cultivar ‘Moneymaker’. On the other hand, Fol‐milR1 overexpression strains exhibit enhanced virulence against the resistant cultivar ‘Motelle’. Several tomato mRNAs are predicted targets of Fol‐milR1. Among these genes, Solyc06g007430 (encoding the CBL‐interacting protein kinase, SlyFRG4) is regulated at the posttranscriptional level by Fol‐milR1. Furthermore, SlyFRG4 loss‐of‐function alleles created using CRISPR/Cas9 in tomato (‘Motelle’) exhibit enhanced disease susceptibility to Fol, further supporting the idea that SlyFRG4 is essential for tomato wilt disease resistance. Notably, our results using immunoprecipitation with specific antiserum suggest that Fol‐milR1 interferes with the host immunity machinery by binding to tomato ARGONAUTE 4a (SlyAGO4a). Furthermore, virus‐induced gene silenced (VIGS) knock‐down SlyAGO4a plants exhibit reduced susceptibility to Fol.
Together, our findings support a model in which Fol‐milR1 is an sRNA fungal effector that suppresses host immunity by silencing a disease resistance gene, thus providing a novel virulence strategy to achieve infection.
See also the Commentary on this article by Thieron et al., 232: 464–467.
Although effects of weather changes on human health have been widely reported, there is limited information regarding effects on pregnant women in developing countries.
We investigated the ...association between maternal exposure to ambient temperature and the risk of preterm birth (< 37 weeks of gestation) in Guangzhou, China.
We used a Cox proportional hazards model to estimate associations between preterm birth and average temperature during each week of gestation, with weekly temperature modeled as a time-varying exposure during four time windows: 1 week (the last week of the pregnancy), 4 weeks (the last 4 weeks of the pregnancy), late pregnancy (gestational week 20 onward), and the entire pregnancy. Information on singleton vaginal birth between 2001 and 2011 was collected. Daily meteorological data during the same period were obtained from the Guangzhou Meteorological Bureau.
A total of 838,146 singleton vaginal births were included, among which 47,209 (5.6%) were preterm births. High mean temperatures during the 4 weeks, late pregnancy, and the entire pregnancy time windows were associated with an increased risk of preterm birth. Compared with the median temperature (24.4°C), weekly exposures during the last 4 weeks of the pregnancy to extreme cold (7.6°C, the 1st percentile) and extreme heat (31.9°C, the 99th percentile) were associated with 17.9% (95% CI: 10.2, 26.2%) and 10.0% (95% CI: 2.9, 17.6%) increased risks of preterm birth, respectively. The association between extreme heat and preterm birth was stronger for preterm births during weeks 20-31 and 32-34 than those during weeks 35-36.
These findings might have important implications in preventing preterm birth in Guangzhou as well as other areas with similar weather conditions.
He JR, Liu Y, Xia XY, Ma WJ, Lin HL, Kan HD, Lu JH, Feng Q, Mo WJ, Wang P, Xia HM, Qiu X, Muglia LJ. 2016. Ambient temperature and the risk of preterm birth in Guangzhou, China (2001-2011). Environ Health Perspect 124:1100-1106; http://dx.doi.org/10.1289/ehp.1509778.
Strategy that can design powerful photothermal‐catalysts to achieve photothermal‐effect assisted coupling‐catalysis is much desired for the improvement of energy conversion efficiency and redox ...product value in CO2 electroreduction system. Herein, a kind of bifunctional viologen‐containing covalent organic framework (Ni‐2CBpy2+‐COF) has been prepared and successfully applied in photothermal‐assisted co‐electrolysis of CO2 and methanol. Specifically, the FECO (cathode) and FEHCOOH (anode) for Ni‐2CBpy2+‐COF can reach up to ≈100 % at 1.9 V with ≈31.5 % saved overall electricity‐consumption when the anodic oxygen evolution reaction (OER) is replaced by methanol oxidation. The superior performance could be attributed to the cyclic diquats in Ni‐2CBpy2+‐COF that enhance the photothermal effect (ΔT=49.1 °C) to accelerate faster charge transfer between catalyst and immediate species as well as higher selectivity towards desired products as revealed by DFT calculations and characterizations.
A kind of bifunctional viologen‐containing covalent‐organic‐framework has been prepared and successfully applied in photothermal‐assisted co‐electrolysis of CO2 and methanol. The superior performance could be attributed to the cyclic diquats in Ni‐2CBpy2+‐COF that enhance the photothermal effect to accelerate faster charge‐transfer between catalyst and immediate species as well as higher selectivity towards desired products.
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