The ongoing outbreak of a new coronavirus (2019‐nCoV, or severe acute respiratory syndrome coronavirus 2 SARS‐CoV‐2) has caused an epidemic of the acute respiratory syndrome known as coronavirus ...disease (COVID‐19) in humans. SARS‐CoV‐2 rapidly spread to multiple regions of China and multiple other countries, posing a serious threat to public health. The spike (S) proteins of SARS‐CoV‐1 and SARS‐CoV‐2 may use the same host cellular receptor, angiotensin‐converting enzyme 2 (ACE2), for entering host cells. The affinity between ACE2 and the SARS‐CoV‐2 S protein is much higher than that of ACE2 binding to the SARS‐CoV S protein, explaining why SARS‐CoV‐2 seems to be more readily transmitted from human to human. Here, we report that ACE2 can be significantly upregulated after infection of various viruses, including SARS‐CoV‐1 and SARS‐CoV‐2, or by the stimulation with inflammatory cytokines such as interferons. We propose that SARS‐CoV‐2 may positively induce its cellular entry receptor, ACE2, to accelerate its replication and spread; high inflammatory cytokine levels increase ACE2 expression and act as high‐risk factors for developing COVID‐19, and the infection of other viruses may increase the risk of SARS‐CoV‐2 infection. Therefore, drugs targeting ACE2 may be developed for the future emerging infectious diseases caused by this cluster of coronaviruses.
Highlights
Virus infection and inflammatory cytokines can stimulate angiotensin‐converting enzyme 2 (ACE2) expression. ACE2 is upregulated by the activation of RNA‐sensing pathways. ACE2 is a novel interferon‐stimulated gene (ISG). The increase in ACE2 induced by various viruses and inflammatory cytokines may facilitate severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and spreading.
Dysregulation of long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and tumor progression, including hepatocellular carcinoma (HCC). Small nucleolar RNA host gene 3 (SNHG3) has ...been considered as an lncRNA to be associated with a poor prognosis in patients with HCC. Here, we reported that SNHG3 expression was significantly higher in the highly metastatic HCC (HCCLM3) cells compared with the lowly metastatic HCC cells (Hep3B and PLC/PRF/5). Furthermore, forced expression of SNHG3 promoted cell invasion, epithelial‐mesenchymal transition (EMT), and sorafenib resistance in HCC. Moreover, SNHG3 overexpression induced HCC cells EMT via miR‐128/CD151 cascade activation. Clinically, our data revealed that increased SNHG3 expression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.
Here, our data revealed that increase in small nucleolar RNA host gene 3 (SNHG3) expression is correlated with poor hepatocellular carcinoma survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.
Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. ...Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
The recent introduction of thermally activated delayed fluorescence (TADF) emitters is regarded as an important breakthrough for the development of high efficiency organic light‐emitting devices ...(OLEDs). The planar D and A groups are generally used to construct TADF emitters for their rigid structure and large steric hindrance. In this work, it is shown that many frequently used nonaromatic (noncontinuous conjugation or without satisfying Hückel's rule) planar segments, such as 9,9‐dimethyl‐9,10‐dihydroacridine, are actually pseudoplanar segments and have two possible conformations–a planar form and a crooked form. Molecules constructed from pseudoplanar segments can thus have two corresponding conformations. Their existence can have significant impact on the performance of many TADF emitters. Two design strategies are presented for addressing the problem by either (1) increasing the rigidity of these groups to suppress its crooked form or (2) increasing the steric hindrance of the linked group to minimize energy of the emitters with the highly twisted form. Following these strategies, two new emitters are synthesized accordingly and successfully applied in OLEDs demonstrating high external quantum efficiencies (20.2% and 18.3%).
A schematic energy level diagram of (2‐(9,9‐dimethylacridin‐10(9H)‐yl) thianthrene‐5,5,10,10‐tetraoxide) shows that molecules constructed from pseudoplanar segments can have two corresponding conformations, which have significant impact on the performance of many thermally activated delayed fluorescence emitters. By either increasing the rigidity of these groups, or by increasing the steric hindrance of the linked group, the problem can be addressed.
Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in ...multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed. Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers. Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy. This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties via a space‐enough and conjugation‐forbidden linkage (D‐Spacer‐A) is proposed to develop efficient ...non‐doped thermally activated delayed fluorescence (TADF) emitters. 10‐(4‐(4‐(4,6‐diphenyl‐1,3,5‐triazin‐2‐yl) phenoxy) phenyl)‐9,9‐dimethyl‐9,10‐dihydroacridine (DMAC‐o‐TRZ) was designed and synthesized accordingly. As expected, it exhibits local excited properties in single‐molecule state as D‐Spacer‐A molecular backbone strongly suppress the intramolecular charge‐transfer (CT) transition. And intermolecular CT transition acted as the vital radiation channel for neat DMAC‐o‐TRZ film. As in return, the non‐doped device exhibits a remarkable maximum external quantum efficiency (EQE) of 14.7 %. These results prove the feasibility of D‐Spacer‐A molecules to develop intermolecular CT transition TADF emitters for efficient non‐doped OLEDs.
Non‐doped OLEDs: A novel molecular model of connecting electron‐donating (D) and electron‐withdrawing (A) moieties through a conjugation‐forbidden spacer is proposed to develop efficient thermally activated delayed fluorescence emitters for non‐doped organic light‐emitting diodes. The structure shows intermolecular charge‐transfer (CT) transitions as the major radiative channel and a suppressed effect of photoluminescence concentration quenching.
Magnetoelectric materials with a large magnetoelectric response, a low operating magnetic (or electric) field, and a room‐temperature (or higher) operating temperature are of key importance for ...practical applications. However, such materials are extremely rare because a large magnetoelectric response often requires strong coupling between spins and electric dipoles. Herein, an example of a magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic ferroelectric, tetramethylammonium tetrachlorogallate(III) (1). Investigation of the magnetoelectric effect of the magnetoelectric laminate composite indicates that its room‐temperature magnetoelectric voltage coefficient (αME) is as high as 186 mV cm−1 Oe−1 at HDC = 275 Oe and at the HAC frequency of ≈39 kHz, providing a valid approach for the preparation of magnetoelectric materials and adding a new member to the magnetoelectric material family.
A magnetoelectric composite is prepared by using a room‐temperature multiaxial molecular–ionic tetramethylammonium tetrachlorogallate(III) ferroelectric. The room‐temperature magnetoelectric voltage coefficient is up to 186 mV cm−1 Oe−1 at HDC = 275 Oe and the HAC frequency is ≈39 kHz. This work demonstrates that multiaxial molecular–ionic ferroelectrics are new excellent candidates for the preparation of magnetoelectric composites.
SUMMARY
Many rice microRNAs have been identified as fine‐tuning factors in the regulation of agronomic traits and immunity. Among them, Osa‐miR535 targets SQUAMOSA promoter binding protein‐like 14 ...(OsSPL14) to positively regulate tillers but negatively regulate yield and immunity. Here, we uncovered that Osa‐miR535 targets another SPL gene, OsSPL4, to suppress rice immunity against Magnaporthe oryzae. Overexpression of Osa‐miR535 significantly decreased the accumulation of the fusion protein SPL4TBS‐YFP that contains the target site of Osa‐miR535 in OsSPL4. Consistently, Osa‐miR535 mediated the cleavage of OsSPL4 mRNA between the 10th and 11th base pair of the predicted binding site at the 3′ untranslated region. Transgenic rice lines overexpressing OsSPL4 (OXSPL4) displayed enhanced blast disease resistance accompanied by enhanced immune responses, including increased expression of defense‐relative genes and up‐accumulated H2O2. By contrast, the knockout mutant osspl4 exhibited susceptibility. Moreover, OsSPL4 binds to the promoter of GH3.2, an indole‐3‐acetic acid‐amido synthetase, and promotes its expression. Together, these data indicate that Os‐miR535 targets OsSPL4 and OsSPL4‐GH3.2, which may parallel the OsSPL14‐WRKY45 module in rice blast disease resistance.
Significance Statement
Previously, Osa‐miR535 was identified to target SPL14 to regulate rice immunity. Here, we identified that Osa‐miR535 targets another SPL family gene, OsSPL4. OsSPL4 binds the promoter of GH3.2 to positively regulate rice immunity, which functionally parallels with OsSPL14‐WRKY45 module downstream of Osa‐miR535.
Cancer cells preferentially metabolize glucose through aerobic glycolysis, a phenomenon known as the Warburg effect. Emerging evidence has shown that long non‐coding RNAs (lncRNAs) act as key ...regulators of multiple cancers. However, it remains largely unexplored whether and how lncRNA regulates glucose metabolism in cancer cells. In this study, we show that lncRNA UCA1 promotes glycolysis in bladder cancer cells, and that UCA1‐induced hexokinase 2 (HK2) functions as an important mediator in this process. We further show that UCA1 activates mTOR to regulate HK2 through both activation of STAT3 and repression of microRNA143. Taken together, these findings provide the first evidence that UCA1 plays a positive role in cancer cell glucose metabolism through the cascade of mTOR–STAT3/microRNA143–HK2, and reveal a novel link between lncRNA and the altered glucose metabolism in cancer cells.
UCA1 plays a positive role in cancer cell glucose metabolism. UCA1 exerts its role in glycolysis through the cascade of mTOR‐STAT3/miR143‐HK2.
To develop high‐performance thermally activated delayed fluorescence (TADF) exciplex emitters, a novel strategy of introducing a single‐molecule TADF emitter as one of the constituting materials has ...been presented. Such a new type of exciplex TADF emitter will have two reverse intersystem crossing (RISC) routes on both the pristine TADF molecules and the exciplex emitters, benefiting the utilization of triplet excitons. Based on a newly designed and synthesized single‐molecule TADF emitter MAC, a highly efficient exciplex emitter MAC:PO‐T2T has been obtained. The device based on MAC:PO‐T2T with a weight ratio of 7:3 exhibits a low turn‐on voltage of 2.4 V, high maximum efficiency of 52.1 cd A−1 (current efficiency), 45.5 lm W−1 (power efficiency), and 17.8% (external quantum efficiency, EQE), as well as a high EQE of 12.3% at a luminance of 1000 cd m−2. The device shows the best performance among reported organic light‐emitting devices based on exciplex emitters. Such high‐efficiency and low‐efficiency roll‐off should be ascribed to the additional reverse intersystem crossing process on the MAC molecules, showing the advantages of the strategy described in this study.
A new type of high‐performance exciplex thermally activated delayed fluorescence TADF emitter is demonstrated by introducing single‐molecule TADF emitter as one of the constituting materials. The OLED based on the novel emitter shows a low turn‐on voltage of 2.4 V and a maximum external quantum efficiency of 17.8% with mild efficiency roll‐off, which offers a new strategy for designing efficient exciplex emitters.
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