One important goal of the current electrocatalysis is to develop integrated electrodes from the atomic level design to multilevel structural engineering in simple ways and low prices. Here, a series ...of oxygen micro‐alloyed high‐entropy alloys (O‐HEAs) is developed via a metallurgy approach. A (CrFeCoNi)97O3 bulk O‐HEA shows exceptional electrocatalytic performance for the oxygen evolution reaction (OER), reaching an overpotential as low as 196 mV and a Tafel slope of 29 mV dec−1, and with stability longer than 120 h in 1 m KOH solution at a current density of 10 mA cm−2. It is shown that the enhanced OER performance can be attributed to the formation of island‐like Cr2O3 microdomains, the leaching of Cr3+ ions, and structural amorphization at the interfaces of the domains. These findings offer a technological‐orientated strategy to integrated electrodes.
A new class of bulk electrodes is designed by incorporating oxide microdomains into the so‐called high‐entropy alloys (HEAs). From these, unprecedented oxygen evolution reaction (OER) activity is achieved, with an ultralow overpotential of 196 mV and a Tafel slope of 29 mV dec−1, and with stability longer than 120 h in 1 m KOH solution at current density of 10 mA cm−2.
The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global crisis. There is no therapeutic treatment specific for COVID-19. It is highly ...desirable to identify potential antiviral agents against SARS-CoV-2 from existing drugs available for other diseases and thus repurpose them for treatment of COVID-19. In general, a drug repurposing effort for treatment of a new disease, such as COVID-19, usually starts from a virtual screening of existing drugs, followed by experimental validation, but the actual hit rate is generally rather low with traditional computational methods. Here we report a virtual screening approach with accelerated free energy perturbation-based absolute binding free energy (FEP-ABFE) predictions and its use in identifying drugs targeting SARS-CoV-2 main protease (Mpro). The accurate FEP-ABFE predictions were based on the use of a restraint energy distribution (RED) function, making the practical FEP-ABFE–based virtual screening of the existing drug library possible. As a result, out of 25 drugs predicted, 15 were confirmed as potent inhibitors of SARS-CoV-2 Mpro. The most potent one is dipyridamole (inhibitory constant Ki = 0.04 μM)which has shown promising therapeutic effects in subsequently conducted clinical studies for treatment of patients with COVID-19. Additionally, hydroxychloroquine (Ki = 0.36 μM) and chloroquine (Ki = 0.56 μM) were also found to potently inhibit SARS-CoV-2 Mpro. We anticipate that the FEP-ABFE prediction-based virtual screening approach will be useful in many other drug repurposing or discovery efforts.
Exon circularization has been identified from many loci in mammals, but the detailed mechanism of its biogenesis has remained elusive. By using genome-wide approaches and circular RNA recapitulation, ...we demonstrate that exon circularization is dependent on flanking intronic complementary sequences. Such sequences and their distribution exhibit rapid evolutionary changes, showing that exon circularization is evolutionarily dynamic. Strikingly, exon circularization efficiency can be regulated by competition between RNA pairing across flanking introns or within individual introns. Importantly, alternative formation of inverted repeated Alu pairs and the competition between them can lead to alternative circularization, resulting in multiple circular RNA transcripts produced from a single gene. Collectively, exon circularization mediated by complementary sequences in human introns and the potential to generate alternative circularization products extend the complexity of mammalian posttranscriptional regulation.
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•Exon circularization is dependent on flanking intronic complementary sequences•Exon circularization efficiency is affected by competition of RNA pairing•Alternative RNA pairing and their competition lead to alternative circularization•Both exon circularization and its regulation are evolutionarily dynamic
The competition of RNA pairing mediated by flanking intronic complementary sequences regulates exon circularization efficiency and alternative circularization.
Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
The human 8q24 gene desert contains multiple enhancers that form tissue-specific long-range chromatin loops with the MYC oncogene, but how chromatin looping at the MYC locus is regulated remains ...poorly understood. Here we demonstrate that a long noncoding RNA (lncRNA), CCAT1-L, is transcribed specifically in human colorectal cancers from a locus 515 kb upstream of MYC. This lncRNA plays a role in MYC transcriptional regulation and promotes long-range chromatin looping. Importantly, the CCAT1-L locus is located within a strong super-enhancer and is spatially close to MYC. Knockdown of CCAT1-L reduced long-range interactions between the MYC promoter and its enhancers. In addition, CCAT1-L interacts with CTCF and modulates chromatin conformation at these loop regions. These results reveal an important role of a previously unannotated lncRNA in gene regulation at the MYC locus.
Long noncoding RNAs (lncRNAs) play roles in the development and progression of many cancers; however, the contributions of lncRNAs to human gallbladder cancer (GBC) remain largely unknown. In this ...study, we identify a group of differentially expressed lncRNAs in human GBC tissues, including prognosis-associated gallbladder cancer lncRNA (lncRNA-PAGBC), which we find to be an independent prognostic marker in GBC. Functional analysis indicates that lncRNA-PAGBC promotes tumour growth and metastasis of GBC cells. More importantly, as a competitive endogenous RNA (ceRNA), lncRNA-PAGBC competitively binds to the tumour suppressive microRNAs miR-133b and miR-511. This competitive role of lncRNA-PAGBC is required for its ability to promote tumour growth and metastasis and to activate the AKT/mTOR pathway. Moreover, lncRNA-PAGBC interacts with polyadenylate binding protein cytoplasmic 1 (PABPC1) and is stabilized by this interaction. This work provides novel insight on the molecular pathogenesis of GBC.
Synopsis
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
LncRNA-PAGBC is up-regulated in GBC and increased levels associate with poor prognosis.
LncRNA-PAGBC promotes tumour growth and metastasis, and activates AKT/mTOR signaling by competitively binding to mirR-133b and mirR-511.
LncRNA-PAGBC interacts with and is stabilized by the polyadenylate binding protein PABPC1.
Graphical Abstract
Long noncoding RNAs play roles in the development and progression of many cancers. In this study the lncRNA PAGBC is identified as promoting tumorigenesis in human gallbladder cancer by competitive binding to the tumour suppressive microRNAs miR-133b and miR-511.
Low-bandgap polymers/molecules are an interesting family of semiconductor materials, and have enabled many recent exciting breakthroughs in the field of organic electronics, especially for organic ...photovoltaics (OPVs). Here, such a low-bandgap (1.43 eV) non-fullerene electron acceptor (BT-IC) bearing a fused 7-heterocyclic ring with absorption edge extending to the near-infrared (NIR) region was specially designed and synthesized. Benefitted from its NIR light harvesting, high performance OPVs were fabricated with medium bandgap polymers (J61 and J71) as donors, showing power conversion efficiencies of 9.6% with J61 and 10.5% with J71 along with extremely low energy loss (0.56 eV for J61 and 0.53 eV for J71). Interestingly, femtosecond transient absorption spectroscopy studies on both systems show that efficient charge generation was observed despite the fact that the highest occupied molecular orbital (HOMO)–HOMO offset (Δ E H ) in the blends was as low as 0.10 eV, suggesting that such a small Δ E H is not a crucial limitation in realizing high performance of NIR non-fullerene based OPVs. Our results indicated that BT-IC is an interesting NIR non-fullerene acceptor with great potential application in tandem/multi-junction, semitransparent, and ternary blend solar cells.
Basing on the systems of linear partial differential equations derived from Mellin-Barnes representations and Miller's transformation, we obtain GKZ-hypergeometric systems of one-loop self energy, ...one-loop triangle, two-loop vacuum, and two-loop sunset diagrams, respectively. The codimension of derived GKZ-hypergeometric system equals the number of independent dimensionless ratios among the external momentum squared and virtual mass squared. Taking GKZ-hypergeometric systems of one-loop self energy, massless one-loop triangle, and two-loop vacuum diagrams as examples, we present in detail how to perform triangulation and how to construct canonical series solutions in the corresponding convergent regions. The series solutions constructed for these hypergeometric systems recover the well known results in literature.
A
bstract
We present the Gel’fand-Kapranov-Zelevinsky (GKZ) hypergeometric systems of the Feynman integrals of the three-loop vacuum diagrams with arbitrary masses, basing on Mellin-Barnes ...representations and Miller’s transformation. The codimension of derived GKZ hypergeometric systems equals the number of independent dimensionless ratios among the virtual masses squared. Through GKZ hypergeometric systems, the analytical hypergeometric series solutions can be obtained in neighborhoods of origin including infinity. The linear independent hypergeometric series solutions whose convergent regions have non-empty intersection can constitute a fundamental solution system in a proper subset of the whole parameter space. The analytical expression of the vacuum integral can be formulated as a linear combination of the corresponding fundamental solution system in certain convergent region.
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