bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA hsa_circ_0110389 promotes gastric cancer progression through upregulating SORT1 via sponging miR-127-5p and miR-136-5p
Authors: Liang Min , Yao Wenxia , Shi Boyun , Zhu Xiongjie , Cai Rui , Yu Zhongjian , Guo Weihong , Wang Huaiming , Dong Zhijie , Lin Mingzhen , Zhou Xinke , Zheng Yanfang 
Published: June 2021

AbstractIncreasing studies have found that circular RNAs (circRNAs) are aberrantly expressed and play important roles in the occurrence and development of human cancers. However, the function of circRNAs on environmental carcinogen-induced gastric cancer (GC) progression remains poorly elucidated. In the present study, hsa_circ_0110389 was identified as a novel upregulated circRNA in malignant-transformed GC cells through RNA-seq, and subsequent quantitative real-time PCR verified that hsa_circ_0110389 was significantly increased in GC tissues and cells. High hsa_circ_0110389 expression associates with advanced stages of GC and predicts poor prognosis. Knockdown and overexpression assays demonstrated that hsa_circ_0110389 regulates proliferation, migration, and invasion of GC cells in vitro. In addition, hsa_circ_0110389 was identified to sponge both miR-127-5p and miR-136-5p and SORT1 was validated as a direct target of miR-127-5p and miR-136-5p through multiple mechanism assays; moreover, hsa_circ_0110389 sponged miR-127-5p/miR-136-5p to upregulate SORT1 expression and hsa_circ_0110389 promoted GC progression through the miR-127-5p/miR-136-5p–SORT1 pathway. Finally, hsa_circ_0110389 knockdown suppressed GC growth in vivo. Taken together, our findings firstly identify the role of hsa_circ_0110389 in GC progression, which is through miR-127-5p/miR-136-5p–SORT1 pathway, and our study provides novel insight for the identification of diagnostic/prognostic biomarkers and therapeutic targets for GC.
Inhibition of Polo-like kinase 4 induces mitotic defects and DNA damage in diffuse large B-cell lymphoma
Authors: Zhao Yi , Yang Juan , Liu Jiarui , Cai Yiqing , Han Yang , Hu Shunfeng , Ren Shuai , Zhou Xiangxiang , Wang Xin 
Published: June 2021

AbstractPolo-like kinase 4 (PLK4), a key regulator of centriole biogenesis, has recently been shown to play key roles in tumorigenesis. Blocking PLK4 expression by interference or targeted drugs exhibits attractive potential in improving the efficacy of chemotherapy. Nevertheless, the role of PLK4 in diffuse large B-cell lymphoma (DLBCL) is still undefined. In this study, we discover that PLK4 is a potential target for the treatment of DLBCL, and demonstrate the efficacy of a PLK4 inhibitor when used in combination with doxorubicin. Pharmaceutical inhibition of PLK4 with CFI-400945 inhibited DLBCL cell proliferation and induced apoptotic cell death. The anti-tumor effects were accompanied by mitotic defects, including polyploidy and cytokinesis failure. Activation of p53 and Hippo/YAP tumor suppressor signaling pathway was identified as the potential mechanisms driving CFI-400945 activity. Moreover, CFI-400945 treatment resulted in activation of DNA damage response. Combining CFI-400945 with doxorubicin markedly delayed tumor progression in DLBCL xenografts. Finally, PLK4 was increased in primary DLBCL tissues and cell lines. High levels of PLK4 expression were associated with poor survival in the patients receiving CHOP-based treatment, implicating PLK4 as a predictive biomarker of DLBCL chemosensitivity. These results provide the therapeutic potential of CFI-400945 both as monotherapy or in combination with doxorubicin for the treatment of DLBCL.
In-silico trial of intracranial flow diverters replicates and expands insights from conventional clinical trials
Authors: Sarrami-Foroushani Ali , Lassila Toni , MacRaild Michael , Asquith Joshua , Roes Kit C. B. , Byrne James V. , Frangi Alejandro F. 
Published: June 2021

AbstractThe cost of clinical trials is ever-increasing. In-silico trials rely on virtual populations and interventions simulated using patient-specific models and may offer a solution to lower these costs. We present the flow diverter performance assessment (FD-PASS) in-silico trial, which models the treatment of intracranial aneurysms in 164 virtual patients with 82 distinct anatomies with a flow-diverting stent, using computational fluid dynamics to quantify post-treatment flow reduction. The predicted FD-PASS flow-diversion success rates replicate the values previously reported in three clinical trials. The in-silico approach allows broader investigation of factors associated with insufficient flow reduction than feasible in a conventional trial. Our findings demonstrate that in-silico trials of endovascular medical devices can: (i) replicate findings of conventional clinical trials, and (ii) perform virtual experiments and sub-group analyses that are difficult or impossible in conventional trials to discover new insights on treatment failure, e.g. in the presence of side-branches or hypertension.
AsCas12a ultra nuclease facilitates the rapid generation of therapeutic cell medicines
Authors: Zhang Liyang , Zuris John A. , Viswanathan Ramya , Edelstein Jasmine N. , Turk Rolf , Thommandru Bernice , Rube H. Tomas , Glenn Steve E. , Collingwood Michael A. , Bode Nicole M. , Beaudoin Sarah F. , Lele Swarali , Scott Sean N. , Wasko Kevin M. , Sexton Steven , Borges Christopher M. , Schubert Mollie S. , Kurgan Gavin L. , McNeill Matthew S. , Fernandez Cecilia A. , Myer Vic E. , Morgan Richard A. , Behlke Mark A. , Vakulskas Christopher A. 
Published: June 2021

AbstractThough AsCas12a fills a crucial gap in the current genome editing toolbox, it exhibits relatively poor editing efficiency, restricting its overall utility. Here we isolate an engineered variant, “AsCas12a Ultra”, that increased editing efficiency to nearly 100% at all sites examined in HSPCs, iPSCs, T cells, and NK cells. We show that AsCas12a Ultra maintains high on-target specificity thereby mitigating the risk for off-target editing and making it ideal for complex therapeutic genome editing applications. We achieved simultaneous targeting of three clinically relevant genes in T cells at >90% efficiency and demonstrated transgene knock-in efficiencies of up to 60%. We demonstrate site-specific knock-in of a CAR in NK cells, which afforded enhanced anti-tumor NK cell recognition, potentially enabling the next generation of allogeneic cell-based therapies in oncology. AsCas12a Ultra is an advanced CRISPR nuclease with significant advantages in basic research and in the production of gene edited cell medicines.
Transition-metal-free allylation of 2-azaallyls with allyl ethers through polar and radical mechanisms
Authors: Deng Guogang , Duan Shengzu , Wang Jing , Chen Zhuo , Liu Tongqi , Chen Wen , Zhang Hongbin , Yang Xiaodong , Walsh Patrick J. 
Published: June 2021

AbstractAllylation of nucleophiles with highly reactive electrophiles like allyl halides can be conducted without metal catalysts. Less reactive electrophiles, such as allyl esters and carbonates, usually require a transition metal catalyst to facilitate the allylation. Herein, we report a unique transition-metal-free allylation strategy with allyl ether electrophiles. Reaction of a host of allyl ethers with 2-azaallyl anions delivers valuable homoallylic amine derivatives (up to 92%), which are significant in the pharmaceutical industry. Interestingly, no deprotonative isomerization or cyclization of the products were observed. The potential synthetic utility and ease of operation is demonstrated by a gram scale telescoped preparation of a homoallylic amine. In addition, mechanistic studies provide insight into these C(sp3)–C(sp3) bond-forming reactions.
Converting copper sulfide to copper with surface sulfur for electrocatalytic alkyne semi-hydrogenation with water
Authors: Wu Yongmeng , Liu Cuibo , Wang Changhong , Yu Yifu , Shi Yanmei , Zhang Bin 
Published: June 2021

AbstractElectrocatalytic alkyne semi-hydrogenation to alkenes with water as the hydrogen source using a low-cost noble-metal-free catalyst is highly desirable but challenging because of their over-hydrogenation to undesired alkanes. Here, we propose that an ideal catalyst should have the appropriate binding energy with active atomic hydrogen (H*) from water electrolysis and a weaker adsorption with an alkene, thus promoting alkyne semi-hydrogenation and avoiding over-hydrogenation. So, surface sulfur-doped and -adsorbed low-coordinated copper nanowire sponges are designedly synthesized via in situ electroreduction of copper sulfide and enable electrocatalytic alkyne semi-hydrogenation with over 99% selectivity using water as the hydrogen source, outperforming a copper counterpart without surface sulfur. Sulfur anion-hydrated cation (S2−-K+(H2O)n) networks between the surface adsorbed S2− and K+ in the KOH electrolyte boost the production of active H* from water electrolysis. And the trace doping of sulfur weakens the alkene adsorption, avoiding over-hydrogenation. Our catalyst also shows wide substrate scopes, up to 99% alkenes selectivity, good reducible groups compatibility, and easily synthesized deuterated alkenes, highlighting the promising potential of this method.
Optical force mapping at the single-nanometre scale
Authors: Yamanishi Junsuke , Yamane Hidemasa , Naitoh Yoshitaka , Li Yan Jun , Yokoshi Nobuhiko , Kameyama Tatsuya , Koyama Seiya , Torimoto Tsukasa , Ishihara Hajime , Sugawara Yasuhiro 
Published: June 2021

AbstractThree-dimensional (3D) information of the optical response in the nanometre scale is important in the field of nanophotonics science. Using photoinduced force microscopy (PiFM), we can visualize the nano-scale optical field using the optical gradient force between the tip and sample. Here, we demonstrate 3D photoinduced force field visualization around a quantum dot in the single-nanometre spatial resolution with heterodyne frequency modulation technique, using which, the effect of the photothermal expansion of the tip and sample in the ultra-high vacuum condition can be avoided. The obtained 3D mapping shows the spatially localized photoinduced interaction potential and force field vectors in the single nano-scale for composite quantum dots with photocatalytic activity. Furthermore, the spatial resolution of PiFM imaging achieved is ~0.7 nm. The single-nanometer scale photoinduced field visualization is crucial for applications such as photo catalysts, optical functional devices, and optical manipulation.
Room-temperature oxygen vacancy migration induced reversible phase transformation during the anelastic deformation in CuO
Authors: Li Lei , Chen Guoxujia , Zheng He , Meng Weiwei , Jia Shuangfeng , Zhao Ligong , Zhao Peili , Zhang Ying , Huang Shuangshuang , Huang Tianlong , Wang Jianbo 
Published: June 2021

AbstractFrom the mechanical perspectives, the influence of point defects is generally considered at high temperature, especially when the creep deformation dominates. Here, we show the stress-induced reversible oxygen vacancy migration in CuO nanowires at room temperature, causing the unanticipated anelastic deformation. The anelastic strain is associated with the nucleation of oxygen-deficient CuOx phase, which gradually transforms back to CuO after stress releasing, leading to the gradual recovery of the nanowire shape. Detailed analysis reveals an oxygen deficient metastable CuOx phase that has been overlooked in the literatures. Both theoretical and experimental investigations faithfully predict the oxygen vacancy diffusion pathways in CuO. Our finding facilitates a better understanding of the complicated mechanical behaviors in materials, which could also be relevant across multiple scientific disciplines, such as high-temperature superconductivity and solid-state chemistry in Cu-O compounds, etc.
A high-throughput screen for TMPRSS2 expression identifies FDA-approved compounds that can limit SARS-CoV-2 entry
Authors: Chen Yanwen , Lear Travis B. , Evankovich John W. , Larsen Mads B. , Lin Bo , Alfaras Irene , Kennerdell Jason R. , Salminen Laura , Camarco Daniel P. , Lockwood Karina C. , Tuncer Ferhan , Liu Jie , Myerburg Michael M. , McDyer John F. , Liu Yuan , Finkel Toren , Chen Bill B. 
Published: June 2021

AbstractSARS-CoV-2 (2019-nCoV) is the pathogenic coronavirus responsible for the global pandemic of COVID-19 disease. The Spike (S) protein of SARS-CoV-2 attaches to host lung epithelial cells through the cell surface receptor ACE2, a process dependent on host proteases including TMPRSS2. Here, we identify small molecules that reduce surface expression of TMPRSS2 using a library of 2,560 FDA-approved or current clinical trial compounds. We identify homoharringtonine and halofuginone as the most attractive agents, reducing endogenous TMPRSS2 expression at sub-micromolar concentrations. These effects appear to be mediated by a drug-induced alteration in TMPRSS2 protein stability. We further demonstrate that halofuginone modulates TMPRSS2 levels through proteasomal-mediated degradation that involves the E3 ubiquitin ligase component DDB1- and CUL4-associated factor 1 (DCAF1). Finally, cells exposed to homoharringtonine and halofuginone, at concentrations of drug known to be achievable in human plasma, demonstrate marked resistance to SARS-CoV-2 infection in both live and pseudoviral in vitro models. Given the safety and pharmacokinetic data already available for the compounds identified in our screen, these results should help expedite the rational design of human clinical trials designed to combat active COVID-19 infection.
Oxoammonium salts are catalysing efficient and selective halogenation of olefins, alkynes and aromatics
Authors: Wang Weijin , Li Xinyao , Yang Xiaoxue , Ai Lingsheng , Gong Zhiwen , Jiao Ning , Song Song 
Published: June 2021

AbstractElectrophilic halogenation reactions have been a reliable approach to accessing organohalides. During the past decades, various catalytic systems have been developed for the activation of haleniums. However, there is still a short of effective catalysts, which could cover various halogenation reactions and broad scope of unsaturated compounds. Herein, TEMPO (2,2,6,6-tetramethylpiperidine nitroxide) and its derivatives are disclosed as active catalysts for electrophilic halogenation of olefins, alkynes, and aromatics. These catalysts are stable, readily available, and reactive enough to activate haleniums including Br+, I+ and even Cl+ reagents. This catalytic system is applicable to various halogenations including haloarylation of olefins or dibromination of alkynes, which were rarely realized in previous Lewis base catalysis or Lewis acid catalysis. The high catalytic ability is attributed to a synergistic activation model of electrophilic halogenating reagents, where the carbonyl group and the halogen atom are both activated by present TEMPO catalysis.
A natural riboswitch scaffold with self-methylation activity
Authors: Flemmich Laurin , Heel Sarah , Moreno Sarah , Breuker Kathrin , Micura Ronald 
Published: June 2021

AbstractMethylation is a prevalent post-transcriptional modification encountered in coding and non-coding RNA. For RNA methylation, cells use methyltransferases and small organic substances as methyl-group donors, such as S-adenosylmethionine (SAM). SAM and other nucleotide-derived cofactors are viewed as evolutionary leftovers from an RNA world, in which riboswitches have regulated, and ribozymes have catalyzed essential metabolic reactions. Here, we disclose the thus far unrecognized direct link between a present-day riboswitch and its inherent reactivity for site-specific methylation. The key is O6-methyl pre-queuosine (m6preQ1), a potentially prebiotic nucleobase which is recognized by the native aptamer of a preQ1 class I riboswitch. Upon binding, the transfer of the ligand’s methyl group to a specific cytidine occurs, installing 3-methylcytidine (m3C) in the RNA pocket under release of pre-queuosine (preQ1). Our finding suggests that nucleic acid-mediated methylation is an ancient mechanism that has offered an early path for RNA epigenetics prior to the evolution of protein methyltransferases. Furthermore, our findings may pave the way for the development of riboswitch-descending methylation tools based on rational design as a powerful alternative to in vitro selection approaches.
Electrochemical activation of C–H by electron-deficient W2C nanocrystals for simultaneous alkoxylation and hydrogen evolution
Authors: Lin Xiu , Zhang Shi-Nan , Xu Dong , Zhang Jun-Jun , Lin Yun-Xiao , Zhai Guang-Yao , Su Hui , Xue Zhong-Hua , Liu Xi , Antonietti Markus , Chen Jie-Sheng , Li Xin-Hao 
Published: June 2021

AbstractThe activation of C–H bonds is a central challenge in organic chemistry and usually a key step for the retro-synthesis of functional natural products due to the high chemical stability of C–H bonds. Electrochemical methods are a powerful alternative for C–H activation, but this approach usually requires high overpotential and homogeneous mediators. Here, we design electron-deficient W2C nanocrystal-based electrodes to boost the heterogeneous activation of C–H bonds under mild conditions via an additive-free, purely heterogeneous electrocatalytic strategy. The electron density of W2C nanocrystals is tuned by constructing Schottky heterojunctions with nitrogen-doped carbon support to facilitate the preadsorption and activation of benzylic C–H bonds of ethylbenzene on the W2C surface, enabling a high turnover frequency (18.8 h−1) at a comparably low work potential (2 V versus SCE). The pronounced electron deficiency of the W2C nanocatalysts substantially facilitates the direct deprotonation process to ensure electrode durability without self-oxidation. The efficient oxidation process also boosts the balancing hydrogen production from as-formed protons on the cathode by a factor of 10 compared to an inert reference electrode. The whole process meets the requirements of atomic economy and electric energy utilization in terms of sustainable chemical synthesis.
Co-benefits of protecting mangroves for biodiversity conservation and carbon storage
Authors: Rahman Md Mizanur , Zimmer Martin , Ahmed Imran , Donato Daniel , Kanzaki Mamoru , Xu Ming 
Published: June 2021

AbstractThe conservation of ecosystems and their biodiversity has numerous co-benefits, both for local societies and for humankind worldwide. While the co-benefit of climate change mitigation through so called blue carbon storage in coastal ecosystems has raised increasing interest in mangroves, the relevance of multifaceted biodiversity as a driver of carbon storage remains unclear. Sediment salinity, taxonomic diversity, functional diversity and functional distinctiveness together explain 69%, 69%, 27% and 61% of the variation in above- and belowground plant biomass carbon, sediment organic carbon and total ecosystem carbon storage, respectively, in the Sundarbans Reserved Forest. Functional distinctiveness had the strongest explanatory power for carbon storage, indicating that blue carbon in mangroves is driven by the functional composition of diverse tree assemblages. Protecting and restoring mangrove biodiversity with site-specific dominant species and other species of contrasting functional traits would have the co-benefit of maximizing their capacity for climate change mitigation through increased carbon storage.
A stochastic quantum program synthesis framework based on Bayesian optimization
Authors: Xiao Yao , Nazarian Shahin , Bogdan Paul 
Published: June 2021

AbstractQuantum computers and algorithms can offer exponential performance improvement over some NP-complete programs which cannot be run efficiently through a Von Neumann computing approach. In this paper, we present BayeSyn, which utilizes an enhanced stochastic program synthesis and Bayesian optimization to automatically generate quantum programs from high-level languages subject to certain constraints. We find that stochastic synthesis can comparatively and efficiently generate a program with a lower cost from the high dimensional program space. We also realize that hyperparameters used in stochastic synthesis play a significant role in determining the optimal program. Therefore, BayeSyn utilizes Bayesian optimization to fine-tune such parameters to generate a suitable quantum program.
The study of differences by region and type of gambling on the degree of gambling addiction in Japan
Authors: Hayano Shingo , Dong Ran , Miyata Yoshie , Kasuga Sakutaro 
Published: June 2021

AbstractWe conducted an online national survey using the South Oaks Gambling Screen (SOGS) on 42,880 people in Japan to identify gambling addiction prevalence differences with regard to gambling type and region. This study included 14,780 individuals (valid responses) who engaged in gambling activities in the past year. There was a large difference in mean SOGS score by gambling type: public gambling and casinos score ≈ 4.0, whereas lotteries (including numbers, etc.) ≈ 1.43. SOGS scores were much higher for those who participated in more than one gambling type than for those who participated in only one type. Regional differences in SOGS scores were also confirmed, with more populous prefectures having lower and less populous having higher SOGS scores. Integrating SOGS scores with existing data concerning hobbies and recreational behaviors across regions indicated that regions characterized by lower SOGS scores were also characterized by greater activity for hobbies and recreational behaviors.
Influence of prokaryotic microorganisms on initial soil formation along a glacier forefield on King George Island, maritime Antarctica
Authors: Krauze Patryk , Wagner Dirk , Yang Sizhong , Spinola Diogo , Kühn Peter 
Published: June 2021

AbstractCompared to the 1970s, the edge of the Ecology Glacier on King George Island, maritime Antarctica, is positioned more than 500 m inwards, exposing a large area of new terrain to soil-forming processes and periglacial climate for more than 40 years. To gain information on the state of soil formation and its interplay with microbial activity, three hyperskeletic Cryosols (vegetation cover of 0–80%) deglaciated after 1979 in the foreland of the Ecology Glacier and a Cambic Cryosol (vegetation cover of 100%) distal to the lateral moraine deglaciated before 1956 were investigated by combining soil chemical and microbiological methods. In the upper part of all soils, a decrease in soil pH was observed, but only the Cambic Cryosol showed a clear direction of pedogenic and weathering processes, such as initial silicate weathering indicated by a decreasing Chemical Index of Alteration with depth. Differences in the development of these initial soils could be related to different microbial community compositions and vegetation coverage, despite the short distance among them. We observed—decreasing with depth—the highest bacterial abundances and microbial diversity at vegetated sites. Multiple clusters of abundant amplicon sequence variants were found depending on the site-specific characteristics as well as a distinct shift in the microbial community structure towards more similar communities at soil depths > 10 cm. In the foreland of the Ecology Glacier, the main soil-forming processes on a decadal timescale are acidification and accumulation of soil organic carbon and nitrogen, accompanied by changes in microbial abundances, microbial community compositions, and plant coverage, whereas quantifiable silicate weathering and the formation of pedogenic oxides occur on a centennial to a millennial timescale after deglaciation.