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Upper tract urothelial carcinoma with pure non-urothelial histology is an exception but variants are present in ~ 25% of cases. Primary upper urinary tract signet -ring cell carcinoma is extremely rare. We report the case of a 65-year-old male diagnosed primary upper urinary tract signet-ring cell carcinoma while underwent percutaneous nephrolithotomy. Radical nephroureterectomy and adjuvant chemotherapy were performed sequentially. The patient is now recovering well with a regular follow-updoi:10.1186/s12894-020-00645-y pmid:32590974 fatcat:dm7qsbp3cbcgpmqxmpd65gsy5q
more »... more than 1 year. The upper urinary tract malignancy often appears as a high grade, high stage tumor and has a uniformly poor prognosis, but a timely multimodal management can bring a good outcome.
Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have sprung up in recent years. Here we construct and characterize a CRISPR-Cas13b-based tool for the first time that targeted m6A methylation of mRNA by fusing the catalytically dead Type VI-B Cas13 enzyme from Prevotella sp.P5-125 (dPspCas13b) with the m6A demethylase ALKBH5, which is named as dm6ACRISPR. Subsequently, such system is shown to specific demethylase the m6A of target mRNA such as CYB5A to increasedoi:10.1101/614859 fatcat:stcxymznm5hcviqlge6xwua2ri
more »... s mRNA stability. In addition, the dm6ACRISPR system appeared to afford efficient demethylation of the target genes with tenuous off-target effects. Together, we provide a programmable and in vivo manipulation tool to study mRNA modification and its potential biological functions of specific gene.
Qu and Luo (2015) ). ... Our chosen parameter values are almost identical to those chosen by Qu and Luo (2015) (except the random effect variance since there is no random effect in Qu and Luo (2015) ). ...arXiv:1904.06384v2 fatcat:4f2fo2bgxbacvlj637sirthx2e
α-Terthiophene is a class of pesticides with predominant photoactivity. In this work, using terthiophene as the lead compound, the important mediator, 2-carbonyl terthiophene, was synthesized by the carbonylation. After reaction with substituted phenylethanone, terthiophene-substituted α,β-unsaturated ketones were synthesized. Followed by the ring closure reaction with hydroxylamine hydrochloride and hydrazine, a series of 3,5-diaryl isoxazole and 3,5-diaryl pyrazoline drivatives containingdoi:10.6023/cjoc201308008 fatcat:jlqlp6sxlfhbtevvhp7d3fajwa
more »... rthiophene were synthesized, respectively. Their structures were confirmed by 1 H NMR, IR and elemental analysis. The biological activity assay indicated that most of the synthesized compounds exhibit strong photoactivities. In addition, the photoactivities of isoxazole derivatives were much better than those of pyrazoline derivatives, where the photoactivity difference of compound 3b was 64.06 before and after illumination, especially. However, some of the pyrazoline derivatives showed higher activities of killing cells, where the activity of the compound 4d was as high as 83.9%.
Aim. To explore acoustic radiation force impulse (ARFI) elastography in assessing residual tumors of hepatocellular carcinoma (HCC) after radiofrequency ablation (RFA).Materials and Methods. There were 83 HCC lesions among 72 patients. All patients were examined with ARFI, contrast enhanced ultrasound (CEUS), and CT or MRI. Tumor brightness on virtual touch tissue imaging (VTI) and shear wave velocity (SWV) were assessed before and approximately one month after RFA.Results. There were 14doi:10.1155/2014/901642 pmid:24895624 pmcid:PMC4033335 fatcat:eq5bbytut5fbfanlgvary4oxkq
more »... l tumors after RFA. VTI showed that all the tumors were darker after RFA. VTI was not able to distinguish the ablated lesions and the residual tumors. 13 residual tumor lesions were detected by CEUS. All completely ablated nodules had SWV demonstration of x.xx., while with those residual nodules, 6 tumors had x.xx measurement and 8 tumors had measurable SWV. nine lesions with residual tumors occurred in cirrhosis subjects and 5 lesions with residual tumors occurred in fibrosis subjects; there was no residual tumor in the normal liver subjects.Conclusion. VTI technique cannot demonstrate residual tumor post RFA. While SWV measurement of less than x.xx is likely associated with residual tumors, measurement of less than x.xx cannot exclude residual tumors. Liver cirrhosis is associated with decreased chance of a complete ablation.
Studies on biological functions of N6-methyladenosine (m6A) modification in mRNA have drawn significant attention in recent years. Here we describe the construction and characterization of a CRISPR–Cas13b-based tool for targeted demethylation of specific mRNA. A fusion protein, named dm6ACRISPR, was created by linking a catalytically inactive Type VI-B Cas13 enzyme from Prevotella sp. P5–125 (dPspCas13b) to m6A demethylase AlkB homolog 5 (ALKBH5). dm6ACRISPR specifically demethylates m6A ofdoi:10.1093/nar/gkaa269 pmid:32356894 fatcat:jathdkxcojap5h4zuuihhusjza
more »... eted mRNA such as cytochrome b5 form A (CYB5A) to increase its mRNA stability. It can also demethylate β-catenin-encoding CTNNB1 mRNA that contains multiple m6A sites to trigger its translation. In addition, the dm6ACRISPR system incurs efficient demethylation of targeted epitranscriptome transcripts with limited off-target effects. Targeted demethylation of transcripts coding for oncoproteins such as epidermal growth factor receptor (EGFR) and MYC can suppress proliferation of cancer cells. Together, we provide a programmable and in vivo manipulation tool to study mRNA modification of specific genes and their related biological functions.
Background Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in polydoi:10.1186/s12951-021-01196-6 pmid:34930284 pmcid:PMC8686264 fatcat:4mvvuzt5dravhfdpzzz26tge2u
more »... ic-co-glycolic acid) (PLGA) nanocarriers. Results The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. Conclusions This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment. Graphical Abstract
Role of protein phosphatases in the activation of CFTR (ABCC7) by genistein and bromotetramisole. Am J Physiol Cell Physiol 279: C108-C119, 2000.-Genistein and bromotetramisole (Br-t) strongly activate cystic fibrosis transmembrane conductance regulator (CFTR; ABCC7) chloride channels on Chinese hamster ovary cells and human airway epithelial cells. We have examined the possible role of phosphatases in stimulation by these drugs using patchclamp and biochemical methods. Genistein inhibited thedoi:10.1152/ajpcell.2000.279.1.c108 pmid:10898722 fatcat:ij6poe24xbceja7t7nqxb77jqe
more »... pontaneous rundown of channel activity that occurs after membrane patches are excised from cAMP-stimulated cells but had no effect on purified protein phosphatase type 1 (PP1), PP2A, PP2B, PP2C, or endogenous phosphatases when assayed as [ 32 P]PO 4 release from prelabeled casein, recombinant GST-R domain fusion protein, or immunoprecipitated full-length CFTR. Br-t also slowed rundown of CFTR channels, but, in marked contrast to genistein, it did inhibit all four protein phosphatases tested. Half-maximal inhibition of PP2A and PP2C was observed with 0.5 and 1.5 mM Br-t, respectively. Protein phosphatases were also sensitive to (ϩ)-p-Br-t, a stereoisomer of Br-t that does not inhibit alkaline phosphatases. Br-t appeared to act exclusively through phosphatases since it did not affect CFTR channels in patches that had low apparent endogenous phosphatase activity (i.e., those lacking spontaneous rundown). We conclude that genistein and Br-t act through different mechanisms. Genistein stimulates CFTR without inhibiting phosphatases, whereas Br-t acts by inhibiting a membrane-associated protein phosphatase (probably PP2C) that presumably allows basal phosphorylation to accumulate.
Metal silicate hydroxides have been recognized as efficient oxygen evolution reaction (OER) electrocatalysts, yet tailoring of their intrinsic activity remains confused. Herein, Fe had been incorporated into cobalt silicate hydroxide nanosheets and the resulted material achieves a competitive OER catalytic activity. It is found that the doping state obviously affects the electrical transport property. Specifically, highly dispersed Fe atoms (low-concentration Fe doping) trigger slight electrondoi:10.1002/eem2.12219 fatcat:7keghmi36jczjfjqj5fysc4dd4
more »... ransfer to Co atoms while serried Fe (high-concentration Fe doping) attract vast electrons. By introducing 6 at.% Fe doping, partial relatively inert Co sites are activated by atomically dispersed Fe, bearing an optimal metal 3d electronic occupation and adsorption capacity to oxygen intermediate. The introduced Co−O−Fe unit trigger the π-donation effect and decrease the number of electrons in π*-antibonding orbitals, which enhance the Fe−O covalency Accepted Article This article is protected by copyright. All rights reserved and the structural stability. As a result, the sample delivers a low overpotential of 293 mV to achieve a current density of 10 mA cm −2 . This work clarifies the superiority of atomically dispersed doping state, which is of fundamental interest to the design of doped catalyst.
The effective removal of uranium from an aqueous solution is a highly valuable process for the environment and health. In this study, we developed a facile and rapid method to synthesize hierarchically porous Cu-BTC (RT-Cu-BTC) using a cooperative template strategy. The as-synthesized RT-Cu-BTC exhibited hierarchically porous structure and excellent thermostability, as revealed by X-ray powder diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, anddoi:10.3390/nano10081539 pmid:32781518 fatcat:qaaawwgfi5ejlnfjjswuoqlssu
more »... ic analysis. Compared with conventional metal–organic frameworks (MOFs) and zeolites, the obtained RT-Cu-BTC exhibited enhanced adsorption capacity (839.7 mg·g−1) and high removal efficiency (99.8%) in the capture of uranium (VI) from aqueous solutions. Furthermore, the conditions such as adsorbent dose, contact time, and temperature in adsorption of uranium (VI) by RT-Cu-BTC were investigated in detail. The thermodynamics data demonstrated the spontaneous and endothermic nature of the uranium (VI) adsorption process. The Langmuir isotherm and pseudo-second-order models could better reflect the adsorption process of uranium (VI) onto RT-Cu-BTC. In addition, the as-synthesized RT-Cu-BTC showed excellent stability in removing uranium (VI) from an aqueous solution. This work provides a facile and rapid approach for fabricating hierarchically porous MOFs to realize a highly efficient removal of uranium (VI) from aqueous systems.
Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs)doi:10.1093/nar/gky1250 pmid:30541109 pmcid:PMC6411830 fatcat:k7uav3ud3zeg5p3kajw6jl2ydi
more »... nd the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.
Long noncoding RNAs (lncRNAs) have emerged as critical players in cancer progression, but their functions in colorectal cancer (CRC) metastasis have not been systematically clarified.doi:10.1186/s12943-019-1014-2 pmid:30979372 pmcid:PMC6461827 fatcat:jd4md5lrsngdrdzrjs36xtfc6m
Pages 13 j m a t e r r e s t e c h n o l . 2 0 2 0;x x x(x x):xxx-xxx w w w . j m r t . c o m . b r Available online xxx Keywords: MWCNT sensor In-situ monitoring DCB test WGF/epoxy composites a b s t r a c t The interlaminar peformance of composites palys an important role in the damage process of fiber reinforced composites. In-situ monitoring by an embedded sensor could avoid the sudden failure. This paper investigates the in-situ monitoring of mode I interlaminar crack propagationg behaviordoi:10.1016/j.jmrt.2020.03.119 fatcat:vdtrzna4wvf4hiw4urjook5pn4
more »... in woven glass fiber reinforced epoxy (WGF/epoxy) composite laminates. The resistance signal of multi-walled carbon nanotube (MWCNT) located in the mid-thickness of WGF/epoxy during the double cantilever beam (DCB) test is recorded. Relationship between the relative resistance and the interlaminar crack length is theoretically built and experimentally verified. Results show that the mode I crack propagating length can be successfully predicted by the relative resistance. A linear relationship between the interlaminar crack propagating length and the total relative resistance is found by the experimental and theoretical results. (B. Yang). and space engineering, civil engineering, and other consumer products as key structures      . In these applications, the composites made of plain woven glass fiber layers and polymers have attracted a significant amount of attention due to their high specific strength and stiffness, supreme formabilhttps://doi.
Work by Lin Luo and A.M.C. was supported by Canadian Institutes of Health Research (FDN-143206) and Simons Foundation Autism Research Initiative (SFARI 608066). ... Zoghbi VGluT1-IRES2- Cre-D Slc17a7 tm1.1(cre)Hze /J Ai34 e A, F, H 33.3% (10/30) 38.5% (5/13) - - Jiexin Wang, Pascal S. ... Huang, Liqun Luo Slc17a6 tm2(cre)Lowl /J Ai14 e E or G 0 (from >3 years breeding) 0 (from >3 years breeding) - - Kevin T. ...doi:10.1016/j.neuron.2020.01.008 pmid:32027825 pmcid:PMC7377387 fatcat:kgqklmfsxndafnnfk7mew4zc5u
Differential regulation of single CFTR channels by PP2C, PP2A, and other phosphatases JIEXIN LUO,! MARY D. PATO,? JOHN R. RIORDAN,’ AND JOHN W. HANRAHAN! ... Johnson Medical Research Center, Mayo Clinic Scottsdale, Scottsdale, Arizona 85259 Luo, Jiexin, Mary D. Pato, John R. Riordan, and John W. Hanrahan. ...
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