Fufang E’jiao Jiang’s effect on immunity,hematopoiesis,and angiogenesis via a systematic“compound-effect-target”analysis

Fufang E’jiao Jiang(FEJ)as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood,and it has a positive impact on women’s health.To find out the material basis and mechanism of FEJ,a systematic“compoundeffect-target”analysis including chemical composition resolution,zebrafish,network pharmacology,molecular docking,transcriptome,and bibliometric analysis was adopted.124 chemical components including ginsenosides,and phenylethanoid glycosides in FEJ were discovered,and effects of FEJ on promoting the generation of immune cells,erythropoiesis and angiogenesis in zebrafish were exhibited.Based on network pharmacology,molecular docking and in vivo activity assay,6 compounds including jionoside A1,isoacteoside,echinacoside,acteoside,lobetyolin,and rehmannioside D were identified as active components of FEJ.Transcriptome data showed that several pathways such as complement and coagulation cascades,ECM-receptor interaction,and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ.19 common targets were obtained through combined analysis of network pharmacology and transcriptomics,and 5 targets of them were verified by PCR.The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism,pathway in cancer,etc.,which was consistent with the results of network pharmacology and transcriptome.The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.

Facet effect on the reconstructed Cu-catalyzed electrochemical hydrogenation of 5-hydroxymethylfurfural(HMF) towards 2,5-bis(hydroxymethy)furan (BHMF)

The electrochemical hydrogenation of HMF to BHMF is an elegant alternative to the conventio nal thermocatalytic route for the production of high-value-added chemicals from biomass resources.In virtue of the wide potential window with promising Faradic efficiency(FE) towards BHMF,Cu-based electrode has been in the center of investigation.However,its structure-activity relationship remains ambiguous and its intrinsic catalytic activity is still unsatisfactory.In this work,we develop a two-step oxidation-reduction strategy to reconstruct the surface atom arrangement of the Cu foam(CF).By combination of multiple quasi-situ/in-situ techniques and density functional theory(DFT) calculation,the critical factor that governs the reaction is demonstrated to be facet effect of the metallic Cu crystal:Cu(110) facet accounts for the most favorable surface with enhanced chemisorption with reactants and selective production of BHMF,while Cu(100) facet might trigger the accumulation of the by-product 5,5'-bis(hydroxy methy)hydrofurion(BHH).With the optimized composition of the facets on the reconstructed Cu(OH)_(2)-ER/CF,the performance could be noticeably enhanced with a BHMF FE of 92.3% and HMF conversion of 98.5% at a potential of -0.15 V versus reversible hydrogen electrode(vs.RHE) in 0.1 M KOH solution.This work sheds light on the incomplete mechanistic puzzle for Cu-catalyzed electrochemical hydrogenation of HMF to BHMF,and provides a theoretical foundation for further precise design of highly efficient catalytic electrodes.

Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well characterized.Here,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and migration.We found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and migration.Notably,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)sites.Our results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

特低渗油藏压裂井产能预测方法研究

针对特低渗透油藏垂直裂缝井的产能预测问题,基于椭圆型流动物理模型,考虑启动压力,引入渗透率变异系数和黏度变异系数,导出油井产能预测理论公式。用S油田23口油井的实际生产测试资料进行验算,结果表明,理论公式的计算值与实际值相对误差达-78.7%。基于实测数据将渗透率变异系数修正为地层变异系数,新的油井产能预测公式预测相对误差降至-0.9%。

Chemoselective hydrogenolysis of tetrahydrofurfuryl alcohol to 1,5-pentanediol over Ir-MoO_x/SiO_2 catalyst

In this work, MoOx promoted Ir/SiO2 catalysts were prepared and used for the selective hydrogenolysis of tetrahydrofurfuryl alcohol （THFA） to 1,5-pentanediol in a continuous flow reactor. The effects of different noble metals （Ir, Pt, Pd, Ru, Rh）, supports and Ir contents were screened. Among the investigated catalysts, 4 wt%Ir-MoOx/SiO2 with a Mo/Ir atomic ratio of 0.13 exhibited the best catalytic performance. The synergy between Ix particles and the partially reduced isolated MoOx species attached on them is essential for the excellent catalytic performance of Ix-MoOx/SiO2. The catalyst exhibited a better hydrogenolysis efficiency of THFA with the selectivity of 1,5-pentanediol of 65%-74% at a conversion of THFA of 70%-75% when the initial THFA concentration is ranging from 20 wt% and 40 wt%. And higher system pressure was also in favor of the conversion of THFA. During a stability test, the conversion of THFA and 1,5-pentanediol yield over Ix-MoOz/SiO2 decreased with reaction time, which can be explained by the leaching of Mo species during the reaction.

Two Inhibitors Against the 3C-Like Proteases of Swine Coronavirus and Feline Coronavirus

Coronaviruses(CoVs)are important human and animal pathogens that cause respiratory and gastrointestinal diseases.Porcine epidemic diarrhoea(PED),characterized by severe diarrhoea and vomiting in pigs,is a highly lethal disease caused by porcine epidemic diarrhoea virus(PEDV)and causes substantial losses in the swine industry worldwide.However,currently available commercial drugs have not shown great therapeutic effects.In this study,a fluorescence resonance energy transfer(FRET)-based assay was applied to screen a library containing 1,590 compounds and identified two compounds,3-(aminocarbonyl)-1-phenylpyridinium and 2,3-dichloronaphthoquinone,that target the 3C-like protease(3CL^(pro))of PEDV.These compounds are of low molecular weight(MW)and greatly inhibited the activity of this enzyme(IC_(50) values were obtained in this study).Furthermore,these compounds exhibited antiviral capacity against another member of the CoV family,feline infectious peritonitis virus(FIPV).Here,the inhibitory effects of these compounds against CoVs on Vero cells and feline kidney cells were identified(with EC_(50) values)and cell viability assays were performed.The results of putative molecular docking models indicate that these compounds,labeled compound 1 and compound 2,contact the conserved active sites(Cys144,Glu165,Gln191)of 3CL^(pro) via hydrogen bonds.These findings provide insight into the antiviral activities of compounds 1 and 2 that may facilitate future research on anti-CoV drugs.

CAIPIRINHA-accelerated T1w 3D-FLASH for small-bowel MR imaging in pediatric patients with Crohn's disease:assessment of image quality and diagnostic performance

Background:The“Controlled Aliasing In Parallel Imaging Results In Higher Acceleration”(CAPIRINHA)technique greatly accelerates T1w 3D fast low angle shot(FLASH)scans while maintaining high image quality.We studied image quality and conspicuity of inflammatory lesions on CAIPIRINHA-accelerated imaging for pediatric small-bowel magnetic resonance imaging(MRI).Methods:Forty-four consecutive patients(mean 14±3 years,18 girls)underwent small-bowel MRI(MR enterography,MRE)at 1.5 T including diffusion-weighted imaging(DWI),contrast-enhanced CAIPIRINHA 3D-FLASH and standard 2D-FLASH imaging.Crohn’s disease(CD)was confirmed in 26 patients,18 patients served as control.Independent blinded readings were performed for grading of image quality and conspicuity of CD lesions on CAIPIRINHA FLASH and standard FLASH images in comparison to a reference standard comprising imaging and endoscopic data.Results:CAIPIRINHA FLASH yielded significantly higher image quality with good inter-observer agreement(κ=0.68)and showed better visual delineation in 40%of the assessed bowel lesions,as compared to standard FLASH.There was full agreement for identification of CD patients between CAIPIRINHA and standard FLASH.CAIPIRINHA FLASH detected two small-bowel lesions that were not seen on standard FLASH.DWI revealed additional inflammatory lesions inconspicuous on contrast-enhanced imaging.MRE showed an overall diagnostic accuracy of 93%.Conclusion:We present first evidence that CAIPIRINHA greatly accelerates T1w imaging in paediatric MRE without trade-off in image quality or lesion conspicuity and is thus preferable to standard FLASH imaging.

On the rapid intensification for Typhoon Meranti(2016):convection,warm core,and heating budget

Through a cloud-resolving simulation of the rapid intensification(RI)of Typhoon Meranti(2016),the convections,warm core,and heating budget are investigated during the process of RI.By investigating the spatial distributions and temporal evolutions of both convectivestratiform precipitation and shallow-deep convections,we find that the inner-core convections take mode turns,from stratiform-precipitation(SP)dominance to convectiveprecipitation(CP)prevalence during the transition stages between pre-RI and RI.For the CP,it experiences fewer convections before RI,and the conversion from moderate/moderate-deep convections to moderate-deep/deep convections during RI.There is a clear upper-level warm-core structure during the process of RI.However,the mid-lowlevel warming begins first,before the RI of Meranti.By calculating the local potential temperature(0)budget of various convections,the link between convections and the warm core(and further to RI via the pressure drop due to the warming core)is established.Also,the transport pathways of heating toward the center of Meranti driven by pressure are illuminated.The total hydrostatic pressure decline is determined by the mid-low-level warm anomaly before RI,mostly caused by SP.The azimuthal-mean diabatic heating is the largest heating source,the mean vertical heat advection controls the vertical downwards transport by adiabatic warming of compensating downdrafts above eye region,and then the radial 6 advection term radially transports heat toward the center of Meranti in a slantwise direction.Accompanying the onset of RI,the heating efficiency of the upper-level warming core rises swiftly and overruns that of the mid-low-level warmanomaly, dominating the total pressure decrease and beingmainly led by moderate-deep and deep convections. Asidefrom the characteristics in common with SP, for CP, theeddy component of radial advection also plays a positiverole in warming the core, which enhances the centripetaltransport effect and accelerates the RI of Meranti.

Diagnostic value of diffusion-weighted MRI for imaging synovitis in pediatric patients with inflammatory conditions of the knee joint

Background Diffusion-weighted imaging(DWI)of synovitis has been suggested as a possible non-invasive alternative to contrast-enhanced T1w imaging(ce-T1w).We aimed to study DWI for diagnosing synovitis in the knee joint of pediatric patients,to quantify inter-observer agreement on DWI and ce-T1w and to calculate quantitative measures of synovial diffusivity and conspicuity.Methods Forty consecutive patients with known or suspected arthritis of the knee(25 girls,median age 12 years)underwent routine 1.5T MRI with ce-T1w and transverse DWI with b values 50 and 800 s/mm2.Mean apparent diffusion coefficient(ADC)values and signal intensity of inflamed synovium,joint effusion and muscle were measured with regions of interest retrospectively.Post-contrast T1 w images(diagnostic standard)and diffusion-weighted images at b=800 s/mm2 with ADC map were separately rated by three independent and blinded readers with different levels of expertise for the presence and degree of synovitis along with the level of diagnostic confidence.Results Thirty-one(78%)patients showed at least some synovial contrast enhancement,17(43%)children were diagnosed with synovitis on ce-T1w.Ratings by the 1st reader on ce-T1w and on DWI for synovitis showed very good agreement(kappa=0.90).Inter-observer agreement on DWI ranged from moderate to substantial with kappa values between 0.68 and 0.79(all P<0.001).Agreement and diagnostic confidence were generally lower in patients with mild and without synovial enhancement,compared to patients with synovitis.DWI yielded higher signal of inflamed synovium vs.muscle tissue,but lower signal vs.joint effusion,compared to ce-T1 w(all P<0.001).Conclusions Diffusion-weighted imaging is a promising,though reader-dependent alternative to contrast-enhanced imaging in patients with arthritis of the knee,based on our preliminary findings.It holds potential for increasing patient safety and comfort.

U1 snRNP proteins promote proximal alternative polyadenylation sites by directly interacting with 3'end processing core factors

In eukaryotic cells,both alternative splicing and alternative polyadenylation(APA)play essential roles in the gene regulation network.U1 small ribonucleoprotein particle(U1 snRNP)is a major component of spliceosome,and U1 snRNP complex can suppress proximal APA sites through crosstalking with 3end processing factors.However,here we show that both knockdown and overexpression of SNRPA,SNRPC,SNRNP70,and SNRPD2,the U1 snRNP proteins,promote the usage of proximal APA sites at the transcriptome level.SNRNP70 can drive the phase transition of PABPN1 from droplet to aggregate,which may reduce the repressive effects of PABPN1 on the proximal APA sites.Additionally,SNRNP70 can also promote the proximal APA sites by recruiting CPSF6,suggesting that the function of CPSF6 on APA is related with other RNA-binding proteins and cell context-dependent.Consequently,these results reveal that,on the contrary to U1 snRNP complex,the free proteins of U1 snRNP complex can promote proximal APA sites through the interaction with 3end processing machinery.