Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) China.Their PNPLA3 polymorphisms were genotyped by gene sequencing.The association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic scoring.The association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV DNA.RESULTS:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB patients.In patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) are correlated with susceptibility to NAFLD,NASH,liver fibrosis,and HBV dynamics in CHB patients.

Effect of Bacillus subtilis,Enterococcus faecium,and Enterococcus faecalis supernatants on serotonin transporter expression in cells and tissues

BACKGROUND Bacillus subtilis(B.subtilis),Enterococcus faecium(E.faecium),and Enterococcus faecalis(E.faecalis)are probiotics that are widely used in the clinical treatment of irritable bowel syndrome(IBS).Whether the supernatants of these three probiotics can improve gastrointestinal sensation and movement by regulating the serotonin transporter(SERT)expression needs to be clarified.AIM To investigate whether B.subtilis,E.faecium,and E.faecalis supernatants can upregulate SERT expression in vitro and in vivo.METHODS Caco-2 and HT-29 cells were stimulated with probiotic culture supernatants for 12 and 24 h,respectively.A male Sprague-Dawley rat model of post-infectious irritable bowel syndrome(PI-IBS)was established and the rats were treated with phosphate-buffered saline(group A)and three probiotics culture supernatants(groups B,C,and D)for 4 wk.The levels of SERT were detected by quantitative PCR and western blotting.RESULTS The levels of SERT at post-treatment 12 and 24 h were significantly elevated in Caco-2 cells treated with B.subtilis supernatant compared with those in the control group(aP<0.05).Those levels were markedly upregulated in Caco-2 cells stimulated with E.faecium and E.faecalis supernatants at 24 h(aP<0.05).In addition,SERT expression in groups B,C,and D was significantly higher than that in group A in the 2nd wk(aP<0.05).Increased SERT expression was only found in group D in the 3rd wk(aP<0.05).However,there was no significant difference in SERT expression between the groups in the last week(P>0.05).CONCLUSION The supernatants of B.subtilis,E.faecium,and E.faecalis can upregulate SERT expression in intestinal epithelial cells and the intestinal tissues in the rat model of PI-IBS.

Numerical Solution for Fractional Partial Differential Equation with Bernstein Polynomials

A framework to obtain numerical solution of the fractional partial differential equation using Bernstein polynomials is presented. The main characteristic behind this approach is that a fractional order operational matrix of Bernstein polynomials is derived. With the operational matrix, the equation is transformed into the products of several dependent matrixes which can also be regarded as the system of linear equations after dispersing the variable. By solving the linear equations, the numerical solutions are acquired. Only a small number of Bernstein polynomials are needed to obtain a satisfactory result. Numerical examples are provided to show that the method is computationally efficient.

潜油电泵的机械可靠性（英文）

Electric submersible pumps(ESP) boost pressure to maintain or increase flow rates in oil wells. ESPs are oriented vertically and include a pump section, a seal section and an electric motor. High cost of subsea installations and recurring failures in specific geographic regions are driving the need for developing ESPs with higher reliability and run life. This work focuses on the reliability of the pump section and a description of the research facilities and ongoing research programs at the Texas A&M Turbomachinery Laboratory. These programs include testing and modeling pump sections operating with multiphase fluids(water, air, sand), evaluating reliability of mechanical seals subjected to large vibration amplitudes and characterizing the static performance of process fluid-lubricated thrust bearings.

L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons

As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in vivo.The latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted neurons.However,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still unclear.Here,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal neurons.By whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal neurons.This phenomenon lasts for>10 min after LIPUS exposure.Together with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein expression.Our work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via LTCCs.This may also explain the multi-activation effects of LIPUS beyond neurons.LIPUS stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.

Spatially charge-separated 2D homojunction for photocatalytic hydrogen production

Suppression of photogenerated charge recombination is crucial for efficient photocatalytic hydrogen production.Homojunctions have garnered more attention than heterojunctions due to their superior crystal binding and band structure matching.However,most homojunctions suffer from redox interference caused by continuous oxidizing and reducing phases that impede the ability to improve photocatalytic activity.Consequently,the preparation of homojunction photocatalysts with completely spatial separation of both in charge and redox phases remains challenging.Here,the preparation of a two-dimensional(2D)homojunction CeO_(2) with a back-to-back geometry and fully separated oxidizing and reducing phases is reported.The prepared CeO_(2) is composed of nanosheets with twocontrasting smooth and rough surfaces.Experimental and theoretical results indicate that the rough surface contains more highly reducing CeO_(2){220}and strongly visiblelight-absorbing CeO_(2){200}facets than the smooth surface.The 2D homojunction CeO_(2) produces three-times more hydrogen than normal CeO_(2) nanosheets,and even more than that of CeO_(2) nanosheets loaded with gold nanoparticles.This work presents a new homojunction photocatalyst model with completely spatial separation of both in charge and redox phases that is expected to inspire further research into homojunction photocatalysts.

基于开环反应构建新型还原响应型支化聚赖氨酸基因载体

通过'一锅法'开环反应构建了一种含有双硫键的还原响应型可降解支化聚赖氨酸基因载体(SS-HP).同时通过相似的方法合成了不含双硫键的支化聚赖氨酸基因载体(CC-HP)作为对照.聚阳离子/pDNA复合物的水合粒径和电位通过动态光散射仪测定,其在还原性环境中的降解情况通过凝胶阻滞电泳、原子力显微镜测试评价. SS-HP和CC-HP的体外转染能力及细胞毒性通过荧光素酶报告基因和MTT法在脑胶质瘤C6和肝癌HepG2细胞中测定.癌细胞中过量表达的谷胱甘肽能够使SS-HP在细胞内降解,加速pDNA的释放,使该载体有良好的基因转染能力.同时,载体的可降解性以及由开环反应给载体引入的大量羟基,使载体有较低的细胞毒性. KillerRed蛋白是一种在可见光照射下能产生单线态氧的红色荧光蛋白.使用SS-HP携载pKillerRed (pKR)质粒进行体外光动力抗癌评价. SS-HP/pKR转染C6细胞后能成功表达出KillerRed蛋白,光照后可以促进肿瘤细胞的凋亡.

Optimization,identification and bioactivity of flavonoids extracted from Moringa oleifera leaves by deep eutectic solvent

Moringa oleifera leaves (MO L) attract extensive attention in agriculture,pharmaceutical and food industry because of its rich biological activity.In this study,ChCl/LA as one of the deep eutectic solvents (DESs) was selected to extract flavonoids from Moringa oleifera leaves (FMO L).The extraction rate of FMO L reached 54.8 mg/g.After separation of FMO L,its biological activities were systematically studied.The IC50 values of FMO L for DPPH radical,ABTS radical scavenging activity,FRAP and ORAC were 27.3 μg/mL,41.2 μg/mL,18.7 mg TE/g and 6008.4 mg TE/g,respectively,indicating FMO L had excellent antioxidant activity.FMO L not only had better antibacterial activity than the positive controls,but also had inhibitory activity to tumor cells.The IC50 values of FMO L on B16 cells,HCT116 cells and Hep G-2 cells were 530.7,328.0,and 533.7 μg/mL,respectively.Nine flavonoid compounds were identified by UPLC-Q-Orbitrap MS/MS,and four of them were confirmed from MO L for the first time.Therefore,FMO L extracted by ChCl/LA had rich bioactive components and is expected to be used in food and pharmaceutical industries.

Greenberger-Horne-Zeilinger test for multi-dimension and arbitrary time nodes entangled histories

Quantum entanglement,since proposed by Einstein,Podolsky and Rosen(EPR)[1]and further explored by Schr?dinger[2]in1935,has always been the focus of quantum physics realm.The EPR paradox revealed the conflict between quantum theory and local realism.Almost 30 years later,in 1964,Bell first came up with the prototype of a family of inequalities,which was later called Bell inequality[3,4],to express certain limitation that every local clas-