PTBP1通过调控FGFR2的可变剪接促进肝癌的发展

肝细胞癌(hepatocellular carcinoma,HCC)是原发性肝癌的主要类型,是一种早期无明显症状、易发生转移、存活率低的恶性肿瘤。多聚嘧啶区结合蛋白1 (polypyrimidine tract binding protein 1,PTBP1)是一种重要的RNA结合蛋白,可诱导促癌剪接事件的发生。虽然PTBP1在肝癌细胞中的促癌功能已被证实,但是其介导的促癌可变剪接事件及作用机制尚未得到完全解析。本文利用免疫共沉淀联合质谱分析发现与PTBP1结合的蛋白复合体显著富集于编码成纤维细胞生长因子受体2(fibroblast growth factor receptor 2,FGFR2)的基因可变剪接调控过程。通过RNA免疫共沉淀和定量PCR实验,证实PTBP1可显著下调肝癌细胞中FGFR2-IIIb异构体的水平,上调FGFR2-IIIc异构体的水平,促进FGFR2-IIIb向FGFR2-IIIc的异构体转换。随后,通过CCK-8、transwell和平板克隆实验,在肝癌细胞系HepG2和Huh7中评价了FGFR2-IIIb和FGFR2-IIIc的肿瘤生物学功能。结果显示FGFR2-IIIb发挥抑癌功能,而FGFR2-IIIc发挥促癌功能。机制研究证实,FGFR2-IIIb向FGFR2-IIIc异构体的转换显著促进肝癌细胞的上皮-间充质转化(epithelial-mesenchymaltransformation,EMT)及FGFR下游ERK和AKT信号通路的活化。本研究揭示了PTBP1促进肝癌进展的分子调控机制,为肝癌的防治提供了新的理论依据。

Evaluation on the Influence of the Timing of Twin Pregnancy Termi­nation on the Outcome of Mother and Infants

Objective:Objective:To observe the maternal and infant outcomes of pregnant women with twins terminating their pregnancy at different timings.Methods:Among the twin pregnant women admitted to our hospital from August 2019 to August 2020,50 primiparous women who opted to terminate their pregnancies at 5 different timings of“34--34^(+6) weeks”,“35--35^(+6) weeks”,“36--36^(+6) weeks”,“37--37^(+6) weeks”,“38--38^(+6) weeks”were selected as the research subjects.According to the timing of pregnancy termination,they were divided into 5 groups,each with 10 cases of pregnant women,and the impact of the timing of pregnancy termination on the outcome of the mothers and infants were compared.Results:The“37--37^(+6) weeks”group had the largest amount of postpartum hemorrhage,and the difference in Hb level before and after delivery was the largest.With the increase in gestational week,the weight of both large and small fetuses increased.In terms of neonatal diseases,the comparison between“34--34^(+6) weeks”,“35--35^(+6) weeks”,“36--36^(+6) weeks”and“37--37^(+6) weeks”,“38--38^(+6) weeks”,P<0.05,the comparison between“37--37^(+6) weeks”and“38--38^(+6) weeks”,P>0.05.Conclusions:The extension of the gestational week of twin pregnancies has no effect on postpartum hemorrhage,but it can improve the outcome of infants.

用沙盘游戏干预一例“精神留守”儿童的案例

探讨沙盘游戏干预“精神留守”儿童心理健康问题的效果。方法:运用个体沙盘游戏,对1名具有社会退缩问题的“精神留守”儿童进行了为期2个月共7次干预。结果:干预结束后,该来访者的沙盘从以空洞、受伤、忽视为主的主题特征转变成以自我培育为主的主题特征,该来访者人格得到整合,性格也变得开朗而乐于表达自我。结论:沙盘疗法对精神留守儿童的心理健康问题具有较好的干预效果。

Hybrid energy harvesting systems for self-powered sustainable water purification by harnessing ambient energy

The development of self-powered water purification technologies for decentralized applications is crucial for ensuring the provision of drinking water in resource-limited regions. The elimination of the dependence on external energy inputs and the attainment of self-powered status significantly expands the applicability of the treatment system in real-world scenarios. Hybrid energy harvesters, which convert multiple ambient energies simultaneously, show the potential to drive self-powered water purification facilities under fluctuating actual conditions. Here, we propose recent advancements in hybrid energy systems that simultaneously harvest various ambient energies (e.g., photo irradiation, flow kinetic, thermal, and vibration) to drive water purification processes. The mechanisms of various energy harvesters and point-of-use water purification treatments are first outlined. Then we summarize the hybrid energy harvesters that can drive water purification treatment. These hybrid energy harvesters are based on the mechanisms of mechanical and photovoltaic, mechanical and thermal, and thermal and photovoltaic effects. This review provides a comprehensive understanding of the potential for advancing beyond the current state-of-the-art of hybrid energy harvester-driven water treatment processes. Future endeavors should focus on improving catalyst efficiency and developing sustainable hybrid energy harvesters to drive self-powered treatments under unstable conditions (e.g., fluctuating temperatures and humidity).

Effect of grain size on ferroelectric and dielectric properties of Bi_(3.25)La_(0.75)Ti_(3)O_(12) thin films prepared by rf-magnetron sputtering

Bi_(3.25)La_(0.75)Ti_(3)O_(12)(BLT)thin films are promising materials used in non-volatile memories.In this work,BLT films were deposited on Pt(111)/Ti/SiO_(2)/Si substrates by rf-magnetron sputtering method followed by annealing treatments.The microstructures of BLT thin films were investigated via X-ray diffraction(XRD),scanning electron microscopy(SEM)and atomic force microscopy(AFM).With the increase in annealing temperature,the grain size increased significantly and the preferred crystalline orientation changed.A well-saturated hysteresis loop with a superior remnant polarization of 15.4μC/cm^(2) was obtained for BLT thin films annealed at 700°C.The results show that the dielectric constant decreased with the increase in grain sizes.

冰川生态系统固碳微生物研究进展

冰川占地球陆地表面的11%,储存了约104 Pg有机碳。随着冰川消融有机碳被释放至下游生态系统中,刺激海洋、湖泊和径流的初级生产力进而影响其生态系统。微生物参与的固碳过程决定了冰川有机碳储量及向下游输出碳量。研究冰川固碳微生物群落构成及其生态功能,可为估算冰川碳积累量和保护下游生态系统提供数据基础。本文综述了冰川碳储量和释放量、冰川生态系统主要固碳途径、固碳微生物群落组成、固碳速率以及影响固碳速率的环境因素。最后基于研究现状展望了冰川生态系统固碳微生物的未来研究和发展方向。

Magnetic evidence for heavy metal pollution of topsoil in Shanghai, China

This study presents the results obtained from magnetic susceptibility and heavy metal （Cu, Zn, Pb, and Cr） concentration measurements of soil profiles collected from arable land and urban parks in Baoshan District, an industrial district of Shanghai, China. The study focuses on the investigation of vertical variations in magnetic susceptibilities and heavy metal concentrations and on correlations between magnetic susceptibilities and heavy metal concentrations in soil profiles. The results demon- strate that magnetic enhancement in the surface layer of the soil profile is associated with increased heavy metal pollution. The enrichment factors （EF） and the Tomlinson Pollution Load Index （PLI-EF） are calculated for estimat- ing the level of heavy metal pollution of soil profiles in the study. The significant positive correlations between heavy metal contents, enrichment factors （EF）, Tomlinson pollution load index （PLI-CF）, modified Tomlinson pollution load index （PLI-EF）, and magnetic susceptibility （X） indicate that much of the heavy metal contamination in the study area is linked to combustion derived particulate emissions. The results confirm that the combined magnetic measurement and heavy metal concentration analysis could provide useful information for soil monitoring in urban environments. However, the use of magnetic technique to locate the heavy metal pollution boundary in the soil profile of this studied area should be confirmed by further geochemical analysis.

Drug resistance mutation profiles of the drug-nave and first-line regimen-treated HIV-1-infected population of Suzhou, China

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance(TDR) and acquired drug resistance mutation(ADR) profiles, we collected blood specimens from 127 drug-naive and 117 first-line drugtreated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified po/fragments from 100 drug-naive and 20 drug-treated samples. We then determined the drugresistant mutations to protease(PR) and reverse-transcriptase(RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted(drug-naive group) and acquired(treated group) resistance mutations, respectively. Six transmitted drugresistant mutations were found, including two mutations(L33F and L76V) in the protease region and four(K70N/E and V179D/E) in the RT region. Only L76 V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

Uncertainty of EIN2^(Ser645/Ser924) Inactivation by CTR1-Mediated Phosphorylation Reveals the Complexity of Ethylene Signaling

ETHYLENE INSENSITIVE2(EIN2)is a key component of ethylene signaling whose activity is inhibited upon phosphorylation of Ser^(645) and Ser^(924) by the Raf-like CONSTITUTIVE TRIPLE-RESPONSE 1(CTR1)in the absence of ethylene.Ethylene prevents CTR1 activity and thus EIN2^(Ser645/Ser924) phosphorylation,and subcellular trafficking of a proteolytically cleaved EIN2 C terminus(EIN2-C)from the endoplasmic reticulum to the nucleus and processing bodies triggers ethylene signaling.Here,we report an unexpected complexity of EIN2-activated ethylene signaling.EIN2 activation in part requires ethylene in the absence of CTR1-mediated negative regulation.The ein2 mutant was complemented by the transgenes encoding EIN2,EIN2 variants with mutations that either prevent or mimic Ser^(645)/Ser^(924) phosphorylation,or EIN2-C;and all the transgenic lines carrying these EIN2-derived transgenes responded to ethylene.Furthermore,we found that the fluorescence protein-tagged EIN2 and its variants were affected little by ethylene and exhibited similar subcellular distribution patterns:in the cytosolic particles and nuclear speckles.Of note,the subcellular localization patterns of EIN2 proteins fused with a fluorescence protein either at the N or C terminus were similar,whereas EIN2-C-YFP was primarily observed in the cytosol but not in the nucleus.Western blots and mass spectrum analyses suggested a high complexity of EIN2,which is likely proteolytically processed into multiple fragments.Our results suggested a nuclear localization of the full-length EIN2,weak association of the EIN2^(Ser645/Ser924) phosphorylation status and ethylene signaling,and the complexity of ethylene signaling caused by EIN2 and its proteolytic products in different subcellular compartments.We propose an alternative model to explain EIN2-activated ethylene signaling.

Elevational patterns of abundant and rare bacterial diversity and composition in mountain streams in the southeast of the Tibetan Plateau

Elevational gradients are powerful ‘natural laboratory' for testing the responses of microbes to geophysical influences. Microbial communities are normally composed of a few abundant and many rare taxa. Abundant and rare taxa play different ecological roles in kinds of environments, but how their diversity and composition patterns response to elevation gradients is still poorly elucidated. In this study, we investigated the elevational patterns of abundant and rare bacterial diversity and composition in a mountain stream from 712 to 3435 m at Gangrigabu Mountain on the Tibetan Plateau, China. Our results revealed abundant and rare bacteria had similar decreasing elevation trend of alpha diversity, and both of them showed a significant elevational distance-decay relationship. However, the turnover rate of the elevational distance-decay of rare bacteria was higher than that of abundant bacteria. The species-abundance distribution patterns of rare taxonomic composition were associated with the elevational gradient, while most of abundant bacterial clades did not display any relationships with elevation.Our results suggested that rare bacteria were more sensitive to changes in elevation gradient.

Synthesis of cobalt single atom catalyst by a solid-state transformation strategy for direct C-C cross-coupling of primary and secondary alcohols

Atomic engineering of single atom catalysts(SACs)with high-density available active sites and optimized electronic properties can substantially boost catalytic efficacy.Herein,we report a solid-state transformation strategy to access Co SACs by introducing Co species from commercial CO_(2)O3 powders into nitrogen-doped carbon support.The catalyst exhibited excellent catalytic activity,with a turnover frequency(TOF)of 2,307 h^(-1)and yield of 95%,in the direct C-C cross-coupling of benzyl alcohol and 1-phenylethanol(1 atm O2@80℃)to yield chaicone.Density functional theory(DFT)calculations demonstrate the coordination environment and electronic metal-support interaction impact the catalytic pathway.In particular,a wide substrate scope and a broad functional-group tolerance of this SAC were validated,and the employment of this strategy for large-scale synthesis was also shown to be feasible.This work might shed light on the facile and scalable synthesis of highly active,selective,and stable SACs for heterogeneous catalysis.