Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.

EGFR突变晚期非小细胞肺癌患者后线接受免疫治疗的疗效分析

背景与目的免疫检查点抑制剂单药治疗在驱动基因阳性的晚期非小细胞肺癌(non-small cell lung cancer, NSCLC)患者中疗效甚微。研究表明,部分驱动基因阳性患者靶向治疗耐药后对免疫联合治疗仍有效。国内研究甚少。本研究旨在分析人表皮生长因子(epidermal growth factor receptor, EGFR)敏感突变NSCLC患者后线接受免疫治疗的疗效,评价真实世界免疫联合化疗在EGFR突变晚期患者后线治疗中的价值。方法收集2018年6月-2020年11月在首都医科大学附属北京胸科医院确诊的EGFR突变的初治晚期肺腺癌患者共27例,均在靶向治疗进展后接受了程序性死亡受体1(programmed cell death protein 1, PD-1)检查点抑制剂联合化疗以及抗血管生成药物治疗。结果27例晚期NSCLC患者中,未合并T790M突变的有19例(70.4%),合并T790M点突变的有8例(29.6%)。总客观缓解率为40.7%。Kaplan-Meier生存分析显示,不同EGFR突变类型之间接受含PD-1单抗治疗的无进展生存期(progression-free survival, PFS)均无统计学差异(χ^(2)=4.15, P=0.23)。未合并T790M突变的患者PFS较合并T790M突变的患者显著延长(9.2个月vs 3.3个月,χ^(2)=2.81,P=0.041),两者总生存时间未见统计学差异(12.2个月vs 7.3个月,χ^(2)=3.22,P=0.062)。未合并T790M的客观缓解率明显优于合并T790M的患者(52.63%vs 12.5%, P=0.045)。结论 EGFR突变患者人群能从后线免疫联合治疗中获益,但合并T790M突变的患者后线接受免疫联合治疗疗效差。因此,这部分患者的后续治疗和全程化管理需要探索更优的治疗策略来提高获益。

1990—2017年中国伤害负担:2017年全球疾病负担研究结果(摘译)

伤害是全球性的公共卫生挑战,涉及各年龄组和不同性别的人群。过去三十年来,中国经济快速发展,人口老龄化趋势加重,社会呈现出城镇化、机动化和老龄化等特征。随着人们生活环境和生活方式的改变,伤害已跃居人群致死原因第五位,仅排在恶性肿瘤、心脑血管疾病、呼吸系统疾病和心肌梗死之后。据估计,中国每年在伤害方面消耗的直接医疗费用约为650亿元人民币.

Progresses of mycobacteriophage-based Mycobacterium tuberculosis detection

Tuberculosis(TB)remains a major cause of morbidity and mortality worldwide,particularly in developing countries.A rapid and efficient method for TB diagnosis is indispensable to check the trend of tuberculosis expansion.The emergence of drug-resistant bacteria has increased the challenge of rapid drug resistance tests.Due to its high specificity and sensitivity,bacteriophage-based diagnosis is intensively pursued.In this review,we mainly described mycobacteriophage-based diagnosis in TB detection,especially two prevalent approaches:fluorescent reporter phage and phage amplified biologically assay(PhaB).The rationale of reporter phage is that phage carrying fluorescent genes can infect host bacteria specifically.Phage amplified biological assay based on the principle that phages can infect the live Mycobacterium tuberculosis in the specimen under suitable conditions and produce plaques.Other phage-based diagnostic methods,such as a combination of the amplified biologically assay and nucleic acid amplification or lateral flow assays,are also actively explored.This review will help us improve the understanding of mycobacteriophages in TB detection and better promote the development of the rapid diagnosis of M.tuberculosis.

Prophages domesticated by bacteria promote the adaptability of bacterial cells

Prophages are temperate phages integrated into the host bacterial genome.They play an important role in the adaptation and the pathogenicity of bacteria,especially pathogenic bacteria.In this review,we described the distribution of prophages in different hosts and different environments,and focused on the significance of prophages.At the singlecell level,prophages can help the host adapt to harsh external environments by directly carrying virulence genes,encoding regulatory factors and activating lysogeny.At the population level,prophages can influence the overall evolutionary direction and ecological function of the host bacterial community.This review will help us understand the important role of prophages as unique organisms in individual bacteria and microbial populations.

Effect of sodium alginate on phosphorus recovery by vivianite precipitation

There are good prospects for phosphorus recovery from excess sludge by vivianite crystallization while a large number of extracellular polymeric substances in sludge will have impact on vivianite precipitation.In this study,as a representative of extracellular polymeric substance,the effect of sodium alginate(SA)on phosphorus recovery by vivianite precipitation under different initial SA concentrations(0–800 mg/L),p H values(6.5–9.0)and Fe/P molar ratios(1:1–2.4:1)was investigated using synthetic wastewater.The results showed that SA in low concentrations(≤400 mg/L)had little inhibitory effect on the phosphorus recovery rate.However,when the concentration of SA was larger than 400 mg/L,the phosphorus recovery rate decreased significantly with increasing SA concentrations.The inhibition rate of 800 mg/L SA was about 3 times as large as that of 400 mg/L SA.It was worth noting that the inhibitory effect of SA on vivianite precipitation decreased with increasing initial p H and Fe/P molar ratios.Additionally,SA has no obvious influence on the composition of products,but the morphology of harvested crystals was transformed from branches to plates or rods in uneven sizes.

Bacteriophages in water pollution control:Advantages and limitations

Wastewater is a breeding ground for many pathogens,which may pose a threat to human health through various water transmission pathways.Therefore,a simple and effective method is urgently required to monitor and treat wastewater.As bacterial viruses,bacteriophages(phages)are the most widely distributed and abundant organisms in the biosphere.Owing to their capacity to specifically infect bacterial hosts,they have recently been used as novel tools in water pollution control.The purpose of this review is to summarize and evaluate the roles of phages in monitoring pathogens,tracking pollution sources,treating pathogenic bacteria,infecting bloom-forming cyanobacteria,and controlling bulking sludge and biofilm pollution in wastewater treatment systems.We also discuss the limitations of phage usage in water pollution control,including phage-mediated horizontal gene transfer,the evolution of bacterial resistance,and phage concentration decrease.This review provides an integrated outlook on the use of phages in water pollution control.

Superconductivity in ThMo_2Si_2C with Mo_2C square net

We report the superconductivity of a new quaternary compound ThMo_(2)Si_(2)C, synthesized with the arc-melting technique. The compound crystallizes in a tetragonal CeCr_(2)Si_(2)C-type structure with cell parameters of a = 4.2296A and c = 5.3571 A. An interlayer Si–Si covalent bonding is suggested by the atomic distance. The electrical resistivity and magnetic susceptibility measurements indicate a Pauli-paramagnetic metal with dominant electron-electron scattering in the normal-state. Bulk superconductivity at 2.2 K is demonstrated with a dimensionless specific-heat jump of △C/γnT = 0.98. The superconducting parameters of the critical magnetic fields, coherence length, penetration depth, and superconducting energy gap are given.

Effect of contamination and relative humidity on the function of thyristor voltage monitoring board

In recent years,shutdown accidents caused by thyristor voltage monitoring(TVM)board failure have occurred several times in converter stations.With the increase of operation time,the working reliability problem of TVM board becomes a challenge to the safe operation.This paper studies the effects of pollution severity and relative humidity(RH)on the function of TVM board.The results show that the increase of RH can lead to the advance or even disappearance of check-back signals.Furthermore,the increase of pollution severity can decrease the failure RH threshold.Through simulation and equivalent experiment,it is verified that the resistance decrease of the voltage balancing resistor under the combined effect of contamination and RH is the main reason for the advance of check-back signals.According to the experiments,it is found that the upper surface contamination has a greater effect on the function of TVM board than the lower surface contamination,resulting in more decrease of the failure RH threshold.In addition,leakage current at different RH is also measured.Results show that the pulse peak of leakage current is closely related to check-back signals.When the pulse peak is too small or disappears,check-back signals also disappear,indicating that the TVM board fails.