Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers,Signaling Pathways and miRNAome

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.     

Vapor linker exchange of partially amorphous metal–organic framework membranes for ultra-selective gas separation

Metal–organic framework (MOF) membranes are promising for efficient separation applications. However, the uncontrollable pathways at atomic level impede the further development of these membranes for molecular separation. Herein we show that vapor linker exchange can induce partial amorphization of MOF membranes and then reduce their transport pathways for precisely molecular sieving. Through exchanging MOF linkers by incoming ones with similar topology but higher acidity, the resulted metal-linker bonds with lower strength cause the transformation of MOF membranes from order to disorder/amorphous. The linker exchange and partial amorphization can narrow intrinsic apertures and conglutinate grain boundary/crack defects of membranes. Because of the formation of ultra-microporous amorphous phase, the MOF composite membrane shows competitive H₂/CO₂ selectivity up to 2400, which is about two orders of magnitude higher than that of conventional MOF membranes, accompanied by high H₂ permeance of 13.4 × 10⁻⁸ mol m⁻² s⁻¹ Pa⁻¹ and good reproducibility and stability.     

Butyrate and Propionate Restore the Cytokine and House Dust Mite Compromised Barrier Function of Human Bronchial Airway Epithelial Cells

Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression.     

Co-Oxidative Transformation of Piperine to Piperonal and 3,4-Methylenedioxycinnamaldehyde by a Lipoxygenase from Pleurotus sapidus

The valuable aroma compound piperonal with its vanilla-like olfactory properties is of high interest for the fragrance and flavor industry. A lipoxygenase (LOX_Psa1) of the basidiomycete Pleurotus sapidus was identified to convert piperine, the abundant pungent principle of black pepper (Piper nigrum), to piperonal and a second volatile product, 3,4-methylenedioxycinnamaldehyde, with a vanilla-like odor through an alkene cleavage. The reaction principle was co-oxidation, as proven by its dependence on the presence of linoleic or α-linolenic acid, common substrates of lipoxygenases. Optimization of the reaction conditions (substrate concentrations, reaction temperature and time) led to a 24-fold and 15-fold increase of the piperonal and 3,4-methylenedioxycinnamaldehyde concentration using the recombinant enzyme. Monokaryotic strains showed different concentrations of and ratios between the two reaction products.     

萝卜硫素介导Akt/p70S6K信号传导诱导人鼻咽癌CNE-2细胞凋亡

目的:研究萝卜硫素对人鼻咽癌CNE-2细胞增殖、凋亡的影响及其对Akt/p70S6K信号传导的作用。方法:采用CCK-8实验分析萝卜硫素对CNE-2细胞生长增殖的影响，流式细胞仪检测萝卜硫素对CNE-2细胞凋亡率及细胞周期分布的影响，Western blot技术检测CNE-2细胞中调控细胞周期的相关蛋白及Akt/p70S6K信号通路关键蛋白的表达水平。结果:采用萝卜硫素干预CNE-2细胞后，细胞增殖抑制率及凋亡率相对于对照组呈浓度依赖的方式显著增高，差异有统计学意义（P<0.05）；流式细胞仪分析提示，萝卜硫素干预能够将细胞停留在S期及G2/M期，并且萝卜硫素还能抑制细胞周期蛋白Cyclin A、Cyclin B、Cyclin D、Cyclin E以及CDK/p34的表达水平，与对照组相比差异有统计学意义（P<0.05）；此外，萝卜硫素还能抑制Akt/p70S6K信号通路关键蛋白p-Akt及p70S6K蛋白表达水平（P<0.05），但萝卜硫素与Akt激动剂IGF-I共同处理细胞后，上述蛋白表达量与对照组相比没有统计学差异（P>0.05）。结论:萝卜硫素可能通过干扰CNE-2细胞中Akt/p70S6K信号传导而发挥有效的抗增殖及促凋亡的作用。     

Identification of Host Cellular Protein Substrates of SARS-COV-2 Main Protease

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-19 (COVID-19) being associated with severe pneumonia. Like with other viruses, the interaction of SARS-CoV-2 with host cell proteins is necessary for successful replication, and cleavage of cellular targets by the viral protease also may contribute to the pathogenesis, but knowledge about the human proteins that are processed by the main protease (3CLpro) of SARS-CoV-2 is still limited. We tested the prediction potentials of two different in silico methods for the identification of SARS-CoV-2 3CLpro cleavage sites in human proteins. Short stretches of homologous host-pathogen protein sequences (SSHHPS) that are present in SARS-CoV-2 polyprotein and human proteins were identified using BLAST analysis, and the NetCorona 1.0 webserver was used to successfully predict cleavage sites, although this method was primarily developed for SARS-CoV. Human C-terminal-binding protein 1 (CTBP1) was found to be cleaved in vitro by SARS-CoV-2 3CLpro, the existence of the cleavage site was proved experimentally by using a His₆-MBP-mEYFP recombinant substrate containing the predicted target sequence. Our results highlight both potentials and limitations of the tested algorithms. The identification of candidate host substrates of 3CLpro may help better develop an understanding of the molecular mechanisms behind the replication and pathogenesis of SARS-CoV-2.     

Precise Molecular Sieving Architectures with Janus Pathways for Both Polar and Nonpolar Molecules

Precise molecular sieving architectures with Janus superhighways are constructed via a molecularly engineered interfacial reaction between cyclodextrin (CD) and trimesoyl chloride (TMC). Interestingly, the CD/TMC nanofilms constructed with both hydrophobic inner cavities and hydrophilic channels exhibit exceptionally high permeances for both polar and nonpolar solvents. The precise molecular sieving functions are determined by the type of CD building blocks and the inner cavities of intrinsic 3D hollow bowls. Positron annihilation spectroscopy (PAS) confirms that a larger inner CD cavity tends to generate a larger free volume and higher microporosity. Based on the rejection ratio of various dyes, the estimated molecular weight cutoff of CD/TMC nanofilms follows the trend of α‐CD/TMC (320 Da) <β‐CD/TMC (400 Da) <γ‐CD/TMC (550 Da), which is in strict accordance with the orders of their free volumes measured by PAS and inner cavity sizes of α‐CD <β‐CD <γ‐CD. This kind of novel CD/TMC molecular sieving membrane with intrinsic microporosity containing tunable pore size and sharp pore‐size distribution can effectively discriminate molecules with different 3D sizes.     

硅酸盐夹杂在集装箱底侧梁脆性开裂过程中的作用

某集装箱底侧梁在正常使用过程中发生开裂,事故发生时箱内载重未超过箱体允许的承重极限。通过对开裂的底侧梁进行化学成分光谱分析、拉伸及冲击性能测试、梁正常部位及断口毗邻区域金相检验、断口分析以及夹杂物综合分析等,分析了底侧梁开裂的原因,研究并解释了夹杂物在开裂过程中所起的作用。检验及分析结果表明,底侧梁钢板强韧性低下,且表面脱碳,存在表面强度进一步低于基体的现象,在服役过程中导致裂纹易于在表面萌生。酸溶铝(Als)含量极低,这也导致钢板存在较高的韧脆转变温度,服役过程中存在较大的安全隐患。同时钢板内存在大量大尺寸的MnO-SiO₂-Al₂O₃系和CaO-SiO₂-Al₂O₃系硅酸盐塑性夹杂,该夹杂在热加工过程中被严重拉长,分布于晶界和晶内,严重破坏了钢材基体连续性,导致其强韧性低下并促进了裂纹的扩展。服役过程中底侧梁R角处作为应力集中部位首先发生开裂,进而裂纹以沿晶+穿晶解理的方式快速扩展,最终脆性开裂。     

Ca2+ enhances algal photolysis hydrogen production by improving the direct and indirect pathways

In this study, Ca²⁺ was applied to enhance the photolysis H₂ production of Chlamydomonas reinhardtii grown in pure culture or co-cultivated with bacterium. With addition of Ca²⁺, the chlorophyll and protein contents in algal cells were maintained at high levels and the reactive oxygen species (ROS) were scavenged to tolerable levels by activities of catalase (CAT) and superoxide dismutase (SOD). High chlorophyll and low ROS are benefit to protect the photosystem II (PS II) activity that responsible for the direct photolysis H₂ production. Moreover, addition of Ca²⁺ was able to promote the acetic acid assimilation as well as the starch synthesis. The starch degradation, in return, contributed to the H₂ production via the indirect photolysis pathway. Based on the improvements of direct and indirect photolysis pathways, the H₂ production of algae grown in co-cultivation adding with 5 mM Ca²⁺ reached a maximum value of 306 mL L⁻¹, which was 2.4 times higher than the production without Ca²⁺ addition. This study gives an efficient and easy strategy to improve the algal photolysis H₂ production, and gets an insight into the mechanisms of the improvement.