Lin28 Regulates Cancer Cell Stemness for Tumour Progression.

Tumours develop therapy resistance through complex mechanisms, one of which is that cancer stem cell (CSC) populations within the tumours present self-renewable capability and phenotypical plasticity to endure therapy-induced stress conditions and allow tumour progression to the therapy-resistant state. Developing therapeutic strategies to cope with CSCs requires a thorough understanding of the critical drivers and molecular mechanisms underlying the aforementioned processes. One such hub regulator of stemness is Lin28, an RNA-binding protein. Lin28 blocks the synthesis of let-7, a tumour-suppressor microRNA, and acts as a global regulator of cell differentiation and proliferation. Lin28also targets messenger RNAs and regulates protein translation. In this review, we explain the role of the Lin28/let-7 axis in establishing stemness, epithelial-to-mesenchymal transition, and glucose metabolism reprogramming. We also highlight the role of Lin28 in therapy-resistant prostate cancer progression and discuss the emergence of Lin28-targeted therapeutics and screening methods.

Deposition potential of 0.003-10 µm ambient particles in the humidified human respiratory tract: Contribution of new particle formation events in Beijing.

Ultrafine particles (UFPs) usually explosive growth during new particle formation (NPF) events. However, the risk of exposure to UFPs on NPF days has been ignored due to the prevalence of mass-based air quality standards. In this study, the daily deposited doses, i.e., the daily deposited particle number dose (DPNd), mass dose (DPMd), and surface area dose (DPSd), of ambient particles in the human respiratory tract in Beijing were evaluated based on the particle number size distribution (3 nm-10 µm) from June 2018 to May 2019 utilizing a Multiple-Path Particle Dosimetry Model (MPPD) after the hygroscopic growth of particles in the respiratory tract had been accounted for. Our observations showed a high frequency (72.6%) of NPF on excellent air quality days, with daily mean PM2.5 concentrations less than 35 µg m-3. The daily DPNd on excellent air quality days was comparable with that on polluted days, although the DPMd on excellent air quality days was as low as 15.6% of that on polluted days. The DPNd on NPF days was ~1.3 times that on non-NPF days. The DPNd in respiratory tract regions decreased in the order: tracheobronchial (TB) > pulmonary (PUL) > extrathoracic (ET) on NPF days, while it was PUL > TB > ET on non-NPF days. The number of deposited nucleation mode particles, which were deposited mainly in the TB region (45%), was 2 times higher on NPF days than that on non-NPF days. Our results demonstrated that the deposition potential due to UFPs in terms of particle number concentrations is high in Beijing regardless of the aerosol mass concentration. More toxicological studies related to UFPs on NPF days, especially those targeting tracheobronchial and pulmonary impairment, are required in the future.

Long-term winter observation of nitrous acid in the urban area of Beijing.

The particulate matter (PM) pollution has been significantly improved by carrying out various valid emission control strategies since 2013 in China. Meanwhile the variation trend of nitrous acid (HONO) is worthy to investigate due to its vital role in the atmospheric oxidation process. In this study, field observation in the winter is conducted to investigate the concentration of HONO in an urban area of Beijing. In the winter of 2019, the mean HONO concentration is 1.38 ppbV during the whole winter. Photo-enhanced NO2 heterogeneous reactions on the ground and aerosol surfaces were found as the possible daytime sources of HONO. Compared to O3, photolysis of HONO dominates the primary OH sources during the winter time. To understand the HONO pollution patterns by years variation, multi-year data is summarized and finds that primary pollutants including CO and NO decreased, but secondary pollutants i.e., HONO (mostly generated via secondary process) increased. Our study highlights the requirement to mitigate secondary pollution by control HONO concentration.

The impact of ammonium on the distillation of organic carbon in PM2.5.

Thermal desorption coupled with different detectors is an important analysis method for ambient carbonaceous aerosols. However, it is unclear how the compounds coexisting in both the gas and particle phases affect carbonaceous aerosol concentrations and measurements during thermal desorption. We observed matrix effects leading to a redistribution of different OC fractions (OC1 to OC4) during the thermal desorption process. These factors led to the formation of OC with low volatility (OC4), mainly from high-volatility OC (OC1 and OC2). Laboratory studies further indicated that ammonium promotes such matrix effects by transforming OC in the particle phase. Therefore, in addition to providing insights into the chemical evolution of OC during haze events, we argue that thermal-desorption-based OC measurements should be used with caution, which is an important step towards a more accurate measurement of OC in the ambient atmosphere.

Molecular Composition of Oxygenated Organic Molecules and Their Contributions to Organic Aerosol in Beijing.

The understanding at a molecular level of ambient secondary organic aerosol (SOA) formation is hampered by poorly constrained formation mechanisms and insufficient analytical methods. Especially in developing countries, SOA related haze is a great concern due to its significant effects on climate and human health. We present simultaneous measurements of gas-phase volatile organic compounds (VOCs), oxygenated organic molecules (OOMs), and particle-phase SOA in Beijing. We show that condensation of the measured OOMs explains 26-39% of the organic aerosol mass growth, with the contribution of OOMs to SOA enhanced during severe haze episodes. Our novel results provide a quantitative molecular connection from anthropogenic emissions to condensable organic oxidation product vapors, their concentration in particle-phase SOA, and ultimately to haze formation.

SFTA1P, LINC00968, GATA6-AS1, TBX5-AS1, and FEZF1-AS1 are crucial long non-coding RNAs associated with the prognosis of lung squamous cell carcinoma.

Lung cancer has high incidence and mortality rates, and lung squamous cell carcinoma (LUSC) is a common form of non-small-cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with LUSC prognosis. RNA-sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database. Using the limma package, differentially expressed genes (DEGs; including differentially expressed lncRNA genes (DELs), coding genes (DECs), and other genes (DEOs)) between LUSC and control samples were analyzed. Using Kaplan-Meier survival analysis, prognosis-associated lncRNAs were further selected. Following the calculation of Pearson's correlation coefficients between DELs and other DEGs, the DEL-DEG co-expression network was visualized using Cytoscape software. Using the clusterProfiler package, potential functions for DECs co-expressed with DELs were predicted. There were 1,305 DEGs in LUSC samples, including 153 DELs, 1,109 DECs, and 43 DEOs. Based on survival analysis, 22 prognosis-associated lncRNAs (including surfactant associated 1, pseudogene (SFTA1P), long intergenic non-protein coding RNA 968 (LINC00968), GATA6 antisense RNA 1, (GATA6-AS1) TBX5 antisense RNA 1 (TBX5-AS1) and FEZF1 antisense RNA 1 (FEZF1-AS1)) in LUSC were selected from these DELs, and the associated abnormal expression levels were also verified in LUSC clinical samples. A DEL-DEG co-expression network was constructed, which involved 93 DELs. Co-expressed DECs were enriched for only 8 prognosis-associated DELs, including LINC00968, SFTA1P, and TBX5-AS1. Specifically, mitogen-activated protein kinase (MAPK) signaling pathway-associated genes were enriched in DECs co-expressed with LINC00968, SFTA1P, GATA6-AS1, TBX5-AS1 and FEZF1-AS1, which may be prognosis-associated lncRNAs in LUSC. In addition, LINC00968 may affect the outcome of patients with LUSC via the MAPK signaling pathway.

3-(4-Hy-droxy-3-meth-oxy-phen-yl)acrylic acid-2,3,5,6-tetra-methyl-pyrazine (2/1).

The asymmetric unit of the title compound, C(8)H(12)N(2)·2C(10)H(10)O(4), contains a tetra-methyl-pyrazine mol-ecule, situated about an inversion center, and two substituted acrylic acid derivatives. The dihedral angle between the phenyl and pyrazine rings is 69.45 (9)°. In the crystal, inter-molecular O-H⋯O, O-H⋯N hydrogen bonds and weak C-H⋯O inter-actions lead to the formation of a supra-molecular network. The acrylic acid side chain is positionally disordered [occupancy ratio 0.852 (7):0.148 (7)].

(3aRS,4SR,7RS,7aSR)-2-(Tricyclo-[3.3.1.1]decan-1-yl)-4,5,6,7-tetra-hydro-4,7-epoxy-isoindoline-1,3-dione.

The title compound, C(18)H(23)NO(3), the adamantane derivative of norcantharidin, which is itself derived from cantharidin, crystallized with three independent mol-ecules in the asymmetric unit. In the crystal, mol-ecules are linked by inter-molecular C-H⋯O inter-actions, leading to the formation of a supra-molecular two-dimensional network.