Dysregulation of long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and tumor progression, including hepatocellular carcinoma (HCC). Small nucleolar RNA host gene 3 (SNHG3) has ...been considered as an lncRNA to be associated with a poor prognosis in patients with HCC. Here, we reported that SNHG3 expression was significantly higher in the highly metastatic HCC (HCCLM3) cells compared with the lowly metastatic HCC cells (Hep3B and PLC/PRF/5). Furthermore, forced expression of SNHG3 promoted cell invasion, epithelial‐mesenchymal transition (EMT), and sorafenib resistance in HCC. Moreover, SNHG3 overexpression induced HCC cells EMT via miR‐128/CD151 cascade activation. Clinically, our data revealed that increased SNHG3 expression is correlated with poor HCC survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.
Here, our data revealed that increase in small nucleolar RNA host gene 3 (SNHG3) expression is correlated with poor hepatocellular carcinoma survival outcomes and sorafenib response. These data suggest that SNHG3 may be a novel therapeutic target and a biomarker for predicting response to sorafenib treatment of HCC.
Major depressive disorder (MDD) is a debilitating psychiatric illness. However, there is currently no objective laboratory-based diagnostic tests for this disorder. Although, perturbations in ...multiple neurotransmitter systems have been implicated in MDD, the biochemical changes underlying the disorder remain unclear, and a comprehensive global evaluation of neurotransmitters in MDD has not yet been performed. Here, using a GC-MS coupled with LC-MS/MS-based targeted metabolomics approach, we simultaneously quantified the levels of 19 plasma metabolites involved in GABAergic, catecholaminergic, and serotonergic neurotransmitter systems in 50 first-episode, antidepressant drug-naïve MDD subjects and 50 healthy controls to identify potential metabolite biomarkers for MDD (training set). Moreover, an independent sample cohort comprising 49 MDD patients, 30 bipolar disorder (BD) patients and 40 healthy controls (testing set) was further used to validate diagnostic generalizability and specificity of these candidate biomarkers. Among the 19 plasma neurotransmitter metabolites examined, nine were significantly changed in MDD subjects. These metabolites were mainly involved in GABAergic, catecholaminergic and serotonergic systems. The GABAergic and catecholaminergic had better diagnostic value than serotonergic pathway. A panel of four candidate plasma metabolite biomarkers (GABA, dopamine, tyramine, kynurenine) could distinguish MDD subjects from health controls with an AUC of 0.968 and 0.953 in the training and testing set, respectively. Furthermore, this panel distinguished MDD subjects from BD subjects with high accuracy. This study is the first to globally evaluate multiple neurotransmitters in MDD plasma. The altered plasma neurotransmitter metabolite profile has potential differential diagnostic value for MDD.
Nitrate (NO3−) is a key component of secondary inorganic aerosols and PM2.5. However, the contributions of nitrogen oxides (NOx) emission sources to NO3− in PM2.5 remain poorly constrained. This ...study measured nitrogen (N) isotopes of NO3− (hereafter as δ15N-NO3-) in PM2.5 collected at Beijing in 2014. We observed that δ15N-NO3- values in PM2.5 (−2.3‰ − 19.7‰; 7.3 ± 5.4‰ annually) were significantly higher in winter (11.9 ± 4.4‰) than in summer (2.2 ± 2.5‰). The δ15N differences between source NOx and NO3− in PM2.5 (hereafter as Δ values) were estimated by a computation module as 7.8 ± 2.2‰ − 10.4 ± 1.6‰ (8.8 ± 2.4‰). Using the Δ values and δ15N values of NOx from major fossil (coal combustion, vehicle exhausts) and non-fossil sources (biomass burning, microbial N cycle), contributions of major NOx sources to NO3− in PM2.5 were further estimated by the SIAR model. We found that seasonal variations of δ15N-NO3- values in PM2.5 of Beijing were mainly caused by those of NOx contributions from coal combustion (38 ± 10% in winter, 20 ± 9% in summer). Annually, NOx from coal combustion, vehicle exhausts, biomass burning, and microbial N cycle contributed 28 ± 12%, 29 ± 17%, 27 ± 15%, and 16 ± 7% to NO3− in PM2.5, respectively, showing actually comparable contributions between non-fossil NOx (43 ± 16%) and fossil NOx (57 ± 21%). These results are useful for planning the reduction of NOx emissions in city environments and for elucidating relationships between regional NOx emissions and atmospheric NO3− pollution or deposition.
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•δ15N-NO3- values of PM2.5 in Beijing were higher in winter than in summer.•Seasonal δ15N-NO3- variations of PM2.5 were mainly caused by those of NOx emission from coal combustion.•Fossil and non-fossil NOx sources contributed equally to NO3− of PM2.5 in Beijing.
Isotope partitioning of major nitrate sources in PM2.5
Scaling in membrane distillation (MD) is a key issue in desalination of concentrated saline water, where the interface property between the membrane and the feed become critical. In this paper, a ...slippery mechanism was explored as an innovative concept to understand the scaling behavior in membrane distillation for a soluble salt, NaCl. The investigation was based on a novel design of a superhydrophobic polyvinylidene fluoride (PVDF) membrane with micro-pillar arrays (MP-PVDF) using a micromolding phase separation (μPS) method. The membrane showed a contact angle of 166.0 ± 2.3° and the sliding angle of 15.8 ± 3.3°. After CF4 plasma treatment, the resultant membrane (CF4-MP-PVDF) showed a reduced sliding angle of 3.0°. In direct contact membrane distillation (DCMD), the CF4-MP-PVDF membrane illustrated excellent anti-scaling in concentrating saturated NaCl feed. Characterization of the used membranes showed that aggregation of NaCl crystals occurred on the control PVDF and MP-PVDF membranes, but not on the CF4-MP-PVDF membrane. To understand this phenomenon, a “slippery” theory was introduced and correlated the sliding angle to the slippery surface of CF4-MP-PVDF and its anti-scaling property. This work proposed a well-defined physical and theoretical platform for investigating scaling problems in membrane distillation and beyond.
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•MicroMolding phase separation (μPS) was utilized to prepare pillared hydrophobic membranes.•Porous micropillars PVDF surface appeared superhydrophobic.•CF4 plasma modification turned the surface from superhydrophobic to slippery.•Slippery surface showed significant resistance to scaling in treating saturated NaCl solutions by membrane distillation.
It remains unclear whether and how cardiomyocytes contribute to the inflammation in chronic heart failure (CHF). We recently reviewed the capacity of cardiomyocytes to initiate inflammation, by means ...of expressing certain immune receptors such as toll‐like receptors (TLRs) that respond to pathogen‐ and damage‐associated molecular patterns (PAMP and DAMP). Previous studies observed TLR4‐mediated inflammation within days of myocardial infarction (MI). This study examined TLR4 expression and function in cardiomyocytes of failing hearts after 4 weeks of MI in rats. The increases of TLR4 mRNA and proteins, as well as inflammatory cytokine production, were observed in both the infarct and remote myocardium. Enhanced immunostaining for TLR4 was observed in cardiomyocytes but not infiltrating leucocytes. The injection of lentivirus shRNA against TLR4 into the infarcted heart decreased inflammatory cytokine production and improved heart function in vivo. Accordingly, in cardiomyocytes isolated from CHF hearts, increases of TLR4 mRNA and proteins were detected. More robust binding of TLR4 with lipopolysaccharide (LPS), a PAMP ligand for TLR4, and heat shock protein 60 (HSP60), a DAMP ligand for TLR4, was observed in CHF cardiomyocytes under a confocal microscope. The maximum binding capacity (Bmax) of TLR4 was increased for LPS and HSP60, whereas the binding affinity (Kd) was not significantly changed. Furthermore, both LPS and HSP60 induced more robust production of inflammatory cytokines in CHF cardiomyocytes, which was reduced by TLR4‐blocking antibodies. We conclude that the expression, ligand‐binding capacity and pro‐inflammatory function of cardiomyocyte TLR4 are up‐regulated after long‐term MI, which promote inflammation and exacerbate heart failure.
High performance superhydrophobic PVDF flat sheet membranes for direct contact membrane distillation (DCMD) were prepared via CF4 plasma surface modification. The performance of the virgin and CF4 ...modified membranes was examined using sodium chloride solution (4wt%) as feed in a DCMD process. Results reveal that CF4 surface modification yielded superhydrophobic membranes (water contact angle: 162.4°) with about 30% higher water flux than the virgin PVDF membrane. The underlying mechanism that leads to the significant improvement in membrane performance was investigated in detail with respect to membrane morphology, gas permeability, liquid entry pressure, and contact angle measurements. Results indicate that the combination of increased gas permeability and superhydrophobicity contributes mostly to the improved water flux.
•Preparation of superhydrophobic membranes for membrane distillation.•Superhydrophobic membranes showed higher water flux than virgin ones.•Flux enhancement mechanism proposed.
The dysregulation of circular RNA (circRNA) expression is involved in the progression of several cancers, including non‐small cell lung cancer (NSCLC). However, the role and underlying molecular ...mechanisms of circRNA FGFR3 (circFGFR3) in NSCLC progression remains unknown. Here, we used quantitative real‐time polymerase chain reaction to validate that circFGFR3 expression was higher in NSCLC tissues than in the paratumor tissues. Furthermore, our study indicated that the forced circFGFR3 expression promoted NSCLC cell invasion and proliferation. Mechanistically, we found that circFGFR3 promoted NSCLC cell invasion and proliferation via competitively combining with miR‐22‐3p to facilitate the galectin‐1 (Gal‐1), p‐AKT, and p‐ERK1/2 expressions. Clinically, we revealed that the high circFGFR3 expression correlates with the poor clinical outcomes in patients with NSCLC. Together, these data provide mechanistic insights into the circFGFR3‐mediated regulation of both the AKT and ERK1/2 signaling pathways by sponging miR‐22‐3p and increasing Gal‐1 expression.
The dysregulation of the circular RNA (circRNA) expression is involved in the progression of several cancers, including non‐small cell lung cancer (NSCLC). Together, these data provide mechanistic insights into circRNA FGFR3 (circFGFR3)‐mediated regulation of both the AKT and ERK1/2 signaling pathways by sponging miR‐22‐3p and increasing Gal‐1 expression.
Long noncoding RNAs (lncRNAs) have been implicated in numerous physiological and pathological processes, including cancer development and progression. However, the role and molecular mechanism of ...lncRNAs in resistance to chemotherapy of colorectal cancer (CRC) remain enigmatic. Here, we found that lncRNA small Cajal body‐specific RNA 2 (SCARNA2) is expressed higher in CRC tissues than in adjacent normal tissues, and a robust expression of SCARNA2 is correlated with a bad prognosis of CRC patients after surgery. SCARNA2 overexpression significantly promoted chemoresistance in CRC cells, and downregulation of SCARNA2 obviously inhibited chemoresistance in vitro. SCARNA2 promotes chemotherapy resistance via competitively binding miR‐342‐3p to facilitate epidermal growth factor receptor (EGFR) and B‐cell lymphoma 2 (BCL2) expression in CRC cells. Together, our results reveal a novel pathway that SCARNA2 regulates CRC chemoresistance through targeting miR‐342‐3p‐EGFR/BCL2 pathway, providing a promising therapeutic target for CRC.
Nitrate (NO3−), which is mainly oxidized from NO2 by the OH radical (OH·) and O3 in the atmosphere, is a major component of inorganic aerosols. However, the contributions of the OH· and O3 pathways ...to NO3− in urban aerosols and the influence of air pollution to both pathways remain unclear. Oxygen isotopes of NO3− were measured for PM2.5 in Beijing in 2014. The Δ17O‐NO3− values (17.0–32.8‰) were significantly higher in winter (27.2 ± 3.6‰) than in summer (24.2 ± 1.3‰). By estimating contributions of O3 to the NOx cycle, the Δ17O values of NO3− endmembers produced via the NO2 + OH· (P1), NO3· + DMS/HC (P2), and N2O5 hydrolysis (P3) pathways were calculated for each observation. The contributions of the three pathways (P1: 32 ± 10%, P2: 34 ± 10%, and P3: 34 ± 20% annually) were calculated using the Stable Isotope Analysis in R model. We found that NO3− formation was dominated by the O3 oxidation pathways (P2 + P3; 68 ± 23% annually, 73 ± 21% in spring, 59 ± 23% in summer, 75 ± 20% in autumn, and 69 ± 22% in winter). Moreover, PM2.5, NO2, and NO3− pollution decreased the importance of the OH· pathway relative to the O3 pathways for NO3− production. However, O3 pollution increased the importance of the OH· pathway relative to the O3 pathways for NO3− production. These results provided a comprehensive analysis on the oxygen isotope records in particulate NO3− for understanding the relative importance of major oxidation pathways of NO2. Atmospheric pollution substantially influenced the pathways of NO2 oxidation to NO3− in city environments.
Plain Language Summary
Air pollution is a major environmental and public health issue; to strengthen studies on haze formation mechanisms is a national environment demand. Although monitoring works have been widely conducted on atmospheric particulates, it has long been difficult to quantify production mechanisms of key chemical components. Combined oxygen isotopes (18O, 17O) of nitrate with the Stable Isotope Analysis in R model, we evaluated the fractional contributions of three major oxidation pathways (NO2 + OH· P1, NO3· + DMS/HC P2, and N2O5 hydrolysis P3) to the NO3− of PM2.5. We found that annually 68 ± 23% of NO3− in PM2.5 at Beijing was produced by the O3 oxidation pathways (P2 + P3). Moreover, PM2.5, NO2, and NO3− pollution decreased the importance of the OH· pathway relative to the O3 pathways for NO3− production. Our results provided a comprehensive analysis on the oxygen isotope records in particulate NO3− for understanding the relative importance of major oxidation pathways of NO2. Atmospheric pollution substantially influenced the pathways of NO2 oxidation to NO3− in city environments.
Key Points
Δ17O signatures of NO3− in PM2.5 at Beijing were reported
Contributions of major oxidation pathways to NO3− of PM2.5 were evaluated
Air pollution changed the importance of OH· pathway relative to O3 pathways for NO3− production
Inspired by the 2D bilayer lipid membranes in nature, a unique supramolecular “push–pull” synergetic strategy toward self‐assembled 2D organic crystals (2DOCs) is proposed in this work, which can ...effectively suppress the interlayer 3D stacking while maintaining the assembly of the intralayer for 2D growth. For this purpose, a model molecule PF‐Py consisting of a planar supramolecular “attractor” and a nonplanar steric “repellor” is designed for the solution self‐assembly process. Well‐defined 2DOCs including crystal nanosheets and millimeter‐sized crystal films with layered amphiphile‐like packing are obtained, which is analogical to the cell membranes of living organisms. Thanks to the special packing mode, the 2DOCs have fascinating integrated photoelectric property, with high mobility of 7.8 × 10−2 cm2 V−1 s−1, high crystalline state photoluminescence quantum yield of 55%, and superior deep‐blue laser characteristics with a low threshold of 5.51 µJ cm−2. This supramolecular synergetic strategy advances the design of 2D organic semiconductor crystals for high performance optoelectronics.
Rational molecular design strategy toward 2D organic crystals (2DOCs) is necessary but rare. Here, a novel supramolecular “push–pull” strategy to guide the molecular design by integrating a planar segment and a nonplanar group into one molecule is developed. Thanks to the synergetic effect of the two groups, size controllable 2DOCs with superior integrated photoelectric property are realized.
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