Hypoxia occurs naturally at high-altitudes and pathologically in hypoxic solid tumors. Here, we report that genes involved in various human cancers evolved rapidly in Tibetans and six Tibetan ...domestic mammals compared to reciprocal lowlanders. Furthermore, m
A modified mRNA binding protein YTHDF1, one of evolutionary positively selected genes for high-altitude adaptation is amplified in various cancers, including non-small cell lung cancer (NSCLC). We show that YTHDF1 deficiency inhibits NSCLC cell proliferation and xenograft tumor formation through regulating the translational efficiency of CDK2, CDK4, and cyclin D1, and that YTHDF1 depletion restrains de novo lung adenocarcinomas (ADC) progression. However, we observe that YTHDF1 high expression correlates with better clinical outcome, with its depletion rendering cancerous cells resistant to cisplatin (DDP) treatment. Mechanistic studies identified the Keap1-Nrf2-AKR1C1 axis as the downstream mediator of YTHDF1. Together, these findings highlight the critical role of YTHDF1 in both hypoxia adaptation and pathogenesis of NSCLC.
Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative ...correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein–binding protein–associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. Conclusion: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515‐528).
The CuS(x wt%)@Cu‐BTC (BTC = 1,3,5‐benzenetricarboxylate; x = 3, 10, 33, 58, 70, 99.9) materials are synthesized by a facile sulfidation reaction. The composites are composed of octahedral ...Cu3(BTC)2·(H2O)3 (Cu‐BTC) with a large specific surface area and CuS with a high conductivity. The as‐prepared CuS@Cu‐BTC products are first applied as the anodes of lithium‐ion batteries (LIBs). The synergistic effect between Cu‐BTC and CuS components can not only accommodate the volume change and stress relaxation of electrodes but also facilitate the fast transport of Li ions. Thus, it can greatly suppress the transformation process from Li2S to polysulfides by improving the reversibility of the conversion reaction. Benefiting from the unique structural features, the optimal CuS(70 wt%)@Cu‐BTC sample exhibits a remarkably improved electrochemical performance, showing an over‐theoretical capacity up to 1609 mAh g−1 after 200 cycles (100 mA g−1) with an excellent rate‐capability of ≈490 mAh g−1 at 1000 mA g−1. The outstanding LIB properties indicate that the CuS(70 wt%)@Cu‐BTC sample is a highly desirable electrode material candidate for high‐performance LIBs.
CuS@Cu‐BTC composites are used as anode materials for lithium‐ion batteries for the first time, which exhibit improved Li‐ion storage abilities originating from the synergistic effect between the Cu‐BTC and nano‐CuS components.
Adrenomedullin (ADM) exerts anti-oxidant, anti-inflammatory and anti-apoptotic effects in Leydig cells. However, the role and mechanism of ADM in the pyroptosis of Leydig cells are poorly understood. ...This study first showed the protective effects of ADM on the pyroptosis and biological functions of Leydig cells exposed to lipopolysaccharide (LPS) by promoting autophagy. Primary rat Leydig cells were treated with various concentrations of LPS and ADM, together with or without N-acetyl-L-cysteine (NAC) or 3-methyladenine (3-MA). Cell proliferation was detected through CCK-8 and BrdU incorporation assays, and ROS level was measured with the DCFDA assay. Real-time PCR, western blot, immunofluorescence, transmission electron microscopy, TUNEL and flow cytometry were performed to examine ADM's effect on the pyroptosis, autophagy and steroidogenic enzymes of Leydig cells and AMPK/mTOR signalling. Like NAC, ADM dose-dependently reduced LPS-induced cytotoxicity and ROS overproduction. ADM also dose-dependently ameliorated LPS-induced pyroptosis by reversing the increased expression of NLRP3, ASC, caspase-1, IL-1β, IL-18, GSDMD, caspase-3, caspase-7, TUNEL-positive and PI and active caspase-1 double-stained positive rate, DNA fragmentation and LDH concentration, which could be rescued via co-incubation with 3-MA. ADM dose-dependently increased autophagy in LPS-induced Leydig cells, as confirmed by the increased expression of LC3-I/II, Beclin-1 and ATG-5; decreased expression of p62 and autophagosomes formation; and increased LC3-II/LC3-I ratio. However, co-treatment with 3-MA evidently decreased autophagy. Furthermore, ADM dose-dependently rescued the expression of steroidogenic enzymes, including StAR, P450scc, 3β-HSD and CYP17, and testosterone production in LPS-induced Leydig cells. Like rapamycin, ADM dose-dependently enhanced AMPK phosphorylation but reduced mTOR phosphorylation in LPS-induced Leydig cells, which could be rescued via co-incubation with 3-MA. In addition, pyroptosis was further decreased, and autophagy was further promoted in LPS-induced Leydig cells upon co-treatment with ADM and rapamycin. ADM may protect the steroidogenic functions of Leydig cells against pyroptosis by activating autophagy via the ROS-AMPK-mTOR axis.
Inspired by a cactus spine and trichomes integrated fog collection system, a strategy is presented to design a micro/nanostructured conical spine and Janus membrane integrative system (MNCS+JM). In ...this strategy, the surface of conical spine can be covered with rough micro and nanostructure (MNCS), so that the tiny fog‐droplets can be captured, coalesced, and transported. Janus membrane (JM) with inside hydrophobic surface and outside hydrophilic surface is further used to control the water collection in process of droplet transport when the Janus membrane is vertically placed with different positions on the MNCS, thus MNCS+JM propel the droplet continuously for transport–coalescence–transport in a circle of droplet transport and collection. It is demonstrated that a higher fog collection rate can be achieved effectively, which is attributed to a cooperation effect between the Laplace pressure in difference and the released surface energy in droplet coalescence, in addition to wettability force of superhydrophobic–hydrophilic difference in the Janus membrane. This strategy of MNCS+JM offers an insight into the surface of materials to control the droplet transport for water collection in efficiency, which is significant to be extended into the realms of applications such as high‐efficiency water collection systems, microfluidics devices, and others.
The effective fog‐droplets collection can be achieved on rough conical spine with micro/nanostructures and Janus membrane.
The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory ...circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901-2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101-213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.
Long noncoding RNAs (lncRNA) have been associated with various types of cancer; however, the precise role of many lncRNAs in tumorigenesis remains elusive. Here we demonstrate that the cytosolic ...lncRNA P53RRA is downregulated in cancers and functions as a tumor suppressor by inhibiting cancer progression. Chromatin remodeling proteins LSH and Cfp1 silenced or increased P53RRA expression, respectively. P53RRA bound Ras GTPase-activating protein-binding protein 1 (G3BP1) using nucleotides 1 and 871 of P53RRA and the RRM interaction domain of G3BP1 (aa 177-466). The cytosolic P53RRA-G3BP1 interaction displaced p53 from a G3BP1 complex, resulting in greater p53 retention in the nucleus, which led to cell-cycle arrest, apoptosis, and ferroptosis. P53RRA promoted ferroptosis and apoptosis by affecting transcription of several metabolic genes. Low P53RRA expression significantly correlated with poor survival in patients with breast and lung cancers harboring wild-type p53. These data show that lncRNAs can directly interact with the functional domain of signaling proteins in the cytoplasm, thus regulating p53 modulators to suppress cancer progression.
A cytosolic lncRNA functions as a tumor suppressor by activating the p53 pathway.
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Active-phase engineering is regularly utilized to tune the selectivity of metal nanoparticles (NPs) in heterogeneous catalysis. However, the lack of understanding of the active phase in ...electrocatalysis has hampered the development of efficient catalysts for CO
2
electroreduction. Herein, we report the systematic engineering of active phases of Pd NPs, which are exploited to select reaction pathways for CO
2
electroreduction.
In situ
X-ray absorption spectroscopy,
in situ
attenuated total reflection-infrared spectroscopy, and density functional theory calculations suggest that the formation of a hydrogen-adsorbed Pd surface on a mixture of the α- and β-phases of a palladium-hydride core (α+β PdH
x
@PdH
x
) above −0.2 V (vs. a reversible hydrogen electrode) facilitates formate production via the HCOO* intermediate, whereas the formation of a metallic Pd surface on the β-phase Pd hydride core (β PdH
x
@Pd) below −0.5 V promotes CO production via the COOH* intermediate. The main product, which is either formate or CO, can be selectively produced with high Faradaic efficiencies (>90%) and mass activities in the potential window of 0.05 to −0.9 V with scalable application demonstration.
We performed the first proteogenomic characterization of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues from 159 patients. Integrated ...proteogenomic analyses revealed consistency and discordance among multi-omics, activation status of key signaling pathways, and liver-specific metabolic reprogramming in HBV-related HCC. Proteomic profiling identified three subgroups associated with clinical and molecular attributes including patient survival, tumor thrombus, genetic profile, and the liver-specific proteome. These proteomic subgroups have distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics. Two prognostic biomarkers, PYCR2 and ADH1A, related to proteomic subgrouping and involved in HCC metabolic reprogramming, were identified. CTNNB1 and TP53 mutation-associated signaling and metabolic profiles were revealed, among which mutated CTNNB1-associated ALDOA phosphorylation was validated to promote glycolysis and cell proliferation. Our study provides a valuable resource that significantly expands the knowledge of HBV-related HCC and may eventually benefit clinical practice.
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•Proteomic subgroups stratify patient survival and allocate specific treatments•Alterations of the liver-specific proteome and metabolism in HCC are identified•Multi-omics profile of key signaling and metabolic pathways in HCC is depicted•CTNNB1 mutation-associated ALDOA phosphorylation promotes HCC cell proliferation
Proteogenomic characterization of HBV-related hepatocellular carcinoma (HCC) using paired tumor and adjacent liver tissues identifies three subgroups with distinct features in metabolic reprogramming, microenvironment dysregulation, cell proliferation, and potential therapeutics.
Facilitating phase conversion efficiency of Li polysulfides to Li2S and restraining the dissolution of Li polysulfides are critical for stable lithium–sulfur (Li–S) batteries. Herein, an in situ ...formed sulfiphilic superfine Fe2O3 nanocrystals confined in lithiophilic N‐doped microporous carbon (Fe2O3/N‐MC) is derived from one‐step hypercrosslinked polymerization. Uniquely, the dual active sites (Fe2O3 and N) in Fe2O3/N‐MC tend to form “FeS, LiO or LiN” bonding, and then synchronically enhancing the chemisorption and interface conversion ability of Li polysulfides. As a result, 80 wt% S is loaded on Fe2O3/N‐MC and the hybrid cathode delivers high mass capacity (730 mA h g‐1) and excellent cycling stability (87.1% capacity retention over 1000 cycles at 5.0 C). Especially, the cathode also exhibits a high reversible areal capacity of 3.69 mA h cm‐2 at a high areal loading (5.1 mg cm‐2) and a lean electrolyte/sulfur (E/S) ratio (7.5 µL mg‐1) over 500 cycles. This work is anticipated to deepen the comprehension of complex Li polysulfides interphase conversion processes and afford new thoughts for designing new host materials.
Facilitating phase conversion efficiency of Li polysulfides to Li2S and restraining the dissolution of Li polysulfides are critical for stable lithium–sulfur (Li–S) batteries. The as‐prepared Fe2O3/N‐microporous carbon (MC) is in favor of enhancing sulfur content, releasing volume expansion, immobilizing soluble lithium polysulfides (LiPSs), and optimizing Li2S nucleation, hence accommodating the S@Fe2O3/N‐MC cathode with excellent cycling stability.
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