MOCS, a novel classifier system integrated multimoics analysis refining molecular subtypes and prognosis for skin melanoma.

PURPOSE: The present investigation focuses on Skin Cutaneous Melanoma (SKCM), a melanocytic carcinoma characterized by marked aggression, significant heterogeneity, and a complex etiological background, factors which collectively contribute to the challenge in prognostic determinations. We defined a novel classifier system specifically tailored for SKCM based on multiomics. METHODS: We collected 423 SKCM samples with multi omics datasets to perform a consensus cluster analysis using 10 machine learning algorithms and verified in 2 independent cohorts. Clinical features, biological characteristics, immune infiltration pattern, therapeutic response and mutation landscape were compared between subtypes. RESULTS: Based on consensus clustering algorithms, we identified two Multi-Omics-Based-Cancer-Subtypes (MOCS) in SKCM in TCGA project and validated in GSE19234 and GSE65904 cohorts. MOCS2 emerged as a subtype with poor prognosis, characterized by a complex immune microenvironment, dysfunctional anti-tumor immune state, high cancer stemness index, and genomic instability. MOCS2 exhibited resistance to chemotherapy agents like erlotinib and sunitinib while sensitive to rapamycin, NSC87877, MG132, and FH355. Additionally, ELSPBP1 was identified as the target involving in glycolysis and M2 macrophage infiltration in SKCM. CONCLUSIONS: MOCS classification could stably predict prognosis of SKCM; patients with a high cancer stemness index combined with genomic instability may be predisposed to an immune exhaustion state.Communicated by Ramaswamy H. Sarma.

Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src.

Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.

Roles of calcium signaling in cancer metastasis to bone.

Bone metastasis is a frequent complication for cancers and an important reason for the mortality in cancer patients. After surviving in bone, cancer cells can cause severe pain, life-threatening hypercalcemia, pathologic fractures, spinal cord compression, and even death. However, the underlying mechanisms of bone metastasis were not clear. The role of calcium (Ca2+) in cancer cell proliferation, migration, and invasion has been well established. Interestingly, emerging evidence indicates that Ca2+ signaling played a key role in bone metastasis, for it not only promotes cancer progression but also mediates osteoclasts and osteoblasts differentiation. Therefore, Ca2+ signaling has emerged as a novel therapeutical target for cancer bone metastasis treatments. Here, the role of Ca2+ channels and Ca2+-binding proteins including calmodulin and Ca2+-sensing receptor in bone metastasis, and the perspective of anti-cancer bone metastasis therapeutics via targeting the Ca2+ signaling pathway are summarized.

Highly efficient Hg2+ removal via a competitive strategy using a Co-based metal organic framework ZIF-67.

The stronger coordination ability of mercury ions with organic ligands than the metal ions in metal organic framework (MOFs) provides an accessible way to separate mercury ions from solution using specific MOFs. In this study, a Co-based MOF (ZIF-67, Co(mIM)2) was synthesized. It did not introduce specific functional groups, such as -SH and -NH2, into its structure through complicated steps. It separate Hg2+ from wastewater with a new strategy, which utilized the stronger coordination ability of Hg2+ with the nitrogen atom on the imidazole ring of the organic ligand than the Co2+ ions. Hg2+ replaced Co2+ nodes from ZIF-67 and formed a more stable precipitate with mIM. The experimental results showed that this new strategy was efficient. ZIF-67 exhibited Hg2+ adsorption capacity of 1740 mg/g, much higher than the known MOFs sorbents. mIMs is the reaction center and ZIF-67 can improve its utilization. The sample color faded from purple to white due to the loss of cobalt ion. It is a great feature of ZIF-67 that allows users to judge whether the sorbent is deactivated intuitively. ZIF-67 can be sustainable recycled by adding organic ligands to the solution after treatment due to its simple synthesis method at room temperature. It's a high-efficient and sustainable sorbent for Hg2+ separation from wastewater.

SO2 Resisting Pd-doped Pr1-x Cex MnO3 Perovskites for Efficient Denitration at Low Temperature.

H2 -SCR is served as the promising technology for the controlling of NOx emission, and the Pd-based derivative catalyst exhibited high NOx reduction performance. Effectively regulating the electronic configuration of the active component is favorable to the rational optimization of noble Pd. In this work, a series of Pr1-x Cex Mn1-y Pdy O3 @Ni were successfully synthesized and exhibited superior NO conversion efficiency at low temperatures. 92.7 % conversion efficiency was achieved at 200 °C over Pr0.9 Ce0.1 Mn0.9 Pd0.1 O3 @Ni in the presence of 4 % O2 with a GHSV of 32000 h-1 . Meanwhile, the outstanding performance was obtained in the resistance to SO2 (200 ppm) and H2 O (8 %). Deduced from the results of XRD, Raman, XPS, and H2 -TPR, the modification of d orbit states in palladium was confirmed originating from the incorporation in the B site of Pr0.9 Ce0.1 Mn0.9 Pd0.1 O3 . The existence of higher valence (Pd3+ and Pd4+ ) than the bivalence in Pr0.9 Ce0.1 Mn0.9 Pd0.1 O3 catalyst was evidenced by XPS analysis. Our research provides a new sight into the H2 -SCR through the higher utilization of Pd.

In Situ Hydrogen Uptake and NO x Adsorption on Bifunctional Heterogeneous Pd/Mn/Ni for a Low Energy Path toward Selective Catalytic Reduction.

Facilitating catalyst accessibility of H2 and NO x at the catalyst surface remains a great challenge in catalytic selective catalytic reduction (SCR). The efficient conversion of NO x into N2 under mild conditions is an attractive pathway as SCR usually requires high operating temperature which consumes extra operating energy and restricts the possible locations of an SCR device. The H2 supply concentration of conventional H2-SCR is relatively sparse (0.5-2%), which leads to a relatively high operating temperature to activate H. We developed a H2-SCR process with the monolithic catalyst which combined with localized rarefied hydrogen enrichment enhanced by porous nickel and adsorption of NO x on Mn oxide with only 0.08, 0.25, and 0.42% palladium can achieve over 80% NO removal efficiency at 120, 100, and 90 °C. Maximizing the role of nickel foam-fixed hydrogen and Mn oxide in combination with NO can provide enriched NO x and H2 atmosphere for adjustable valence state Pd to yield positive catalytic behavior.

Metal-Organic Framework (MOF) Template Based Efficient Pt/ZrO2 @C Catalysts for Selective Catalytic Reduction of H2 Below 90 °C.

Selective catalytic reduction (SCR) of NOx with H2 as a reductant is the most promising denitration technology at low temperature. Achieving the conversion of NOx into N2 at ambient temperature not only prolongs the service life of the catalyst, but also provides more freedom for the arrangement of denitration units throughout the flue gas treatment equipment. However, the development of highly efficient, stable, and environmentally benign supported platinum-based catalysts for H2 -SCR at ambient temperature is still a major challenge. Herein, a 0.5 wt % Pt/ZrO2 @C catalyst, which was composed of carbon-coated octahedral ZrO2 with highly dispersed Pt particles, was prepared by using a new stabilization strategy based on UiO-66-NH2 (a zirconium metal-organic framework) as a template. The catalytic performance of this Pt/ZrO2 @C in H2 -SCR was tested and confirmed to achieve near 100 % NOx conversion at 90 °C. Also, 70 % N2 selectivity of the catalyst was achieved. The morphology, structure, and porous properties of the as-synthesized nanocomposites were characterized by using data obtained from field-emission SEM, TEM, XRD, Raman spectroscopy, thermogravimetric analysis, X-ray photoelectron spectroscopy, and N2 adsorption-desorption isotherms. The results show that residual carbon formed by pyrolysis treatment is coated on octahedral ZrO2 , and effectively prevents the agglomeration of platinum particles on the surface.

Di-metal-doped sulfur resisting perovskite catalysts for highly efficient H2-SCR of NO.

Lanthanide perovskite catalysts doped with limited palladium (to improve activity) and cerium (to improve sulfur resistance) were prepared using sol-gel method. In different B sites, lanthanide perovskites were studied at harsh conditions for H2 selective catalytic reduction of NO. The activity sequence was as follows: LaCeMnPd > LaCeCoPd > LaCeFePd. LaCeMnPd had a high NO conversion of 96.6% at only 150 °C. And it also had a surprising SO2 resistance in different SO2 concentrations. After cutting out SO2, NO conversion recovered rapidly to its original level, indicating that the slight deactivation was reversible. In addition, the effect of gas hourly space velocity, H2/NO ratio, O2, and SO2 concentration was studied. And XRD, energy-dispersive X-ray, SEM, XPS, H2-temperature programmed reduction, and NH3-temperature programmed desorption were performed to characterize the catalysts. Graphical abstract ᅟ.