Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

METAL CLUSTER DERIVATIVES OF TRIFLUOROMETHYL-SUBSTITUTED PHOSPHINES AND ARSINES

Ph.DDOCTOR OF PHILOSOPH

Synthesis and Structure of Two Acentric Heterometallic Inorganic–Organic Hybrid Frameworks with Both Nonlinear Optical and Ferroelectric Properties

Solvothermal reactions of Cd­(NO₃)₂·4H₂O with aromatic polycarboxylic acids in the presence of sodium nitrate led to two acentric three-dimensional (3D) heterometallic inorganic–organic hybrid frameworks, namely, [Me₂NH₂]­[Cd₂Na₃(2,4-PYDC)₄]·2H₂O (<b>1</b>) and [Me₂NH₂] [CdNa­(OH-<i>m</i>-BDC)₂(H₂O)₂]·2H₂O (<b>2</b>) (2,4-H₂PYDC = 2,4-pyridinedicarboxylic acid, OH-<i>m</i>-H₂BDC = 5-hydroxyisophthalic acid). The framework of <b>1</b> is constructed by a 3D inorganic Cd–Na connectivity, which resembles a concrete reinforcement structure and features a {CdNa}_<i>n</i> rod-shaped chain, a {CdNa₂}_<i>n</i> helical chain, and a 20-membered {Cd₆Na₁₄} ring. Compound <b>2</b> is built up by one-dimensional inorganic {CdNa}_<i>n</i> rod-shaped chains which are further connected by OH-<i>m</i>-BDC^2– ligands, affording a 3D polymeric framework. Compounds <b>1</b> and <b>2</b> crystallize in acentric space groups, and both display powder second harmonic generation efficiencies approximately 0.8 and 0.7 times, respectively, than that of the potassium dihydrogen phosphate (KDP) powder. In addition, they also exhibit luminescence and potential ferroelectric properties

Synthesis and Structure of Two Acentric Heterometallic Inorganic–Organic Hybrid Frameworks with Both Nonlinear Optical and Ferroelectric Properties

Solvothermal reactions of Cd­(NO₃)₂·4H₂O with aromatic polycarboxylic acids in the presence of sodium nitrate led to two acentric three-dimensional (3D) heterometallic inorganic–organic hybrid frameworks, namely, [Me₂NH₂]­[Cd₂Na₃(2,4-PYDC)₄]·2H₂O (<b>1</b>) and [Me₂NH₂] [CdNa­(OH-<i>m</i>-BDC)₂(H₂O)₂]·2H₂O (<b>2</b>) (2,4-H₂PYDC = 2,4-pyridinedicarboxylic acid, OH-<i>m</i>-H₂BDC = 5-hydroxyisophthalic acid). The framework of <b>1</b> is constructed by a 3D inorganic Cd–Na connectivity, which resembles a concrete reinforcement structure and features a {CdNa}_<i>n</i> rod-shaped chain, a {CdNa₂}_<i>n</i> helical chain, and a 20-membered {Cd₆Na₁₄} ring. Compound <b>2</b> is built up by one-dimensional inorganic {CdNa}_<i>n</i> rod-shaped chains which are further connected by OH-<i>m</i>-BDC^2– ligands, affording a 3D polymeric framework. Compounds <b>1</b> and <b>2</b> crystallize in acentric space groups, and both display powder second harmonic generation efficiencies approximately 0.8 and 0.7 times, respectively, than that of the potassium dihydrogen phosphate (KDP) powder. In addition, they also exhibit luminescence and potential ferroelectric properties

Three New Three-Dimensional Frameworks Based on Hepta‑, Hexa‑, and Pentanuclear Cobalt Clusters Derived from Substituted Isophthalic Acids: Synthesis, Structures, and Magnetic Properties

Three new cluster-based cobalt/carboxylate frameworks, formulated as {[H₃O]­[Co^II₇­(μ₃-OH)₃­(MeO-ip)₆­(H₂O)₃]­·4.5H₂O}_<i>n</i> (<b>1</b>), {[Co^II₆­(μ₃-OH)₂­(Bu^t-ip)₄­(Bu^t-Hip)₂­(H₂O)₂]­·2CH₃CN}_<i>n</i> (<b>2</b>), and {[Co^II₅(Me-ip)₄­(Me-Hip)₂­(H₂O)₄]­·6H₂O}_<i>n</i> (<b>3</b>) (MeO-H₂ip = 5-methoxyisophthalic acid, Bu^t-H₂ip = 5-<i>tert</i>-buthylisophthalic acid, and Me-H₂ip = 5-methylisophthalic acid) have been synthesized by the hydro­(solvo)­thermal reactions of Co₂(CO)₈ with the corresponding isophthalic acids in CH₃CN, Pr^<i>i</i>OH, and water. Single-crystal X-ray diffraction studies reveal that <b>1</b> and <b>2</b> both exhibit a three-dimensional (3D) <b>pcu</b> net based on hepta- and hexanuclear cobalt hydroxyl clusters {Co^II₇(μ₃-OH)₃} and {Co^II₆(μ₃-OH)₂}, respectively. Compound <b>3</b> is a 3D porous framework with an eight-connected <b>bcu</b> topology constructed from a pentanuclear cobalt cluster. It has been found that the structures of cobalt clusters in these compounds largely depend on the substituents on isophthalic acids. The magnetic studies indicate that both <b>1</b> and <b>2</b> show spin-canting antiferromagnetism, while <b>3</b> exhibits a magnetocaloric effect (MCE). The resulting entropy change of <b>3</b> is 13.23 J kg^–1 K^–1 for Δ<i>H</i> = 80 kG at 4 K

Environmental fate of the anti-parasitic ivermectin in an aquatic micro-ecological system after a single oral administration

Background Ivermectin (IVM) has been widely used in the aquaculture industry since its efficacy against parasites. However, the degradation of IVM was very slow in aquatic environments and the environmental fate of IVM in a complete aquatic system was still not clear. Therefore, comparable studies in a complete aquatic system were merited and helped to elucidate the environmental fate and effects of IVM. Methods An aquatic micro-ecological system containing an aquatic environment (water and sediment) and aquatic organisms (invertebrates, aquatic plants and fish) was built to simulate the natural rearing conditions. A single dose of 0.3 mg kg−1 body weight of IVM was given to the fish by oral gavage. Water, sediment, the roots and leaves of the aquatic plants, the soft tissue of the invertebrates and the visceral mass and muscle of fish samples were collected at 0.5 hours, 1 day, 7 days, 15 days, 30 days, 45 days, 60 days and 70 days after the treatment. IVM concentration in each sample was determined using ELISA method. Results IVM was quickly and widely distributed into the whole aquatic system in one day, and then was highly accumulated in organisms resulting in long-term residues. IVM was exchanged multiple times between the different media, which caused continuous fluctuations in the concentration of IVM in the water and sediment. It was worth noting that there was a second peak value of IVM in the fish and invertebrates after 30 days. The environmental fate of the IVM in the aquatic micro-ecological system showed that the drug was transferred from the fish to aquatic plants in the first seven days, and then gathered in the water and sediment, finally accumulating in the invertebrates. Our results indicated that an effective aquatic micro-ecological system was successfully established, and it could be applied to the study the environmental fate of IVM, which will aid the scientific use of this anti-parasitic agent during aquaculture

Synthesis of Petal-Like MnO2 Nanosheets on Hollow Fe3O4 Nanospheres for Heterogeneous Photocatalysis of Biotreated Papermaking Effluent

Owing to the implementation of increasingly stringent water conservation policies and regulations, the pulp and paper mill industry must make increased efforts to meet the limits for pollutant emissions. The primary pretreatment and secondary biochemical treatment methods used currently generally fail to meet the country-specific environmental regulations, and the wastewater must be processed further even after being subjected to secondary biochemical treatments. In this work, we synthesized Fe3O4/MnO2 nanocomposites (FMNs) with a flower-like structure for use in the heterogeneous photocatalytic treatment of biotreated papermaking wastewater. FMNs1.25, which were formed using a KMnO4/Fe3O4 molar ratio of 1.25, could be separated readily using an external magnetic field and exhibited higher photocatalytic activity than those of the other samples as well as MnO2 and Fe3O4. The effects of various experimental parameters on the photocatalytic activity of FMNs1.25, including the initial pH of the wastewater and the catalyst dosage, were determined. The common chemical oxygen demand (CODCr) reduction rate in the case of this sample reached 56.58% within 120 min at a pH of 3, the CODCr of effluent after treatment was 52.10 mg/L. Further, even under neutral conditions, the CODCr of the treated effluent was below the current limit for discharge in China. Moreover, the nanocomposites exhibited good recyclability, and their catalytic activity did not decrease significantly even after five usage cycles. This study should serve as a platform for the fabrication of effective photocatalysts for the advanced treatment of biotreated papermaking effluent and refractory organic wastewater