Exploring active and low-cost transition metal oxides (TMOs) based catalysts for volatile organic compounds (VOCs) abatement is vital for air pollution control technologies. Since 18 oxygen atoms are required for the complete mineralization of a toluene molecule, the participation of a large amount of active oxygen is a key requirement for the catalytic oxidation of toluene. Here, toluene degradation was improved by weakening the Co–O bond strength on the surface of cobalt oxide, so as to increase the amount of active oxygen species, while maintaining the high stability of the catalyst for toluene combustion. The bond strength of Co–O and the amount of surface active O2 was regulated by tuning the pyrolysis temperature. The catalyst’s redox ability and surface oxygen species activity are improved due to the weakening of the Co–O bond strength. It has been demonstrated that active oxygen plays a crucial role in boosting toluene combustion by engineering Co–O strength in cobalt oxide catalysts. This work provides a new understanding of the exploration and development of high-performance TMO catalysts for VOCs abatement.

SUMMARY Similar to the mammalian intestine, the Drosophila adult midgut has resident stem cells that support growth and regeneration. How the niche regulates intestinal stem cell activity in both mammals and flies is not well understood. Here we show that the conserved germinal center protein kinase Misshapen restricts intestinal stem cell division by repressing the expression of the JAK-STAT pathway ligand Upd3 in differentiating enteroblasts. Misshapen, a distant relative to the prototypic Warts activating kinase Hippo, interacts with and activates Warts to negatively regulate the activity of Yorkie and the expression of Upd3. The mammalian Misshapen homolog MAP4K4 similarly interacts with LATS (Warts homolog) and promotes inhibition of YAP (Yorkie homolog). Together, this work reveals that the Misshapen-Warts-Yorkie pathway acts in enteroblasts to control niche signaling to intestinal stem cells. These findings also provide a model in which to study requirements for MAP4K4-related kinases in MST1/2-independent regulation of LATS and YAP.

The proproliferative transcription factor KLF5 plays an important role in promoting cell proliferation and tumorigenesis. KLF5 is a short-lived protein that can be rapidly degraded through the ubiquitin-proteasome pathway in cancer cells. However, the mechanisms regulating protein stability remain poorly understood. In this study, the tumor suppressor Fbw7, a component of the SCF complex (SCF Fbw7 ) E3 ubiquitin ligase, specifically promoted the degradation and ubiquitination of KLF5 but had little effect on the stability of KLF4. Fbw7 interacted with KLF5 in a CDC4 phosphodegron (CPD)-dependent manner. Three CPDs were found in the KLF5 protein. Simultaneous mutation of these CPDs significantly abolished Fbw7-mediated ubiquitination and degradation. Furthermore, Fbw7 deficiency dramatically delayed KLF5 turnover and led to the accumulation of KLF5 protein in cancer cells. Glycogen synthase kinase-3␤ could phosphorylate and promote Fbw7-mediated KLF5 degradation. More importantly, Fbw7 negatively regulated the biological activity of KLF5 in gene regulation and cell proliferation. Taken together, these data indicate that Fbw7 is a key negative regulator controlling KLF5-mediated cell proliferation and suggest an additional mechanism linking the loss of Fbw7 function to tumorigenesis. Sp/Krüppel-like factor (KLF) 2 transcription factors are involved in various biological processes and human diseases (1, 2). KLF5 (also known as IKLF and BTEB2) is a basic KLF transcription factor that regulates cell proliferation and plays an important role in diverse physiological and pathological processes, including stemness, inflammation, and atherogenesis (3, 4). As a proproliferative factor, KLF5 also has essential functions in tumorigenesis (3). Increasing evidence indicates that KLF5 can function as an oncogenic protein by promoting cell proliferation in many cancers (5-10). For example, a high expression level of KLF5 correlates with a shorter survival time in breast cancer patients (11). Inhibition of KLF5 expression by pharmacological or genetic methods significantly reduces colorectal cancer cell proliferation (6, 12). However, under certain conditions, KLF5 can also act as a tumor suppressor in some cancers (13,14). The exact mechanisms underlying these apparently contradictory functions are not completely understood.The function of KLF5 is regulated at multiple levels. KLF5 transcription is regulated by several signaling molecules such as Wnt and lysophosphatidic acid (15,16). At the post-translational level, KLF5 function is modulated by phosphorylation, sumoylation, and acetylation (3). Phosphorylation of KLF5 by protein kinase C enhances its transactivation activity and its interaction with CBP (cAMP-responsive element-binding protein-binding protein) (17), whereas sumoylation regulates KLF5-mediated lipid metabolism and its subcellular localization (18,19).KLF5 is an unstable protein with a short half-life in cells. Its protein levels are regulated negatively by the ubiquitin-proteasome pathway (20). The E3 ubiquiti...

No abstract

A preclinical trial identified 4 of 20 (20%) gastric cancer (GC) patient-derived xenografts responded to cetuximab. Genome-wide profiling and additional investigations revealed that high EGFR mRNA expression and immunohistochemistry score (3+) are associated with tumor growth inhibition. Furthermore, EGFR amplification were observed in 2/4 (50%) responders with average copy number 5.8 and >15 respectively. Our data suggest that a GC subtype with EGFR amplification and overexpression benefit from cetuximab treatment.