Rho‐associated coiled‐coil kinase 1 activation mediates amyloid precursor protein site‐specific Ser655 phosphorylation and triggers amyloid pathology

Rho‐associated coiled‐coil kinase 1 (ROCK1) is proposed to be implicated in Aβ suppression; however, the role for ROCK1 in amyloidogenic metabolism of amyloid precursor protein (APP) to produce Aβ was unknown. In the present study, we showed that ROCK1 kinase activity and its APP binding were enhanced in AD brain, resulting in increased β‐secretase cleavage of APP. Furthermore, we firstly confirmed that APP served as a substrate for ROCK1 and its major phosphorylation site was located at Ser655. The increased level of APP Ser655 phosphorylation was observed in the brain of APP/PS1 mice and AD patients compared to controls. Moreover, blockade of APP Ser655 phosphorylation, or inhibition of ROCK1 activity with either shRNA knockdown or Y‐27632, ameliorated amyloid pathology and improved learning and memory in APP/PS1 mice. These findings suggest that activated ROCK1 targets APP Ser655 phosphorylation, which promotes amyloid processing and pathology. Inhibition of ROCK1 could be a potential therapeutic approach for AD.     

Senescence‐associated tissue microenvironment promotes colon cancer formation through the secretory factor GDF15

The risk of colorectal cancer (CRC) varies between people, and the cellular mechanisms mediating the differences in risk are largely unknown. Senescence has been implicated as a causative cellular mechanism for many diseases, including cancer, and may affect the risk for CRC. Senescent fibroblasts that accumulate in tissues secondary to aging and oxidative stress have been shown to promote cancer formation via a senescence‐associated secretory phenotype (SASP). In this study, we assessed the role of senescence and the SASP in CRC formation. Using primary human colon tissue, we found an accumulation of senescent fibroblasts in normal tissues from individuals with advanced adenomas or carcinomas in comparison with individuals with no polyps or CRC. In in vitro and ex vivo model systems, we induced senescence using oxidative stress in colon fibroblasts and demonstrated that the senescent fibroblasts secrete GDF15 as an essential SASP factor that promotes cell proliferation, migration, and invasion in colon adenoma and CRC cell lines as well as primary colon organoids via the MAPK and PI3K signaling pathways. In addition, we observed increased mRNA expression of GDF15 in primary normal colon tissue from people at increased risk for CRC in comparison with average risk individuals. These findings implicate the importance of a senescence‐associated tissue microenvironment and the secretory factor GDF15 in promoting CRC formation.     

Subcellular cadmium distribution and antioxidant enzymatic activities in the leaves of four Hylotelephium spectabile populations exhibit differences in phytoextraction potential

Hylotelephium spectabile with high tolerance to cadmium (Cd) might be a potential candidate for phytoremediation. However, the mechanisms for Cd accumulation and tolerance in H. spectabile are poorly understood. Four H. spectabile populations, namely HB1, HB2, JS, and LN, were selected to investigate their Cd extraction potential and the underlying mechanism of Cd accumulation, focusing on subcellular distribution and antioxidant enzymes. The Cd concentration, bioconcentration factor and transfer factor of the LN was significantly higher than other populations, particularly with increasing Cd exposure, and no obvious growth inhibition observed. Segregation of excessive Cd to Cd-rich granule in LN was much higher than other populations which reveal one possible mechanism of Cd accumulation. A significant increase in superoxide dismutase (SOD) and catalase (CAT) activities with increasing Cd stress suggested SOD and CAT contribute to the Cd tolerance of H. spectabile. LN displayed significantly higher and constant peroxidase (POD) activities than other populations, which indicated that an effective mechanism existed in the LN to cope with Cd stress. Therefore, the subcellular distribution and antioxidant enzymes might play important roles in Cd accumulation and tolerance of H. spectabile. LN possessed high Cd extraction potential, and further studies under field conditions are warranted.     

A molecularly imprinted polymer based chemiluminescence array sensor for one‐step determination of phenothiazines and benzodiazepines in pig urine

The residues of phenothiazines and benzodiazepines in foods of animal origin are dangerous to consumers. For inspection of their abuses, this study for the first time reported on the use of a chemiluminescence array sensor for the simultaneous determination of four phenothiazines and five benzodiazepines in pig urine. Two molecularly imprinted polymers were coated in different wells of a conventional 96‐well microtiter plate as the recognition reagents. After sample loading, the absorbed analytes were initiated directly by using an imidazole enhanced bis(2,4,6‐trichlorophenyl)oxalate–hydrogen peroxide system to emit light. The assay process consisted of only one sample‐loading step prior to data acquisition, so one test was finished within 10 min. The limits of detection for the nine drugs in the pig urine were in a range of 0.1 to 0.6 pg/mL, and the recoveries from the fortified blank urine samples were in a range of 80.3 to 95%. Furthermore, the sensor could be reused six times. Therefore, this sensor could be used as a simple, rapid, sensitive and reusable tool for routine screening for residues of phenothiazines and benzodiazepines in pig urine.     

The structure and luminescence properties of Mn2+/Eu2+/Er3+‐doped MgO‐Ga2O3‐SiO2 glasses and glass‐ceramics

The MgO–Ga₂O₃–SiO₂ glasses and glass‐ceramics samples doped with Eu²⁺/Mn²⁺/Er³⁺ and heated in reductive atmosphere were prepared by the sol–gel method. The structure, morphology and the luminescence properties were studied using X‐ray diffraction, high‐resolution transmission electron microscope, fluorescence spectra, and up‐conversion emission. The luminescence characteristics of doped ions could be influenced by temperature and matrix component. The characteristic emission of Mn²⁺, Eu²⁺ and Er³⁺ were seen and the energy transfer efficiency from Eu²⁺ to Mn²⁺ was enhanced as Mn²⁺ concentration was increased. In addition, the two‐photon process was determined for the Er³⁺‐doped samples.     

A novel function of anaphase promoting complex subunit 10 in tumor progression in non-small cell lung cancer

The anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase, is responsible for the transition from metaphase to anaphase and the exit from mitosis. The anaphase promoting complex subunit 10 (APC10), a subunit of the APC/C, executes a vital function in substrate recognition. However, no research has reported the connection between APC10 and cancer until now. In this study, we uncovered a novel, unprecedented role of APC10 in tumor progression, which is independent of APC/C. First, aberrant increase of APC10 expression was validated in non-small cell lung cancer (NSCLC) cells and tissues, and the absence of APC10 repressed cell proliferation and migration. Of great interest, we found that APC10 inhibition induced cell cycle arrest at the G0/G1 phase and reduced the expression of the APC/C substrate, Cyclin B1; this finding is different from the conventional concept of the accumulation of Cyclin B1 and cell cycle arrest in metaphase. Further, APC10 was found to interact with glutaminase C (GAC), and the inhibition of APC10 weakened glutamine metabolism and induced excessive autophagy. Taken together, these findings identify a novel function of APC10 in the regulation of NSCLC tumorigenesis and point to the possibility of APC10 as a new target for cancer therapy.     

Flexible Na/K‐Ion Full Batteries from the Renewable Cotton Cloth–Derived Stable,Low‐Cost,and Binder‐Free Anode and Cathode

Flexible Na/K‐ion batteries (NIBs/KIBs) exhibit great potential applications and have drawn much attention due to the continuous development of flexible electronics. However, there are still many huge challenges, mainly the design and construction of flexible electrodes (cathode and anode) with outstanding electrochemical properties. In this work, a unique approach to prepare flexible electrode is proposed by utilizing the commercially available cotton cloth–derived carbon cloth (CC) as a flexible anode and the substrate of a cathode. The binder‐free, self‐supporting, and flexible cathodes (FCC@N/KPB) are prepared by growing Prussian blue microcubes on the flexible CC (FCC). Na/K‐ion full batteries (FCC//FCC@N/KPB) are assembled by using FCC and FCC@N/KPB as anode and cathode, respectively. Electrochemical performance, mechanical flexibility, and practicability of FCC//FCC@N/KPB Na/K‐ion full batteries are evaluated in both coin cells and flexible pouch cells, demonstrating their superior energy‐storage properties (excellent rate performance and cycling stability) and remarkable flexibility (they can work under different bending states). This work provides a new and profound strategy to design flexible electrodes, promoting the development of flexible NIBs/KIBs to be practical and sustainable.