Vanillin is a natural compound endowed with antioxidant and anti-mutagenic properties. We previously identified the vanillin derivative VND3207 with strong radio-protective and antioxidant effects ...and found that VND3207 confers survival benefit and protection against radiation-induced intestinal injury (RIII) in mice. We also observed that VND3207 treatment enhanced the expression level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in human lymphoblastoid cells with or without γ-irradiation. DNA-PKcs is a critical component of DNA double strand break repair pathway and also regulates mitotic progression by stabilizing spindle formation and preventing mitotic catastrophe in response to DNA damage. In the present study, we found that VND3207 protected intestinal epithelial cells in vitro against ionizing radiation by promoting cell proliferation and inhibiting cell apoptosis. In addition, VND3207 promoted DNA-PKcs activity by increasing autophosphorylation at S2056 site. Consistent with this, VND3207 significantly decreased the number of γH2AX foci and mitotic catastrophe after radiation. DNA-PKcs deficiency abolished these VND3207 radio-protective effects, indicating that DNA-PKcs activation is essential for VND3207 activity. In conclusion, VND3207 promoted intestinal repair following radiation injury by regulating the DNA-PKcs pathway.
•VND3207 promotes proliferation and inhibits apoptosis in HIEC cells post IR.•VND3207 promotes DNA-PKcs activity increasing autophosphorylation at S2056 site.•VND3207 reduces DNA DSBs and mitotic catastrophe after IR by activating DNA-PKcs.•The activation of DNA-PKcs is essential for the protective effect of VND3207 on RIII.
Colorectal cancer is the 4th common cancer in China. Most colorectal cancers are due to modifiable lifestyle factors, but few studies have provided a systematic evidence-based assessment of the ...burden of colorectal cancer incidence and mortality attributable to the known risk factors in China.
We estimated the population attributable faction (PAF) for each selected risk factor in China, based on the prevalence of exposure around 2000 and relative risks from cohort studies and meta-analyses.
Among 245,000 new cases and 139,000 deaths of colorectal cancer in China in 2012, we found that 115,578 incident cases and 63,102 deaths of colorectal cancer were attributable to smoking, alcohol drinking, overweight and obesity, physical inactivity and dietary factors. Low vegetable intake was the main risk factor for colorectal cancer with a PAF of 17.9%. Physical inactivity was responsible for 8.9% of colorectal cancer incidence and mortality. The remaining factors, including high red and processed meat intake, low fruit intake, alcohol drinking, overweight/obesity and smoking, accounted for 8.6%, 6.4%, 5.4%, 5.3% and 4.9% of colorectal cancer, respectively. Overall, 45.5% of colorectal cancer incidence and mortality were attributable to the joint effects of these seven risk factors.
Tobacco smoking, alcohol drinking, overweight or obesity, physical inactivity, low vegetable intake, low fruit intake, and high red and processed meat intake were responsible for nearly 46% of colorectal cancer incidence and mortality in China in 2012. Our findings could provide a basis for developing guidelines of colorectal cancer prevention and control in China.
The histone acetyltransferases (HATs) adenovirus E1A-associated protein (p300) and CREB binding protein (CBP) serve as coactivators during a diverse assortment of cellular processes. In the present ...study, p300 and CBP were highly expressed in 5 gastric cancer (GC) cell lines (SGC‑7901, MKN45, MGC-803, BGC-823 and KATO III) compared with human normal gastric epithelial cell line (GES-1). C646, a selective inhibitor of p300 and CBP, inhibited cell viability and cell cycle and promoted cell apoptosis in all 5 GC cell lines. In addition, C646 suppressed the migration and invasion capability of the GC cell lines, except for the middle-differentiated SGC-7901 cell line. Furthermore, we detected the differential expression of corresponding oncogenic signalling molecules, such as c-Met, Akt, Bcl-2, Bax, cyclin D1, MMP7 and MMP9, in GC cells following C646 treatment. In conclusion, our results suggest that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment.
In steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) systems, traditional flickering stimulation patterns face challenges in achieving a trade-off in both BCI ...performance and visual comfort across various frequency bands. To investigate the optimal stimulation paradigms with high performance and high comfort for each frequency band, this study systematically compared the characteristics of SSVEP and user experience of different stimulation paradigms with a wide stimulation frequency range of 1-60 Hz. The findings suggest that, for a better balance between system performance and user experience, ON and OFF grid stimuli with a Weber contrast of 50% can be utilized as alternatives to traditional flickering stimulation paradigms in the frequency band of 1-25 Hz. In the 25-35 Hz range, uniform flicker stimuli with the same 50% contrast are more suitable. In the higher frequency band, traditional uniform flicker stimuli with a high 300% contrast are preferred. These results are significant for developing high performance and user-friendly SSVEP-based BCI systems.
The electrolyte solvation structure and the solid-electrolyte interphase (SEI) formation are critical to dictate the morphology of lithium deposition in organic electrolytes. However, the link ...between the electrolyte solvation structure and SEI composition and its implications on lithium morphology evolution are poorly understood. Herein, we use a single-salt and single-solvent model electrolyte system to systematically study the correlation between the electrolyte solvation structure, SEI formation process and lithium deposition morphology. The mechanism of lithium deposition is thoroughly investigated using cryo-electron microscopy characterizations and computational simulations. It is observed that, in the high concentration electrolytes, concentrated Li
and anion-dominated solvation structure initiate the uniform Li nucleation kinetically and favor the decomposition of anions rather than solvents, resulting in inorganic-rich amorphous SEI with high interface energy, which thermodynamically facilitates the formation of granular Li. On the contrary, solvent-dominated solvation structure in the low concentration electrolytes tends to exacerbate the solvolysis process, forming organic-rich mosaic SEI with low interface energy, which leads to aggregated whisker-like nucleation and growth. These results are helpful to tackle the long-standing question on the origin of lithium dendrite formation and guide the rational design of high-performance electrolytes for advanced lithium metal batteries.
Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD
)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated ...diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing.
To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms.
We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of occludin and zona occludens 1 (ZO-1) was assessed by Western blot analysis. Annexin V-APC/7-AAD assays were performed to evaluate Caco-2 apoptosis. Dextran sodium sulfate (DSS)-induced colitis mice were exposed to SRT1720 or NAM for 7 d. Transferase-mediated dUTP nick-end labeling (TUNEL) assays were conducted to assess apoptosis in colon tissues. The expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, caspase-9, and caspase-3 in Caco-2 cells and the colon tissues of treated mice were examined by quantitative real-time PCR and Western blot.
SRT1720 treatment increased the protein levels of occludin and ZO-1 and inhibited Caco-2 apoptosis, whereas NAM administration caused the opposite effects. DSS-induced colitis mice treated with SRT1720 had a lower disease activity index (
< 0.01), histological score (
< 0.001), inflammatory cytokine levels (
< 0.01), and apoptotic cell rate (
< 0.01), while exposure to NAM caused the opposite effects. Moreover, SIRT1 activation reduced the expression levels of GRP78, CHOP, cleaved caspase-12, cleaved caspase-9, and cleaved caspase-3 in Caco-2 cells and the colon tissues of treated mice.
SIRT1 activation reduces apoptosis of IECs
the suppression of endoplasmic reticulum stress-mediated apoptosis-associated molecules CHOP and caspase-12. SIRT1 activation may be a potential therapeutic strategy for UC.
Iron and nitrogen co-doped carbon (Fe-N-C) catalysts hold great promise to replace platinum group metal used for the oxygen reduction reaction (ORR) in low-temperature fuel cells. However, general ...synthesis routes require tedious acid washing and extensive heat treatment, usually resulting in uncontrollable morphologies and undesirable compounds. In this work, a zeolitic imidazolate framework (ZIF-8) was employed as a self-template for one-pot synthesis of a Fe-N-C catalyst consisting of uniformly dispersed Fe single atoms. Atomically dispersed Fe atoms were well distributed along the edges of the porous carbon matrix. Each of the Fe atoms was coordinated with four N atoms in the plane and two O atoms in the axial direction. The optimized Fe-N-C catalyst showed excellent ORR activities with half-wave potentials of 0.81 and 0.90 V in acidic and alkaline solutions, respectively. The results may be important for the optimization of single-atom-based catalysts for various reactions.
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•Fe-N-C catalyst with atomically dispersed Fe atoms was synthesized using ZIF-8 as the self-template.•The optimized Fe-N-C catalyst showed superior activity for the oxygen reduction reaction in both acid and alkaline solutions.•The half-wave potential only shifted 16 mV after 10,000 potential cycles.
Optimized Fe-N-C catalyst with atomically dispersed Fe atoms showed excellent activity and high stability for the oxygen reduction reaction. Each Fe atom (yellow) is coordinated with four N atoms (blue) in the plane and two oxygen atoms (red) in the axial direction.
We report systematic studies of the microstructural changes of uncoated and AlF3-coated Li-rich Mn-rich (LMR) cathode materials (Li1.2Ni0.15Co0.10Mn0.55O2) before and after cycling using a ...combination of aberration-corrected scanning/transmission electron microscopy (S/TEM) and electron energy loss spectroscopy (EELS). TEM coupled with EELS provides detailed information about the crystallographic and electronic structure changes that occur after cycling, thus revealing the fundamental improvement mechanism of surface coating. The results demonstrate that the surface coating reduces oxidation of the electrolyte at high voltage, suppressing the accumulation of a thick solid electrolyte interface (SEI) layer on electrode particle surface. Surface coating significantly enhances the stability of the surface structure and protects the electrode from severe etching/corrosion by the acidic species in the electrolyte, reducing the formation of etched surfaces and corrosion pits. Moreover, surface coating alleviates the undesirable voltage fade by mitigating layered to spinel-like phase transformation in the bulk region of the material. These fundamental findings may also be widely applied to explain the functioning mechanisms of other surface coatings used in a broad range of electrode materials.
Solid superbases can catalyze diverse reactions under mild conditions, while they suffer from aggregation of basic sites and poor stability during recycling. Here we report a new generation of solid ...superbases derived from K single atoms (SAs) prepared by a tandem redox strategy. The initial redox reaction takes place between base precursor KNO3 and graphene support, producing K2O at 400 °C. Further increasing the temperature to 800 °C, the graphene reduces K2O to K anchored by its vacancies, leading to the generation of K SAs (denoted as K1/G). The source of basicity in the K1/G is K SAs, and neighboring single atoms (NSAs) possess superbasicity, which is different from conventional basicity originated from oxygen and nitrogen atoms. Due to the superbasicity as well as high dispersion and anchoring of basic sites, the K1/G shows excellent catalytic activity and stability in transesterification reaction, which is much superior to the reported catalysts.
A new generation of solid superbase derived from potassium single atoms anchored on graphene is developed by a tandem redox strategy. The source of the basicity is the single K atoms, thus differing from conventional basicity which originates from oxygen and nitrogen atoms. The high dispersion and anchoring of superbasic sites endows the catalyst with excellent activity and stability in transesterification reactions.
Aqueous zinc-ion batteries, in terms of integration with high safety, environmental benignity, and low cost, have attracted much attention for powering electronic devices and storage systems. ...However, the interface instability issues at the Zn anode caused by detrimental side reactions such as dendrite growth, hydrogen evolution, and metal corrosion at the solid (anode)/liquid (electrolyte) interface impede their practical applications in the fields requiring long-term performance persistence. Despite the rapid progress in suppressing the side reactions at the materials interface, the mechanism of ion storage and dendrite formation in practical aqueous zinc-ion batteries with dual-cation aqueous electrolytes is still unclear. Herein, we design an interface material consisting of forest-like three-dimensional zinc-copper alloy with engineered surfaces to explore the Zn plating/stripping mode in dual-cation electrolytes. The three-dimensional nanostructured surface of zinc-copper alloy is demonstrated to be in favor of effectively regulating the reaction kinetics of Zn plating/stripping processes. The developed interface materials suppress the dendrite growth on the anode surface towards high-performance persistent aqueous zinc-ion batteries in the aqueous electrolytes containing single and dual cations. This work remarkably enhances the fundamental understanding of dual-cation intercalation chemistry in aqueous electrochemical systems and provides a guide for exploring high-performance aqueous zinc-ion batteries and beyond.
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